Pharmaceutical Quality Systems (ICH Q10)

Concepts & Implementation

SAPRAA Meeting19th June 2009Chris Stubbs

Presentation Outline

• What is the objective of any System ?• What is expected of us in terms of Quality

Systems?• Fundamentals of ICH Q10 ?• Implementation advice • Summary

ICH Q10

What is the Objective of any System?(Using ICH Q10 as an example)

Development + Tech transfer + Commercial + Discontinuation

ProductRealization

State ofControl

ContinualImprovement

Compliance

ORGANIZATIONAL OPTIMIZATION

System Boundaries ie full Life Cycle

“Quality is a side effect of a system that is running well”

What is expected of us in terms of Quality Systems?

MEDICINES CONTROL COUNCIL

GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINES IN SOUTH AFRICA

MCC Guide

SA Guide to GMP (Common to all GMP Guides)

CHAPTER 1QUALITY MANAGEMENT1.1 PRINCIPLE1.1.1 The holder of a manufacturing licence must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the medicine registration and do not place patients at risk due to inadequate safety, quality or efficacy.

1.1.2 The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company's suppliers and by the distributors.

1.1.3 To achieve the quality objective reliably, there must be a comprehensively designed and correctly implemented system of Quality Assurance, Incorporating Good Manufacturing Practice and thus Quality Control and Quality Risk Management.

QUALITYMANAGEMENT

GMP – MCC/PICs Guide

PRODUCTS&

MATERIALS

FACILITIES

QUALITYUNIT

EQUIPMENT

PRODUCTIONMNGMENT

PEOPLE

FDA – 6 Systems Approach

Quality System

Production System

Facilities & EquipmentSystem

Laboratory ControlsSystem

Materials System

Packaging & LabelingSystem

FDA Quality Systems

FUNDAMENTALS OF ICH Q10

FDA for the 21st Century approach provides the road map for Q10

ICH Q10 OBJECTIVES

Product Realization

State of Control

Continual Improvement

(Compliance)

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

GMP

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

GMP

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

GMP

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

ChangeManagement

GMP

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

ManagementReview

ChangeManagement

GMP

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

ManagementReview

ChangeManagement

Quality RiskManagement

GMP

Risk Review

Risk Assessment

Risk Evaluationunacceptable

Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

InitiateQuality Risk Management Process

Output / Result of theQuality Risk Management Process

Risk M

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Q9 Risk Based Approach (2005)

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

ManagementReview

ChangeManagement

Quality RiskManagement

KnowledgeManagement

GMP

IntegrityUniformity

Weight Control

In vitroDissolution

ChemicalPurity

API, Excipients, Manufacturing Process

PharmaceuticsProfile

API Particle Size

API Salt Selection

ChemicalCompatibility

DegradationPathway

Prediction

Material PropertyCharacterization

Process Simulation

Design

Christopher Sinko, Ph.D.Christopher Sinko, Ph.D.Pfizer Global Research & Pfizer Global Research & DevelopmentDevelopment

Knowledge Management Example:Quality By Design

manag

Fundamentals of Q10

Development Tech Transfer DiscontinueCommercialSupply

MonitoringSystems

CAPASystems

ManagementReview

ChangeManagement

Quality RiskManagement

KnowledgeManagement

SENIOR MANAGEMENT RESPONSIBILITY

GMP

Q10 Management Responsibilities for a Pharmaceutical Quality System (P4 Section 2)

• Senior Management has ultimate responsibility• Have to participate• Demonstrate strong & visible support • Effective communication to appropriate levels of management• Define roles, responsibilities authorities & inter-relationships• Conduct Management reviews of product Quality, Process

performance & Pharmaceutical Quality System performance• Advocate continual improvement• Commit appropriate resource

Why do we need more guidance when the is all covered in GMP – refer section 1.1.2 & 1.1.3 of the GMP Guide ?

IMPLEMENTATIONADVICE FOR Q 10

IMPLEMENTATION REALITIES• The guidance specifically states that: "ICH Q10 is not intended to create any new expectations

beyond current regulatory requirements", and anything within ICH Q10 that is additional to current GMP requirements is "optional" rather than obligatory

• Implementation of these initiatives on top of current “rules based Quality Management Systems” will drown your Company in additional Resources and associated expenses

• Re-implementation of your Quality Management System based on these initiatives can create innovative ways to explore the latest efficiency improvements while still complying to GMP

Quality System Implementation

Start End

Management

Team

Leadership

High

Low

Advice on how NOT to start

Kick Off Fanfare

Get System Ready

Management Team willSee Value and IntegrateInto Daily Performance

Quality System Implementation

Start End

Management

Team

Leadership

High

Low

Advice on What Works

Kick Off Fanfare

Get System Ready

Integrate into Business Objectives STOP

Management Team see Value and have IntegratedInto Daily Performance

Advice on approaches that work• The Head of the Unit and not the QA Manager/RP has to

be seen as the driver of any implementation (think like a fox!)

• Always have a separate meeting (called by Head) to discuss the status of your QMS until implementation is complete: paradox- NOT at normal management meetings as QMS issues will be diluted by “more important issues”

• STOP and wait if you have to – Sub optimization leads to negative perceptions of value & results in management doubts

• A good Quality System should eventually be the backbone of a “Business Excellence System” but if it gets weighed down too early it will breakdown – Allow it to get strong before adding additional “modules” - irony: As the management team get excited they will want to use it for more (and break it) so you have to defend the system until the entire system is strong enough (and mature enough) to take on more processes

Summary

• ICH Q10 requires an understanding of FDA for the 21st Century, ICH Q8 (Design), ICH Q9 (Risk) as well as ISO 9000 (2005) to maximize benefit

• ICH Q10 is an ISO SYSTEMS approach to GMP• NOT additional to GMP but integral to GMP• Covers full life Cycle of a Product• Objectives: Product Realization, Control & Improvement• DEMANDS Management Team to lead Quality System• Seek compliance only and you will get compliance only

• The toughest implementation battles are internal so look for internal Allies before going outside for support

THANK YOU

Selected References follow

References

• References• GMP for the 21st century

www.fda.gov/cder/gmp/gmp2004/GMP_finalreport2004.htm • International Conference on Harmonisation, ICH Q8:

Pharmaceutical Development, November 2005. http://www.ich.org/

• International Conference on Harmonisation, ICH Q9: Quality Risk Management, November 2005. http://www.ich.org/

• International Conference on Harmonisation, Draft Consensus Guideline, ICH Q10: Pharmaceutical Quality System, May 2007. http://www.ich.org/

• FDA, Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations, September 2006. http://www.fda.gov/

• 01 January 2008By:Adrian KirkPharmaceutical Technology Europe