Biotechnology-Quality Assurance and Validation

285 Pages·1998·7.586 MB·\285

by  Kenneth E. Avis (Editor), Carmen M. Wagner (Editor), Vincent L. Wu (Editor)

Biotechnology
Quality Assurance
and Validation
Drug Manufacturing
Technology Series
Volume 4
Edited by
Kenneth E. Avis
Carmen M. Wagner
Vincent L. Wu
CRC Press
Taylor &. Francis Group
Boca Raton London New York
CRC Press is an imprint of the
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First issued in paperback 2019
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ISBN-13: 978-1-57491-089-6 (hbk)
ISBN-13: 978-0-367-40025-5 (pbk)
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Library of Congress Card Number 98-40953
Library of Congress Cataloging-in-Publication Data
Biotechnology : quality assurance and validation / Kenneth E. Avis, Carmen M.
Wagner, Vincent L. Wu, editors.
p. cm. - (Drug manufacturing technology series : v. 4.)
Includes bibliographical references and index.
ISBN 1-57491-089-2
I. Pharmaceutical biotechnology— Quality control. I. Avis, Kenneth E., 1918-.
II. Wagner, Carmen M. III. Wu, Vincent L. IV. Series.
53
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CONTENTS
Foreword xi
Author Biographies xiii
1. Introduction 1
Kenneth E. Avis
Carmen M. Wagner
Vincent L. Wu
Chapter Contents 3
2. Cryopreservation: Storage and
Documentation Systems 7
Frank P. Simione
Selection of Material for Cryopreservation 8
Public Collections 9
iii
iv Biotechnology: Quality Assurance and Validation
Private Collections 9
Research Collections 10
Characterization 11
Identity 13
Viability and Utility 13
Contamination 13
Genetic Stability 14
Cell Banking 14
Preservation 15
Inventory 17
Segregated Inventory 18
Physical Inventory 19
Inventory Access 23
Security 25
Data Management 26
Removal of Collection Materials 27
Handling and Distribution of Collection Holdings 27
Training 28
Personnel Safety 29
References 30
3. Quality Control and Quality Assurance
Issues in Biopharmaceutical Processing 33
Gary D. Christiansen
Quality Assurance or Quality Control? 36
Quality Assurance Compliance Programs 37
Documentation 37
Standard Operating Procedures 38
Personnel Training 38
Calibration 39
Maintenance 39
Contents v
Audits 39
Validation 40
Change Control 40
Environmental Control 41
Facility and Equipment Cleaning 41
Special Concerns for Biotechnology Products 43
Biotechnology Test Methods 43
Final Product Lot Release 47
General Safety Testing 48
Sterility Testing 48
Pyrogen Testing 49
Mycoplasma Testing 50
DNA Testing 50
Virus Testing 51
Concluding Comments 52
Process Validation 52
Process Parameters 53
Cell Line Characterization 54
Virus Removal and Inactivation 54
DNA and Nucleic Acid Removal 55
Other Contaminant Removal 56
Inspections: FDA Inspection Guides 56
Documentation Review 57
Out-of-Specification Results 58
Laboratory Records and Documents 60
Laboratory Standards 60
Testing Methods 60
Laboratory Equipment 61
Computerized Data Acquisition 61
Other Considerations 62
Microbiological Quality Control
Laboratory Inspections 62
Future Trends 63
Increased Responsibilities for Quality Control 64
Quality Assurance Responsibilities 65
Validation Requirements 66
Contamination Control 67
Biotechnology Product Quality 67
vi Biotechnology: Quality Assurance and Validation
International Impacts 68
References 69
4. Biotechnology Manufacturing Issues:
A Field Investigator's Perspective 73
Gregory Bobrowicz
Regulation of Biotechnology Products 74
The Centers and the Field 74
Problems Noted at Biopharmaceutical Plants 75
FDA's Concerns 77
Related Impurities 77
Viruses 82
Mycoplasma 83
Microorganisms/Endotoxins 83
Process Contaminants 91
Potency 95
Identity 96
Strategies for Compliance 98
Importance of Planning 98
Importance of Review 99
Importance of Audits 100
Management Involvement 101
Corporate Culture 102
Importance of Investigations 103
Conclusion 105
Addendum 106
Acknowledgments 106
References 107
Contents vii
Validation of
Biopharmaceutical Processes 111
Howard L. Levine
Francisco J. Castillo
Cell Bank Testing and Qualification 114
Cell Banks 114
Virus Banks for Gene Therapy 117
Cellular and Tissue-Based Products 122
Equipment Qualification 122
Installation Qualification 123
Operational Qualification 125
Performance Qualification 127
Validation of Fermentation/Cell Culture Processes 128
Raw Material Validation 128
Process Validation 128
Validation of Downstream Processing 129
Process Chemicals and Raw Materials 130
Column Packing Materials 131
Membranes for Tangential Flow Filtration 132
Performance Qualification of Downstream
Processes 132
Concurrent Versus Prospective Validation 133
Chromatography Column Packing 133
Column Lifetime 134
Process Robustness 138
Clearance Studies 139
Nucleic Acids 143
Host Cell Proteins 145
Pyrogens 148
Viruses 149
Validation of Tangential Flow Filtration 154
Protein Concentration and Diafiltration 155
Cell Debris Removal 155
Cell Harvesting 156
viii Biotechnology: Quality Assurance and Validation
Summary 157
References 157
6. Ensuring Virological Safety of
Biologicals: Virus Removal from
Biological Fluids by Filtration 167
Hazel Aranha-Creado
The Need to Ensure the Safety of Biologicals 167
Historical Perspective 169
Contemporary Approach 171
Sources of Viral Contamination 173
Endogenous Viral Contamination in
Continuous Cell Lines 173
Potential for Association of Viral Zoonoses
with Continuous Cell Lines 175
Adventitious Virus Contamination of Continuous
Cell Lines and Manufacturing Processes 176
Detection of Viral Contamination 178
Biological (Infectivity) Assays 178
Antibody Production Tests 180
Biochemical Assays 180
Molecular Probes 180
Morphological Assays 181
Summary 181
Methods of Viral Clearance 181
Regulatory Considerations in Viral Clearance 184
Validation Considerations in the
Documentation of Viral Clearance 188
Aspects of Virus Validation Studies 188
Model Viruses Used in Process Validation 190
Calculation of Virus Reduction Factor 193
Validation of Viral Clearance 196
Contents ix
Methodologies for Virus Removal by
Filtration 197
Direct Flow Filtration 198
Tangential Flow Filtration 200
Integrity Testing 202
Positioning of Viral Clearance Methodologies 208
Conclusions 210
References 210
7. Cleaning and Validation of Cleaning
in Biopharmaceutical Processing:
A Survey 221
Jon R. Voss
Robert W. O'Brien
Cleaning 222
Uniqueness and Types of Soils 222
Chemistry and Agents 222
Cleaning Approaches for Equipment 224
Cleaning Process Design 226
Special Cleaning Applications 229
Cleaning Validation 234
What Is Cleaning Validation? 234
The Basics 234
Cleaning Equipment Validation 237
Validation of the Cleaning Process:
A Three-Step Approach 241
Change Control 245
Revalidation 248
Current and Future Trends in Cleaning 249
References 250