Transcript Slide 1

ICH Q10 –
Delivering a Modern
Effective Pharmaceutical
Quality System
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Discussion Topics
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Why do we need a modern PQS?
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Structure and key areas of ICH
Q10
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Implementation opportunities
and challenges
Why do we Need a ‘Modern Effective PQS’?
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Good business practice !
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Significant changes in external business environment
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Fewer new products / ‘blockbusters’
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Reduced margins / greater competition / low-cost sources
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Focus on efficient, effective organisations and lean
processes
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Public health issues
Pharmaceutical industry way behind other industries
in Quality Management philosophies / practices
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Marketed products ARE safe and efficacious
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BUT costs of quality are high
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Often reactive, not designed-in / preventative
THE STATUS QUO IS NO LONGER AN OPTION !!
Why do we Need a ‘Modern Effective PQS’?
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Historically innovation and improvement have
been constrained
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Inflexible regulatory environment
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Focus on Compliance, not Science and RiskBased approach = BLIND COMPLIANCE
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Industry margins didn’t provide drive for change
GMPs do not provide a ‘full modern’ Quality
System
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Originated in 1970s – only incrementally added
to
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ISO Quality Management thinking not
embedded
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SOPs focused on GMP compliance
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Need to be complemented
Where are we Currently ?
 Evolution of regional GMPs
1970s
 Evolution of ISO 9000 approaches
1980s
 FDA 21st Century initiative
2002
 ICH Quality Vision / Q8, Q9, Q10
2003
 FDA Quality Systems guide
2006 *
 ICH Q10 Pharmaceutical Quality System
2008
 ICH Q8/9/10 IWG
2008
* FDA commitment to update or withdraw when Q10 issued
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ICH Quality Vision
“Develop a harmonised pharmaceutical quality system applicable
across the lifecycle of the product emphasising an integrated
approach to quality risk management and science.”
Brussels July 2003
Resulting in ICH Q Guidelines:
Q8: Pharmaceutical Development (step 5)
Q8 (R): (step 2/3)
Q9: Quality Risk Management (step 5)
Q10: Pharmaceutical Quality System (step 4)
Q11: Development and Manufacture of Drug Substances (step 1)
For maximum utility need to consider 8/9/10 together
Q8/9/10 Implementation Work Group
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What is the Purpose of Q10?
 ICH Q10 aims to promote a paradigm
shift from discrete GMP compliance
procedures at each stage of the
product lifecycle to a comprehensive
quality systems approach over the
lifecycle of the product
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ICH Q10 Pharmaceutical Quality System
 The objective of Q10 is to establish a new
tripartite guideline describing the model for an
effective quality management system for the
pharmaceutical industry, referred to as the
Pharmaceutical Quality System
 It describes one approach deemed acceptable
to regulators
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Q10 Key Messages - Introduction
 Q10 will complement and facilitate implementation of
Q8 ‘Pharmaceutical Development’ and Q9 ‘Quality
Risk Management’
 ICH Q10 is not intended to create any new
expectations beyond current regulatory requirements
 The content of ICH Q10 that is additional to current
GMP requirements is optional
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‘Strongly recommended’
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Within the EU having a ‘Quality System’ is
mandated
 A Q10 approach would satisfy expectations
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Q10 Key Messages - Scope
 Applies to systems supporting the
development and manufacture of
pharmaceutical drug substances (API) and
drug products, including biotechnology and
biological products, throughout the product
lifecycle
 Both newly developed and existing products
fall within the scope
 Apply in a manner appropriate and
proportionate to the stage of lifecycle
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Q10 Key Messages - Enablers
 The enablers provide the means for science
and risk based decisions related to product
quality through the lifecycle
 Knowledge Management
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Manage knowledge from development
through commercialisation to discontinuation
 Quality Risk Management (Q9)
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Proactive approach to managing risks to
quality
Q10 Key Messages Pharmaceutical Quality System
Implementation of Q10 should facilitate:
 Innovation and continual improvement
throughout the product lifecycle; and
 Strengthen the link between
pharmaceutical development and
manufacturing organisations
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Q10 Key Messages - Regional GMPs
Q10 will:
 Augment existing GMPs with specific PQS
elements and management responsibilities
 Encourage science and risk based
approaches
 Be used together with existing GMPs
 Cover all stages of the product lifecycle as
defined (beyond GMPs)
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Q10 Key Messages Regulatory Approaches
 Regulatory approaches for a specific
product or manufacturing facility
should be commensurate with:
 The level of product and process
understanding
 The results of quality risk management
 The effectiveness of the PQS
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Q10 Key Messages Regulatory Approaches
 The effectiveness of the PQS can normally be
confirmed during a regulatory inspection at the
manufacturing site
 Potential opportunities to enhance science and
risk based regulatory approaches are identified in
Annex 1of Q10
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ICH Q8/9/10 IWG set up to clarify
implementation questions
 Regulatory processes will be determined by
region
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ICH Q10 - Summary of Aims
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If adopted by industry (on a voluntary basis) would:
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Complement and serve as a bridge between regional
GMP regulations
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Facilitate application of ICH Q8, Q9…
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Link development and manufacturing through product
the lifecycle
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Facilitate continual improvement in pharmaceutical
manufacturing
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Be based upon the well accepted ISO 9000
structure within a pharmaceutical context
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Facilitate ‘appropriate levels of regulatory scrutiny’
 Post approval change
 Inspections
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Composition of the Q10 Document
The document is divided into 5 sections and 2 annexes
 Pharmaceutical Quality System
 Management responsibility
 Continual improvement of process performance and
product quality
 Continual improvement of the pharmaceutical quality
system
 Glossary
Annex 1 - potential opportunities to enhance science
and risk based regulatory approaches
Annex 2 - diagram of the Q10 model
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Q10 - Structure
1. Pharmaceutical Quality System
a) Introduction
b) Scope
c) Relationship of ICH Q10 to regional
GMP requirements and ISO Standards
d) Relationship of ICH Q10 to Regulatory
Approaches
e) ICH Q10 Objectives
f) Enablers - KM and QRM
g) Design and Content Considerations
h) Quality Manual
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Q10 - Structure
2.
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Management Responsibility
a)
Management Commitment
b)
Quality Policy
c)
Quality Planning
d)
Resource Management
e)
Internal Communication
f)
Management Review
g)
Management of Outsourced Activities and
Purchased Materials
h)
Management of Change in Product Ownership
Q10 - Structure
3. Continual Improvement of
Process Performance and
Product Quality
a) Lifecycle Stage Goals
b) Pharmaceutical Quality System
Elements
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Q10 - Structure
4. Continual Improvement of the
Pharmaceutical Quality System
a) Management Review of the Pharmaceutical
Quality System
b) Monitoring of Internal and External Factors
impacting the Pharmaceutical Quality System
c) Outcomes of Management Review and
Monitoring
5. Glossary
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Q10 - Structure
 Annex 1 - Potential Opportunities
to Enhance Science and Risk
Based Regulatory Approaches
 Annex 2 - Diagram of the ICH
Q10 PQS Model
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So What are the Key Q10 Areas?
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GMPs
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Management Responsibility
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Continual Improvement
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Products and Processes
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PQS itself
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Quality Risk Management
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Knowledge Management
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Lifecycle approach
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Opportunities for science and risk based regulatory
approaches
Q10 and GMP / ISO Augments Existing Documents
GMP
GMPs
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Management
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Continual Imp
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QRM
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Knowledge
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Lifecycle
Opportunities
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ISO 9000
FDA QS
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ICH Q10 Pharmaceutical Quality System
Pharmaceutical
Development
Technology
Transfer
Commercial
Manufacturing
Discontinuation
Investigational products
GMP
Management Responsibilities
PQS
elements
Enablers
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Process Performance & Product Quality Monitoring
Corrective Action / Preventive Action (CAPA)
Change Management
Management Review
Knowledge Management
Quality Risk Management
ICH Q10 and the ‘Bigger Picture’
Another diagram - The EU regulatory point of view on
integration of different ICH quality concepts
The Regulatory
System
Quality Risk
Management
(Q9)
Quality system
Management
Quality Risk
Management
Pharmaceutical
Development
Existing
ExistingGMP
GMP s
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Pharmaceutical
Development
(Q8)
Quality
System
(Q10)
Key Implementation
Points to Consider
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The PQS Must be Adaptable
 To meet the needs of the organisational structure
 Site, Region, Division, Corporate
 Inclusive of Outsourcing Activities
 To meet the needs of the goals of the lifecycle
 Development
 Tech Transfer
 Commercial Manufacturing
 Discontinuance
 The effectiveness of a PQS should be demonstrated
at a commercial site
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ICH Q10 - Implementation Approach
 How do we see implementation of Q10 occurring?
 Firms / sites choose to implement Q10
 Gap analysis of current quality system - action plans
 PQS will formally integrate QbD / QRM / Knowledge
Management / Corporate PQS processes
 Internal evaluations at site level, including any corporate
PQS processes
 Request regulatory assessment of Q10 by inspection at
manufacturing site
 Regulators confirm and document Q10 status
 Regulators need to take the lead role in implementing the
opportunities described in the Annex
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ICH Q10 - Implementation Approach
 Where are we now?
 Unlikely any firm is fully Q10 compliant?
 Many have undertaken a gap analysis
 Several at different stages of implementation plans
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Many examples of real $ benefits / case studies
 CAPA
 Product and process understanding and monitoring
 Management reviews
 Quality Risk Management
 Others waiting to see how things develop
 It is simply good business practice – so why wait???
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Implementation - Management
Responsibilities
 Essential component
 Not just about compliance
 Visible leadership to establish and
maintain a company wide culture and
commitment to quality and improvement
 Monitor performance of the PQS and act
 Internal and Outsourced activities
 Quality cannot be owned by the Q Unit
 Management is accountable
 But independent assessments / audits are
key
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Implementation - Management
Responsibilities
 Clear roles, responsibilities and governance
processes are essential
 Quality Policy - standards and direction of
organisation
 Quality Planning - convert into objectives / plans
 Resources - allocations and competence
 Communication - Q items to appropriate audiences
 Management Reviews
 Product and Process performance
 PQS performance
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Implementation - Continual
Improvement
 CAPA system
 Investigation of non-conformances
 e.g. deviations, rejections, complaints, recalls,
observations from audits & inspections = reactive
 e.g. feedback from trends = proactive
 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
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Implementation - Continual
Improvement
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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 track
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Assure no unintended consequences
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> Self management by competent manufacturers
Implementation - Continual
Improvement
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Product Quality and Process Performance Monitoring
System
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Use knowledge, QbD, Product and Process
understanding and QRM to set Control Strategy
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What and when to monitor / measure / test
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Based on critical product quality attributes and
critical process parameters to deliver them
Confirm and maintain a state of control
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Feed-back and feed-forward loops
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Reduce and control variation to appropriate levels
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Drive continual improvement
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Continual verification
Implementation - Quality Risk
Management (Q9)
 Essential integrated part of PQS – 2 key principles
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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
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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 decisions through lifecycle
 Integrate into key parts of PQS
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e.g. change management, CAPA, GMPs, Validation, etc
 Help set meaningful specifications / CPPs to ensure product
CQAs are met
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Implementation - Knowledge
Management
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Systematic and lifecycle approach to
acquiring, analysing, storing and
disseminating knowledge on products,
processes, components…
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Not just an IT solution
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Processes, Organisation, People
Provides the basis for science and risk
based approaches in the PQS
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Product and process development
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Manufacturing
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Change management
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Continual improvement
Implementation - Lifecycle
Approach
 A modern PQS needs to be holistic and
cover the product lifecycle
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Design and development
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Manufacturing
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Withdrawal
 Challenges and removes some
traditional organisational silos
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Within Industry
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Within Regulatory Agencies
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With outsourcing partners
Q10 Implementation
- Opportunities and
Challenges
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How Might Industry and Regulators
use Q10 with Q8 & Q9?
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Potential opportunity for:
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Increased use of risk based approaches for
regulatory inspections
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To facilitate science based pharmaceutical quality
assessment
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To optimise science and risk based post-approval
change processes to maximise benefits from
innovation and continual improvement
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To enable innovative approaches to process
validation / establish real time release
mechanisms
Challenges to a Future Successful
Implementation
 Trust and culture change - enhanced two-way trust
 Clear understanding of the stakeholders’ needs and options
 Industry - regulator trust and openness in working together
towards the new vision - learning together
 Culture change in both Industry and Regulators
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Overcome internal conservatism and ‘silo’ thinking
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Organisational change management – resistance to change, new
competencies needed, e-access to data…
 Harmonisation and mutual understanding
 ICH members and observers, ROW, emerging markets
 Big Pharma is a global operation, but often with regional /
national regulatory processes
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ICH Q10 - Implementation
 How can we work together to ensure consistent
implementation?
 At ICH level - via IWG for Q8/9/10
 At regional level regular interactions (e.g. joint work
groups, external events) needed to address e.g.
 How Q10 implementation will be confirmed
 How Q10 Annex opportunities will be delivered
 What is ‘regular GMP’ (mandated) versus what is
Q10 (optional)
 Understanding of Lifecycle and Knowledge
Management
 Engage other regions (e.g. via PICS and ICH GCG)
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Special Thanks To
 ICH Q10 EWG members
 Efpia Q10 Topic team
members
 PDA-FDA Quality Systems
team members
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Thank you
David Begg Associates
www.DBA-global.com
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