Transcript Pfizer Quality System Model Training

Quality System Model
ICH Q10
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Agenda
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What is ICH Q10
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History
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Why do we need a ‘modern effective Quality
System’?
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The elements and enablers of a Quality System
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Model of Pfizer’s Quality System
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Review the website
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.
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History
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Evolution of regional GMPs
Evolution of ISO 9000 approaches
1970s
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
Comprehensive Model
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Based on International Standards
Organization (ISO) quality concepts
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Includes applicable GMP regulations
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Complements both
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ICH Q8 Pharmaceutical Development,
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ICH Q9 Quality Risk Management
Not intended to create new expectations
beyond current regulatory environment
A ‘Modern Effective Quality System’?
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Good business practice!
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Significant changes in external business
environment
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Pharmaceutical industry is behind other industries in
Quality Management philosophies / practices
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Fewer new products / ‘blockbusters’
Reduced margins / greater competition / low-cost sources
Focus of efficient, effective organizations
Lean processes
Marketed products ARE safe and efficacious
BUT costs of quality are high
Often reactive, not designed-in / preventative
Why do we need a ‘Modern Effective Quality System’?
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Implementation should
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Facilitate innovation and continual improvement
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Strengthen the link between pharmaceutical development and
manufacturing
GMPs do not provide a ‘full modern’ Quality System
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Inflexible regulatory environment
Focus on Compliance, not Science and Risk-Based approach
Industry margins did not provide drive for change
Originated in 1970s – incremental additions
ISO Quality Management thinking not embedded
Need to be complemented with Q8 and Q9
Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuation
Investigational Products
GMP
Management Responsibilities
Quality
System
Elements
Process Performance & Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
Knowledge Management
Enablers
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Quality Risk Management
An Effective Quality System
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GMPs
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Management Responsibility
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Elements - Continual Improvement
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Enablers – Knowledge and Risk Management
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Lifecycle approach
An Effective Quality System
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GMPs
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Management Responsibility
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Elements - Continual Improvement
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Enablers – Knowledge and Risk Management
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Lifecycle approach
Management Responsibilities
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Essential component of a Quality System
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Not just about compliance
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Quality can not be owned only
by the ‘Q’ Unit
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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
Management is accountable
But independent assessments are key
Management Responsibilities
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Management Commitment
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Quality Policy
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Quality Planning
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Resource Management
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Internal Communication
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Management Review
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Outsourced Activities
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Change in Product Ownership
Management Commitment
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Signed Quality Commitments are
commonplace and are not indicative of
Management Commitment
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What is Indicative?
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Plant Managers aware of the issues
Management Team that works together
Quality as a Trusted Partner
Clear Roles, Responsibilities, Processes
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Quality Policy: Sets the standards and direction of
organization
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Quality Planning: Converts into objectives & plans
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Resources: Allocations and competence
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Communication: Quality items to appropriate
audience
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Management Reviews
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Product and Process performance
Quality System performance
Quality Policies
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Comprehensive and Balanced
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Flexibility/adaptability defined is consistent
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Interconnectivity of a Quality System requires
a comprehensive approach in the design
Quality Plans
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Written Quality Plans are becoming more
common
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What is Indicative?
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Quality Planning Process is dynamic
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Defined process for evaluating issues to bring into the
quality planning process.
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Tracking progress against an agreed upon Quality
Plan
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Adequate resources are made available
Resource Management
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Adequate resources are made available
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Resources include time, money, equipment
and people
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What is Indicative?
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Clear prioritization of resources in line with
Reasonable number of projects with
Realistic commitment time frames
Internal Communication
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Issues will occur
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Escalation of issues, actions, decisions and impact
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What is Indicative?
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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
Management Review
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Grounded in the device regulations, periodic
Management Reviews are becoming more common
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What is Indicative?
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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?
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Opportunity to align priorities and resources
Not punitive
Outsourced Activities and Purchased
Materials
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Pharmaceutical firm (i.e., Management) is ultimately
responsible to assure processes are in place
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Process must be in place to:
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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
An Effective Quality System
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GMPs
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Management Responsibility
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Elements - Continual Improvement
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Process Performance and Product Quality
Corrective Action / Preventive Action
Change Management
Management Review
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Enablers – Knowledge and Risk Management
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Lifecycle approach
Continual Improvement
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Continuous Improvement of product quality is a
key objective of the quality system, irrespective
of the stage of the lifecycle.
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Four specific elements of the quality system
support achieving continuous improvement:
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Process performance and product quality monitoring
Corrective action and preventative action
Change management
Management review of process
performance and product quality
Product Quality and Process Performance
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Use knowledge, Quality by Design, Product and
Process understanding and QRM to set Control
Strategy
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Reduce and control variation to appropriate levels
Confirm and maintain a state of control
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What and when to monitor / measure / test
Based on critical product quality attributes and critical
process parameters to deliver them
Feed-back and Feed-forward loops
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Drive continual improvement
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Continual verification
CAPA System
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Investigation of non-conformances
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Reactive → deviations, rejections, complaints, recalls,
observations from audits and inspections
Proactive → feedback from trends
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Structured investigations to seek root cause
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Use QRM to ensure degree and formality is commensurate
with level of risk
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Should result in enhanced knowledge and improvement
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Not just reacting to non-conformances
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Focus on preventative actions
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Need effective tracking / follow up processes
Change Management System
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Change can be good!
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Proactively driven by outputs from monitoring / trending /
improvement / innovation
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Not just by reacting to problems
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Use expert teams and knowledge to evaluate and set
success criteria
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Use QRM commensurate with level of risk
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Consider impact on regulatory filings
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Undertake in timely and effective way and tracked
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Assure no unintended consequences
Management Review
Process Performance and Product Quality
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Results from inspections and assessments
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Periodic quality reviews
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Appropriate actions
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Customer satisfaction – complaints, recalls
Conclusions of process performance and product quality
monitoring
Effectiveness of process and product changes
Improvements to manufacturing processes
Training and/or realignment of resources
Capture and share knowledge
Continual Improvement of the Quality System
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Assessment of the Quality System against
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Outcomes of the Assessment
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Internal factors (audits, CAPAs, complaints, recalls, etc.)
External factors (regulatory inspectional findings)
Emerging regulations
New technology
Change in business strategies
Improvements communicated throughout a business
Resource reallocation
Changes in policies, practices
An Effective Quality System
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GMPs
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Management Responsibility
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Elements - Continual Improvement
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Enablers – Knowledge and Risk Management
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Lifecycle approach
Knowledge Management
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Systematic and lifecycle approach to
acquiring, analyzing, storing and
disseminating knowledge on products,
processes, components
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Provides the basis for science and riskbased approaches in the Quality System
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Product and process development
Manufacturing
Change management
Continual improvement
Quality Risk Management (Q9)
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Essential, integrated part of Quality System
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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
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Proactive use to identify and control risk
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Support decision through lifecycle
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Integrate into key parts of Quality System
e.g., change management, CAPA, GMPs – Validation, etc.
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Help set meaningful specification / control
parameters to ensure product quality control
requirements are met
Key to an Effective Quality System
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GMPs
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Management Responsibility
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Continual Improvement
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Knowledge Management
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Quality Risk Management
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Lifecycle approach
Lifecycle Approach
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Holistic and cover the product lifecycle
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Challenges and removes some traditional
organizational silos
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Design and Development
Manufacturing
Withdrawal
Within industry
Within Regulatory Agencies
With outsourcing partners
Application of Quality System Elements at
each stage of the Product Lifecycle
Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuation
Investigational Products
GMP
Management Responsibilities
Quality
System
Elements
Process Performance & Product Quality Monitoring System
Corrective Action/Preventive Action (CAPA) System
Change Management System
Management Review
Knowledge Management
Enablers
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Quality Risk Management
Pharmaceutical Development Stage
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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
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Develop knowledge of product
and processes
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Utilize Quality Risk
Management
principles to
identify and
control risk to
product quality
Pharmaceutical
Development
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Technology Transfer Stage
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Transfer product and
process knowledge
between development and
manufacturing or between
manufacturing units.
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Develop further knowledge
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Refine Quality Risk
Management
and control
strategies
Technology
Transfer
nt
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Commercial Manufacturing Stage
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Provide product with
appropriate quality attributes
consistently in a state of
control and facilitating
continual improvement.
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Continually expand product
and process knowledge
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Adjust the Quality
Risk Management
and control
strategy as
needed.
Commercial
Manufacturing
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Product Discontinuation Stage
Product
Discontinuation
Manage the terminal
stage of the product
lifecycle using a predefined approach
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product complaint
management
stability studies
documentation
GMPs over the Product Lifecycle
Pharmaceutical
Development
Technology
Transfer
Investigational Products
Product
Discontinuation
GMP
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Compliance with applicable GMPs is the
foundation of the quality system
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The intended use and market of any material
produced during the lifecycle must be understood
and the appropriate GMPs must be met
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Applicable GMPs must be incorporated into the
quality system for each stage of the lifecycle
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Commercial
Manufacturing
Documentation
Quality Unit Responsibilities
Facilities and Equipment
Management Controls - Product Lifecycle
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Product
Discontinuation
Management Controls
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Essential over all stages of Product Lifecycle
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Includes: Management Commitment, Policy
and Planning, Resource Management,
Review and Communication
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Extends to management controls of
outsourced operations
Pharmaceutical
Development
Application of Quality System Elements
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Monitoring
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CAPA
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Change is inherent part of this phase
Change must be documented
Increase formality as development progresses
Management Review
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Use methodology to identify and implement
improvements
Change Management
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Use to provide data and knowledge
Use to ensure the adequacy of product and
process design
Technology
Transfer
Application of Quality System Elements
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Monitoring
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CAPA
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Proactively manage change and thoroughly
Management Review
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Used to make improvements to development and
to commercial manufacturing
Change Management
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Use to provide indication of how process
performs in manufacturing
Use to ensure the developed process can be
manufactured at scale
Commercial
Manufacturing
Application of Quality System Elements
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Monitoring
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CAPA
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Formal change management must be used
Must have oversight by the quality unit
Management Review
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CAPA methodology must be used and the effectiveness
evaluated
Change Management
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Well-defined monitoring of process performance & product
quality to assure performance within a state of control
A structured review which identifies and
supports continual improvement
Product
Discontinuation
Application of Quality System Elements
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Monitoring
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CAPA
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Should continue for any appropriate changes
Oversight by quality unit
Management Review
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Should be used to determine and address any impact on
product remaining on the market and on any other products
Change Management
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Relevant monitoring should continue (e.g., completion of
stability studies, and product compliant analysis)
Continue reviews and include such activities as
stability and complaints
Enablers Over the Product Lifecycle
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Knowledge Management
Quality Risk Management
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Knowledge increases throughout the
product lifecycle and must be captured,
transferred and used systematically
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Quality Risk Management provides
proactive approach to identifying and
controlling risks throughout the lifecycle
Product
Discontinuation
Framework of a Quality System
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Achieve Product Realization
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Establish and Maintain a State of Control
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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
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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
Reducing project and process variability
Looking for areas of improvement not
self-evident but important
Summary
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The Quality System defines our Quality Culture
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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
Pfizer Quality System Model
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References
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International Conference on Harmonization, Harmonized
Tripartite Guideline, Pharmaceutical Quality System, ICH
Q10, Step 4, 04June2008
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Kaufman, Zena G., Divisional VP, Quality Center of
Excellence, Abbott, “Considerations for Designing a
Pharmaceutical Quality System”, Nov 2008
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Allen, Barbara, Director, Global Quality Systems, Eli Lilly
and Company, “Quality Systems over the Product
Lifecycle”, Nov 2008
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Wilkinson, Neil, David Begg Associates, “The Elements of a
Modern Effective Pharmaceutical Quality System”, Nov 2008