Quality%20System%20Model%20ICH%20Q10

1
Quality System ModelICH 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 Pfizers 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

8
Pharmaceutical Quality System
9
An Effective Quality System

• GMPs
• Management Responsibility
• Elements - Continual Improvement
• Enablers Knowledge and Risk Management
• Lifecycle approach

10
An Effective Quality System

• GMPs
• Management Responsibility
• Elements - Continual Improvement
• Enablers Knowledge and Risk Management
• Lifecycle approach

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

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

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

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

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

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

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
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
• 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
• 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
• 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
• 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

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