Process Scale Purification of Antibodies (2nd Ed.)

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Language: Anglais
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721 p. · Hardback
Promoting a continued and much-needed renaissance in biopharmaceutical manufacturing, this book covers the different strategies and assembles top-tier technology experts to address the challenges of antibody purification.

• Updates existing topics and adds new ones that include purification of antibodies produced in novel production systems, novel separation technologies, novel antibody formats and alternative scaffolds, and strategies for ton-scale manufacturing
• Presents new and updated discussions of different purification technologies, focusing on how they can address the capacity crunch in antibody purification
• Emphasizes antibodies and innovative chromatography methods for processing
1 - Downstream Processing of Monoclonal Antibodies: Current Practices and Future Opportunities
. 1.1 Introduction
. 1.2 A Brief History of Current Good Manufacturing Process mAb and Intravenous Immunoglobulin Purification
. 1.3 Current Approaches in Purification Process Development: Impact of Platform Processes
. 1.4 Typical Unit Operations and Processing Alternatives
. 1.5 VLS Processes: Ton ]Scale Production and Beyond
. 1.6 Process Validation
. 1.7 Product Life Cycle Management
. 1.8 Future Opportunities
. 1.9 Conclusions

2 - The Development of Antibody Purification Technologies
. 2.1 Introduction
. 2.2 Purification of Antibodies by Chromatography Before Protein A
. 2.3 Antibody Purification After 1975
. 2.4 Additional Technologies for Antibody Purification
. 2.5 Purification of mAbs Approved in North America and Europe
. 2.6 Current Antibody Process Technology Developments

3 - Harvest and Recovery of Monoclonal Antibodies: Cell Removal and Clarification
. 3.1 Introduction
. 3.2 Centrifugation
. 3.3 Microfiltration
. 3.4 Depth Filtration
. 3.5 Flocculation
. 3.6 Absolute Filtration
. 3.7 Expanded Bed Adsorption Chromatography
. 3.8 Harvesting in Single ]Use Manufacturing
. 3.9 Comparison of Harvest and Clarification Unit Operations

4 - Next -Generation Clarification Technologies for the Downstream Processing of Antibodies
. 4.1 Introduction
. 4.2 Impurity Profiles in Cell Cultures
. 4.3 Precipitation
. 4.4 Affinity Precipitation
. 4.5 Flocculation
. 4.6 Toxicity of Flocculants and Precipitants and Their Residual Clearance
. 4.7 Depth Filtration
. 4.8 Considerations for the Implementation of New Clarification Technologies
. 4.9 Conclusions and Future Perspectives

5 - Protein A -Based Affinity Chromatography
. 5.1 Introduction
. 5.2 Properties of Protein A and Commercially Available Protein A Resins
. 5.3 Protein A Chromatography Step Development
. 5.4 Additional Considerations During Development and Scale -Up
. 5.5 Virus Removal/Inactivation
. 5.6 Validation and Robustness
. 5.7 Conclusions

6 - Purification of Human Monoclonal Antibodies: Non -Protein A Strategies
. 6.1 Introduction
. 6.2 Integrated Process Design for Human Monoclonal Antibody Production
. 6.3 Purification Process Designs for HuMabs
. 6.4 Conclusions

7 - Hydrophobic Interaction Chromatography for the Purification of Antibodies
. 7.1 Introduction
. 7.2 HIC With mAbs
. 7.3 HIC with Membrane Adsorbers
. 7.4 Future Perspectives

8 - Purification of Monoclonal Antibodies by Mixed -Mode Chromatography
. 8.1 Introduction
. 8.2 A Brief History
. 8.3 Prerequisites for Industrial Implementation
. 8.4 Mechanisms, Screening, and Method Development
. 8.5 Capture Applications
. 8.6 Polishing Applications
. 8.7 Sequential Capture/Polishing Applications
. 8.8 Future Prospects

9 Advances in Technology and Process Development for Industrial -Scale Monoclonal Antibody Purification
. 9.1 Introduction
. 9.2 Affinity Purification Platform
. 9.3 Advances in the Purification of mAbs by CEX Chromatography
. 9.4 High ]Performance Tangential Flow Filtration
. 9.5 A New Nonaffinity Platform

10 - Alternatives to Packed -Bed Chromatography for Antibody Extraction and Purification
. 10.1 Introduction 2
. 10.2 Increasing the Selectivity of Harvest Procedures: Flocculation and Filter Aids
. 10.3 Solutions for Antibody Extraction, Concentration, and Purification
. 10.4 Antibody Purification and Formulation Without Chromatography
. 10.5 Membrane Adsorbers
. 10.6 Conclusions

11 - Process -Scale Precipitation of Impurities in Mammalian Cell Culture Broth
. 11.1 Introduction
. 11.2 Precipitation of DNA and Protein—Other Applications
. 11.3 A Comprehensive Evaluation of Precipitants for the Removal of Impurities
. 11.4 Industrial -Scale Precipitation
. 11.5 Cost of Goods Comparison
. 11.6 Summary

12 - Charged Ultrafiltration and Microfiltration Membranes for Antibody Purification
. 12.1 Introduction
. 12.2 Charged UF Membranes
. 12.3 Concentration Polarization and Permeate Flux
. 12.4 Stagnant Film Model
. 12.5 Sieving Coefficient
. 12.6 Mass Transfer Coefficient
. 12.7 Mass Balance Models
. 12.8 Scale -Up Strategies and the Constant Wall Concentration (Cw) Approach
. 12.9 Membrane Cascades 2
. 12.10 Protein Fractionation Using Charged UF Membranes
. 12.11 Case Study
. 12.12 Charged MF Membranes
. 12.13 Virus Clearance
. 12.14 Salt Tolerance
. 12.15 Conclusions

13 - Disposable Prepacked -Bed Chromatography for Downstream Purification: Form, Fit, Function, and Industry Adoption
. 13.1 Introduction
. 13.2 Development -Scale Prepacked Column Applications
. 13.3 Process -Scale Prepacked Column Applications
. 13.4 Basic Technical Datasets
. 13.5 Independent Industry Assessments of “Fit for Purpose”
. 13.6 Case Study 1: Cation -Exchange Polishing Chromatography
. 13.7 Case Study 2: Prepacked Columns for Pilot -/Large -Scale Bioprocessing
. 13.8 Prepacked Columns—Fit
. 13.9 The Economics of Prepacked Column Technologies
. 13.10 The Implementation of Disposable Prepacked Columns
. 13.11 Conclusions

14 - Integrated Polishing Steps for Monoclonal Antibody Purification
. 14.1 Introduction
. 14.2 Polishing Steps for Antibody Purification
. 14.3 Integration of Polishing Steps
. 14.4 Conclusions

15 - Orthogonal Virus Clearance Applications in Monoclonal Antibody Production
. 15.1 Introduction
. 15.2 Model Viruses and Virus Assays
. 15.3 Virus Clearance Strategies at Different Development Stages
. 15.4 Orthogonal Virus Clearance During mAb Production
. 15.5 Conclusions and Future Perspectives

16 - Development of a Platform Process for the Purification of Therapeutic Monoclonal Antibodies
. 16.1 Introduction
. 16.2 Chromatography Steps in the Platform Process
. 16.3 Virus Inactivation
. 16.4 UF/DF Platform Considerations
. 16.5 Platform Development: Virus Filtration and Bulk Fill
. 16.6 Addressing Future Challenges in Downstream Processing
. 16.7 Representative Platform Processes
. 16.8 Developing a Virus Clearance Database Using a Platform Process
. 16.9 Summary

17 - The Evolution of Platform Technologies for the Downstream Processing of Antibodies
. 17.1 Introduction
. 17.2 The Definition of a Platform Purification Process
. 17.3 The Dominant Process Design
. 17.4 The Evolution of Unit Operations
. 17.5 Adapting the Platform Process for Product -Specific Issues
. 17.6 Future Perspectives—Future Evolutionary Pathways
. 17.7 Concluding Remarks

18 - Countercurrent Chromatography for the Purification of Monoclonal Antibodies, Bispecific Antibodies, and Antibody–Drug Conjugates
. 18.1 Introduction
. 18.2 Chromatography to Reduce Product Heterogeneity
. 18.3 Definition of Performance Parameters
. 18.4 Gradient Chromatography for Biomolecules
. 18.5 Continuous and Countercurrent Chromatography
. 18.6 Multicolumn Countercurrent Solvent Gradient Purification
. 18.7 Scalability of Multicolumn Countercurrent Chromatography
. 18.8 Online Process Monitoring for Multicolumn Countercurrent Chromatography
. 18.9 Outlook

19 - The Evolution of Continuous Chromatography: From Bulk Chemicals to Biopharma
. 19.1 Introduction
. 19.2 Continuous Chromatography in Traditional Process Industries
. 19.3 Continuous Chromatography in the Biopharmaceutical Industry
. 19.4 Advantages of Continuous Chromatography
. 19.5 Implementation Aspects of Continuous Chromatography
. 19.6 Regulatory Aspects
. 19.7 Conclusions

20 - Accelerated Seamless Antibody Purification: Simplicity is Key
. 20.1 Introduction
. 20.2 Accelerated Seamless Antibody Purification
. 20.3 Advantages of the ASAP Process
. 20.4 Scaling Up the ASAP Process
. 20.5 New Perspectives
. 20.6 Conclusion

21 - Process Economic Drivers in Industrial Monoclonal Antibody Manufacture
.Introduction
. 21.2 Challenges When Striving for the Cost -Effective Manufacture of mAbs
. 21.3 Cost Definitions and Benchmark Values
. 21.4 Economies of Scale
. 21.5 Overall Process Economic Drivers
. 21.6 DSP Drivers At High Titers
. 21.7 Process Economic Trade -Offs for Downstream Process Bottlenecks
. 21.8 Summary and Outlook

22 - Design and Optimization of Manufacturing
. 22.1 Introduction
. 22.2 Process Design and Optimization
. 22.3 Modeling Approaches
. 22.4 Process Modeling in Practice
. 22.5 Impact of the Process on the Facility

23 - Smart Design for an Efficient Facility With a Validated Disposable System
. 23.1 Design and Optimization of a Manufacturing Facility
. 23.2 Validation of a Disposable System
. 23.3 Conclusion

24 - High -Throughput Screening and Modeling Technologies for Process Development in Antibody Purification
. 24.1 Introduction
. 24.2 Adsorption Isotherms
. 24.3 Batch Chromatography
. 24.4 Column Chromatography

25 - Downstream Processing of Monoclonal Antibody Fragments
. 25.1 Introduction
. 25.2 Production of Antibody Fragments for Therapeutic Use
. 25.3 Downstream Processing
. 25.4 Improving the Pharmacological Characteristics of Antibody Fragments
. 25.5 Conclusions

26 - Downstream Processing of Fc Fusion Proteins, Bispecific Antibodies, and Antibody–Drug Conjugates
. 26.1 Introduction
. 26.2 Biochemical Properties
. 26.3 Purification From Mammalian Expression Systems
. 26.4 Purification From Microbial Production Systems
. 26.5 Future Innovations

27 - Manufacturing Concepts for Antibody–Drug Conjugates
. 27.1 Introduction
. 27.2 Targeting Components
. 27.3 Cytotoxic Drugs
. 27.4 Chemically Labile Linkers
. 27.5 General Process Overview
. 27.6 Facility Design and Supporting Technology
. 27.7 Single -Use Equipment
. 27.8 Manufacturing ADCs
. 27.9 Analytical Support for ADC Manufacturing
. 27.10 Raw Materials Supply Chain
. 27.11 Conclusion

28 - Purification of IgM and IgA
. 28.1 Introduction
. 28.2 Purification of IgM
. 28.3 Purification of IgA
. 28.4 Conclusion

29 - Purification of Monoclonal Antibodies From Plants
. 29.1 Introduction 6
. 29.2 Antibody Production in Plants
. 29.3 Downstream Processing of Antibodies Produced in Plants
. 29.4 Purification of Plant -Derived Antibodies Using Protein A Resins
. 29.5 Purification of Plant -Derived Antibodies Using Non -Protein A Media
. 29.6 Polishing Steps
. 29.7 Conclusions

30 - Very -Large -Scale Production of Monoclonal Antibodies in Plants
. 30.1 Introduction
. 30.2 Process Schemes for mAb Production in Plants
. 30.3 Scalable Process Models
. 30.4 Process Adaptation for VLS Requirements
. 30.5 Translation into VLS Applications

31 - Trends in Formulation and Drug Delivery for Antibodies
. 31.1 Introduction
. 31.2 Degradation Pathways
. 31.3 Physical Instability
. 31.4 Chemical Instability
. 31.5 How to Achieve Product Stability
. 31.6 Developability: Molecule Selection and Elimination of Degradation Hotspots
. 31.7 Stabilizing an Antibody in a Liquid Formulation
. 31.8 Stabilizing an Antibody by Drying
. 31.9 Choice of Adequate Primary Packaging
. 31.10 Minimizing Stress During Drug Product Processing
. 31.11 Implementation of a Formulation Strategy
. 31.12 Hot Topics
. 31.13 Summary

32 - Antibody Purification: Drivers of Change
. 32.1 Introduction
. 32.2 The Changing Regulatory Environment—Pharmaceutical Manufacturing for the 21st Century
. 32.3 Technology Drivers—Advances and Innovations
. 32.4 Economic Drivers
. 32.5 Conclusions

Index
Uwe Gottschalk, PhD,is Chief Technology Officer at Lonza Pharma/Biotech, Switzerland. Previously, he served as Group Vice President at Sartorius Stedim Biotech (2004-2014) and in various development and manufacturing capacities at Bayer Health Care (1991–2004). Dr. Gottschalk received a doctorate in chemistry from the University of Münster (Germany) for work on antibody-drug conjugates at the Cancer Research Campaign Laboratories in Nottingham (UK).