Pharmaceutical and Biopharmaceutical Manufacturing:

Understanding Your Process Series

Risk Management Library, Volume 4

Practical Approaches to Risk

Assessment and Management
Problem Solving:
Tips and Case Studies

Tim Sandle

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 Risk Management Library, Volume 4

Practical Approaches to Risk

Assessment and Management
Problem Solving:
Tips and Case Studies

Tim Sandle

PDA
Bethesda, MD, USA
DHI Publishing, LLC
River Grove, IL, USA
www.pda.org/bookstore
10 9 8 7 6 5 4 3 2 1

ISBN: 978-1-942911-21-0
Copyright © 2018 Tim Sandle
All rights reserved.

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 CONTENTS

INTRODUCTION: RISK ASSESSMENT AND THE

PRODUCTION OF SAFE HEALTHCARE PRODUCTS vii
The Application of Risk Management viii
Risk Assessment x
Conclusion xvi
References xvi

1 REGULATORY PERSPECTIVES ON RISK 1

Introduction 1
Risk Management and the ICH Q8, Q9 and Q10 Documents 3
Global Approaches to Risk Management 5
Quality Risk Management 9
The ICH Risk Management Approach 15
Other Regulatory Aspects of Quality 18
Rapid Methods 27
Data Integrity 27
Summary 28
References 28

iii

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iv Risk Assessment and Management Problem Solving

2 PROBLEM SOLVING QUESTION BASED

APPROACHES:THE FIVE “WHYS” AND
“WHAT IF” METHODS 35
Introduction 35
Five Whys Approach 36
“What If” Approach 39
Summary 41
Reference 41

3 CASE STUDIES:
ASEPTIC TRANSFER RISK ASSESSMENT 43
Introduction 43
Approaches to Risk Assessment 44
Applications to Cleanroom Environments and
Pharmaceutical Processes 46
HACCP 46
The Case Study 49
Deconstructing the Process 50
Risk Assessment 55
Conclusion 55
References 56

RISK ASSESSMENT FOR INTERVENTION

SCORING IN RELATION TO ASEPTIC
PROCESSING 59
Introduction 59
Aseptic Processing 61
Interventions 61
Intervention Risks 63
Defining an Intervention and Key Steps 64
Intervention Scoring 64
Summary 75
References 75

RISK CONSIDERATIONS FOR AGING

PHARMACEUTICAL CONSIDERATIONS 79
Introduction 79
What is an Aging Facility? 80
Risk 1: Incremental Upgrades 82

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 Contents v
Risk 2: Obsolescence 83
Risk 3: Insufficient Time Allocated to Upgrade 84
Risk 4: Bringing New Products On-Line 85
Risk 5: Failing to Embrace New Innovations 85
Risk 6: Microbiological Contamination 86
Risk 7: Regulatory Concerns 88
Risk 8: Knowledge Base 89
Risk 9: Validation Status 89

Risk 10: Quality Systems 89

Managing the Risks 90
Summary 93
References 94

RISK MANAGEMENT AND THE SUPPLY CHAIN 97

Introduction 97
Supply Chain Risks 100
Summary 112
References 113

ERROR RISK REDUCTION:

CONCEPT AND CASE STUDY 115
Introduction 115
Types of Errors 116
Error Risk Reduction 118
Case Study 120
Summary 125
References 126

CURRENT REGULATIONS, GUIDANCES,

TECHNICAL REPORTS AND TEXTS
USEFUL FOR FURTHER REFERENCE 127

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