1. Quality System Model ICH Q10

2. Agenda What is ICH Q10 History
Why do we need a ‘modern effective Quality System’?
The elements and enablers of a Quality System
Model of Pfizer’s Quality System
Review the website

3. Pharmaceutical Quality System
The ICH Q10 document on Pharmaceutical Quality System was recommended for adoption to the regulatory bodies of the EU, Japan and USA, June 2008.
The document establishes a tripartite guideline describing a model for an effective quality management system; a management system to direct and control a pharmaceutical company with regard to quality.
The specifics of a pharmaceutical quality system vary depending with the stage of the product lifecycle, but the overall principles and components are the same.

4. History Evolution of regional GMPs 1970s
Evolution of ISO 9000 approaches
1980s
FDA 21st Century initiative
2002
ICH Quality Vision / Q8, Q9
2003
Guidance for Industry - Quality System Approach to Pharmaceutical cGMP Regulations
2006
ICH Q10 Pharmaceutical Quality System
2008

5. Comprehensive Model
Based on International Standards Organization (ISO) quality concepts
Includes applicable GMP regulations
Complements both
ICH Q8 Pharmaceutical Development,
ICH Q9 Quality Risk Management
Not intended to create new expectations beyond current regulatory environment

6. A ‘Modern Effective Quality System’?
Good business practice!
Significant changes in external business environment
Fewer new products / ‘blockbusters’
Reduced margins / greater competition / low-cost sources
Focus of efficient, effective organizations
Lean processes
Pharmaceutical industry is behind other industries in Quality Management philosophies / practices
Marketed products ARE safe and efficacious
BUT costs of quality are high
Often reactive, not designed-in / preventative

7. Why do we need a ‘Modern Effective Quality System’?
Implementation should
Facilitate innovation and continual improvement
Inflexible regulatory environment
Focus on Compliance, not Science and Risk-Based approach
Industry margins did not provide drive for change
Strengthen the link between pharmaceutical development and manufacturing
GMPs do not provide a ‘full modern’ Quality System
Originated in 1970s – incremental additions
ISO Quality Management thinking not embedded
Need to be complemented with Q8 and Q9
This is in direct alignment with Pfizer’s philosophies and vision

8. Pharmaceutical Quality System
The diagram illustrates the major features of the ICH Q10 Pharmaceutical Quality System model. The model covers the entire lifecycle of a product including pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation. The diagram also illustrates that GMPs apply to the manufacture of investigational products. The next horizontal bar illustrates the importance of management responsibilities to all stages of the product lifecycle. The following horizontal bar lists the Quality System elements which are the mainstays of a quality system. These elements should be applied appropriately and proportionally to each lifecycle stage. The bottom set of horizontal bars illustrate the enablers: knowledge management and quality risk management, which are applicable throughout the lifecycle stages. These enablers support the quality system goals of achieving product realization, establishing and maintaining a state of control, and facilitating continual

9. An Effective Quality System
GMPs
Management Responsibility
Elements - Continual Improvement
Enablers – Knowledge and Risk Management
Lifecycle approach
ICH Q10 describes a single comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts. It includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. The additional content is optional, but its use should facilitate innovation and continual improvement, and strengthen the link between pharmaceutical development and manufacturing activities.
It does not restate GMP requirements, ICH Q10 is intended to augment requirements to achieve the Pharmaceutical Quality System objectives
Cover Management Responsibility and Continual improvement in a bit more detail

10. An Effective Quality System
GMPs
Management Responsibility
Elements - Continual Improvement
Enablers – Knowledge and Risk Management
Lifecycle approach
ICH Q10 describes a single comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts. It includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. The additional content is optional, but its use should facilitate innovation and continual improvement, and strengthen the link between pharmaceutical development and manufacturing activities.
It does not restate GMP requirements, ICH Q10 is intended to augment requirements to achieve the Pharmaceutical Quality System objectives
Cover Management Responsibility and Continual improvement in a bit more detail

11. Management Responsibilities
Essential component of a Quality System
Not just about compliance
Visible leadership to establish and maintain a company wide culture and commitment to Quality and improvement
Monitor performance of the Quality System for both internal and outsourced activities
Quality can not be owned only by the ‘Q’ Unit
Management is accountable
But independent assessments are key

12. Management Responsibilities
Management Commitment
Quality Policy
Quality Planning
Resource Management
Internal Communication
Management Review
Outsourced Activities
Change in Product Ownership
Essential component of a Quality system
Not just about compliance but
Visible leadership to establish and maintain a company wide culture and commitment to Quality and improvement
Monitor performance of the Quality System for both internal and outsourced activities
Quality can not be owned only by the Q Unit
Management is accountable
But independent assessments / audits are key

13. Management Commitment
Signed Quality Commitments are commonplace and are not indicative of Management Commitment
What is Indicative?
Plant Managers aware of the issues
Management Team that works together
Quality as a Trusted Partner

14. Clear Roles, Responsibilities, Processes
Quality Policy: Sets the standards and direction of organization
Quality Planning: Converts into objectives & plans
Resources: Allocations and competence
Communication: Quality items to appropriate audience
Management Reviews
Product and Process performance
Quality System performance

15. Quality Policies Comprehensive and Balanced
Flexibility/adaptability defined is consistent
Interconnectivity of a Quality System requires a comprehensive approach in the design

16. Quality Plans Written Quality Plans are becoming more common
What is Indicative?
Quality Planning Process is dynamic
Defined process for evaluating issues to bring into the quality planning process.
Tracking progress against an agreed upon Quality Plan
Adequate resources are made available

17. Resource Management Adequate resources are made available
Resources include time, money, equipment and people
What is Indicative?
Clear prioritization of resources in line with
Reasonable number of projects with
Realistic commitment time frames

18. Internal Communication
Issues will occur
Escalation of issues, actions, decisions and impact
What is Indicative?
Trusting relationship between manufacturing & quality assurance
Understanding of why timeliness is important
Communication uses defined processes and is transparent
Escalation of issue is not viewed as punitive
The Operations Team is wholly accountable
Adequate resources are made available

19. Management Review
Grounded in the device regulations, periodic Management Reviews are becoming more common
What is Indicative?
Linkage between Quality Plan and Management Reviews
Linage between Key Quality Indicators
In a hierarchal company, how information flows
Depth and frequency of Reviews
Attendance at the Management Review
How is the information used?
Opportunity to align priorities and resources
Not punitive

20. Outsourced Activities and Purchased Materials
Pharmaceutical firm (i.e., Management) is ultimately responsible to assure processes are in place
Process must be in place to:
Assess suitability of contractors / suppliers before use
Ensure use of approved suppliers and a defined supply chain
Define responsibilities and communication processes for quality related activities
Review performance and make improvements
Quality System must extend to the control and review of outsourced activities and the quality of purchased materials

21. An Effective Quality System
GMPs
Management Responsibility
Elements - Continual Improvement
Process Performance and Product Quality
Corrective Action / Preventive Action
Change Management
Management Review
Enablers – Knowledge and Risk Management
Lifecycle approach
ICH Q10 describes a single comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts. It includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. The additional content is optional, but its use should facilitate innovation and continual improvement, and strengthen the link between pharmaceutical development and manufacturing activities.
It does not restate GMP requirements, ICH Q10 is intended to augment requirements to achieve the Pharmaceutical Quality System objectives
Cover Management Responsibility and Continual improvement in a bit more detail

22. Continual Improvement
Continuous Improvement of product quality is a key objective of the quality system, irrespective of the stage of the lifecycle.
Four specific elements of the quality system support achieving continuous improvement:
Process performance and product quality monitoring
Corrective action and preventative action
Change management
Management review of process
performance and product quality

23. Product Quality and Process Performance
Use knowledge, Quality by Design, Product and Process understanding and QRM to set Control Strategy
What and when to monitor / measure / test
Based on critical product quality attributes and critical process parameters to deliver them
Reduce and control variation to appropriate levels
Confirm and maintain a state of control
Feed-back and Feed-forward loops
Drive continual improvement
Continual verification

24. CAPA System Investigation of non-conformances
Reactive → deviations, rejections, complaints, recalls, observations from audits and inspections
Proactive → feedback from trends
Structured investigations to seek root cause
Use QRM to ensure degree and formality is commensurate with level of risk
Should result in enhanced knowledge and improvement
Not just reacting to non-conformances
Focus on preventative actions
Need effective tracking / follow up processes

25. Change Management System
Change can be good!
Proactively driven by outputs from monitoring / trending / improvement / innovation
Not just by reacting to problems
Use expert teams and knowledge to evaluate and set success criteria
Use QRM commensurate with level of risk
Consider impact on regulatory filings
Undertake in timely and effective way and tracked
Assure no unintended consequences

26. Management Review Process Performance and Product Quality
Results from inspections and assessments
Periodic quality reviews
Customer satisfaction – complaints, recalls
Conclusions of process performance and product quality monitoring
Effectiveness of process and product changes
Appropriate actions
Improvements to manufacturing processes
Training and/or realignment of resources
Capture and share knowledge
All three come together in management review

27. Continual Improvement of the Quality System
Assessment of the Quality System against
Internal factors (audits, CAPAs, complaints, recalls, etc.)
External factors (regulatory inspectional findings)
Emerging regulations
New technology
Change in business strategies
Outcomes of the Assessment
Improvements communicated throughout a business
Resource reallocation
Changes in policies, practices

28. An Effective Quality System
GMPs
Management Responsibility
Elements - Continual Improvement
Enablers – Knowledge and Risk Management
Lifecycle approach
ICH Q10 describes a single comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts. It includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. The additional content is optional, but its use should facilitate innovation and continual improvement, and strengthen the link between pharmaceutical development and manufacturing activities.
It does not restate GMP requirements, ICH Q10 is intended to augment requirements to achieve the Pharmaceutical Quality System objectives
Cover Management Responsibility and Continual improvement in a bit more detail

29. Knowledge Management
Systematic and lifecycle approach to acquiring, analyzing, storing and disseminating knowledge on products, processes, components
Provides the basis for science and risk-based approaches in the Quality System
Product and process development
Manufacturing
Change management
Continual improvement

30. Quality Risk Management (Q9)
Essential, integrated part of Quality System
The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; and
The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk
Proactive use to identify and control risk
Support decision through lifecycle
Integrate into key parts of Quality System
e.g., change management, CAPA, GMPs – Validation, etc.
Help set meaningful specification / control parameters to ensure product quality control requirements are met

31. Key to an Effective Quality System
GMPs
Management Responsibility
Continual Improvement
Knowledge Management
Quality Risk Management
Lifecycle approach
ICH Q10 describes a single comprehensive model for an effective pharmaceutical quality system that is based on International Standards Organization (ISO) quality concepts. It includes applicable Good Manufacturing Practice (GMP) regulations and complements ICH Q8 “Pharmaceutical Development” and ICH Q9 “Quality Risk Management”. ICH Q10 is a model for a pharmaceutical quality system that can be implemented throughout the different stages of a product lifecycle. Much of the content of ICH Q10 applicable to manufacturing sites is currently specified by regional GMP requirements. ICH Q10 is not intended to create any new expectations beyond current regulatory requirements. The additional content is optional, but its use should facilitate innovation and continual improvement, and strengthen the link between pharmaceutical development and manufacturing activities.
It does not restate GMP requirements, ICH Q10 is intended to augment requirements to achieve the Pharmaceutical Quality System objectives
Cover Management Responsibility and Continual improvement in a bit more detail

32. Lifecycle Approach Holistic and cover the product lifecycle
Design and Development
Manufacturing
Withdrawal
Challenges and removes some traditional organizational silos
Within industry
Within Regulatory Agencies
With outsourcing partners
Application of Quality System Elements at each stage of the Product Lifecycle

33. Pharmaceutical Quality System
The diagram illustrates the major features of the ICH Q10 Pharmaceutical Quality System model. The model covers the entire lifecycle of a product including pharmaceutical development, technology transfer, commercial manufacturing, and product discontinuation. The diagram also illustrates that GMPs apply to the manufacture of investigational products. The next horizontal bar illustrates the importance of management responsibilities to all stages of the product lifecycle. The following horizontal bar lists the Quality System elements which are the mainstays of a quality system. These elements should be applied appropriately and proportionally to each lifecycle stage. The bottom set of horizontal bars illustrate the enablers: knowledge management and quality risk management, which are applicable throughout the lifecycle stages. These enablers support the quality system goals of achieving product realization, establishing and maintaining a state of control, and facilitating continual

34. Pharmaceutical Development Stage
Design a product and its manufacturing process to consistently deliver the intended performance and meet the needs of patients, health-care professionals, and regulatory authorities
Develop knowledge of product and processes
Utilize Quality Risk Management principles to identify and control risk to product quality

35. Technology Transfer Stage
Transfer product and process knowledge between development and manufacturing or between manufacturing units.
Develop further knowledge
Refine Quality Risk Management and control strategies

36. Commercial Manufacturing Stage
Provide product with appropriate quality attributes consistently in a state of control and facilitating continual improvement.
Continually expand product and process knowledge
Adjust the Quality Risk Management and control strategy as needed.

37. Product Discontinuation Stage
Manage the terminal stage of the product lifecycle using a pre-defined approach
product complaint management
stability studies documentation

38. GMPs over the Product Lifecycle
Compliance with applicable GMPs is the foundation of the quality system
The intended use and market of any material produced during the lifecycle must be understood and the appropriate GMPs must be met
Applicable GMPs must be incorporated into the quality system for each stage of the lifecycle
Documentation
Quality Unit Responsibilities
Facilities and Equipment

39. Management Controls - Product Lifecycle
Essential over all stages of Product Lifecycle
Includes: Management Commitment, Policy and Planning, Resource Management, Review and Communication
Extends to management controls of outsourced operations

40. Monitoring CAPA Change Management Management Review
Use to provide data and knowledge
CAPA
Use methodology to identify and implement improvements
Change Management
Change is inherent part of this phase
Change must be documented
Increase formality as development progresses
Management Review
Use to ensure the adequacy of product and process design

41. Monitoring CAPA Change Management Management Review
Use to provide indication of how process performs in manufacturing
CAPA
Used to make improvements to development and to commercial manufacturing
Change Management
Proactively manage change and thoroughly
Management Review
Use to ensure the developed process can be manufactured at scale

42. Monitoring CAPA Change Management Management Review
Well-defined monitoring of process performance & product quality to assure performance within a state of control
CAPA
CAPA methodology must be used and the effectiveness evaluated
Change Management
Formal change management must be used
Must have oversight by the quality unit
Management Review
A structured review which identifies and supports continual improvement

43. Monitoring CAPA Change Management Management Review
Relevant monitoring should continue (e.g., completion of stability studies, and product compliant analysis)
CAPA
Should be used to determine and address any impact on product remaining on the market and on any other products
Change Management
Should continue for any appropriate changes
Oversight by quality unit
Management Review
Continue reviews and include such activities as stability and complaints

44. Enablers Over the Product Lifecycle
Knowledge increases throughout the product lifecycle and must be captured, transferred and used systematically
Quality Risk Management provides proactive approach to identifying and controlling risks throughout the lifecycle

45. Framework of a Quality System
Achieve Product Realization
From the start of an idea for a product, to the culmination of the product available for the patients.
Manufacturing and release of finished goods so that prodcut is available for patients
Establish and Maintain a State of Control
Effective monitoring & control systems are in place which assure continued process performance and prodcut quality
A confidence when scheduling production, product will be available according to planned dates.
Facilitate Continual Improvement
Reducing project and process variability
Looking for areas of improvement not
self-evident but important
Start with the End in Mind – Define your objectives

46. Summary The Quality System defines our Quality Culture
Defines the responsibilities and authorities
Defines communication models to all levels in the organization
Provides a clear governance model defining how quality decisions are made
Monitors to assure necessary resources are available for completion of quality plans
Assures alignment of the quality objectives with the business strategy
Makes life easier

47. Pfizer Quality System Model

48. References
International Conference on Harmonization, Harmonized Tripartite Guideline, Pharmaceutical Quality System, ICH Q10, Step 4, 04June2008
Kaufman, Zena G., Divisional VP, Quality Center of Excellence, Abbott, “Considerations for Designing a Pharmaceutical Quality System”, Nov 2008
Allen, Barbara, Director, Global Quality Systems, Eli Lilly and Company, “Quality Systems over the Product Lifecycle”, Nov 2008
Wilkinson, Neil, David Begg Associates, “The Elements of a Modern Effective Pharmaceutical Quality System”, Nov 2008