gmp_asq1
TRANSCRIPT
Good Manufacturing Practices
in 21st Century
By :Ady Sadek M.Sc. , P.Chem.
proGamma Science Corporation
2011
proGamma Science Corporation
About Us
proGamma Science Corp: www.progamma.ca
Based in Montreal 1985. We provide implementation consulting and professional training in the
following major divisions of the Pharmaceutical, biopharmaceutical , Natural Health Products
and medical devices industries :
1.Quality assurance and Regulatory Affairs
2. Technical Operations : Product development, Manufacturing, Packaging, Validation services,
Automation , Process Validation , Equipment qualification
3. Quality System Management , Risk Assessment
4. Computerization including: Software Engineering, PAT, Computer system validation services
5. Professional cutting edge training
Partial Client List :
Abbott Labs Ltd , AeternaLabs , Astra-Zenica, Apotex, Agilent Technologies , Bioniche ,
Confab Labs., Church & Dwight Canada, Delmar Chemicals , Dermtek Pharmaceuticals Ltd.,
DraxisPharma Inc. PharmaLab, Pharmetics, Galderma Production, Health Canada (TPD), Merck-
FrosstCanada ,Novopharm , Novartis Pharmaceuticals ,Omega ValtecLtd. , PharmaScience,
Pfizer Canada ,ProDoc,RivaLabs , Sandoz , Sanofi-Aventis , Schering-Plough, Sandoz
,ratiopharm Inc, Tyco HealthCare, Valeant Pharma
proGamma Science Corporation
Ady Sadek M.Sc, P.Chem
is president of proGamma Science Corporation, previously he spent 20 years
in the pharmaceutical industry with BioResearch, Schering-Plough and
Novartis Pharmaceuticals, holding positions such as Manager of Analytical &
Development Labs, Director of Quality and Director of QualityAudit. He
holds two master degrees in Organic and analytical chemistry and is an ISO
9000 lead auditor . Ady’s vast experience in GMP compliance ,process design
and validation started in 1981, when developing new formulations for FDA
submissions. He has been involved in many Plant GMP training , Audits
validations and his experience extends from formulation development to scale
up commercial batches and technology transfer. He has consulted and lectured
throughout Canada, USA and Europe to several multinationals.
proGamma Science Corporation
Agenda
The History
What is GMP?
Why we need GMP?
GMP sections
Modern GMP progress in 21st century
Pharmaceutical Plant management in the 21st Century
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proGamma Science Corporation
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What is GMP ?
Although quality assurance has its value in almost every industry, it has
special justification in the drug and medical device industries due to the
nature of the product and complex government regulations.
During the past 30 years many new regulations passed into law have
required drug and medical device industries to substantially modify their
business methods
One of the most well known sets of regulations that have had a major
impact on the drug and medical device industries are called Good
Manufacturing Practices (GMP)
a document published by Health Canada which sets out the minimum
activities required for drug manufacturers in Canada. Legally enforced
through the Canadian Food & Drugs Regulations, Division 2, Part C.
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These regulations describe the minimum requirements that
governments consider necessary for the production of human drugs,
veterinary drugs, or medical device products
GMP refers to the Good Manufacturing Practice Regulations
promulgated by Health Canada under the authority of the Food and
Drug Act.
The branch responsible for GMP of health Canada is : Health
Products and Food Branch Inspectorate (HPFBI)
These regulations, which have the force of law, require that
manufacturers, packager/Labeller, Importor and distributor of drug
product take proactive steps to ensure that their products are :
Safe
pure
and effective
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GMP regulations require a quality approach to
manufacturing, enabling companies to minimize or
eliminate instances of contamination, mix ups, and errors.
This in turn, protects the consumer from purchasing a
product which is not effective or even dangerous.
Failure of firms to comply with GMP regulations can
result in very serious consequences including recall,
seizure and fines.
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WHAT IS GMP?….
These regulations apply to:
Buildings
Equipment
Personnel
proGamma Science Corporation
WHAT IS GMP?….
Ensures that:
Procedures
Controls (QA)
Are available in place and followed
proGamma Science Corporation
GMP regulations address issues including recordkeeping,
personnel qualifications, sanitation, cleanliness, equipment
verification, process validation, and complaint handling.
Most GMP requirements are very general and open-ended,
allowing each manufacturer to decide individually how to best
implement the necessary controls.
This provides much flexibility, but also requires that the
manufacturer interpret the requirements in a manner which
makes sense for each individual business.
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Why we need GMP?
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Example
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GMP sections
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Quality Management
Determines and implements the “quality policy”
The basic elements are:
an appropriate infrastructure or “quality system” encompassing the Procedures, Processes, and Resources
the systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for “Quality”
The totality of these actions is termed “Quality Assurance”
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Adopted Health Canada QA Systems
1. Drugs are designed and developed in a way that takes into account the GMP requirements
2. Managerial responsibilities are clearly specified
3. Systems, facilities and procedures are adequate
4. Production and control operations are clearly specified and validated
5. Arrangements are made for the supply and use of the correct raw and packaging materials;
6. All necessary controls on intermediates, and any other in-process monitoring, and is carried out;
7. Outsourced activities are subject to appropriate oversight controls and meet GMP requirements;
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8. Fabrication, packaging/labelling, testing, distribution, importation, and wholesaling are performed in accordance with established procedures
9. Drugs are not sold or supplied before the quality control department has indicated certified that each lot has been produced and controlled in accordance with the marketing authorization and of any other regulations relevant to the production, control and release of drugs;
10. Satisfactory arrangements exist for ensuring that the drugs are stored, distributed, and subsequently handled in such a way that quality is maintained throughout their shelf life
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11.The effectiveness and applicability of the quality management system
is ensured through regular self-inspection and management review
12. Annual product quality review of all drugs should be conducted with
the objective of verifying the consistency of the existing process, the
appropriateness of current specifications for both raw materials and
finished product to highlight any trends and to identify product and
process improvements.
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Quality Management
GMP
Ensure that products are consistently produced
and controlled
Diminishes risks that cannot be controlled by
testing of product
Cross-contamination
Mix-ups
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Quality Management
Basic Requirements for GMP
1. Clearly defined and systematically reviewed processes
2. Critical steps of manufacturing processes and significant
changes to the process are validated.
3. Appropriate resources: personnel, buildings, equipment,
materials
4. Clearly written procedures
5. Trained operators
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Quality Management
6. Records :
manually or by instruments
demonstrate that all the steps are followed
Deviations are investigated and documented;
7. Records of fabrication, packaging, labelling, testing, distribution,
importation and wholesaling that enable the complete history of a lot
to be traced are retained in a comprehensible and accessible form
8. Control of storage, handling, and transportation distribution of the
drugs minimizes any risk to their quality
9. Recall system
10.Complaint handling
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Quality Management
Quality relationships
Quality Management
Quality Assurance
GMP
Quality Control
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Quality Management
Quality Control (QC)
QC is part of GMP that is concerned with
sampling, specifications, testing,
documentation and release procedures
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Quality Management
Quality Control (QC) Department
Each holder of a Establishment Licence should
have a QC Department
Independence from production and other
departments is considered to be fundamental
Under the authority of an appropriately qualified
and experienced person with one or several
control laboratories at his or her disposal.
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Quality Management
Basic Requirements for Quality Control
Resources Adequate facilities
Trained personnel
Approved procedures
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Quality Management
Basic Requirements for Quality Control
Tasks Sampling
Inspecting
Testing
Monitoring
Releasing/rejecting
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Quality Management
Basic Requirements for Quality Control
1. Sampling approved by QC department
2. Validated test methods
3. Records
4. Review and evaluation of production documentation
5. Failure investigations for all deviations
6. Ingredients comply with the marketing authorization
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Quality Management
Basic Requirements for Quality Control
7. Ingredients are of the required purity
8. Proper containers
9. Correct labelling
10. Release of batches by the authorized person
11. Retained samples of starting materials and
products
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Quality Management
Other Duties of the Quality Control Department
1. Establish QC procedures
2. Reference standards
3. Correct labelling
4. Stability testing
5. Complaint investigations
6. Environmental monitoring
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Quality Management
Assessment of Finished Products
Should embrace all relevant factors. For example:
production conditions
in-process test results
manufacturing documentation
compliance with finished product specification
examination of the finished pack
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Quality Management
Quality Control - summary
QC is part of GMP
sampling
specifications
testing
release procedures
recalls and complaints
decision-making in all
quality matters
authorization
definition of product
quality
laboratory operations
release decisions
investigation and
reporting
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Sanitation
Influence on quality:
Sanitation in a pharmaceutical plant influences the quality
of drug products as well as employee attitude.
The quality requirement for drug products demand that
such products be fabricated and packaged in areas that
are free from environmental contamination and free from
contamination by another drug.
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Examples
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Why is this Important?
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Why is this Important?
Hair nets are important for two reasons : They help keep hair out of products and help keep human hands away from hair
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Jewelry is not allowed
Jewelry should be limited to a plain wedding band. Jewelry can be a physical hazard and can be heavily contaminated with bacteria. Wearing jewelry can also be dangerous to the employee. For example, a necklace could get caught in a mixing machine and cause harm to the operator.
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Who is responsible
Integrates all your quality systems
Document Management
Valid
atio
n
CHANGE
CONTROL
Training
State of
Control
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Modern GMP progress in 21st century
FDA initiative 2002
Risk management approach
Process Analytical Technology PAT
Goal to ensure final product quality
Enhance process understanding and control
of manufacturing process
World acceptance of FDA initiative
ICH , FDA and EMEA new regulations
proGamma Science Corporation
Modern GMP progress in 21st century
ICH Q8 pharmaceutical development Quality by design
Design space
ICH Q9 quality Risk management Risk Management process
Risk Assessment and risk control
Risk Management tools : FMEA, FTA ....
ICH Q10 Pharmaceutical Quality System Product Realization
Knowledge Management and quality risk management
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Process Validation : the magic 3 is no longer magic
Process Design
Process qualification
Continued Process Verification
Quality by Design – CMC
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Why QBD?
Existing Existing GMP GMP ’ ’ s s
Quality by Design
(Pharmaceutical Development)
Quality Risk Management
The Regulatory Quality System
The future Pharmaceutical Quality System
Quality
Systems
Quality Systems (Q10)
For companies with : 1. Good design and
control strategies 2. Good Risk
Management strategies 3. Good Quality Systems
Quality Risk Management
(Q9)
Quality by Design
(Q8)
Reduced regulatory burden:
• Reduction of submissions on changes/variations
• Inspection of quality systems
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Tremendous Opportunity
Lower Risk Operations Innovation and Continual Improvement Optimized Change Management Process Flexible Regulatory Approaches
Pharmaceutical Development: Quality by Design Q8
Quality Risk Management Q9
Modern Effective Pharmaceutical Quality Systems Q10
+ +
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Perhaps our vision should be updated?
Our vision: Quality By Design
Reduced regulatory
burden:
• Reduction of
submissions on
changes/variations
• Inspection of quality
systems
Existing Existing GMP GMP ’ ’ s s
Quality Risk Management
The Regulatory Quality System
Quality
Systems
Quality Systems (Q10)
Quality Risk Management
(Q9)
(Q8)+ Product & Process Dev
Quality by Design
For companies implementing Quality by Design
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Process Validation and product life cycle
Progress in Quality system application in
pharmaceutical industry
ISO 9000
Six Sigma
Multivariate statistics to measure and better
improve process performance
Modern Facility Management in the
21st Century
Overall Customer Satisfaction
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
Course Outline
1. Operational Excellence
2. Compliance and Quality Control
3. Human Resources
4. Business Processes and Systems
5. Technical Services
6. Engineering
7. Environment and Safety
8. Regulatory Excellence
9. Business Development and Commercial
10. Supply Chain
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
1. Operational Excellence i. Customer Satisfaction
ii. Capacity and Utilization
iii. Do it right the first time
iv. Improve Operational Efficiency
v. Compliance and Regulatory Affairs
vi. Business Processes and Systems
vii. Measurement
viii. Philosophy of Continuous Improvement
ix. PAT
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
2. Compliance and Quality Control
i. Product Release
ii. Quality Systems
iii. CAPA Program
iv. Self Inspection Program
v. Incoming, in-process, Finished Goods Testing
vi. Stability Programs
vii. Documentation
viii. Technical transfers, Method Validations
ix. Paperless
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
3. Human Resources
i. Succession Planning
ii. Personnel Development Action Plans
iii. Hi Potentials/Mentorship Programs
iv. Union Negotiations
v. Employee Relations
vi. Employee Benefits
vii. Retention Programs
viii. Management Training
ix. Recognition Programs
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
4. Business Processes and Systems
i. ERP
ii. Planning/Forecasting
iii. Capacity Planning
iv. Purchasing
v. Inventory Control and Management
vi. Warehousing/Logistics
vii. Finance
viii. Shop Floor Control
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Facility Management for the 21st
Century
5. Technical Operations i. Validation Master Plan
ii. IQ/OQ/PQ
iii. Cleaning Validation
iv. Computer Validation
v. ERP Validation
vi. Change Control Program
vii. Documentation Control
viii. New Product Introduction Process
ix. Label Control
x. Process Development
xi. Scale Up
xii. Clinical Considerations
xiii. Formulation
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
6. Engineering
I. Preventative Maintenance
II. Predictive Maintenance
III. Calibration Program
IV. Demand work orders
V. Capital Programs
VI. Specialization
VII. Troubleshooting
VIII. Utilities
IX. Daily Production Support
X. Project Management
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
7. Environment and Safety
i. Recycle, reuse, reduce
ii. Regulations
iii. Hazardous Waste
iv. Inspections
v. Committees
vi. Employee Involvement
vii. Training
viii. Safety Programs
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
8. Regulatory Excellence
i. Plant Master Files
ii. Licenses
iii. Government Inspections
proGamma Science Corporation
Pharmaceutical Plant Management in
the 21st Century
9. Business Development/Commercial
i. Pipeline/New Sales
ii. Current Account/Product Management
iii. New Product Management
iv. Negotiation
v. Pricing/Contracts
vi. Legal
vii. Market Research
viii. Marketing of product portfolio
10. Supply Chain
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Thank you for inviting me
Ady Sadek