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ICH Q10 – Delivering a Modern

Effective Pharmaceutical Quality

System

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Discussion Topics

Why do we need a modern PQS?

Structure and key areas of ICH Q10

Implementation opportunities and challenges

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Why do we Need a ‘Modern Effective PQS’? Good business practice ! Significant changes in external business environment

Fewer new products / ‘blockbusters’

Reduced margins / greater competition / low-cost sources

Focus on efficient, effective organisations and lean processes

Public health issues

Pharmaceutical industry way 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

THE STATUS QUO IS NO LONGER AN OPTION !!

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Why do we Need a ‘Modern Effective PQS’?

Historically innovation and improvement have been constrained

Inflexible regulatory environment

Focus on Compliance, not Science and Risk-Based approach = BLIND COMPLIANCE

Industry margins didn’t provide drive for change

GMPs do not provide a ‘full modern’ Quality System Originated in 1970s – only incrementally added to

ISO Quality Management thinking not embedded

SOPs focused on GMP compliance

Need to be complemented

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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

‘Strongly recommended’

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 Manage knowledge from development through

commercialisation to discontinuation

Quality Risk Management (Q9) Proactive approach to managing risks to quality

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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

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 If adopted by industry (on a voluntary basis) would: Complement and serve as a bridge between regional GMP regulations Facilitate application of ICH Q8, Q9… Link development and manufacturing through product the lifecycle Facilitate continual improvement in pharmaceutical manufacturing Be based upon the well accepted ISO 9000 structure within a

pharmaceutical context Facilitate ‘appropriate levels of regulatory scrutiny’

Post approval change

Inspections

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Composition of the Q10 Document

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

The document is divided into 5 sections and 2 annexes

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Q10 - Structure

1. Pharmaceutical Quality Systema) 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. 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

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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?

GMPs

Management Responsibility

Continual Improvement Products and Processes

PQS itself

Quality Risk Management

Knowledge Management

Lifecycle approach

Opportunities for science and risk based regulatory approaches

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Q10 and GMP / ISO - Augments Existing Documents

Lifecycle

Opportunities

Knowledge

QRM

Continual Imp

Management

GMPs

Q10FDA QSISO 9000

GMP

Δ

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GMP

ICH Q10 Pharmaceutical Quality System

Pharmaceutical Development

CommercialManufacturing

DiscontinuationTechnology

Transfer

Investigational products

Management Responsibilities

Process Performance & Product Quality MonitoringCorrective Action / Preventive Action (CAPA)

Change ManagementManagement Review

PQSelements

Knowledge Management

Quality Risk ManagementEnablers

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Existing GMP ss

Management

The RegulatorySystem

Another diagram - The EU regulatory point of view on integration of different ICH quality concepts

Quality System (Q10)

Quality Risk Management

(Q9)

PharmaceuticalDevelopment

(Q8)

ICH Q10 and the ‘Bigger Picture’

Quality system

Existing GMP

Quality Risk Management

Pharmaceutical

Development

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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 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

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 track

Assure no unintended consequences

> Self management by competent manufacturers

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Implementation - Continual Improvement Product Quality and Process Performance Monitoring System

Use knowledge, QbD, 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

Confirm and maintain a state of control Feed-back and feed-forward loops

Reduce and control variation to appropriate levels

Drive continual improvement

Continual verification

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Implementation - Quality Risk Management (Q9)

Essential integrated part of PQS – 2 key principles 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 decisions through lifecycle

Integrate into key parts of PQS e.g. change management, CAPA, GMPs, Validation, etc

Help set meaningful specifications / CPPs to ensure product CQAs are met

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Systematic and lifecycle approach to acquiring, analysing, storing and disseminating knowledge on products, processes, components…

Not just an IT solution Processes, Organisation, People

Provides the basis for science and risk based rovides the basis for science and risk based approaches in the PQSapproaches in the PQS

Product and process developmentProduct and process development

ManufacturingManufacturing

Change management

Continual improvement

Implementation - Knowledge Management

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Implementation - Lifecycle Approach

A modern PQS needs to be holistic and cover the product lifecycle

Design and development

Manufacturing

Withdrawal

Challenges and removes some traditional organisational silos

Within Industry

Within Regulatory Agencies

With outsourcing partners

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Q10 Implementation - Opportunities and

Challenges

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How Might Industry and Regulators use Q10 with Q8 & Q9?

Potential opportunity for: Increased use of risk based approaches for regulatory

inspections

To facilitate science based pharmaceutical quality assessment

To optimise science and risk based post-approval change processes to maximise benefits from innovation and continual improvement

To enable innovative approaches to process validation / establish real time release mechanisms

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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 Overcome internal conservatism and ‘silo’ thinking

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