Risk-based Compliance Handbook

Announcement

The application of risk management to the processes within the healthcare industry is not just good
practice, but an essential must do for any competitive and compliant enterprise. Whereas the ICH Q9
guideline “Quality Risk Management” describes the fundamental concepts, additional information is
needed to further describe how risk management can and should be applied to the regulated
healthcare environment. Although many publications exist on the subject, none cover it from the
perspective of the entire drug lifecycle. The “Risk-based Compliance Handbook” now fills this gap.
This publication puts into context the various risk assessment methodologies with the business needs
at the various stages of the life cycle. The emphasis is on implementing and achieving competitive
compliance through the application of risk management.

In this book you will find crucial information on:

• An introduction to the various risk methodologies and their terminology
• Selecting the best method for a particular stage in the drug lifecycle
• Building risk management into the Quality Management System
• Many practical examples from real industry applications, including PAT
• The application of risk management for optimising the benefit / risk ratios

This book has been written by several authors who are experts in their field. It covers all stages of the
drug lifecycle from R&D, to the clinical phases, the launch and pharmacovigilance stages, and the
discontinuation step. It is written for the practitioner in the operational part of the organisation, who
wishes to select from practical examples, and it will be equally of interest to those working in quality
assurance / compliance, who wish to learn more about implementing risk management as a quality
concept.

Siegfried Schmitt
July 2008

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Dr Siegfried Schmitt, PAREXEL Page 1 of 1 02 July 2008
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Risk Based Compliance Handbook

CONTENTS

About the Authors

1 Introduction 1
ICH Q9 Quality Risk Management 4
Terminology 7
Risk Quantification 11
Probability of Occurrence of Harm 11
Hazard (Harm) Severity 13
Hazard Detectability 15
Risk Evaluation 15
Risk Mitigation And Risk Reduction 17
Risk Acceptance And Risk Review 19
Risk Communication 19
ICH Q8, Q9 And Q10 19
References 22

2 Compliance and the Lifecycle Concept 25

References 31

3 Impact on Quality Management Systems 33

Societal Impact 35
Environment, Health And Safety Impact 36
Economic Impact 36
Technological Impact 37
Scientific Impact 39

iii

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iv Risk-Based Compliance Handbook

Change Management 39
Traceability 40
Quality Risk Management 40
Legacy Systems 41
Regulatory Affairs 41
Quality System Risk Assessment Example 42
References 58

4 Risk-Based Approach to Compliance 61

Drug Development 61
Active Pharmaceutical Ingredients (API) 63
Inspectorates 65
Computerised Systems 70
Facility Risk Management 73
Pharmacovigilance 75
References 77

5 Implementing Process Analytical Technology:

The Challenges and Pitfalls of Applying a Science
and Risk-Based Approach in Research
and Manufacturing 79
Siegfried Schmitt and Jennifer Thompson
PAT Applications 80
Applying PAT — Worth the Risk? 81
From Data to Knowledge 85
PAT and the Regulatory Environment 90
References 92

6 The Applicability Of ICH Q9 95

The Methodologies 95
Risk Assessment Examples/Forms 103
Business and Lifecycle Scope 105
References 109

7 Benefit Risk Assessment During R&D 111

Siegfried Schmitt,Yvonne Lis and Michael Carter
Background 111
Assessing Benefit 113
Assessing Risk 113
General Models 115
Models for Clinical Trial Data 117
Models Taking Consideration of Stakeholder Preferences 119

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Contents v

Regulatory Position 121

Conclusions 122
R&D Benefit Risk Assessment Example 124
References 129

8 The Cost Of Quality 131

References 136

9 How To Implement? 139

Siegfried Schmitt and Jan Olsen
References 145

10 Documented Evidence 147

How Much Paper is Needed to Sustain
and Support Validation Compliance? 147
Documenting Compliance Activities 148
Manual Documentation Risks 149
Solutions Overview 150
Compliance Data Capture 153
Change Management 155
Test Management 156
Traceability 157
Risk Analysis 161
Collaboration 162
A Next Generation Solution 163
Conclusions and Recommendations 169

11 Quo Vadis? 171

Index 177

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