Table Of ContentValidation
Fundamentals
How to, What to,
When to Validate
William Gibson
Keith Powell-Evans
informa
healthcare
New York London
CRC Press
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Version Date: 20130325
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Contents
Foreword ix
Introduction xiii
1. What Is Validation? 1
Validation Categories 3
The Validation Life Cycle 6
Design Qualification 6
Risk Assessment 7
Develop Room Data 10
Validation Master Plan 11
Protocols 13
Installation Qualification Protocol 13
Operational Qualification Protocol 14
Performance Qualification Protocol 15
Change Control/Deviation 15
iii
iv Validation Fundamentals
Cleaning Validation 16
The Cleaning Validation Master Plan 17
Computer Validation 18
Hardware 20
Software 20
Computer Validation at the Design Stage 20
Computer Validation in Installation
Qualification 20
Computer Validation in Operational
Qualification 21
Quality of Validation 21
Process Validation 24
Analytical Validation 26
Validation Activities 28
Retrospective Validation 30
Prospective Validation 30
Concurrent Validation 30
Utilities and Equipment Validation 30
Information for HVAC System for
Clean Rooms (Example) 32
Information for a Compressed Air
System (Example) 34
2. The History and Roots of
Validation 37
Early History 37
The United States 40
The United Kingdom 44
Computer System Validation 45
Recent History 46
Prerequisites for the Validation Professional 47
Contents v
3. Why Do We Validate?
How Much Does It Cost? 51
The Law Appertaining to GMP 54
What Is the Cost of Validation? 56
Training 59
4. Who Is Responsible for Validation? 63
The Dedicated Working Party 63
The Role of Consultants 66
The Working Party and Task Groups 66
The Qualified Person 67
The Validation Effort 68
5. How Does Validation Mfect You? 71
Training 73
Federal Standards 74
Manufacturing Personnel
(Company Structure) 75
6. Validation Policy, Strategy
Protocols and the
Validation Report 79
Validation Policy 79
Validation Strategy 80
Analytical Validation 81
Validation Protocols 83
The Validation Report 92
The Report Development 93
vi Validation Fundamentals
7. What Activities Support the
Validation Effort? 99
8. What Are the Consequences of
Not Validating? 105
9. For Whom Are We Validating? 111
The Food and Drug Administration 111
What Happens During an Inspection? 114
The UK Medicines Control Agency 115
10. Preparing Standard Operating
Procedures and the Validation
Master Plan 117
Standard Operating Procedures 118
The Validation Master Plan 126
Master Plan Review and Approvals 130
Document Preparation Audit Trail 131
Master Plan Revision History 133
Definitions 133
Overview 135
Introduction 135
Project Purpose and Scope 137
Training 139
Instrumentation 140
Planned Preventive Maintenance 140
Validation Team 140
Approach 141
Contents vii
11. How Do We Plan and
Programme Validation? 145
Time Scales 148
Protocol Execution 149
12. A Lexicon of Validation
Terminology 151
References 157
Appendices 159
A. Quality Control: Present Problems,
Future Possibilities 159
B. Regulatory Approaches to GMP and
Inspection 179
C. Validation vs. Verification, Testing,
Calibration and Qualification 201
D. The Commitment to Validate 207
E. Validation vs. Verification 209
F. Revalidation 211
G. ISO 9000 and Validation 219
Index 221
Forew-ord
Practitioners of validation have always had reference
material and benchmark standards with which to mea
sure their own performance and activities. A handbook
of fundamentals would seem to be a must have" for all
11
who validate or indeed those who intend to approach
and apply the basic subject methodologies for the first
time in a structured and systematic way.
There have been many excellent books on validation
written since good manufacturing practices were first
declared substantive. Some of these go to great lengths
to explain, in explicit detail, the various facets of vali
dation work. Others teach how to go about validation in
isolation from other activities, but not how to get there
or how the various elements are configured and hang
together. This book is intended as a primer; the purpose
is to explain in layman's terms just how the whole thing
works. It takes us through the history and evolution of
the subject. It explains what validation is, why it is nec
essary, who is responsible and, perhaps most impor
tantly, how to go about it.
ix
x Validation Fundamentals
As with any growing subject, there are the inevitable
variations on a general theme, but these cannot be un
derstood until the basics have been clearly established
and are readily available as a source of reference. These
variations often can make the subject ·seem convoluted
to the beginner; therefore, it would seem that a book of
validation fundamentals is long overdue.
This book deals with the essential, generic elements of
validation work-principles which can be applied to
qualify almost anything in a structured, methodical
manner. It should be of interest not only to those in the
pharmaceutical industry but also to people within the
biotechnology, cosmetics and food industries-indeed
any industry which values the quality of their products.
The conception of this book was prompted by Sue Hor
wood of Medi-Tech. Publications and the Institute of
Validation. They reasoned that despite all the detailed
study material currently available on validation, a book
on the fundamentals was missing.
As members of the Institute of Validation, we were keen
to put in place a set of benchmarks on the subject. It
was not until Sue approached us and convinced us that
a book was the ideal vehicle for such an endeavour that
we sat down to do something about it. We would like to
thank Sue and also Amy Davis of Interpharm Press, who
has been a constant source of encouragement from the
book's conception to fruition. Her advice during the
writing and editing of the book is a testament to a true
professional.
Foreword xi
We would be remiss if we were not to take this oppor
tunity. to acknowledge the efforts of Jane Steinmann
and the editorial staff at Interpharm, who have opened
our eyes on how to analyse, edit and check a docu
ment-moreover, tum it into a book.
W. Gibson
K. Powell-Evans
