Process Scale Purification of Antibodies 2e

פרטים

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

מידע נוסף

מידע נוסף
מהדורה	2nd Edition
עמודים	752
פורמט	Hardback
ISBN10	1119126916
יצא לאור ב	Hoboken
תאריך יציאה לאור	26 במאי 2017
תוכן עניינים	1 Downstream Processing of Monoclonal Antibodies: Current Practices and Future Opportunities 1 Brian Kelley 1.1 Introduction 1 1.2 A Brief History of Current Good Manufacturing Process mAb and Intravenous Immunoglobulin Purification 2 1.3 Current Approaches in Purification Process Development: Impact of Platform Processes 4 1.4 Typical Unit Operations and Processing Alternatives 7 1.5 VLS Processes: Ton ]Scale Production and Beyond 10 1.6 Process Validation 12 1.7 Product Life Cycle Management 13 1.8 Future Opportunities 16 1.9 Conclusions 18 2 The Development of Antibody Purification Technologies 23 John Curling 2.1 Introduction 23 2.2 Purification of Antibodies by Chromatography Before Protein A 25 2.3 Antibody Purification After 1975 28 2.4 Additional Technologies for Antibody Purification 31 2.5 Purification of mAbs Approved in North America and Europe 34 2.6 Current Antibody Process Technology Developments 40 3 Harvest and Recovery of Monoclonal Antibodies: Cell Removal and Clarification 55 Abhinav A. Shukla and Eric Suda 3.1 Introduction 55 3.2 Centrifugation 59 3.3 Microfiltration 62 3.4 Depth Filtration 67 3.5 Flocculation 70 3.6 Absolute Filtration 71 3.7 Expanded Bed Adsorption Chromatography 73 3.8 Harvesting in Single ]Use Manufacturing 74 3.9 Comparison of Harvest and Clarification Unit Operations 74 4 Next -Generation Clarification Technologies for the Downstream Processing of Antibodies 81 Nripen Singh and Srinivas Chollangi 4.1 Introduction 81 4.2 Impurity Profiles in Cell Cultures 83 4.3 Precipitation 84 4.4 Affinity Precipitation 89 4.5 Flocculation 90 4.6 Toxicity of Flocculants and Precipitants and Their Residual Clearance 96 4.7 Depth Filtration 97 4.8 Considerations for the Implementation of New Clarification Technologies 102 4.9 Conclusions and Future Perspectives 103 5 Protein A -Based Affinity Chromatography 113 Suresh Vunnum, Ganesh Vedantham and Brian Hubbard 5.1 Introduction 113 5.2 Properties of Protein A and Commercially Available Protein A Resins 114 5.3 Protein A Chromatography Step Development 118 5.4 Additional Considerations During Development and Scale -Up 123 5.5 Virus Removal/Inactivation 127 5.6 Validation and Robustness 128 5.7 Conclusions 129 6 Purification of Human Monoclonal Antibodies: Non -Protein A Strategies 135 Alahari Arunakumari and Jue Wang 6.1 Introduction 135 6.2 Integrated Process Design for Human Monoclonal Antibody Production 136 6.3 Purification Process Designs for HuMabs 136 6.4 Conclusions 149 7 Hydrophobic Interaction Chromatography for the Purification of Antibodies 155 Judith Vajda and Egbert Muller 7.1 Introduction 155 7.2 HIC With mAbs 156 7.3 HIC with Membrane Adsorbers 173 7.4 Future Perspectives 174 8 Purification of Monoclonal Antibodies by Mixed -Mode Chromatography 181 Pete Gagnon 8.1 Introduction 181 8.2 A Brief History 182 8.3 Prerequisites for Industrial Implementation 183 8.4 Mechanisms, Screening, and Method Development 185 8.5 Capture Applications 192 8.6 Polishing Applications 193 8.7 Sequential Capture/Polishing Applications 193 8.8 Future Prospects 193 9 Advances in Technology and Process Development for Industrial -Scale Monoclonal Antibody Purification 199 Nuno Fontes and Robert Van Reis 9.1 Introduction 199 9.2 Affinity Purification Platform 200 9.3 Advances in the Purification of mAbs by CEX Chromatography 201 9.4 High ]Performance Tangential Flow Filtration 209 9.5 A New Nonaffinity Platform 211 10 Alternatives to Packed -Bed Chromatography for Antibody Extraction and Purification 215 Jorg Thommes, Richard M. Twyman and Uwe Gottschalk 10.1 Introduction 215 10.2 Increasing the Selectivity of Harvest Procedures: Flocculation and Filter Aids 216 10.3 Solutions for Antibody Extraction, Concentration, and Purification 218 10.4 Antibody Purification and Formulation Without Chromatography 220 10.5 Membrane Adsorbers 223 10.6 Conclusions 225 11 Process -Scale Precipitation of Impurities in Mammalian Cell Culture Broth 233 Judy Glynn 11.1 Introduction 233 11.2 Precipitation of DNA and Protein Other Applications 235 11.3 A Comprehensive Evaluation of Precipitants for the Removal of Impurities 236 11.4 Industrial -Scale Precipitation 241 11.5 Cost of Goods Comparison 243 11.6 Summary 244 12 Charged Ultrafiltration and Microfiltration Membranes for Antibody Purification 247 Mark R. Etzel and Abhiram Arunkumar 12.1 Introduction 247 12.2 Charged UF Membranes 248 12.3 Concentration Polarization and Permeate Flux 248 12.4 Stagnant Film Model 249 12.5 Sieving Coefficient 250 12.6 Mass Transfer Coefficient 251 12.7 Mass Balance Models 251 12.8 Scale -Up Strategies and the Constant Wall Concentration (Cw) Approach 253 12.9 Membrane Cascades 255 12.10 Protein Fractionation Using Charged UF Membranes 256 12.11 Case Study 257 12.12 Charged MF Membranes 259 12.13 Virus Clearance 260 12.14 Salt Tolerance 261 12.15 Conclusions 264 13 Disposable Prepacked -Bed Chromatography for Downstream Purification: Form, Fit, Function, and Industry Adoption 269 Stephen K. Tingley 13.1 Introduction 269 13.2 Development -Scale Prepacked Column Applications 271 13.3 Process -Scale Prepacked Column Applications 275 13.4 Basic Technical Datasets 278 13.5 Independent Industry Assessments of Fit for Purpose 285 13.6 Case Study 1: Cation -Exchange Polishing Chromatography 285 13.7 Case Study 2: Prepacked Columns for Pilot -/Large -Scale Bioprocessing 287 13.8 Prepacked Columns Fit 292 13.9 The Economics of Prepacked Column Technologies 295 13.10 The Implementation of Disposable Prepacked Columns 297 13.11 Conclusions 300 14 Integrated Polishing Steps for Monoclonal Antibody Purification 303 Sanchayita Ghose, Mi Jin, Jia Liu, John Hickey and Steven Lee 14.1 Introduction 303 14.2 Polishing Steps for Antibody Purification 304 14.3 Integration of Polishing Steps 316 14.4 Conclusions 320 15 Orthogonal Virus Clearance Applications in Monoclonal Antibody Production 325 Joe X. Zhou 15.1 Introduction 325 15.2 Model Viruses and Virus Assays 326 15.3 Virus Clearance Strategies at Different Development Stages 328 15.4 Orthogonal Virus Clearance During mAb Production 328 15.5 Conclusions and Future Perspectives 338 16 Development of a Platform Process for the Purification of Therapeutic Monoclonal Antibodies 343 Yuling Li, Min Zhu, Haibin Luo and Justin R. Weaver 16.1 Introduction 343 16.2 Chromatography Steps in the Platform Process 345 16.3 Virus Inactivation 352 16.4 UF/DF Platform Considerations 352 16.5 Platform Development: Virus Filtration and Bulk Fill 354 16.6 Addressing Future Challenges in Downstream Processing 356 16.7 Representative Platform Processes 356 16.8 Developing a Virus Clearance Database Using a Platform Process 359 16.9 Summary 361 17 The Evolution of Platform Technologies for the Downstream Processing of Antibodies 365 Lee Allen 17.1 Introduction 365 17.2 The Definition of a Platform Purification Process 366 17.3 The Dominant Process Design 367 17.4 The Evolution of Unit Operations 372 17.5 Adapting the Platform Process for Product -Specific Issues 382 17.6 Future Perspectives Future Evolutionary Pathways 382 17.7 Concluding Remarks 383 18 Countercurrent Chromatography for the Purification of Monoclonal Antibodies, Bispecific Antibodies, and Antibody Drug Conjugates 391 Thomas Muller -Spath and Massimo Morbidelli 18.1 Introduction 391 18.2 Chromatography to Reduce Product Heterogeneity 392 18.3 Definition of Performance Parameters 394 18.4 Gradient Chromatography for Biomolecules 394 18.5 Continuous and Countercurrent Chromatography 395 18.6 Multicolumn Countercurrent Solvent Gradient Purification 397 18.7 Scalability of Multicolumn Countercurrent Chromatography 403 18.8 Online Process Monitoring for Multicolumn Countercurrent Chromatography 404 18.9 Outlook 405 19 The Evolution of Continuous Chromatography: From Bulk Chemicals to Biopharma 409 Marc Bisschops 19.1 Introduction 409 19.2 Continuous Chromatography in Traditional Process Industries 410 19.3 Continuous Chromatography in the Biopharmaceutical Industry 413 19.4 Advantages of Continuous Chromatography 420 19.5 Implementation Aspects of Continuous Chromatography 422 19.6 Regulatory Aspects 424 19.7 Conclusions 426 20 Accelerated Seamless Antibody Purification: Simplicity is Key 431 Benoit Mothes 20.1 Introduction 431 20.2 Accelerated Seamless Antibody Purification 432 20.3 Advantages of the ASAP Process 437 20.4 Scaling Up the ASAP Process 438 20.5 New Perspectives 440 20.6 Conclusion 442 21 Process Economic Drivers in Industrial Monoclonal Antibody Manufacture 445 Suzanne S. Farid 21.1 Introduction 445 21.2 Challenges When Striving for the Cost -Effective Manufacture of mAbs 446 21.3 Cost Definitions and Benchmark Values 448 21.4 Economies of Scale 450 21.5 Overall Process Economic Drivers 453 21.6 DSP Drivers At High Titers 457 21.7 Process Economic Trade -Offs for Downstream Process Bottlenecks 459 21.8 Summary and Outlook 461 22 Design and Optimization of Manufacturing 467 Andrew Sinclair 22.1 Introduction 467 22.2 Process Design and Optimization 468 22.3 Modeling Approaches 470 22.4 Process Modeling in Practice 481 22.5 Impact of the Process on the Facility 491 23 Smart Design for an Efficient Facility With a Validated Disposable System 495 Joe X. Zhou, Jason Li, Michael Cui and Haojun Chen 23.1 Design and Optimization of a Manufacturing Facility 495 23.2 Validation of a Disposable System 507 23.3 Conclusion 512 24 High -Throughput Screening and Modeling Technologies for Process Development in Antibody Purification 515 Tobias Hahn, Thiemo Huuk and Jurgen Hubbuch 24.1 Introduction 515 24.2 Adsorption Isotherms 516 24.3 Batch Chromatography 519 24.4 Column Chromatography 524 25 Downstream Processing of Monoclonal Antibody Fragments 537 Mariangela Spitali 25.1 Introduction 537 25.2 Production of Antibody Fragments for Therapeutic Use 538 25.3 Downstream Processing 539 25.4 Improving the Pharmacological Characteristics of Antibody Fragments 552 25.5 Conclusions 553 26 Downstream Processing of Fc Fusion Proteins, Bispecific Antibodies, and Antibody Drug Conjugates 559 Abhinav A. Shukla and Carnley L. Norman 26.1 Introduction 559 26.2 Biochemical Properties 562 26.3 Purification From Mammalian Expression Systems 576 26.4 Purification From Microbial Production Systems 585 26.5 Future Innovations 587 27 Manufacturing Concepts for Antibody Drug Conjugates 595 Thomas Rohrer 27.1 Introduction 595 27.2 Targeting Components 596 27.3 Cytotoxic Drugs 600 27.4 Chemically Labile Linkers 602 27.5 General Process Overview 602 27.6 Facility Design and Supporting Technology 604 27.7 Single -Use Equipment 607 27.8 Manufacturing ADCs 608 27.9 Analytical Support for ADC Manufacturing 609 27.10 Raw Materials Supply Chain 611 27.11 Conclusion 611 28 Purification of IgM and IgA 615 Charlotte Cabanne and Xavier Santarelli 28.1 Introduction 615 28.2 Purification of IgM 616 28.3 Purification of IgA 621 28.4 Conclusion 623 29 Purification of Monoclonal Antibodies From Plants 631 Zivko L. Nikolov, Jeffrey T. Regan, Lynn F. Dickey and Susan L. Woodard 29.1 Introduction 631 29.2 Antibody Production in Plants 632 29.3 Downstream Processing of Antibodies Produced in Plants 636 29.4 Purification of Plant -Derived Antibodies Using Protein A Resins 641 29.5 Purification of Plant -Derived Antibodies Using Non -Protein A Media 642 29.6 Polishing Steps 643 29.7 Conclusions 645 30 Very -Large -Scale Production of Monoclonal Antibodies in Plants 655 Johannes F. Buyel, Richard M. Twyman and Rainer Fischer 30.1 Introduction 655 30.2 Process Schemes for mAb Production in Plants 656 30.3 Scalable Process Models 661 30.4 Process Adaptation for VLS Requirements 663 30.5 Translation into VLS Applications 666 31 Trends in Formulation and Drug Delivery for Antibodies 673 Hanns -Christian Mahler and Roman Mathas 31.1 Introduction 673 31.2 Degradation Pathways 674 31.3 Physical Instability 674 31.4 Chemical Instability 676 31.5 How to Achieve Product Stability 678 31.6 Developability: Molecule Selection and Elimination of Degradation Hotspots 679 31.7 Stabilizing an Antibody in a Liquid Formulation 679 31.8 Stabilizing an Antibody by Drying 681 31.9 Choice of Adequate Primary Packaging 682 31.10 Minimizing Stress During Drug Product Processing 683 31.11 Implementation of a Formulation Strategy 685 31.12 Hot Topics 685 31.13 Summary 689 32 Antibody Purification: Drivers of Change 699 Narahari Pujar, Duncan Low and Rhona O Leary 32.1 Introduction 699 32.2 The Changing Regulatory Environment Pharmaceutical Manufacturing for the 21st Century 701 32.3 Technology Drivers Advances and Innovations 707 32.4 Economic Drivers 708 32.5 Conclusions 711 INDEX 717
זמן אספקה	21 ימי עסקים