quality systems for continuous manufacturing
TRANSCRIPT
Engineering Conferences InternationalECI Digital Archives
Integrated Continuous Biomanufacturing II Proceedings
Fall 11-4-2015
Quality systems for continuous manufacturingRon BranningRBC LLC, [email protected]
Follow this and additional works at: http://dc.engconfintl.org/biomanufact_ii
Part of the Biomedical Engineering and Bioengineering Commons
This Conference Proceeding is brought to you for free and open access by the Proceedings at ECI Digital Archives. It has been accepted for inclusion inIntegrated Continuous Biomanufacturing II by an authorized administrator of ECI Digital Archives. For more information, please [email protected].
Recommended CitationRon Branning, "Quality systems for continuous manufacturing" in "Integrated Continuous Biomanufacturing II", Chetan Goudar,Amgen Inc. Suzanne Farid, University College London Christopher Hwang, Genzyme-Sanofi Karol Lacki, Novo Nordisk Eds, ECISymposium Series, (2015). http://dc.engconfintl.org/biomanufact_ii/91
Con$nuous Manufacturing A Quality System Approach To Process Monitoring and Control
ICB II Ron Branning November 2015 President, RBC LLC
Implemen$ng World-‐Class Produc$on Quality Systems The Focus of My Career
• J&J – 1968 – Beginning of Modern GMPs
• 45 years of prac$cal, world wide, science and compliance solu$on implementa$on : J&J, Searle, Boehringer Ingelheim, Serono, Gene$cs Ins$tute, Aven$s Behring, Somatogen, Genentech, Gilead, Genzyme
• VP, SVP Quality and Compliance Issues Experience: – Quality Organiza$on and Opera$onal Performance – FDA 483s and WW Regulatory Inspec$on Observa$ons – FDA CRLs, WLs, CDs and DOJ Inves$ga$ons – MHRA, IMB, TGA, ANVISA, JMOH, SFDA, PICS Commitments – CHMP Oral Presenta$on:Commitments and Implementa$on
FDA’s (World Regulator’s) Expecta$ons : Produc$on Quality Systems
“We rely upon the manufacturing controls and standards to ensure that $me and $me again, lot aaer lot, year aaer year the same clinical profile will be delivered because the product will be the same in its quality…We have to think of the primary customers as people consuming that medicine and we have to think of the statute and what we are guaranteeing in there, that the drug will con$nue to be safe and effec$ve and perform as described in the label”
Janet Woodcock, M.D.
Presenta$on Outline
• Con$nuous Manufacturing • Quality System • Process Development • Technology Transfer • Manufacturing • Process Monitoring and Control • Quality Control • Quality Assurance
Con$nuous Manufacturing
• Glass, Plas$c Manufacturing • Radia$on Steriliza$on • McNeil Tylenol Response • Serono – Perfusion Disks • GI – Batch Harvest / Re-‐Feed • Con$nuus -‐ MIT / Novar$s Collabora$on • DARPA – Tractor / Trailer Sized BioManufacturing • Genzyme – Integrated Con$nuous BioMFG Plajorm
Product & Process Improvement
Supply Chain Management
Management of Documentation
Personnel Qualification & Training
Control and Release
Qualification and Validation
Quality Audit
Manufacturing and Packaging
Environmental and Critical Utilities Monitoring
Cleaning Validation
Process Validation
Document and Records Control and Retention
Facilities Utilities and Equipment
Quality Risk Management
Design and Development
Management of Suppliers & Subcontractors
Counterfeiting, Product Diversion, and Tampering
VisioDocument
Quality Process
XXXXXX
LEGEND
Terminal Sterilization
Aseptic Process Validation
Laboratory Equipment Qualification
Quality Technical Agreements
Rework, Reprocessing, And Re-inspection
Sampling
Supplier Qualification & Lifecycle Management
Stability Monitoring
Document Architecture, Format, and Content
Standards
Laboratory Investigations
Pharmaceutical Quality System
Technology Transfer
Investigational Products
Master & Batch Production Records
Governance Structure, Notification, and Escalation
Production Labeling Controls
Sterilization & Depyrogenation Control
External GMP Inspections
Management of Computerized Systems
Material Management
Certificates of Analysis
Purchasing Control
Lot DispositionRecall Management
Facility and Engineering Documents, Content & Format
Hygiene & Gowning
Design Control
XXX
Drug Development
Quality Management Review
Product Event Management
Change Control
Training
Personnel Qualification
Risk Management
Deviations & Investigations
Calibration
Maintenance of Facilities & Equipment
Environmental Control
Production Control
Validation Program
Materials Control
Laboratory Controls
Trending & Statistical Analysis
Corrective and Preventive Action (CAPA)
Design & Construction of Facilities,Utilities, and Equipment
Periodic Product Review
Lifecycle Management of Computer Systems
Product Event Reporting to Regulatory/Competent Authorities for Drugs and Biologics
Specification Development
XXX
Product Lifecycle Processes Organizational Processes
Quality Systems Management
Transversal Processes
Method Development and Validation
Aseptic And Controlled Area Processing
Requalification
Viral Risk Mitigation & Contamination Response
Sterilization & Depyrogenation Validation
Labeling Development and Labeling Change Management
Technology Transfer
Audits & Walk-Through Inspections
Quality and Supplier Audits
Warehousing and Distribution
Storage & Distribution
Collection, Communication and Review of Safety Information
Validation of the Transportation of Temperature-Sensitive Material
Product Discontinuation
See: Drug Development Standard Quality Organization,
Management, Planning, and Objectives
Quality Management Of Subcontractors
Integrated Product / Process Quality System Organiza$on Chart – SME’s, Risk Assessment, Culture Building
Quality System – Process Map
Knowledge Management
Change Management Deviation Management/CAPAAudit ManagementPersonnel Management
Supplier ManagementValidation
Quality Control
Production Management
Facility & Equipment Management
Risk Management
Product/Process Development
ComplaintManagement
VisioDocument
Printed Thursday, June 28, 2012
QSE
LEGEND
Pharmaceutical Quality System
Management Control
Regulatory Materials ManagementQuality Assurance
Follow-up and complete CAPA for Outcomes
Schedule Periodic Quality Management Review Meetings
Conduct Quality Management Review Meetings
Determine Outcomes
Report Outcomes
CAPA
Governance & Management Notification
CAPA
Periodic Product Review
Quality Planning & Objectives
Governance & Management Notification
CAPA
Evaluate Data For Abnormal Trends
Establish And Maintain Quality Organization, Quality Manual,
GQS, QSEs & Standards
Communicate Quality Program To All Employees
Develop Dashboard, KPIs, KQIs (as Applicable)
Report Periodically KPIs, KQIs & QSE Gaps, Integration And Effectiveness Of The GQS
CAPA
Training
Risk Management
Deviation & Investigations
CAPA
Escalate Issues To Appropriate Senior Management Risk Management
Sampling
Test Preparation
Preparation Of Reagents And
Standards
Test Performance
Results Review
Report Results
Maintain Reserve Samples
Training
Lot Disposition Laboratory Investigations
Sampling
Sampling
Personnel Qualifications
Method ValidationCalibration
Laboratory Equipment Qualification
Supplier QualificationPurchasing Controls
Establish Procedures For Sampling Of Materials And Product
Store Samples As Required By Procedure
Destroy Or Retain Samples As Required By Procedure
Maintain Sample Chain Of Custody Records
Test Samples As Required By Procedure
Training
Document Control
Perform & Label Samples As Required By Procedure
Train Sampling Personnel
Laboratory Controls
Laboratory Controls
Design Environmental Monitoring Program
Identify Monitoring Locations & Frequencies
Validate Environmental
Monitoring Program
Establish Alert & Action Limits
Collect Samples
Change Control
Laboratory Controls
Laboratory Investigations
Risk Mangement
Determine Environmental Control
Requirements
Lot Disposition
Environmental Control
Method Validation
Test Samples
Report Results
Data/Trend Analysis Reports
Sampling
Trending & Statistical Analysis
Qualification & Validation
Commissioning
Planning & Feasibility
Requirements Or Conceptual Design
Preliminary & Detail Design
Construction
Decommission
Purchase
Establish Operational Procedures &
Maintenance & Calibration Schedules
Operate & Maintain Records
Repair Or Improve
Purchasing Controls
Validation Program
Change Control
Deviation & Investigations
Preventive & Routine Maintenance
Preventive & Routine Maintenance
Calibration
Qualification
Identification Of Product & Process
Environmental Control Requirements And Critical Elements
Identification Of Environmental
Controls
Implementation Of Environmental Control
System
Control System Maintenance By
Review Of Environmental
Monitoring Data
Identification Of Monitoring Plan
Changes Made As Required To Ensure
System Requirements Are Continually Met
Change Control
Facility & Utility Design, Architecture & Construction
Environmental Monitoring
Change Control
Preventive & Routine Maintenance
Environmental Monitoring
Facility & Utility Design Architecture & Construction
Environmental Control
Laboratory Controls
Sampling
Environmental Monitoring
Laboratory Investigation
Generate Stability Protocol
Perform Time Zero Test
Perform Scheduled Testing
Obtain Interval Results
Store Samples
Evaluate & Report Results
Incomplete Stability Study
Laboratory Controls
Environmental Monitoring
Laboratory Investigation
Regulatory Reporting
Complete Stability Study
Regulatory Affairs
Laboratory Controls
Perform SamplingSampling
Stability Monitoring
Materials Control
Laboratory Controls
Environmental MonitoringProduction Control Records
Change Control
Perform Lot And Data Record Review
Disposition Lot
Communicate Lot Disposition
Approve Lot Record Submit To QA
QA Account For All Records And Data
Perform Lot Record Review
Ensure All Changes & Deviations Closed &
Regulatory Filings Approved
Resolve DeviationsDeviation & Investigations
Deviation & Investigations
Regulatory Affairs
Quality Management Review
Governance & Management Notification
Lot Disposition
Establish GQS Standards & Practices
Inform & Train Genzyme Employees
Measure Performance Against Quality
Objectives
Establish GQS Quality Manual & Quality
Objectives
Management ReviewGovernance & Management Notification
Design & Maintain GQS QSEs
Document Control
Document Control
Training
Recommend Improvements To
GQSManagement Review
Quality Planning & Objectives
Establish Procedures & Collect KQI & KPI
Data
Report Adverse Trends Or Issues
Issue Routine Reports
Analyze Data For Adverse Trends Or
Issues
Deviation & Investigations
Management ReviewGovernance &
Management Notification
Management ReviewGovernance & Management Notification
Trending & Statistical Analysis
Periodic Product Review
Generate Or Change Controlled Documents
Review, Approve Controlled Documents
Implement Controlled Documents
Retire Obsolete Versions
Conduct Training As Applicable Training
Records Control
Initiate New Document Or
Document Change
CAPA
Review Periodically Controlled Documents
Change Control
Establish Procedures And Genzyme
Engineering Practices For Documents
Project Plan
Change Control
Project Management
Facility & Engineering Documents, Content & Format
Construction & Configuration
Development
Planning, Feasibility & System Specification
Risk Assessment
User Requirements Specification
Decommission
Supplier Review, Approval & Purchase
Design
Qualification & Validation
Operation & Improvement
Document Control
Purchasing
Routine & Preventive Maintenance
Calibration
Deviation Investigation
Change Control
Change Control
Risk Management
Supplier Qualification
Computer Validation
QualificationRisk Management
Routine & Preventive Maintenance
Calibration
Qualification
Design & implementation of Computer Systems/Automation Systems
Commission
Qualify & Establish Maintenance Schedules & Procedures
Perform Preventive Maintenance
Repair Or Improve
Decommission
Change Control
Qualification
Deviation & Investigations
Deviation & Investigations
Change Control
Supplier Control
Maintenance of Facilities & Equipment
Commission
Qualify & Establish Calibration
Schedules, Master List & Instructions
Perform Calibration
Repair Or Adjust
Decommission
Change Control
Qualification
Deviation & Investigations
Deviation & Investigations
Change Control
Supplier Control
Yes
Within Calibration Limits
No
Continue To Use
Perform Final Calibration
Deviation & Investigations
Supplier Control
YesWithin Calibration
Limits NoEnd Deviation & Investigation
Calibration
Validation Risk Assessment & Planning
Protocol Development & Execution
Data Analysis & Reporting
Installation Qualification
Operational Qualification
Design Qualification
Process Validation
Performance Qualification
Method Validation
Cleaning Validation
Re-Qualification Re-Validation
Change Control
Change Control
Training
Production Control
Aseptic Production Control
Deviation Investigation
Laboratory Control
Calibration
Facility & Utility Design, Architecture, & Construction
Design & Construction of Equipment
Maintenance of Facility & Equipment
Sterilization & Depyrogenation Control
Trending & Statistical Analysis
Process Control Strategy
Establish User Requirements
Perform Commissioning
Perform Operational Qualification
Perform Design Qualification
Perform Installation Qualification
Perform Performance Qualification
Laboratory Controls
Deviation Investigations
TrainingChange Control
Develop Functional Requirements And Design
SpecificationsRisk Management
Laboratory Controls
Perform Periodic Qualification Assessment
Requalify As Required
Change Control
Design & Construction of Equipment
Facility & Utility Design, Architecture & Construction
TrainingCalibration
Maintenance of Facilities & Equipment
Requalification
Document Control
Design & Implementation of Computer Systems
Validation Program
Facility, Utility & Equipment Qualification
Establish User Requirements
Perform Commissioning
Perform Operational Qualification
Perform Design Qualification
Perform Installation Qualification
Perform Performance Qualification
Obtain Functional Requirements And Design
Specifications
Perform Periodic Qualification Assessment
Requalify As Required
Change Control Training
Laboratory Controls
Laboratory ControlsLaboratory Investigations
Laboratory Investigations
Change Control
Laboratory Equipment Qualification Identify Product Contact Equipment
Develop or identify cleaning requirements including cleaning & disinfection agents, procedures,
critical soils, sampling & analytical methods
Conduct Pre-Validation Engineering trials if needed
Generate a Qualification & Cleaning Validation Protocols
Complete Equipment/System Qualifications
Execute Cleaning Validation
Generate Qualification & Validation Protocol Reports
Validate Sampling & Test Methods
Develop & Establish Quantitative Acceptance Criteria
Design ControlDrug Development
Method Validation
Lot Disposition
Material Control
Facility, Utility, & Equipment Qualification
Design & Construction of Equipment
Validation Program
Change Control
Design & Construction of Equipment
Cleaning Validation
Establish Product Development File & Approved Development Report
Including Control Strategy
Train Personnel And Approve Procedures Including Batch Records
Execute Process Validation Protocol
Qualify Process Facility, Utilities, Equipment
Approve Process Validation Protocol
Approve Protocol Report
Perform Risk Assessment Based On ISs, IPCs, CPPs, PARs, kPPs & ARs
Traning
Risk Management
Drug Development Change Control
Change Control
Deviation Investigations Laboratory Controls
Change Control
Production Control Records
Facility, Utility & Equipment Qualification
Process Validation
Receive New Or Revised Method
Perform Instrument Qualification By Generating IQ, OQ, PQ Protocols As Needed. Qualify Facilities & Systems
Generate, Review & Approve Validation Protocol
Generate, Review & Approve Protocol Report
Assess Requirements For Validation
Execute Protocol
Laboratory Equipment Qualification
Change Control
Document Control
Laboratory InvestigationsTraining
Record Control
Laboratory Controls
Change Control
Facility, Utility & Equipment Qualification
Revalidate As Appropriate Change Control
Method Validation
Determine Method Of Sterilization For Material Or Product
Perform DQ, IQ, OQ, PQ Of Sterilization Process
Execute Process Validation Protocol
Design Terminal Sterilization
Approve Process Validation Protocol
Approve Protocol Report
Yes
Terminal Sterilization ?
No
Design ControlDrug Development
Aseptic Process Validation
Change Control Training
Laboratory Control
Sampling
Laboratory Investigations
Deviation & Investigation
Validation ProgramFacility, Equipment & Utility Qualification
Terminal Sterilization Validation
Determine Method Of Sterilization For Component Or Equipment
Perform DQ, IQ, OQ, PQ Of Sterilization Process
Execute Validation Protocols
Design Sterilization Or Depyrogenation Process
Approve Protocol Report
Yes Aseptic Process?
No
Design ControlDrug Development
Aseptic Process Validation
Change Control Training
Laboratory Control
Sampling
Laboratory Investigations
Deviation & Investigation
Validation ProgramFacility, Equipment & Utility Qualification
Change Control
Sterilization & Depyrogenation Validation
Minimize Bacterial Load on Materials &
Equipment
Maintain & Control Clean Manufacturing
Conditions
Maintain Time Limits On Processing
Control Product Sterilization
Sterilize Components And Equipment
Maintain & Control Product Integrity
Hygiene & Gowning
Validation
Facility, Equipment & Utility Qualification
Laboratory Controls
Deviation & Investigations
Certify Personnel for Clean Room Operations
Aseptic Process Validation
Establish User Requirements
Perform Commissioning
Perform Operational Qualification
Perform Design Qualification
Perform Installation Qualification
Perform Performance Qualification
TrainingChange Control
Develop Functional Requirements And Design
SpecificationsRisk Management
Perform Periodic Qualification Assessment
Requalify As Required
Qualification
Change Control
Design & Implementation of Computer Systems
Design & Implementation of Computer Systems
Design & Implementation of Computer Systems
Qualification
Validation Program
Validation Program
Change Control
Computer System Validation
Periodic Review Of Equipment, Facilities, Or Utilities
Perform Requalification
Report Requalification
Develop And Approve Requalification Protocol
Risk ManagementDocument Control
Change To Equipment, Facility, Or Utility Change Control
Other Quality System Element Reviews
Deviations & Investigations
Periodic Product Review
Quality Management Review
Governance & Management Notification
Calibration
Maintenance of Facility & Equipment
Change Control
Dev
iatio
ns &
Inve
stig
atio
ns
Per
iodi
c P
rodu
ct R
evie
w
Qua
lity
Man
agem
ent R
evie
w
Gov
erna
nce
&
Man
agem
ent N
otifi
catio
n
Calibration
Maintenance of Facility & Equipment
Requalification
Prepare detailed site Schedule and Communicate within the site (Site
Quality)
Assemble Site Management Team for Review of draft SIte PPR Report
and recommendations (Site Quality)
Distribute Site PPR Report
No
PPR Schedule
Compilation of PPR Elements
Site Management Review and Approval
Compilation of Final PPR Report
Create Master Schedule and Communicate to Sites
(CQO QA)
Assemble Multi-Site Management Team for Review of draft PPR Report and recommendations
(Lead Site Quality)
Is PPR Report Approved?
No
Issue PPR and make available
Compile data into PPR template, evaluate, and provide conclusions/
recommendations
Compile PPR Templates into site PPR Report and draft Executive
Summary(Site Quality)
Is Site PPR Report
approved?
Yes
Compile Site PPR reports into Final PPR Report and draft Executive
Summary(Lead Site Quality)
Yes
Multi-Site Management Review and Approval
Issuance of PPR
Is this a Multi-Site
PPR?
No
Yes
Deviation & Investigations
CAPA
CAPA
Initiate QC testing
Retain study materials
Knownlaboratory erroror atypical event
duringtesting?
Identifying and Documenting Events
Phase I Investigation
Interpretation of Phase II investigation results
Investigation closure
Discontinue testing. Document
and invalidate results. Reinitiate testing
Notify QA
Lab assignable cause?
No
Reinitiate testing
Phase II Investigation
Close Phase I Investigation (QA)
Laboratory assignable
cause confirmed?
Yes
Document and invalidate results.
Reinitiate testing
Invalidate results Close Phase I
Investigation (QA)Yes
Close Phase II investigation (QA)
Accept original result?Yes
Execute approved retesting plan
No
Is original test result confirmed?
Yes
Prepare and execute approved Phase II Plan
Review of production-related
activities
Additional Laboratory
Testing
No
Yes
Initiate Laboratory Management review
No
Atypicalor failingtest result
Report results as per
procedureNo
Yes
Phase I checklist and confirmatory testing
Review dataReview data
Assignablecause identified/
confirmed?
Yes
NoNo
Deviation Investigations
Deviation Investigations
Laboratory Controls
Determine deviation
classification(QA)
Investigation Initiation: Initial impact assessment and
Immediate actions (containment, initial data gathering)
Root Cause Determination
Minor
Is CAPA required?
QA review and approval
Enter CAPA plan into CAPA
system
No
Yes
Deviation closed
Impact Assessment
(product, other lots and systems)
Formal Root Cause Analysis
Determine appropriate CAPA plan
Final review and approval
Deviation closed
Deviationpotentially impact
distributed product?
Assign cross-functional team
with leader
Develop investigation plan
Escalation and post-marketing
assessment
Yes
Management Notification
Deviation classification appropriate?
Yes
Yes
Escalation and post-marketing
assessment
Impact Assessment
(product, other lots and systems)
Deviationimpact distributed
product?
Enter CAPA plan into CAPA
system
No
Event is Deviation?
Follow alternate system such as good
documentation practices or change control practifces
Yes
No
Deviation identification and QA notification
Deviation classification appropriate?
No
No
No
Critical/Major
Assign a cross-
functional team with
leader
Approve the CAPA Plan
(QA)
Perform Effectiveness
Review
Generate a site CAPA
plan
Implement and manage the CAPA Plan
CAPA Approved and Closed
(QA)
Verify CAPA completion
(QA)
CAPAMulti-Site?
(QA)
Prepare Multi-Site Master
Plan
Assign a Corporate
CAPA Team and Corporate CAPA Team
Leader
Multi-Site CAPA required?
(Corp. QA)
Approve Multi-Site Master
Plan (Corporate QA)
Multi-Site CAPA Approved and Closed
(Corp. QA)
CAPAEffective?
(QA)
Corporate ManagementNotification (Corp. QA)
No
Multi-Site CAPA
Team needed?(Corp. QA)
No
Risk Assessment
(QA)
Implement CAPA
Verify CAPA Completion
(QA)
Minor Impact
Major/Critical Impact
Yes
No
Yes
Yes
Classification and Establishment of a CAPA Team
CAPA Plan Implementation and Management
Development of a CAPA plan
CAPA Approval and Closure (In Control)
Effectiveness Review (In Use)
Verification of CAPA Completion (In Place)
Change Control
If Applicable
No
Yes
Reg
ulat
ory
Rep
ortin
g
Regulatory Reporting
CAPA
Deviations & Investigations
Change Multi-Site?
Assign SMEs for assessment
Prepare change plan with prerequisite, post-execution, post-implementation, and effectiveness
review activities
Perform Prerequisite Activities
Execute change and perform Post-Execution Activities
Yes
No
Change Closed
Perform Effectiveness Review activities required by plan
Effectiveness Review complete and approved
System Owner Approve?
Change rejected
Modify change?No Noyes
Yes
Plan approved?
No
Authorize execution
Review of Change Approved?
Perform Post-Implementation Activities
Approve implementation of change for production
Submit Change Request with detailed description
Proposed change identified
Return system to original state
according to plan
Yes
Initiation
Change Assessment
Change Authorization
Change Execution
Change Closure
Change Effectiveness
Identify Change Owner
Evaluate business and compliance strategies and commitments to
identify change
Quality review
CAPAs and proposed
improvements
Confirm Plan
Change Implementation
yes
Initiate a new Change
Request to describe required activities
No
Rejected change closed.Product impact evaluation per
plan
Permanent
Temporary
Review of Change
Product impact evaluation per plan
Change Plan Development and Approval
Initiate investigation to review impact
on product produced
under change
Submit Multi-Site Change Request
Assign SME’s for assessment
Prepare Multi-Site Change Plan including Prerequisite Activities
Multi-Site Plan Approval?
Close new Change
Request and associated
investigation
No
Change Control
Risk Management
Initiate Project
Construction and Verification
Initiate Engineering Change Management
Establish Requirements
Specification, Design, and Approval
Generate detailed project plan
Approve project plan
Create and approve User Requirements Specification
(URS)
Assign a Project Manager and assemble Project Team
Create and approve
Technical Specifications
Perform technical and commercial bid analyses
Perform Risk Assessments
Design Development
Select vendor and award contract
Approve Design?
Create and approve basis
of design
Initiate Engineering Change Management
Commence Construction
FAT Acceptable?
Commissioning and Verification
Installation
Close Engineering Change Management
Acceptance and ReleaseRelease equipment for validation
or use
Prepare Request for Quote (RFQ)
Create and approve project charter
Submit Capital Approval Form (CAF)
ReviseDocument Project
Closeout No
Yes
Verification SAT Acceptable?
Document Control
Purchasing Control
Supplier Qualification
Document Control
No
Calibration
Maintenance of Facility & Equipment
Validation Program
Document Control
No
Yes
Yes
No
Yes
No
Design & Construction of Equipment
Generate Data
Review & Approve Data Or Record
Archive Record For Retention Period
Retrieve Record As Needed
Destroy Records At End Of Retention
Deviation & Investigations
Regulatory Inspections
Document Control
Generate Or Change Controlled Documents
Review, Approve Controlled Documents
Implement Controlled Documents
Retire Obsolete Versions
Conduct Training Training
Records Control
Initiate Change Request For Non-
Substantive Changes
Close Document Change Request As
Applicable
Change Control
Review Periodically Controlled Documents
Regulatory Reporting
Change Control
Change Control
Document Control
Record Control
Select Qualified Personnel For GMP
Activities
Identify Training Requirements And
Plan Training
Design Training Curriculum Materials
Execute Training
Monitor Training Effectiveness
Retrain As Appropriate
Audit & Walk Through Inspections
Deviation & Investigations
Personnel Qualifications
Document Control
Management Review
CAPA
CAPA
Develop & Identify Organizational
Structure Necessary To Support GQS
Define Organizational Relationships &
Numbers Of Personnel
Create Job Descriptions &
Organization Charts
Assess Personnel Qualifications
Acquire Or Assign Personnel According
To Qualifications
Train Qualified Personnel
Audit & Walk Through Inspections
Deviation & Investigations
Training
Quality Management Review
CAPA
Business & QMS Requirements
Document Control
Design Gowning Program
Train & Implement Gowning Procedures
Determine Gowning Control Requirements
Change Control
Risk Mangement
Train & Certify Personnel For Aseptic
AreasTraining
Personnel Qualifications
Training
Hygiene & Gowning
Prepare and Communicate Audit Plan
Draft Audit Report
Generate/Submit Response
Approve Response?
(QA)
No
Execute post-audit activities
All post-audit activities
complete?
Close Audit
No
Yes
Communicate Audit Schedule
Assign Lead Auditor and Audit Team
Execute Audit
Prepare Annual Audit Schedule
Approve Schedule?
(Site Quality Head)
Yes
No
Yes
Notify Lead Auditor
Audit Schedule
Audit Preparation
Approve Audit Report?
(QA)
Issue Audit Report
Yes
No
Audit Response
Post-Audit Activities
Audit Closure
Audit Execution
Inspection/Audit Preparation
Receive Inspector/Auditor
Conduct Inspection/Audit
Inspection/Audit Wrap-up
Develop Response And Commitment/
CAPA
Submit Responses For Commitment/
CAPA
Complete Commitment/CAPA & Close Inspection/Audit
CAPA
Regulatory Reporting
CAPA
Governance & Management Notification
Audit & Walk Through Inspections
Regulatory Inspections & Customer Audits
Consider Possible RecallDeviation Investigations
Develop Strategy And Planning
Determine Health Hazard & Class As
AppropriateNotify Regulatory
Agency Or Competent Authority As Required
Reg
ulat
ory
Rep
ortin
g
Implement Plan Storage & Distribution
Periodic Reports As Required
Complete & Close Regulatory ReportingDeviation Investigations
Report Event To Regulatory Agency
Report Followup To Regulatory Agency
Yes
Receive Product Event Information
Periodic Product Review
Quality Management Review
Governance & Management Notification
Complaint Management
Counterfeiting, Product Diversion, & Tampering
Event Reportable? No Trend
Deviations & InvestigationsLaboratory Investigations
Evaluate Labeling Change Risk Assessment
Initiate Labeling Change Request For Review & Approval
Implement Labeling Change
Validation
Production Labeling Controls
Facility &Equipment Management
Materials Control
Close Labeling Change
Materials Controls
ValidationRegulatory Authority
Submission
Labeling Change Planning
Qualification
Regulatory Authority Submission
Train & Certify Licensed
Representative
Perform Duties in Accordance with
Licensed Requirements
Maintain Certification As Required
Regulatory Affairs
Management Review
Lot Disposition
Training
Designate Sufficient Number of Licensed
Representatives
Training
Other GQS Standards
Labeling Development & Change Management
Recall
Regulatory Reporting
Licensed Representatives
Form a Technology Transfer Team
Assess Sending & Receiving Unit readiness
Define project scope and requirements
Process/method ready for transfer?
Generate a detailed Transfer Plan
Technology Transfer Initiation
Perform technical gap analysis and Risk Assessment
Technology Transfer Plan
Item has been identified for transfer to an identified Receiving Unit
Transfer Plan approved?
Execution of Plan Execute
Transfer Plan
Transfer meet acceptance
criteria?
Compile transfer final report
Post-Transfer monitoring
Post-Transfer Monitoring
Identify a Technical Leader/project manager
Project approved to proceed?
Technology Transfer Proposal
Document and File
Document and File
No
Yes
No
Complete Technology Transfer and lessons learned
Completion of Technology Transfer
Drug DevelopmentDesign Control
Risk Assessment
More information
Cancel
More information
Cancel
Change Control
Change Control
Deviations & Investigations
Quality Management ReviewPeriodic Product Review
Technology Transfer
Develop Design Plan
Conduct Review
Design Product & Develop Design Outputs
Develop & Execute Verification Protocol
Develop & Document Design Inputs
Design Validation (Clinical Trial, Animal
Studies, IDE) Activities
Conduct Review
Select Product to Market & Determine Product
Regulatory ClassificationResearch Report
Manufacture Commercial Product, Improve Design,
Update DHF
Lab Investigations
Deviation Investigations
Research
Complaint Management
Change Control
Risk Management
Risk Management
Transfer Activities
Conduct Transfer Review
Environmental Monitoring
Stability Monitoring
Governance & Management Notification
Quality Management Review
Change Control
Production Controls
Risk Management
Technology Transfer
Regulatory Affairs
Design Control
Develop Test Method
Develop Stability (Shelf Life)
Specification Specifications
Develop Finished Product Specifications
Develop In-Process Specifications
Validate Test Method
Transfer Method
Identify CQA Or CPP Drug Development
Use & Improve Specifications
Lab Investigations
Deviation Investigations
Research
Complaint ManagementEnvironmental Monitoring
Stability Monitoring
Governance & Management Notification
Quality Management Review
Change Control
Technology Transfer
Design Control
Method Validation
Determine Instrumentation And
Sampling
Laboratory Instrument QualificationSampling
Specification Development
Specification Development
Develop, Characterize API, Develop PCS
With QTPP
Develop DP Formulation Process
& PCS
Develop & Validate Cleaning Process &
Methods
Develop & Transfer Manufacturing
Process & MBR, Update PCS
Transfer & Qualify API Manufacturer Based
Upon PCS
Validate Process, Update PCS
Manufacture Clinical Supplies
Validation
Identify Molecule Research Report
Manufacture Commercial Product
& Improve PCS
Lab Investigations
Deviation Investigations
Research
Complaint ManagementEnvironmental Monitoring
Stability Monitoring
Governance & Management Notification
Quality Management Review
Change Control
Technology Transfer
Drug Development
Receive & Document Complaint
Complaint Investigation
Complaint Report
Acknowledge Complaint
Pharmacovigiliance
Communication To Complainant
Deviation & Investigations
Deviation & Investigations
Regulatory Reporting
Counterfeit, Product Diversion, & Tampering
Receive Complaint Where Counterfeiting, Diversion
Or Tampering Is Suspected
Request & Receive Sample
Notify Senior Management &
Regulatory Authorities
Perform Assessment And Testing
Continue In Accordance With Complaint Policy
Laboratory Controls
Counterfeit, Diverted, Tampered
Product?Yes
No
Pharmacovigiliance
Regulatory Reporting
Recall
Storage & Distribution
Pharmacovigiliance
Periodic Product Review
Complaint Management
Verify & Move to Distribution Inventory
Receive Customer Order
Material Picked, Verified, & Staged
Material Shipped
Store Product
Product destroyed
Product Returned?
Yes
End No
Is product to be returned to
Distribution?Yes No
Release Lot for Distribution
Verify Product Storage & Integrity
Deviation & Investigations
Deviation & InvestigationsEnvironmental Monitoring
Lot Disposition
Deviation & Investigations
Dev
iatio
n &
Inve
stig
atio
ns
Com
plai
nt
Cou
nter
feiti
ng, P
rodu
ct
Div
ersi
on, a
nd T
ampe
ring
Rew
ork,
Rep
roce
ssin
g,
Rei
nspe
ctio
n, R
ecov
ery
Receipt
Material Quarantine & Disposition
Warehousing
Product Quarantine & Disposition
Shipping/Distribution
Deviations & Investigations
Production Controls
Environmental Monitoring
Purchasing
Lot Disposition
Supplier Control
Sampling
Lot Disposition
Storage & Distribution
Production Labeling Controls
Investigational Products
Labeling Development & Change Management
Completed Product Batch Record And
Testing
Generate Certificate Of Analysis (CofA)
Verify That CofA Is Consistent With Raw
Data
Verify That CofA Meets Requirements
Final Approval
Send To Customer And Archive Copy
Laboratory ControlsReceive Certificate Of Analysis (CofA) From
Supplier
Review For Completeness
Verify CofA Results Meet Specifications
Resolve Discrepancies Or
Issues
File With Material Lot Record
Purchasing Controls
Lot Disposition
Supplier Qualification
Purchasing Controls
Deviation & Investigations
Material Control
Storage & Distribution
Material Control
Certificate of Analysis
Risk Assessment Categorize Supplier
Initial Assessment & Questionnaire
Qualify Supplier
Re-Qualify Or Disqualify Supplier
Prepare For Audit
Execute Audit
Response And CAPAClose Audit
Schedule Supplier Audit
Laboratory Controls
Supplier Control
Supplier Control
Deviations & Investigations
Deviation & Investigation
Monitor SupplierCAPA
Complaints Regulatory Inspection
Supplier Control
Supplier Qualification
Qualify Supplier that will be subject to a Quality Agreement (QAG)
Determine Risk Mitigation
Generate QAG
Review QAG & Corresponding Supply
Agreement (SAG)
Submit QAG for review and approval of Stakeholders
Submit approved Quality Agreement to Customer
Obtain signed approval from Customer
Monitor, Review, & Modify Quality Agreements
Supplier Qualification
Risk Management
Document Control
Quality Agreements
Receive Purchase Request
Supplier Qualified?
Initiate Supplier Qualification
Process
No
Yes
Maintain Purchasing Records
Place Order with Supplier
Corrective Action
Required?
No
Yes
Initiate Supplier Corrective Action
Process
Receive Sourced Product or Services
Supplier Qualification
Material Control
CAPA
Develop/Revise Specifications/Quality
Agreement
Qualify Supplier
Purchase Material, Product Or Service
Monitor, Re-qualify, Disqualify Supplier
Approve Supplier
Supplier Qualification
Supplier Qualification
Quality Agreement
Identify Supplier (s)
Issue Batch Record
Complete Batch Record
Monitor Production
Generate Records
Manufacture Product
Master Batch Record
Sample & Inspect
Completed Batch Record
Materials Control
Training
Lot Disposition
Deviation & Investigations
Preventive & Routine Maintenance
Laboratory Controls
Change Control
Document Control
Complaint ManagementProduction Control
Purchasing Control
Counterfeiting, Product Diversion, Tampering
Produce Non-Conforming Material
or Product
Deviation Investigation
Perform Remediation As Rework,
Reprocessing, Reinspection,
Recovery
Evaluate & Report Results
Deviation Investigation
Covered by Procedure?
Yes
No
Deviation Investigation
Lot DispositionSampling
Laboratory Controls
Material Control
Production Controls
Production Control Records
Develop & Approve Protocol
Issue Batch Record
Complete Batch Record
Monitor Production
Generate Records
Manufacture Product
Master Batch Record
Sample & Inspect
Completed Batch Record
Materials Control
Training
Lot Disposition
Deviation & Investigations
Preventive & Routine Maintenance
Laboratory Controls
Change Control
Document Control
Production Control Records
Rework, Reprocessing, Reinspection, Recovery
Minimize Bacterial Load on Materials &
Equipment
Maintain & Control Clean Manufacturing
Conditions
Maintain Time Limits On Processing
Control Product Sterilization
Sterilize Components And Equipment
Maintain & Control Product Integrity
Hygiene & Gowning
Validation
Facility, Equipment & Utility Qualification
Laboratory Controls
Deviation & Investigations
Certify Personnel for Clean Room Operations
Aseptic Production Control
Issue Batch Record
Complete Batch Record
Monitor Production
Generate Records
Manufacture Product
Master Batch Record
Sample & Inspect
Completed Batch Record
Materials Control
Environmental Control
Laboratory Controls
Sampling
Change Control
Deviation Investigations
Training
Lot Disposition
Document Control
Production Control
Production Labeling Controls
Aseptic Production Control
Investigational Products
Minimize Bacterial Load on Components
& Equipment
Maintain & Control Clean Manufacturing
Conditions
Maintain Time Limits On Processing
Control Equipment & Component
Sterilization Or Depyrogenation
Sterilize Components And Equipment
Validation
Facility, Equipment & Utility Qualification
Environmental Monitoring
Deviation & Investigations
Aseptic Processing Controls
Sterilization & Depyrogenation Control
Issue Approved Packaging And
Labeling
Sample & Inspect Product Labeling &
Packaging
Reconcile Labeling & Packaging Materials
Perform Line Clearance
Label & Package Product
Receipt Of First Supply
Issue Approved Printed Labels
Laboratory ControlsDeviations & Investigations
Return Or Destroy Packaging & Labeling
Sampling
Deviations & Investigations
Materials Control
Materials Control
Production Labeling Controls
InitiateQuality Risk Management Process
Risk Identification
Review Events
Risk Acceptance
Risk Reduction
Risk Evaluation
Risk Analysis
Risk M
anagement ToolsR
isk
Com
mun
icat
ion
Output/Result Of TheQuality Risk Management Process
Risk Assessment
Risk Review
Unacceptable
Risk Control
.
Current Standard
KPC
Cri$cality Assessment : Quality System Map Annual Product Review
Change Control
Regulatory Agency Submissions
Validation
Testing Lot Release Training
Discrepancy Management
Complaint/Adverse Event
Audits Facility & Equipment Maintenance Facility & Equipment Engineering
Production Packaging & Labeling
Environmental Control
Materials Management
Record Management PROP Systems Program
Interfaces
Design Environmental
Controls Design
Environmental Monitoring Procedures
Analyze Data for Trends
Implement Environmental
Monitoring Program
F & E Engineering Validation Change Control
Testing Validation F & E Engineering F & E Maintenance
Lot Release Discrepancy
Change Control Testing
Discrepancy Change Control
Validation Study Planning
Protocol Development and
Execution Data analysis and
Reporting
Production (I) Facilities & Equipment
Engineering (I) Document Control (I)
Testing (I) Facilities &
Equipment Engineering
(I) Change Control Discrepancy
Testing Production
Training Materials
Management Change Control
Identify Facility or Equipment
Equipment and Facility
Maintenance Facilities & Equipment Preventative Maintenance
Facilities & Equipment Calibration
Facilities & Equipment
Cleaning and Sanitization Pest Control
Change Control (I) F & E Engineering (I)
Production (I) Discrepancy
Discrepancy Discrepancy Discrepancy Discrepancy
Change Control Change Control
Training
Collection of Data Evaluation &
Analysis of Data Reporting of Findings &
Implementation of CAPA
Lot Release (I) Change Control (I)
Discrepancy Management (I)
Product Complaints (I) Testing (I) Audit (I)
Discrepancy Change Control
Change Control (I) Regulatory Assessment
Strategy Development
Implement Strategy Change Control
Lot Release Receiving/
Warehouse Quarantine Warehousing
Shipping/ Distribution
Change Control (I)
Audit Lot Release
Testing Discrepancy
Lot Release Testing
Production Packaging &
Labeling
Issuance & Inspection Perform,
Reconcile, Review Production Materials
Record
Discovery and Initial Assessment
Validation (I) Regulatory Agency Submissions (I)
Testing (I) Audits (I)
Materials Management (I) Complaints/Adverse Events (I)
Annual Product Review (I) Lot Release (I)
F & E Maintenance (I) Production (I)
Labeling & Packaging (I) Environmental Control (I)
Immediate Corrective Action Investigation, root Cause Analysis, and Preventative
Action Follow through and Closure
Document/Report/ Analyze
Change Control Change Control Regulatory Agency
Submission Lot Release
Annual Product Review (I) Lot Release (I)
Validation (I) Training (I)
Deviation Management (I) Change Control (I)
Complaint/Adverse Event (I) Audit (I)
F & E Maintenance (I) F & E equipment (I)
Production (I) Labeling & Packaging (I)
Environmental Monitoring (I) Materials Management (I)
Testing (I) Regulatory Agency
Submissions (I) Record Management (I)
Audit Preparation Audit Execution
Creation & Issuance of Audit
Report Follow-up and
Closure
Responding to Audit/Inspection
Observations Audit/Inspection Closure
Inte
rnal
/Ext
erna
l Aud
it H
ostin
g A
udit Audit/Inspection
Execution Audit/Inspection Audit/Inspection Preparation
Discrepancy Change Control
Discrepancy Change Control
Change Control (I) Production (I)
Packaging and Labeling (I)
Material Management (I) F & E Maintenance (I)
Regulatory Agency Submissions (I)
Environmental Control (I) Planning or Feasibility
Requirements or Conceptual
Design Preliminary and Detail Design Construction,
Commissioning and Qualification
Change Control Change Control
F & E Maintenance Validation
Operation & Maintenance F & E Maintenance Decommission Change Control
Batch Planning Raw Material/ Component
Allocation Process
Preparation Bulk Production Final Production
Materials Management (I)
Records Environmental
Change Control (I)
Training (I) Validation (I)
Change Control (I) F & E Maintenance (I)
Materials Management (I)
Materials Training
Change Control Records
Environmental Materials Training
Records Testing
Lot Release Environmental Materials
Training Records
Testing Lot Release
Discrepancy
Discrepancy
Record Design Record
Generation Record Review Record Archive and Destruction
Production (I) Maintenance-
Facilities&Equipment (I) Engineering-
Facilities&Equipment (I) Testing (I)
Materials Management (I) Lot Release (I)
Change Control (I) Validation (I)
Environmental Monitoring (I) Annual Product Review (I) Packaging and Labeling (I)
Discrepancies Management (I) Complaints/Adverse Events (I)
Audits (I) Training (I)
Change Control
Discrepancy
Initiate & Evaluate Change
Change Review & Approval
Implement Change Close Change &
Monitor Effectiveness
Validation (I) Regulatory Agency
Submissions (I) Lot Disposition (I)
Testing (I) Training (I)
F&E Maintenance (I) F&E Engineering (I)
Packaging & Labeling (I) Production (I)
Environmental Control (I)
Lot Release Training
F & E Engineering F & E Maintenance Validation Environmental Control Regulatory Agency
Submissions Lot Release
Audit (I) Annual Product Review (I)
Production Support Testing Support Training Support
Validation Support Discrepancy Management Action
Regulatory Agency Submissions Support Materials Management Support Change Control Support
Lot Release (I) Environmental Control (I) Materials Management (I)
Validation (I) Complaint/Adverse Event (I)
Production (I) Packaging & Labeling (I) Annual Product Review (I)
Scheduling & Planning Testing
Preparation Sample Receipt
Test Performance & Reporting
Test Evaluation Laboratory
Investigation Discrepancy
Validation Training Records Records Records
Record Management Support Change Control (I)
Discrepancy Management (I) Testing (I)
Environmental Control (I) Production (I)
Packaging and Labeling (I) Regulatory Submissions (I)
Collection of Records and Data
QA Review of Records and Data
Approval and Disposition Materials
Records Discrepancy
Production Discrepancy
Material Management Support Complaint Receipt
Adverse Event Notification/
Sample Retrival Product
Nonconformance Investigation
Report, Corrective Action & Close Out
Testing Regulatory Agency
Submission Change Control
Trend Analysis Regulatory Submissions (I)
Production (I) Testing (QC) (I)
Production (I)
Discrepancy Discrepancy
Identify Training Events
Determine Training Needs
Implement Training
Monitor Training Effectiveness
Production (I) F&E Maintenance (I) F&E Engineering (I)
Testing (I) Materials Management(I)
Lot Release (I) Change Control (I)
Validation (I) Environmental Control (I) Annual Product Review (I) Packaging and Labeling (I)
Discrepancy Management (I) Compliant/Adverse Events (I)
Audits (I) Regulatory Agency Submissions (I)
Audit Record
Testing Production
Production
Materials Management
Materials Management Packaging &
Labeling
Packaging & Labeling
Discrepancy
Discrepancy Action
Training Support
Record Management Action Record Management Support
Rec
ord
Man
agem
ent A
ctio
n R
ecor
d M
anag
emen
t Sup
port
Discrepancy Action Change Control Action Lot Release Action
Change Control Action
Audit Support A
udit Support
Production Support
Blue Lines Are Good; Red Lines … Not So Much
Core Quality System Elements TM
Product & Process Improvement
Supply Chain Management
Management of Documentation
Personnel Qualification & Training
Control and Release
Qualification and Validation
Quality Audit
Manufacturing and Packaging
Environmental and Critical Utilities Monitoring
Cleaning Validation
Process Validation
Document and Records Control and Retention
Facilities Utilities and Equipment
Quality Risk Management
Design and Development
Management of Suppliers & Subcontractors
Counterfeiting, Product Diversion, and Tampering
VisioDocument
Quality Process
XXXXXX
LEGEND
Terminal Sterilization
Aseptic Process Validation
Laboratory Equipment Qualification
Quality Technical Agreements
Rework, Reprocessing, And Re-inspection
Sampling
Supplier Qualification & Lifecycle Management
Stability Monitoring
Document Architecture, Format, and Content
Standards
Laboratory Investigations
Pharmaceutical Quality System
Technology Transfer
Investigational Products
Master & Batch Production Records
Governance Structure, Notification, and Escalation
Production Labeling Controls
Sterilization & Depyrogenation Control
External GMP Inspections
Management of Computerized Systems
Material Management
Certificates of Analysis
Purchasing Control
Lot DispositionRecall Management
Facility and Engineering Documents, Content & Format
Hygiene & Gowning
Design Control
XXX
Drug Development
Quality Management Review
Product Event Management
Change Control
Training
Personnel Qualification
Risk Management
Deviations & Investigations
Calibration
Maintenance of Facilities & Equipment
Environmental Control
Production Control
Validation Program
Materials Control
Laboratory Controls
Trending & Statistical Analysis
Corrective and Preventive Action (CAPA)
Design & Construction of Facilities,Utilities, and Equipment
Periodic Product Review
Lifecycle Management of Computer Systems
Product Event Reporting to Regulatory/Competent Authorities for Drugs and Biologics
Specification Development
XXX
Product Lifecycle Processes Organizational Processes
Quality Systems Management
Transversal Processes
Method Development and Validation
Aseptic And Controlled Area Processing
Requalification
Viral Risk Mitigation & Contamination Response
Sterilization & Depyrogenation Validation
Labeling Development and Labeling Change Management
Technology Transfer
Audits & Walk-Through Inspections
Quality and Supplier Audits
Warehousing and Distribution
Storage & Distribution
Collection, Communication and Review of Safety Information
Validation of the Transportation of Temperature-Sensitive Material
Product Discontinuation
See: Drug Development Standard Quality Organization,
Management, Planning, and Objectives
Quality Management Of Subcontractors
Development Engineering & Maintenance Manufacturing Q C Q A
ICH Q10 Quality System – Organiza$on Chart
QC QA Development Manufacturing Engineering
Quality System -‐ Development
• PD Experiments Define Process CQAs, CPPs • CQA Test Method Development • Produc$on Opera$ons Risk Assessment (RA) • Process Development Report (PDR) • Verify CQAs & CPPs – Valida$on Protocols • Verify CQAs & CPPs – Batch Records, • Ongoing Test Method Support • Monitor Process Data • Monitor QC Test Data • APQR Assessment
KNOWLEDGE SPACE
DESIGN
SPACE
CO
NTR
OL STR
ATEGY
CRITICALITY
Development of Product A:ributes, Process Parameters, Design Space & Control Strategy
Quality System – Engineering Basis : Process Development Report
• Design Facili$es, Equipment, Instruments, U$li$es
• Develop Engineering, Cal/ Maintenance Program
• Install Control System • Qualifica$on • Rou$ne Manufacturing Support • Engineering, Cal/ Maintenance data to QA
Quality System – Manufacturing Basis : Process Development Report
• Drive Process Valida$on • Finalize Process Monitoring and Control • Complete Produc$on Batch Record • Devia$ons • Inves$ga$ons • Correc$ve and Preven$ve Ac$on (CAPA)
• Manufacturing • Data to QA
Quality System -‐ Quality Control Basis : Process Development Report
• Define Environmental Monitoring Requirements • Test Method Transfer Valida$on
• Rou$ne IP, QC Sampling and Tes$ng • IP and QC data to QA
Quality System -‐ Quality Assurance Oversight Basis : Process Development Report
• Engineering Design • Training Materials • Calibra$on and Maintenance Program, • Manufacturing BR & SOPs • In-‐Process and QC Test Methods • Process Valida$on • CPPs and Cri$cal Unit Opera$ons • Review IP and QC Test Results • QA Produc$on Data Review – Product Disposi$on
Core Quality System Elements TM
Product & Process Improvement
Supply Chain Management
Management of Documentation
Personnel Qualification & Training
Control and Release
Qualification and Validation
Quality Audit
Manufacturing and Packaging
Environmental and Critical Utilities Monitoring
Cleaning Validation
Process Validation
Document and Records Control and Retention
Facilities Utilities and Equipment
Quality Risk Management
Design and Development
Management of Suppliers & Subcontractors
Counterfeiting, Product Diversion, and Tampering
VisioDocument
Quality Process
XXXXXX
LEGEND
Terminal Sterilization
Aseptic Process Validation
Laboratory Equipment Qualification
Quality Technical Agreements
Rework, Reprocessing, And Re-inspection
Sampling
Supplier Qualification & Lifecycle Management
Stability Monitoring
Document Architecture, Format, and Content
Standards
Laboratory Investigations
Pharmaceutical Quality System
Technology Transfer
Investigational Products
Master & Batch Production Records
Governance Structure, Notification, and Escalation
Production Labeling Controls
Sterilization & Depyrogenation Control
External GMP Inspections
Management of Computerized Systems
Material Management
Certificates of Analysis
Purchasing Control
Lot DispositionRecall Management
Facility and Engineering Documents, Content & Format
Hygiene & Gowning
Design Control
XXX
Drug Development
Quality Management Review
Product Event Management
Change Control
Training
Personnel Qualification
Risk Management
Deviations & Investigations
Calibration
Maintenance of Facilities & Equipment
Environmental Control
Production Control
Validation Program
Materials Control
Laboratory Controls
Trending & Statistical Analysis
Corrective and Preventive Action (CAPA)
Design & Construction of Facilities,Utilities, and Equipment
Periodic Product Review
Lifecycle Management of Computer Systems
Product Event Reporting to Regulatory/Competent Authorities for Drugs and Biologics
Specification Development
XXX
Product Lifecycle Processes Organizational Processes
Quality Systems Management
Transversal Processes
Method Development and Validation
Aseptic And Controlled Area Processing
Requalification
Viral Risk Mitigation & Contamination Response
Sterilization & Depyrogenation Validation
Labeling Development and Labeling Change Management
Technology Transfer
Audits & Walk-Through Inspections
Quality and Supplier Audits
Warehousing and Distribution
Storage & Distribution
Collection, Communication and Review of Safety Information
Validation of the Transportation of Temperature-Sensitive Material
Product Discontinuation
See: Drug Development Standard Quality Organization,
Management, Planning, and Objectives
Quality Management Of Subcontractors
Development Engineering & Maintenance Manufacturing Q C Q A
ICH Q10 Quality System – Organiza$on Chart
11/19/15 17
QC QA Development Manufacturing Engineering
FDA Quality Metrics -‐ Repor$ng • Lots Anempted • Rejected Lots • Anempted Batches • OOS (Including Stability) • Lot Release Tests • Stability Tests • Invalid OOS (Including Stability) • Product Quality Complaints • Lots Anempted • APR (QPR) On Time Comple$on • AQRs (PQRs) Required
Management Governance • Corporate Product Quality & Compliance Goals • Rou$ne Produc$on Monitoring and Control • Devia$ons, Inves$ga$ons • Rejected Materials / Products • Product Complaints • Adverse Events • Recalls • Annual/Periodic Product Quality Reviews • Correc$ve and Preven$ve Ac$ons • Con$nuous Improvement • Periodic Management Reviews – Goals / Progress
Final Thoughts
• Put in Place an ICH Q 10 Based QS • Understand the Product (CQAs) • Understand the Process and its Impact on the Product (CPPs, QbD and Control Strategy)
• Validate QC Test Methods • Validate, Monitor and Control the Process • Inves$gate and CAPA all Devia$ons • Con$nuously Improve all Opera$ons