Guidelines for Process Safety in Bioprocess Manufacturing Facilities

Since 1985, the Center for Chemical Process Safety (CCPS) has been the world leader in developing and disseminating information on process safety management and technology. CCPS, an industry technology alliance of the American Institute of Chemical Engineers (AIChE), has published over 80 books in its process safety guidelines and process safety concepts series, and over 100 training modules through its Safety in Chemical Engineering Education (SACHE) series.

• List of Tables xiList of Figures xiiiItems on the Web Accompanying This Book xvAcknowledgements xviiPreface xix1 INTRODUCTION 11.1 Bioprocess Engineering Information Transfer and Management Practices 31.2 The Need for Bioprocess Safety Management Systems 71.2.2 Bioprocessing Incidents and Releases 81.3 Our Target Audience 141.4 How to use this Guideline 152 AN OVERVIEW OF THE BIOPROCESSING INDUSTRY 172.1 Bioprocessing’s History 172.1.1 Bioprocessing’s Historical Advancement 182.1.1.1 Microbiological Advancements 182.1.1.2 Food Science and Food Process Technology Advancements 192.1.1.3 Genetic Advancements 192.1.1.4 Future Bioprocessing Developments 202.2 Industrial Applications 202.2.1 Processes 212.2.2 Products 212.3 The Bioprocess Lifecycle 222.3.1 Discovery 232.3.2 Development Phase: Laboratory and Pilot Plant 232.3.3 Scale-up Phase 242.3.4 Upstream Operations and Downstream Operations 262.3.4.1 Inoculation / Seed and Production Biosafety Containment and Production Risk 272.3.4.2 Fermentation / Cell Culture 312.3.4.3 Scale of Manufacturing 362.3.5 General Biosafety Recommendations for Large Scale Work 382.3.5.1 Facility Design 392.3.5.2 Equipment Design 392.3.5.3 Cleaning, Inactivation, and Sterilization 412.3.5.4 Maintenance 422.3.5.5 Air and Gas Emissions 422.3.5.6 Waste Handling 422.3.5.7 Accidental Release 432.3.6 Product Safety Information 432.3.6.1 Product Handling 442.3.6.2 Material Disposal 442.3.63 Disposable Process Technology 442.3.7 Outsourced Manufacturing Concerns 453 BIOPROCESSING SAFETY MANAGEMENT PRACTICES 473.1 Sample Approach 483.1.2 Develop and Document a System to Manage Bioprocess Safety Hazards 503.1.3 Appoint a Biological Safety Officer 503.1.4 Collect Bioprocess Hazard Information 513.1.5 Identify Bioprocess Safety Hazards 513.1.5.1 Point of Decision 513.1.6 Assess Bioprocess Safety Risks and Assign Bioprocess Safety Hazard Level 523.1.7 Identify Bioprocess Controls and Risk Management Options 523.1.8 Document Bioprocess Safety Hazard Risks and Management Decisions 533.1.9 Communicate and Train on Bioprocess Safety Hazards 533.1.10 Investigate & Learn from Bioprocess Incidents 533.1.11 Review, Audit, Manage Change, and Improve Hazard Management Practices and Program 543.2 Existing Management Systems 543.2.1 Product Stewardship for Byproducts 613.3 Establishing a Bioprocess Safety Management System 623.3.1 Select a Management System Model Based Upon Your Needs 633.3.2 Identifying the Elements that Apply to Your Operations 643.3.3 Establish a Review and Approval Cycle for the Documents 653.3.4 Rolling Out the Management System to the Users 663.4 Biosafety Training for the Workforce 673.5 Investigating Incidents 693.5.1 A Generic Procedure for Initial Biohazard Incident Response 713.6 Managing Change 753.7 Reviewing and Auditing for Continuous Improvement 763.8 Applying Behavior-Based Safety to Bioprocesses 764.IDENTIFYING BIOPROCESS HAZARDS 794.1 Key Considerations for Assessing Risk to Manage Bioprocess Safety 794.1.1 Testing for Bioactivity 794.1.2 Non-biological Hazards 804.2 Bioprocess Risk Assessment 804.2.1 Three Types of Assessment 804.2.2 Agent Considerations 804.2.3 Process Considerations 814.2.4 Environmental Considerations 824.2.5 Microorganisms 834.3 Recombinant Organisms 854.4 Cell Culture 865 BIOPROCESS DESIGN CONSIDERATIONS AND UNIT OPERATIONS 895.1 Physical Plant Design 895.1.1 Architectural Aspects 905.1.1.1 Finishes and Materials 905.1.1.2 Layout Strategies 915.1.1.3 People and Material Flow 945.1.1.4 Non-bio logical Hazards 945.1.1.5 Seismic and Building Loads 965.1.1.6 Hardened Construction 975.1.1.7 Equipment Mezzanines and Subfloors 975.1.1.8 Heating, Ventilation, and Air Conditioning Aspects 98(a) Supply and Exhaust Systems 98(b) Special Exhaust Stream Mitigation 100(c) HVAC Issues from a Biosafety Perspective 101(d) Microenvironments 103(e) Cascading Pressure Differentials 105(f) Containment versus Clean Room Environments 1075.1.1.9 Waste and Waste Treatment 1095.1.1.10 Process Support Systems: High Purity Water 1125.1.1.11 Process Support Systems: Hand Washing Sinks and Personnel showers 1125.1.2 Plant Siting Issues 1135.1.2.1 Zoning & Permitting 1135.1.2.2 Regional Environmental Agencies and Environmental Impact Reports 1135.1.2.3 Building and Site Security 1145.2 Bioprocess Unit Operations 1165.2.1 General Equipment Design Considerations 1175.2.2 Closed-System Design 1185.2.2.2 Impact on Operations 1235.2.3 Upstream Equipment and Facility Design 1245.2.3.1 Additional Upstream Design Considerations 1245.2.3.2 Equipment and Facility Integration 1275.2.3.3 Production Segregation and Flows 1275.2.3.4 Segregation from a Biosafety Perspective 1295.2.3.5 Cleaning the Equipment 1305.2.4.1 Harvest and Recovery 1345.2.4.2 Centrifugation 1345.2.4.3 Filtration 1355.2.4.4 Chromatography 1375.2.5 Facility Support Issues 1395.2.6 Biosafety for Personnel: SOP, Protocols, and PPE 1406 THE EFFECTS OF EMERGING TECHNOLOGY ON BIOPROCESSING RISK MANAGEMENT 1436.1 Researching and Staying Informed 1436.1.1 Biopharmaceutical 1446.1 .1 .1 Drug Discovery and Development 1446.1.1.2 Gene-based Pharmaceuticals 1446.1.1.3 Drug Delivery Research 1466.1.2 Renewable-resources 1476.1.3 Environmental 1486.1.3.1 Bioprocessing and Waste Management 1486.2 Communicating the Impacts of New Technology 1496.2.1 Industry (Communication at Your Site) 150APPENDIX A - REFERENCES & SELECTED REGULATIONS 153APPENDIX B - LARGE SCALE BIOSAFETY GUIDELINES 161APPENDIX C - A GENERIC LABORATORY/LARGE SCALE BIOSAFETY CHECKLIST 177APPENDIX D - BIOLOGICAL ASSESSMENT QUESTIONNAIRE & BIOPROCESS SAFETY CHECKLIST 179APPENDIX E - BIOPROCESS FACILITY AUDIT CHECKLIST 189APPENDIX F - DIRECTIVE 2000/54/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL 199APPENDIX G - COMPARISON OF GOOD LARGE SCALE PRACTICE (GLSP) AND BIOSAFETY LEVEL (BL) - LARGE SCALE (LS) PRACTICE 203GLOSSARY 209ACRONYMS AND ABBREVIATIONS 217INDEX 221