GMP Compliance, Productivity, and Quality: Achieving Synergy in Healthcare Manufacturing

525 Pages·1998·19.94 MB·\525

by  Vinay Bhatt (Editor)

GMP Compliance,
Productivity, and Quality
Achieving Synergy in Healthcare
Manufacturing
Vinay Bhatt
Taylor &. Francis
Taylor &. Francis Group
Boca Raton London New York Singapore
CRC PRESS, a Taylor & Francis title, part of the Taylor and Francis Group.
Transferred to Digital Printing 2010
Library of Congress Cataloging-in-Publication Data
GMP compliance, productivity, and quality : achieving synergy in healthcare manufacturing /
Vinay Bhatt, editor,
p. cm.
Includes bibliographical references and index.
ISBN 1-57491-077-9 (alk. paper)
1. Pharmaceutical technology. 2. Pharmaceutical industry—Quality control. II. Bhatt, Vinay.
RS192.P76 1998
615M9—dc21 98-6591
This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with
permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish
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© 1998 by CRC Press
No claim to original U.S. Government works
International Standard Book Number 1-57491-077-9
Library of Congress Card Number 98-6591
Publisher’s Note
The publisher has gone to great lengths to ensure the quality
of this reprint but points out that some imperfections in the original may be apparent.
for Rhea,
Siya,
and Bhavna

Contents
FOREWORD xiii
PREFACE xv
Acknowledgments xviii
CONTRIBUTORS xix
1. PROCESS IMPROVEMENT AND GMP
COMPLIANCE: PARTNERS, NOT ADVERSARIES 1
Vinay Bhatt
From Research to Marketing 3
Raising the Buffer Zones 3
From Inspection to Process Control 5
Compliance and Process Performance Seek the Bottom Line 6
Compliance Strengthening Factors 8
Prevention of Process Improvement Programme Failure 24
Conclusions 25
References 26
v
vi GMP Compliance, Productivity, and Quality
PHARMACEUTICAL DEVELOPMENT:
WELL BEGUN IS HALF DONE
27
Gary L. Fourman & Tommy C. Morris
The Three-Legged Stool on Which Development
Rests: Homogeneity, Stability, and Bioavailability 28
Planning the Development of a New Product 32
Characterization of the Drug Substance 33
Selection of the Manufacturing Process 36
The Selection of Excipients 39
Design of Experiments 41
Characterization of Excipients 48
Limits and Controls 49
Setting Specifications 53
Scale-Up 54
Concurrent Activities to Be Coordinated with
the Product Development Effort 56
Development Reports 59
Technology Transfer 60
Validation 61
Preapproval Inspection 65
Pharmaceutical Development: The Future 66
Retrieval of Development Data "After the Development Is Done" 69
Suggested Readings 70
Acknowledgments 71
References 71
3. PROCESS AND EQUIPMENT OPTIMIZATION:
GETTING THE COMBINATION RIGHT 73
Alan Kwong, David R. Timms, & Kent Chiu
Equipment Design for Process Optimization 74
Product Development 77
Process/Equipment Optimization 78
Compliance Issues 102
Contents vii
Conclusion 111
Acknowledgment 111
4. FACILITIES AND SUPPORT SYSTEMS OPTIMIZATION:
CRITICAL FOR A WINNING STRATEGY 113
Jack C. Chu, Gregory S. Cierpial, & Alan Kwong
Industry Trends 114
Facility Impact 116
Capacity Planning 116
Architectural Issues 133
Critical Utilities in cGMP-Compliant Facilities 139
Conclusion 155
References 156
Bibliography 156
Acknowledgment 156
5. SUPAC AND REGULATORY CONSEQUENCES:
THE BALANCING ACT 157
Suva B. Roy & Sherry Watson
Scale-Up and Post-Approval Changes Guidance Documents 163
References 198
6. LABORATORY OPERATIONS: A VITAL LINK 201
David L. Mulligan & Christopher Smith
Instrument Qualification, Calibration, and Maintenance 201
Reference Standards. Reagents, and Working Solutions 206
Samples 207
Specifications 208
Method Development, Validation, and Transfer 208
Raw Material Testing 211
Stability Testing 211
viii GMP Compliance, Productivity, Quality
Standard Operating Procedures 212
Laboratory Investigations 213
Data Security/Integrity 216
Change Control 219
Training 220
Housekeeping 221
The Microbiology Laboratory 221
Laboratory Efficiency and Productivity 224
Conclusion 227
Bibliography 227
Acknowledgments 228
7. VALIDATION: WHERE ARE THE OPPORTUNITIES? 229
Vinay Bhatt, Jack Basarke, & Eric M. Mittleberg
The Benefits of Validation 231
The Validation Master Plan 235
GMP Concerns 236
Change Management 241
Matrixing/Bracketing and Validation 242
Validation and Its Role in Technology Transfer 246
Measuring Validation Productivity 248
Conclusion 252
Acknowledgment 252
References 252
8. INTEGRATED SUPPLY CHAIN PLANNING:
FROM STOCK TO DOCK 253
Naishadh Kapadia, Ying Chang, & Steven M. Moyer
Supply Chain Concepts 254
Characteristics of the Pharmaceutical Industry Supply Chain 255
Types of Systems and Applications in the Supply Chain 259
The Case for Better Decision Support Tools 263
Demand Management 267
Contents ix
Planning Applications 270
Scheduling Applications 272
Integration 279
Implementation Considerations 283
9. OUTSOURCING: A LONG-RANGE
BUSINESS STRATEGY 287
Pierre Beaumier, Paul Pickles, & Ravi Joshi
Definitions 288
Selecting a Contractor 290
Selecting a Contract Laboratory 301
Subcontractor Quality System Questionnaire 308
Steps to Establish the Third-Party Manufacturing Contract 314
Appendix A: Confidentiality Agreement 316
Appendix B: Quality Assurance Agreement 318
Appendix C: Manufacturing and Product Supply Contract 326
10. INSPECTION OF AUTOMATED SYSTEMS:
HOW TO STAY IN THE GAME 329
Arthur D. Perez & Kathleen Pelley
What Is a Computerized System? 330
The FDA's Perception of Problems in
Pharmaceutical Computerized Systems 331
How Much Is Enough? 333
Recent FDA Initiatives 341
Future Directions 360
References 362
11. PAI PREPARATION: PRESCRIPTION FOR SUCCESS 363
David L. Mulligan, John F. Goetz, & Andreas Werner
Early Preparation 364
Late Development 372