iso series, guide of pharmaceutical manufacturing facilities, productivity by kailash vilegave
DESCRIPTION
ISO series, guide of pharmaceutical manufacturing facilities, productivity ISO: 9000 series. ISO:14000 series. Guide to Pharmaceutical Manufacturing Facilities, ProductivityTRANSCRIPT
04122023Department of Pharmaceutics 1
Seminar on helliphellip
ISO series guide of pharmaceutical manufacturing facilities productivity
By
Mr Kailash Vilegave
Assit prof
Shivajirao S Jondhle college of pharmacy Asangaon 421601
04122023Department of Pharmaceutics 2
Contents
Introduction History ISO 9000 series ISO14000 series Guide to Pharmaceutical
Manufacturing Facilities Productivity References
04122023Department of Pharmaceutics 3
IntroductionWhat are ISO 9000 Standards
ISO 9000 Standards Define the required elements of an effective
quality management system Can be applied to any company Adopted by the United States as the
ANSIASQC Q90 series
154 COUNTRIES
Bureau of Standards Jamaica
STANDARD BODIES
04122023Department of Pharmaceutics 4
bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA
bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness
bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996
Background Who Created Standards
04122023Department of Pharmaceutics 5
How did ISO get started
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 2
Contents
Introduction History ISO 9000 series ISO14000 series Guide to Pharmaceutical
Manufacturing Facilities Productivity References
04122023Department of Pharmaceutics 3
IntroductionWhat are ISO 9000 Standards
ISO 9000 Standards Define the required elements of an effective
quality management system Can be applied to any company Adopted by the United States as the
ANSIASQC Q90 series
154 COUNTRIES
Bureau of Standards Jamaica
STANDARD BODIES
04122023Department of Pharmaceutics 4
bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA
bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness
bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996
Background Who Created Standards
04122023Department of Pharmaceutics 5
How did ISO get started
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 3
IntroductionWhat are ISO 9000 Standards
ISO 9000 Standards Define the required elements of an effective
quality management system Can be applied to any company Adopted by the United States as the
ANSIASQC Q90 series
154 COUNTRIES
Bureau of Standards Jamaica
STANDARD BODIES
04122023Department of Pharmaceutics 4
bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA
bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness
bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996
Background Who Created Standards
04122023Department of Pharmaceutics 5
How did ISO get started
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 4
bull ISO WAS FORMED FEBRUARY 23 1947 IN GENEVA
bull FIRST FAMILY OF QUALITY STANDARD RELEASED 1987ndash To eliminate country to country differencesndash To eliminate terminology confusionndash To increase quality awareness
bull FIRST ENVIRONMENTAL STANDARD RELEASED IN 1996
Background Who Created Standards
04122023Department of Pharmaceutics 5
How did ISO get started
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 5
How did ISO get started
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1906 - International Electro-technical Commission
1926 - International Federation of the National Standardizing Associations (ISA)
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1946 London - delegates from 25 countries decided to create a new international organization the object of which would be to facilitate the
international coordination and unification of industrial standards
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
1947 - ISO began to officially function
1951 - The first ISO standard was published
Standard reference temperature for industrial length measurement
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 6
ISO 9000 Consists of 5 Documents
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9000 Quality Management and Quality Assurance Standards
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9001 Quality Systems - QA Model for DesignDevelopment Production Installation and Service
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9002 Quality Systems - QA Model for Production and Installation (no design)
ISO 9003 Quality Systems - QA Model for Final Inspection and TestISO 9003 Quality Systems - QA Model for Final Inspection and Test
ISO 9004 Quality Management and Quality System Elements - Guidelines
ISO 9004 Quality Management and Quality System Elements - Guidelines
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 7
ISO 9000 Family of Standards
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
bull ISO 9000-2 - Generic guidelines for applying ISO 9001 ISO 9002 and bull ISO 9003
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-3 - Guidelines for applying ISO 9001 to the development supply and maintenance of software
ISO 9000-4 Application for dependability managementISO 9000-4 Application for dependability management
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-2 Guidelines for services
ISO 9004-3 Guidelines for processed material
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
ISO 9004-4 Guidelines for quality improvement
ISO 9004-5 Guidelines for quality plans
bull ISO 9004-67- Guidelines for project amp configuration managementbull ISO 9004-67- Guidelines for project amp configuration management
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 8
What has ISO Accomplishedbull ISO film speed codebull TL9000 Standard format for telephone and banking cardsbull ISO 9000 which provides a framework for quality
management and quality assurancebull ISO 14000 series provides a similar framework for
environmental managementbull Internationally standardized freight containersbull Standardized paper sizesbull Automobile control symbolsbull ISO international codes for country names currencies
and languages
bull AS 9100 the Aerospace Basic Quality System Standard
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 9
ISO 90001987 seriesISO 90001987 series
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
International Organisation for Standards (ISO) adopted
a series of quality standards ISO 90001987
based on BS5750
strongly influenced by the US Department of Defence
Military Standards (MILspecs)
initial version was focused on quality control using
retroactive checkingand corrective actions
ISO 90001994 seriesISO 90001994 series
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
ISO 9000 was revised in 1994
greater emphasis on quality assurance via preventive
actions
required evidence of compliance with
documented procedures
tended to create a significant volume of associated procedure
(do it as you document it) manuals and bureaucracy
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 10
QS-9000QS-9000
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
Ford Chrysler General Motors and other automotivetruck
manufacturers identified deficiencies in ISO90001994
undertook a re-interpretation and
extension to develop QS-9000
additionally addressed continuous improvement manufacturing capability
and production part approval processes
ISO90002000 seriesISO90002000 series
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
2nd revision of Quality Management System
Requirement Standard from International Organization for
Standards
moved towardsprocess performance metrics
reduced the need fordocumented procedures
where clear evidence exists that the process is working
well
Replacement for previous ISO 9001 9002 and 9003
standards of 1994
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 11
ISO90002000 series standards provide criteria
for companies to certify their quality
management recertification is
required every three years
achieve registration by third-party auditor
the system verifies practice and
processes provides objective 3rd
party validation enables benchmarking
TC 176 the ISO 9001 technical committee has started its review on the next version of ISO 9001 which will in all likelihood be termed the ISO 90012008 standard assuming its planned release date of 2008 is met Early reports are that the standard will not be substantially changed from its 2000 version
Future Version 2008
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 12
New ISO 9001
QMSResource
management
Measurement analysis amp
improvements
Product Realization
Management
Responsibility
Continual Improvement cycle
General requirements
General requirements
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 13
ISO 9001 Model
CU
ST
OM
ER
SC
US
TO
ME
RS
Quality Management
System
5ManagementResponsibility
7 ProductRealization
6 ResourceManagement
8 MeasurementAnalysis and Improvement
Requirements
Satisfaction
Continual Improvement ofthe Quality Management System
ConsumptionProduct
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 14
Principle Of New Standards
Based on eight quality
management principles
Based on eight quality
management principles
LeadershipLeadership
Process approach
Process approach
Involvement of people
Involvement of people
System approach
to Manageme
nt
System approach
to Manageme
nt
Continual improveme
nt
Continual improveme
nt
Factual approach
to decision making
Factual approach
to decision making
Mutual beneficial supplier
relationship
Mutual beneficial supplier
relationship
Customer focus
Customer focus
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 15
Principles of new standard
Customer focusbull Organization depends customers bull Understand current amp future customer needsbull Meet exceed customer expectations
Leadershipbull Leaders establish purpose amp direction of the organizationbull Should create amp maintain environment to achieve
organizationrsquos objectives
Involvement of Peoplebull People of all levels are essence of an organizationbull Their full involvement for organizationrsquos benefit
Process approachDesired results are achieved more efficiently when activities and
resources are managed as process
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 16
Principles of new standard
System approach to ManagementIdentifying understanding and managing interrelated process as a system contributes to the organizationrsquos effectiveness amp efficiency
Continual improvementsContinual improvement of the organizationrsquos overall performance
should be a permanent objective of the organization
Factual approach to decision makingEffective decisions are based on the analysis of data and information
Mutually beneficial supplier relationshipsbull An organization amp its suppliers are interdependentbull Mutually beneficial relationship enhances the ability of both to
create value
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 17
Expectations of the new Standard
Avoid the application of systems that are separate from the organizationrsquos business process
Avoid the application of systems that are separate from the organizationrsquos business process
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable the development of a Quality system that is fully integrated into the normal operations of organizationrsquos business
Enable Continual improvements of the system for enhanced customer satisfaction
Enable Continual improvements of the system for enhanced customer satisfaction
Enable compliance to statutory amp regulatory requirementsEnable compliance to statutory amp regulatory requirements
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 18
Important changes
+ Why it is to be doneWhat to do When Whom amp How to do
Involvement of people
Continual improvements should be achieved
Maintain the system requirements
Improvements
+ Statutory amp regulatory requirements
Requirements specified by customer organization
Product requirements
Value adding processes20 quality elementsApproach
Customer satisfactionProductsMain focus
New VersionPrevious versionCriteria
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 19
Process approach
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Process definition Set of interrelated or interacting activities which transforms
inputs into outputs
Ensure continual
improvements
Ensure continual
improvements
Identify the
processes
Identify the
processes
Do it for all value adding processes Do it for all value adding processes
Establish measuring criteria
Establish measuring criteria
Identify the Interactions to other processes
Identify the Interactions to other processes
Identify the Inputs amp outputs
Identify the Inputs amp outputs
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 20
Process approach ndash Continual improvements of Process
PDCA Cycle
Processes in terms
Of Added Value
DO
Continual improvements
of Processes based on
objective measurements
ACTION
Measure results of process
Performance and effectiveness
- Objective Measurements
CHECK
Understandings amp
meeting requirements
PLAN
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 21
System Requirements Structure of the Standard
Provision of resources
Human resources
Infrastructures
Work environment
6 ISO9000 structure II Resource Management
General requirements
Documentation Requirements
Planning
Customer related processes
Design amp development
Purchasing
Production amp service provision
Management Commitment
Customer focus
Quality policy
Planning
Responsibility authority amp communication
Management Reviews
5 ISO9000 structure I Management Responsibility
8 ISO9000 structure IV Measurement Analysis ampimprovement
4 Quality Management System
7 ISO9000 structure III Product Realization
General
Monitoring amp measurement
Control of NCP
Analysis of data
Improvements
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 22
4 - Quality management system
41 General
requirements
Identification
of processes
required
Criteria and
methods to ensure
Operation amp control
Availability of
information amp
resources for
operation amp control
Monitoring and
Measuring of
processes
Continual
improvements
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 23
4 - Quality management system
Quality Policy
Quality Objectives
Quality Manual
Procedures required by the Standard
Procedures required for planning operation
amp control of Organization activities
Records
42 Document requirements
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 24
5 - Management Responsibility
56 Responsibility authority amp communicate
54 Planning
51 Management commitment
52 Customer focus
57 Management Review
53 Quality policy
Quality objectives
QMS planning
General
Review inputs
Review outputsInternal
communication
Management representative
Responsibility amp authority
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 25
5 - Management Responsibility
Development implementation and continually improvement of QMS
Development implementation and continually improvement of QMS
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
Communication of importance ofbull Regulatory amp statutory requirementsbull Meeting customer requirementsbull Quality Policy amp Quality objectivesbull Responsibilities amp authorities
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
bull Appointment of Management Representativebull Conducting Management
Reviews
bull Providing required resources
Establishment ofbull Quality Policybull Quality Objectives
Establishment ofbull Quality Policybull Quality Objectives
Identification of Customer requirementsIdentification of Customer requirements
Top Managementrsquos commitment
Top Managementrsquos commitment
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 26
6 - Resource Management
64
Work Environment
63 Infrastructures
62
Human Resources
General
Competence awareness amp training
61
Provision of resources
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 27
6 - Resource Management
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Resources required toImplementing monitoring amp continual improvementsEnhance Customer satisfaction by meeting customer requirements
Human ResourcesHuman Resources
InfrastructuresInfrastructures needed to achieve product conformity
InfrastructuresInfrastructures needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Work environmentWork environment needed to achieve product conformity
Resource Managemen
t
Resource Managemen
t
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 28
6 - Human Resources
Competent on the basis of appropriate education skill and experience
Competent on the basis of appropriate education skill and experience
Define competencies for people performing work affecting product quality
Define competencies for people performing work affecting product quality
Provide training or actionsProvide training or actions
Evaluate effectiveness of the training actions
Evaluate effectiveness of the training actions
Employees should aware importance of the activity being performed
Employees should aware importance of the activity being performed
62 Human
Resources
62 Human
Resources
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 29
7 - Product Realization
76
Control of monitoring measuring devices
Control
Preservation of product
Validation of processes
Identification amp traceability
Customer property
75
Production amp service provision
Verification of purchased products
Purchasing process
Purchasing information
74
Purchasing
Design planning
Design inputs
Design outputs
Design review
Design Changes
Design validation
Design verification
73
Design and development
71
Planning of product realization
Identification of customer requirement
Review of customer requirement
Customer communication
72
Customer related processes
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 30
7 - Product Realization
Quality objectives of ProductsQuality objectives of Products
Processes procedures to realize product
Processes procedures to realize product
Verification validation monitoring inspection and testing of product
Verification validation monitoring inspection and testing of product
Record to demonstrate conformanceRecord to demonstrate conformance
71
Planning of Product realization
71
Planning of Product realization
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 31
7 - Product Realization
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Review of requirements related product prior to acceptance commitment to customers - ability to meet customer requirements
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Effective communication with customer in relation to
bull Product informationbull Sales order handlingbull Customer feedback bull Customer complaints
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements
Identification of Customer Market requirements
bull Specified by customerbull Requirements taken for grantedbull Statutory Regulatory requirements 72
Customer related processes ndash (Sales)
72
Customer related processes ndash (Sales)
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 32
7 - Product Realization
Design inputs and outputsDesign inputs and outputs
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Review and verification validation and control of changesbull Accuracybull Potential hazards amp faultsbull Correctionsbull Evaluations against lessons learned
Planningbull Effective amp efficientbull Expectations of interested parties
Planningbull Effective amp efficientbull Expectations of interested parties
73
Design and Development ndash
(Product)
73
Design and Development ndash
(Product)
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 33
7 - Product Realization
Supplier evaluationSupplier evaluation
Verification of purchased product ndash Inspection and testing
Verification of purchased product ndash Inspection and testing
Degree of control depends on effects of subsequent processes and effect on final product
Degree of control depends on effects of subsequent processes and effect on final product
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
74
Purchasing
Purchasing is done in controlled manner to ensure that purchased products conforms to specific requirements
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 34
7 - Product Realization
Product characteristics
Product characteristics
Procedures and work instructionsProcedures and work instructions
Suitable equipments to manufacture Monitoring and inspection amp testing
Suitable equipments to manufacture Monitoring and inspection amp testing
Product release delivery and post delivery
Product release delivery and post delivery
Process validationProcess validation
Identification and traceability Identification and traceability
Customers property
Material supplied by customers ndash eg 3rd party blending
Customers property
Material supplied by customers ndash eg 3rd party blending
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
75
Production and service provision
Manufacturing service provision under controlled condition to ensure conformity of product
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 35
8 - Measurement analysis and improvement
82
Monitoring amp measurements
84
Analysis of data
85
Improvement
83 Control of non conforming product
Measurement of product
Internal audits
Customer satisfaction
Measurement of processes
Corrective action
Preventive action
Continual improvements
81
General
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 36
8 - Measurement analysis and improvement
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
82 - Monitoring and Measurementsbull Customer satisfaction perceptionbull Internal audits - conformity planned arrangements of QMS and
ISO9001bull Monitoring and measurements of processes ndash to determine
demonstrate ability of processes to achieve required resultsbull Monitoring and measurements of product ndash Conformity to
product requirements
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
83 - Control of NCPbull To assure that NCP products are identified and controlled to
prevent unintended use delivery
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
81 - To demonstratebull Conformity of the productbull Conformity to QMS requirementsbull Continually improvements and the effectiveness of the system
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 37
8 - Measurement analysis and improvement
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
84 - Analysis of dataCollection and analysis of data generated through QMS activities to verify suitability effectiveness and continual improvement of the system
Analysis shall provide information related to
bull Customer satisfaction perceptionbull Conformity to specs requirementsbull Trends of processes and productsbull Opportunities for preventive actionsbull Suppliers
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 38
8 - Measurement analysis and improvement
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
85 - ImprovementsContinual Improvements
bull QMS needed to be continually improved
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Corrective actionbull Actions to prevent recurrence of NCP NCR etcbull Includes reviews determination of causes need of action
implementation of action review of action and maintenance
of relevant records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
Preventive actionbull Actions against potential non conformities to avoid their
occurrencebull Includes identification of potential non conformities cause
need for action implementation of action review of action
and maintenance of records
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 39
Criteria for measurements
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Internal auditsbull Effectiveness amp efficiency of processesbull Opportunities for improvementsbull Use of data informationbull Effective amp efficient use of resourcesbull Adequacy accuracy and performance of measurementsbull Relationships with customers suppliers other interested
parties
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
ndash Financial measurementsbull Prevention costbull Non conforming failure costbull Lifecycle cost
Self assessment
Self assessment
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
ndash Satisfaction surveys for customers and other interested parties
bull Feedback on productsbull Customer amp market requirements
System performanc
e
System performanc
e
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 40
Criteria for measurements
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Inspection and testing of incoming in process and final
productndash Product verificationndash Product validation
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ndash Process capability process validation
ndash Reaction timendash Cycle time throughput (Capacity)ndash Utilization of technologyndash Waste reductionndash Cost reduction
ProductsProducts
Processes
Processes
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 41
What is ISO 14000
Primarily concerned with Environmental ManagementPrimarily concerned with Environmental Management
Minimize harmful effects on the environmentMinimize harmful effects on the environment
Continual Improvement of environmental performanceContinual Improvement of environmental performance
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
The formation of ISO Technical Committee 207 (TC 207) in 1993 marks the beginning of the development of the ISO 14000 series The US Technical Advisory Group (TAG) for ISOTC 207 (USTAG for ISOTC 207) represents the United States in international negotiation on ISO 14000
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14000
EMS- General Guidelines on Principles Systems and Supporting Techniques
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
ISO 14001
EMS- Specification with Guidance for Use requires a
substantial commitment of time and resources
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 42
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14004
EMS - General Guidelines on Systems Principles and
Supporting Techniques
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14010
EA- General Principles of Environmental Auditing
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14011
EA- Auditing of Environmental Management
Systems
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14012
EA- Qualification Criteria for Environmental Auditors
ISO 14013
Management of Environmental Audit
Programs
ISO 14013
Management of Environmental Audit
Programs
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14014
Initial Reviews
ISO 14015
Environmental Site Assessments
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14020
EL- Basic Principles of Environmental Labeling
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
ISO 14021
EL- Self Declaration- Environmental Claims- Terms
and Definitions
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 43
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14022 EL- Symbols
ISO 14023
EL- Testing and Verification Methodologies
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14024
EL- Practitioner Programs- Guiding principles practices and certification procedures of multiple criteria (type1)
ISO 14031
Environmental Performance Evaluation
ISO 14031
Environmental Performance Evaluation
ISO 14040
LCA- General Principles and Practices
ISO 14040
LCA- General Principles and Practices
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14041
LCA- Goal and DefinitionScope and
Inventory Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14042
LCA- Impact Assessment ISO 14043
LCA- Improvement Assessment
ISO 14050
Terms and Definitions
ISO 14050
Terms and Definitions
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
ISO 14060
Guide for the Inclusion of Environmental Aspects in
Product Standards
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 44
Guides To Pharmaceutical Manufacturing Facilities amp Productivity
Quality Facilities and Equipment Materials Production PackagingLabeling Laboratory Controls
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 45
Need of guidelines in pharmaceuticals
facilities amp productivity Detailed guidelines of a system so that
the findings reflect the state of control in that system for every product (profile) class
If one of the six systems is out of control the firm is considered out of control
A system is considered out of control based on GMP deficiencies which suggest lack of assurance of quality
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 46
Quality System
Quality must be built into the process
Quality must be built into the process
Quality is not tested into the productQuality is not tested into the product
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Assurance of Quality comes from- Design of robust process based on
thorough knowledge of that process and the sources of variability
Effective Quality System in place Effective Quality System in place
Quality System
Quality System
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 47
Role of Management in QS
Management is responsible for
Organizational structure All Processes All Procedures Facilities amp Resources
In short everything to insure product quality customer satisfaction and continuous improvement
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 48
Quality System Responsibilities
Assures overall compliance with cGMPs
Review and approval duties for
1)Product Quality Reviews (at least annually)
2)Complaint reviews
3)Discrepancy failure investigations
4)Change Control
5)CAPA (Corrective And Preventive Action)
6) Reprocess Rework
7) Validation Revalidation
8) Rejects
9) Stability Failures Out of trend data
10) Quarantine products
11) Documented GMP amp Job Related Training
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 49
Laboratory Control System (I)
Adequately staffed laboratories (supervisory and bench personnel)
Adequately staffed laboratories (supervisory and bench personnel)
Written specifications for raw materials intermediates APIs labels amp packaging
Written specifications for raw materials intermediates APIs labels amp packaging
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Written procedures for sampling testing approval or rejection of materials and for the recording and storage of data
Method validation revalidationMethod validation revalidation
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Validation and Security for computerized handling of test results and related data system for assuring integrity of all lab data
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
Laboratory Control System
Adequate lab facilities under the Quality Unit which is independent from Production
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 50
Laboratory Control System (II)
Reference Standards (primary secondary)Reference Standards (primary secondary)
Laboratory controls followed and documented
Laboratory controls followed and documented
Calibration written procedures schedule documentation
Calibration written procedures schedule documentation
Equipment QualificationEquipment Qualification
Written procedure (SOP) covering out of specification ldquooosrdquo resultsWritten procedure (SOP) covering out of specification ldquooosrdquo results
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 51
Laboratory Control System (III)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Investigation of ldquooosrdquo results conducted in a timely manner as per SOP and documented (complete records maintained)
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
Conclusions from ldquooosrdquo investigations documented and corrective actions need for addition investigation identified and implemented
ldquooosrdquo review included in Product Quality Reviews
ldquooosrdquo review included in Product Quality Reviews
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Description of samplesIdentification of method used
Raw data for sample standard preparation reagents
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 52
Laboratory Control System (IV)
Complete record of all data from testingRecord of all calculations
Complete record of all data from testingRecord of all calculations
Statement of the test results how compare with established acceptance criteria
Statement of the test results how compare with established acceptance criteria
Signature of the person who performed each test dates tests performed
Signature of the person who performed each test dates tests performed
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Date signature of second qualified person who reviewed original test records for accuracy completeness and compliance with established standards
Laboratory Control System
Laboratory Control System
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 53
Production System (I)
Production System (I)
Master production and control
records
Master production and control
records
Change control
procedure
Change control
procedure
Batch production and control
records
Batch production and control
records
Contemporaneous accurate and complete
batch production documentation
Contemporaneous accurate and complete
batch production documentation
Implementation and documentation of in-process controls tests and examinations
Implementation and documentation of in-process controls tests and examinations
Training (documente
d job-related)
Training (documente
d job-related)
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 54
Production system (II)
Identification of equipment with contents
stage of manufacturing status
Equipment cleaning records
Established time limits for completion of
production steps stages
Deviations investigated and documented
contemporaneously with investigation
Adequate written procedures amp practice
for charge-in of materials
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 55
Production system (III)
Justification and consistency of in-process specifications and final product specifications
Data information documented and available to Quality Unit for review (trending investigations etc)
Process validation based on knowledge of process (scientific basis for identifying critical steps critical process parameterscontrol points)
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 56
Facilities amp Equipment System
Location design construction appropriate to facilitate cleaning maintenance operations
Location design construction appropriate to facilitate cleaning maintenance operations
Layout and air handling designed and constructed to prevent cross-
contamination
Layout and air handling designed and constructed to prevent cross-
contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Flow of materials amp personnel designed to prevent mix-ups or contamination
Defined areas or other control systems to prevent mix-ups or contamination includes as
Defined areas or other control systems to prevent mix-ups or contamination includes as
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 57
Facilities amp Equipment System
Incoming materials (id quarantine)
Incoming materials (id quarantine) Sampling area (prevent
contamination)
Sampling area (prevent contamination)
Quarantine (intermediates APIs)Quarantine (intermediates APIs)
Released materialsReleased materials
RejectionRejection
b) EQUIPMENTSb) EQUIPMENTS
Appropriate design size location non-reactive product contact surfaces
Appropriate design size location non-reactive product contact surfaces
Facilities amp Equipment System
Facilities amp Equipment System
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 58
Facilities amp Equipment System
Identification clearly marked
Identification clearly marked CalibrationCalibration
Preventive Maintenance schedule and procedures
Preventive Maintenance schedule and procedures
Cleaning procedures and validationCleaning procedures and validation
Records of use cleaning maintenance
Records of use cleaning maintenance
Closed or contained equipment - Inspection prior to use
Closed or contained equipment - Inspection prior to use
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Separate facilities or containment where needed (penicillins highly potent compounds etc)
Facilities amp Equipment System b) EQUIPMENTS
Facilities amp Equipment System b) EQUIPMENTS
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 59
Utilities
Qualified and appropriately monitored drawings should be available
Qualified and appropriately monitored drawings should be available
Designed and constructed to prevent contamination or cross-contamination
Designed and constructed to prevent contamination or cross-contamination
Recirculated air to production (same concern)
Recirculated air to production (same concern)
Permanently installed pipe work should be appropriately identified
Permanently installed pipe work should be appropriately identified
Drains of adequate size with air breakDrains of adequate size with air break
UtilitiesUtilities
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 60
Water
Process water at minimum meeting WHO guidelines for potable water
Process water at minimum meeting WHO guidelines for potable water
Justify quality of water used to achieve stated API quality and
establish specifications
Justify quality of water used to achieve stated API quality and
establish specifications
Water treatment facilities validationWater treatment facilities validation
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
API to be used for incorporation into sterile dosage form ndash water used in later stages should be monitored and controlled for total microbial counts
objectionable organisms and endotoxins
WaterWater
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 61
Materials System
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
Written procedures for receipt identification quarantine storage handling sampling testing and
approval or rejection of materials
System to evaluate suppliers (critical materials)Purchased against agreed specification
System to evaluate suppliers (critical materials)Purchased against agreed specification
Change control process for changing suppliers
Change control process for changing suppliers
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Upon receipt check for correct labeling seals
Before co-mingling bulk material idtest
Assurances obtained from non-dedicated tankers
Assurances obtained from non-dedicated tankers
Materials System
Materials System
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 62
Materials System
Identification on large storage containers and associated manifolds filling and discharge lines
Identification on large storage containers and associated manifolds filling and discharge lines
Code given to received batches status identityCode given to received batches status identity
At minimum a specific identity test on incoming batches
At minimum a specific identity test on incoming batches
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Supplier evaluation should include three fully tested batches one fully tested
batchyear
Written sampling plan with justificationPrevent contamination of sampled containers
Written sampling plan with justificationPrevent contamination of sampled containers
Materials System
Materials System
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 63
Materials SystemStored in manner to prevent degradation
contamination no adverse effect on quality
Stored in manner to prevent degradation contamination no adverse effect on quality
Drums bags boxes off the floorDrums bags boxes off the floor
First in first outFirst in first out
Rejected materials identified and controlled under a quarantine system
Rejected materials identified and controlled under a quarantine system
Established re-test re-evaluation periodsEstablished re-test re-evaluation periods
Materials System
Materials System
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 64
Packaging amp Labeling System
PampL should conform to specifications
Records maintained for each shipment
(showing receipt examination amp result)
Containers protective clean not alter product quality if re-used cleaned amp labeling defaced
Access to label storage area limited
Written procedures for reconciliation
- investigation if discrepancy
Written procedures for receipt identification quarantine sampling examination andor testing PampL
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 65
Packaging amp Labeling System
Obsolete labels destroyed
Printing devices controlled to insure accuracy of label (against batch record)
Print labels checked against master and a copy placed into the batch record
Documented procedures to assure correct
packaging materials labels used
Operations designed to prevent mix-ups
All excess labels with batch destroyed
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 66
Packaging amp Labeling System
Shipped API Name address manufacturer special
transport conditions expiry retest date
Documented clearance before operations
Packaged labeled intermediates or APIs examined as part of packaging (documented)
Seal employed to assure package integrity
Labels API name batch storage conditions
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 67
Benefits Certification demonstrates the
recognition of quality throughout organization
Decrease in wasted time materials and efforts
Inculcating values of excellence and best practices
Establish leadership role within organization
Increased recognition by international partners
Ability to maintain standards of quality and excellence
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 68
References
Lachman L Lieberman A Kanig JL The
Theory Of Industrial Pharmacy 2nd edi
Varghese Publication House Bombay-14
Gilbert s Banker Christoher T Rhodes
Modern Pharmaceutics 3rd edi New York
Sharma PP How To Practice GMPs 2nd edi
Vandana Publication Agra
wwwgooglecom
wwwwikipediacom
wwwkwalitegcozaiso9000com
wwwfdacom
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-
04122023Department of Pharmaceutics 69
- Seminar on helliphellip ISO series guide of pharmaceutical manufacturin
- Contents
- Introduction What are ISO 9000 Standards
- Slide 4
- How did ISO get started
- ISO 9000 Consists of 5 Documents
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- ISO90002000 series
- New ISO 9001
- ISO 9001 Model
- Principle Of New Standards
- Principles of new standard
- Principles of new standard (2)
- Expectations of the new Standard
- Important changes
- Process approach
- Process approach ndash Continual improvements of Process
- System Requirements Structure of the Standard
- 4 - Quality management system
- 4 - Quality management system (2)
- 5 - Management Responsibility
- 5 - Management Responsibility
- 6 - Resource Management
- 6 - Resource Management (2)
- 6 - Human Resources
- 7 - Product Realization
- 7 - Product Realization (2)
- 7 - Product Realization (3)
- 7 - Product Realization (4)
- 7 - Product Realization (5)
- 7 - Product Realization (6)
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement
- 8 - Measurement analysis and improvement (2)
- 8 - Measurement analysis and improvement (2)
- Criteria for measurements
- Criteria for measurements (2)
- What is ISO 14000
- Slide 42
- Slide 43
- Guides To Pharmaceutical Manufacturing Facilities amp Productivit
- Need of guidelines in pharmaceuticals facilities amp productivity
- Slide 46
- Role of Management in QS
- Quality System Responsibilities
- Slide 49
- Slide 50
- Slide 51
- Slide 52
- Slide 53
- Production system (II)
- Production system (III)
- Slide 56
- Slide 57
- Slide 58
- Slide 59
- Slide 60
- Slide 61
- Slide 62
- Slide 63
- Slide 64
- Slide 65
- Slide 66
- Benefits
- References
- Slide 69
-