Biotechnology: Quality Assurance and Validation

Transcription

1 r Biotechnology: Quality Assurance and Validation Drug Manufacturing Technology Series Volume 4 Kenneth E. Avis Carmen M. Wagner Vincent L. Wu Editors Interpharm Press, Inc. Buffalo Grove, Illinois

2 CONTENTS Foreword Author Biographies xi 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 til

3 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 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

4 Contents 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

5 vi Biotechnology: Quality Assurance and Validation International Impacts 68 References 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

6 Contents vii 5. 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

7 viii Biotechnology: Quality Assurance and Validation Summary 157 References 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

8 Contents ix Methodologies for Virus Removal by Filtration 197 Direct Flow Filtration Tangential Flow Filtration Integrity Testing Positioning of Viral Clearance Methodologies Conclusions References Cleaning and Validation of Cleaning in Biopharmaceutical Processing: A Survey 221 Jon R. Voss Robert W. O'Brien Cleaning Uniqueness and Types of Soils Chemistry and Agents Cleaning Approaches for Equipment Cleaning Process Design Special Cleaning Applications Cleaning Validation What Is Cleaning Validation? The Basics Cleaning Equipment Validation Validation of the Cleaning Process: A Three-Step Approach Change Control Revalidation Current and Future Trends in Cleaning References

9 x Biotechnology: Quality Assurance and Validation Index 251 Drug Manufacturing Technology Series Key-Concept Cross-Reference Index for Sterile Dosage Forms 266