Biopharmaceutical Processing
10.2.3 General Reviews on Classic and Alternative Separation Methods 212
10.3 General Comparison of Alternative Separation Methods 213
10.3.1 Preliminary Comparison of Alternative Separation Methods 213
10.4 Alternative Separation Operations 215
10.4.1 Separation Factors and Partition K Values 215
10.4.2 Process and Cost-of-Goods Modeling of Standard and AS Methods 215
10.4.3 Comparisons Related to mAb Processing 216
10.5 Acknowledgements, Notices, and Disclaimers
11. Alternative Separation Methods: Flocculation and Precipitation
James M. Van Alstine, Günter Jagschies, Karol M. Łącki
11.1 Introduction 221
11.2 Clarification and Primary Recovery Challenges 221
11.2.1 Self-Associating and Nonassociating Flocculation/ Precipitation Agents 225
11.3 Cell Debris Reduction and Clarification 226
11.3.1 PEI, Chitosan, or CaCl2 Plus K2PO4-Based Cell Flocculation 226
11.3.2 Cell Flocculation Using Poly (Diallyldimethylammonium Chloride) (pDADMAC) 226
11.3.3 Cell Flocculation Using Benzylated Poly(Allylamine) Phosphate Responsive Polymer 227
11.3.4 Cell Flocculation Using EOPO Temperature-Responsive Polymer 227
11.4 Precipitation and Flocculation of Target 229
11.4.1 Ammonium Sulfate Precipitation of Clarified NS0 Cell mAb Feed 229
11.4.2 Protein A Chromatography Versus Polyacid Target Precipitation in an mAb Process 229
11.4.3 Selective Precipitation of Polyclonal Ig by Polyacrylic Acid and Kosmotropic Salts 230
11.4.4 Sequential Precipitation of Protein Mixture Components With NaPAA 231
11.5 Examples of Contaminant Precipitation 233
11.5.1 Contaminant Precipitation With Polyelectrolytes 233
11.5.2 Impurity Precipitation With Caprylic Acid 233
11.6 Sequential and Continuous Precipitation 234
11.6.1 Sequential Precipitation 234
11.6.2 Batch Versus Continuous Precipitation 234
11.7 Process Economics Notes 235
11.7.1 Introduction 235
11.7.2 Simple Cost of Goods Comparison of Caprylic Acid and Protein A 235
11.7.3 Precipitation Versus Protein A—Hammerschmidt, Jungbauer 235 11.8 Conclusions
Acknowledgments, Notices, and Disclaimers
12. Alternative Separation Methods: Crystallization and Aqueous Polymer Two-Phase Extraction
James M. Van Alstine, Günter Jagschies, Karol M. Łącki
12.1 Introduction 241
12.1.1 Two Classic Separation Methods Based on Phase Transfer 241
12.1.2 Related Notes From Previous Chapters in This Book 241
12.2 Crystallization 242
12.2.1 Introduction 242
12.2.2 Preparative Small Protein Crystallization 246
12.2.3 Monoclonal Antibody Fragment and Antibody Crystallization 246
12.2.4 Monoclonal Antibody Crystallization Phase Diagrams 246
12.2.5 Crystallization From Mixtures of Proteins 248
12.2.6 Crystallization of mAb From Clarified Feed 249
12.2.7 Scale-Up of Protein Crystallization 249
12.2.8 Discussion and Conclusions 249
12.3 Aqueous Polymer Two-Phase Extraction 249
12.3.1 Introduction 250
12.3.2 Phase Systems, Phase Diagrams and Partition Coefficients 251
12.3.3 Recent Trends in ATPE 256
12.3.4 Key References on the Partitioning of Monoclonal Antibodies 256
20.3
20.4
20.2.2 Process Development for Capture of Recombinant ProInsulin From E. coli
20.2.3 Purification of Influenza A/H1N1 Using Capto Core 700
20.5 CIP/SIP
20.6
20.7
20.8
20.9
21. Size Exclusion Chromatography (SEC)
Martin
21.1
21.2
21.3
21.5
21.6
21.7
21.8
21.9
21.4.1
21.4.2 Group Separation—Large Proteins
21.4.3 Group Separation—Virus
21.4.4 Fractionation—Monoclonal
23. Filtration Methods for Use in Purification Processes (Concentration and Buffer Exchange)
Jakob Liderfelt, Jonathan Royce 23.1
23.4.3
Section V
Bioprocessing Equipment
24. Upstream Processing Equipment
Kenneth P. Clapp, Andreas Castan, Eva K. Lindskog
24.1 Introduction
24.2 Common Design Aspects in Bioprocessing Equipment
24.2.1 Process-Contacting Components
24.2.2 Nonprocess Contacting
22. Reversed Phase Chromatography
Kjell O. Eriksson
22.1
24.3.1 General Design Principles
24.3.2 Gas and Liquid Management
24.3.3 Mechanical Design
24.4.1 Stainless-Steel Bioreactors 468
24.4.2 Autoclavable Glass Bioreactors 468
24.4.3 Single-Use Stirred Tank Reactors 469
24.4.4 Rocking Bioreactors 470
24.5 Vessels for Adherent Processes 471
24.5.1
24.5.2 Packed-Bed Reactors
24.5.3 Bioreactors for Microcarrier Culture 473
24.6 High-Throughput Process Development Bioreactors 474
24.7 Modeling and Simulation 475 References 476
25. Downstream Processing Equipment
Mikael I. Johansson, Martin Östling, Günter Jagschies
25.1 Introduction 477
25.2 Critical Aspects of the User Requirement Specification 478
25.2.1 Chemical Compatibility and Hygienic Aspects 478
25.2.2 Hygienic Design and Cleaning 480
25.3 Common Components in Equipment for Bioprocessing 481
25.3.1 Monitors, Meters, and Sensors 481
25.3.2 UV Monitoring 481
25.3.3 Conductivity Monitoring 481
25.3.4 pH Monitoring 482
25.3.5 Temperature 482
25.3.6 Flow Meters 482
25.3.7 Air Sensors and Air Traps 482
25.3.8 Pressure Sensor 483
25.4 System Flow Path 483
25.4.1 General Design Criteria for Flow Paths 484
25.4.2 Sloped Pipes 484
25.5 Pumps 484
25.5.1 Pulsations 485
25.5.2 Suction Lines to the Pump 485
25.5.3 Cavitation 485
25.5.4 Pump Types 486
25.6 Valves 487
25.6.1 Valve Characteristics 488
25.6.2 Valve Details 488
25.7 In-Line Filtration (Sterile Filtration and Particle Filtration) 489
25.8 Engineering Documents 490
25.8.1 Process Flow Diagrams and P&I Diagrams 490 References 492
26. Chromatography Columns
Klaus Gebauer, Johan Tschöp
26.1 Introduction 493
26.1.1 Application Requirements 493
26.2 Column Design 493
26.2.1 Column Types 493
26.2.2 Mechanical Design 496
26.2.3 Design for Chromatographic Performance 497
26.3 Column Packing 502
26.3.1 General Considerations for Column Packing 503
26.3.2 Packing Methods 505
26.3.3 Preparation of Column and System for Packing 507
26.4 Assessing Column Performance: Efficiency Testing 508
26.4.1 Pulse Method 509
26.4.2 Step Method 510
26.5 Conclusions and Outlook 510 References 511
27. Simplification of Buffer Formulation and Improvement of Buffer Control with In-Line Conditioning (IC)
Enrique N. Carredano, Roger Nordberg, Susanne Westin, Karolina Busson, Tomas M. Karlsson, Torbjörn S. Blank, Henrik Sandegren, Günter Jagschies
27.1 Introduction 513
27.2 Buffers for Downstream Processing 513
27.2.1 Basic Buffer Specifications 514
27.2.2 Buffer Calculations 514
27.3 In-Line Dilution (ILD)—Addressing the Footprint Issue 517
27.4 In-Line Conditioning—Controlled Production of Any Buffer 518
27.4.1 IC System Layout 519
27.4.2 IC Control Modes 519
27.5 Testing and Verifying the IC Buffer Preparation Capabilities 520
27.5.1 Variable Input and Reproducibility 520
27.5.2 Gradient Delivery 521
27.5.3 Model Albumin Process 522
27.5.4 Model Monoclonal Antibody Process 523
27.6 Straight-Through Processing (STP), an Extension of IC Use 524 Acknowledgments 525 References 525 Further Reading 525
28. Continuous Capture of mAbs— Points to Consider and Case Studies
Günter Jagschies
28.1 Introduction 527
28.2 The Rationale for Continuous Processing in Biopharma 528
28.2.1 Upstream Process 528
28.2.2 Purification Process 529
28.3 Technical Options for Continuous Purification 530
28.3.1 Utilization of Resin Capacity 530
28.3.2 Parallel Execution of Load and Turnaround Cycles 532
28.4 Systems for Continuous Purification 534
28.4.1 Overview of the Commercial Offering for SMB/PCC Systems in Biopharma 534
28.4.2 Aspects of Column Selection for PCC or SMB Systems 536
28.4.3 PAT Approach to Process Control in Periodic CounterCurrent Chromatography 537
28.5 Process Development Guidance 540
28.5.1 Manufacturing Scenario and Objective 540
28.5.2 Key Information to be Developed for PCC 540
28.6 Case Studies—Capture and Polishing 544
28.6.1 Capture—PCC to Increase Chromatography Media Capacity Utilization 544
28.6.2 Polishing Steps Using StraightThrough Processing 546
28.7 Selected Economic Considerations 548
28.7.1 Management Review 548
28.7.2 Points to Consider in Financial Comparisons 549
28.7.3 Example Calculations 550
28.7.4 Summary—Putting Things in Perspective 553
28.8 Acknowledgments 554 References 555
29. Single Use Technology and Equipment
Parrish M. Galliher
29.1 Introduction 557
29.1.1 History of Bioprocessing— 1970–80s 557
29.1.2 Industry Drivers and Developing Trends—1990–2010 557
29.1.3 Perfect Storm: Industry Pressures, Changing Markets, and New Technologies 558
29.1.4 Cost, Quality, Speed, Flexibility—Agile and Flexible Single-Use Manufacturing 558
29.1.5 Single Use Technologies Evolving From Support Systems to Production Systems 559
29.1.6 Increasing Need for Flexibility, Agility and Economy— Increased Drug Diversity and Emerging Markets 559
29.1.7 Maturation From Development to GMP Clinical and Commercial Manufacturing 560
29.2 Overview of Single Use Technologies 561
29.2.1 Long History of Use of Plastics in the Medical Field and Stainless Steel Biomanufacturing Facilities 561
29.2.2 Potential Toxicity and Effects of Leachables From Polymeric Materials on Cells and Product 561
29.2.3 Best Practices for Qualification and Use of Single-Use Technologies 562
29.2.4 Regulatory Agency Guidelines for Validation of Extractables and Leachables From SingleUse Technologies 562
29.2.5 Leachables in Manufacturing—Risk Assessment of Potential Product Exposure 563
29.2.6 Leachables in the Upstream Process—Risk Assessment and Mitigation 563
29.2.7 Leachables in the Downstream Process—Risk Assessment and Mitigation 563
29.2.8 Mitigation of Overall Risk—Produce the Toxicological Batches in Small Scale Single Use Systems 564
29.2.9 Commercial Licensure Viability of Single Use Technologies 564
29.2.10 Broad Impact on Operations, Flexibility, Agility, Process Economics, Product Quality and the Environment 565
29.3 Single Use Material of Construction, Componentry, Assembly, Sterilization, Integrity and Use 566
29.3.1 Materials of Construction and Assembly 566
29.3.2 Sterilization of Single-use Films and Components 566
29.3.3 Assurance of Single-Use Bag and Assembly Integrity 566
35.2.2 Economic Cost Analysis of Single-Use Technology 722
35.3 Designing and Implementing a SingleUse Technology Process 725
35.3.1 Creating a Single-Use Technology Based Process 725
35.3.2 Basis of Process Design and Equipment Selection 726
35.3.3 Regulatory Requirements for SUT Implementation 726
35.3.4 Process Architecture and the Control Strategy for Maintaining Product Quality 726
35.3.5 End User Expectations of SUT Suppliers 728
35.3.6 Extractable & Leachables of SUT 729
35.3.7 Particulate Matter With SUT 730
35.3.8 Standards for Single-Use Technology 730
35.3.9 Securing the Single-Use Technology Supply Chain and Change Control 731
35.3.10 Single-Use Technology Reliability and Improvement 731
35.3.11 Biosafety Applications 733
35.4 Case Studies of Next Generation Processes Enabled by SUT 733
35.4.1 Vaccine Manufacturing 733
35.4.2 Monoclonal Antibody Production 736
35.5 Future State Summary 738 Acknowledgments 738 References 738
36. Points to Consider for Design and Control of Continuous Bioprocessing
Oliver Kaltenbrunner
36.1 Introduction 741
36.2 Development and Implementation 742
36.3 Design of Unit Operations 743
36.3.1 Production Cell Culture 743
36.3.2 Continuous Cycling Capture Chromatography 744
36.3.3 Virus Inactivation 746
36.3.4 Continuous Polishing Chromatography 747
36.3.5 Virus Filtration 747
36.3.6 Continuous Concentration and Formulation 748
36.4 Integration of Unit Operations 749
36.4.1 Bioburden Control 749
36.4.2 Equipment and Plant Utilization 749
36.4.3 Fault Recovery 750
36.4.4 Disposable Equipment and Devices 751
36.4.5 Right-Sizing Batch Size and Lot Size 751
36.5 Summary 752 References 752
37. Perfusion N-1 Culture— Opportunities for Process Intensification
John M. Woodgate
37.1 Introduction 755
37.2 N-1 Perfusion Seed Culture 756
37.3 Available Technology 757
37.4 Bioreactor Types 757
37.4.1 Rocking Bioreactors 757
37.4.2 Stirred Bioreactors 758
37.5 Perfusion Filtration Systems 759
37.5.1 Floating Filter 759
37.5.2 Alternating Flow Filtration (ATF) 759
37.5.3 Tangential Flow Filtration (TFF) 761
37.5.4 Equipment Conclusions 761
37.6 Process
37.6.1
37.6.2
37.7
37.8
38. Process Development and Intensification for a Recombinant Protein Expressed in E.coli
Shuang Chen, William B. Wellborn, John T. Cundy, Ratish Mangalath-Illam, Scott A. Cook, Matthew J. Stork, Joseph P. Martin, Maire H. Caparon, Stephen E. Sobacke, Sriram Srinivasan, Joost P. Quaadgras
38.1 Introduction
38.2 Microbial (E. coli) Expression System and Culture Process Overview
38.3 Cell Line Development
38.4 Culture Process Development and Optimization
38.5 Microbial (E. coli) Downstream Process Overview
38.6 The Baseline Downstream Process and Process Intensification Goals
38.7 Downstream Process Intensification and Improvement 776
38.7.1 IB Wash and Recovery 776
38.7.2 High Concentration High Efficiency Refolding 777
38.7.3 Clarification by Acid Precipitation 780
38.7.4 Chromatography Development: Increasing Throughput, Yield, and Improving HCP Removal 781
38.8 Summary 785
38.9 Materials and Methods 786
38.9.1 Materials 786
38.9.2 Methods 786 Acknowledgments 790 References 790
39. Next-Generation Process Design for Monoclonal Antibody Purification
Krunal K. Mehta, Ganesh Vedantham
39.1 Introduction 793
39.2 Current Practices and Emerging Process Alternatives for Downstream Unit Operations 794
39.2.1 Harvest Recovery 795
39.2.2 Capture Step 799
39.2.3 Viral Inactivation and Depth Filtration 801
39.2.4 Polishing Step 802
39.3 Enabling Technologies for NextGeneration Manufacturing Facilities 805
39.3.1 Single-Use Technology 805
39.3.2 Continuous Processing 805
39.3.3 Process Analytical Technology (PAT) 806
39.4 Concluding Remarks 807 Acknowledgments 808 References 808
40. Process Development and Manufacturing of Antibody-Drug Conjugates
Matt H. Hutchinson, Rachel S. Hendricks, Xin Xin Lin, Dana A. Olsson
40.1 Introduction 813
40.1.1 Design of an ADC 814
40.2 Process Development and Manufacturing Considerations 816
40.2.1 ADC Quality Attributes 816
40.2.2 ADC Process Overview 816
40.2.3 ADC Conjugation Process 819
40.3 ADC Conjugation Equipment 832
40.3.1 Conjugation Scale-Down Model 832
40.3.2 GMP Manufacturing 834 40.4 Conclusions 834 References 834
41. Process Design for Bispecific Antibodies
Ambrose J. Williams, Glen S. Giese, Andreas Schaubmar, Thomas von Hirschheydt
41.1 Introduction 837
41.1.1 Evolution of Next-Generation Formats 837
41.1.2 Clinical Applications for Bispecifics 837
41.1.3 Bispecific Formats 838
41.1.4 Knob-Hole Assembly Approach 839
41.1.5 CrossMab Bispecific Approach 840
41.2 Process Designs for Bispecific Antibodies 841
41.2.1 In Vitro Assembly of Individually Expressed Knob and Hole Half-Antibodies 841
41.2.2 Process Development for Knob and Hole Bispecifics 846
41.2.3 Process Development for CrossMabs 848
41.3 Conclusion 854 References 854
42. Current Manufacturing of Human Plasma Immunoglobulin G
Andrea Buchacher, John M. Curling
42.1 Introduction 857
42.2 Plasma Fractionation Technologies 858
42.2.1 Ethanol Fractionation 858
42.2.2 Caprylate Fractionation 862
42.2.3 Polyethylene Glycol Fractionation 862
42.2.4 Chromatographic Fractionation 862
42.2.5 Current Hybrid Methods of Plasma Fractionation 863
42.3 Processing Technologies to Assure Viral Safety 864
42.3.1 Solvent/Detergent Treatment 864
42.3.2 Caprylate Treatment 864
42.3.3 Pasteurization 864
42.3.4 Nanofiltration (Viral Filtration) 864
42.3.5 Chromatography 865
47.5 Analytical Support of Process Development 1034
47.5.1 Introduction 1034
47.5.2 Improving Developability During Sequence Selection 1034
47.5.3 Analytical Support of Cell Line Development 1035
47.5.4 Analytical Support of Upstream Processing 1039
47.5.5 Analytical Support of Downstream Processing 1041
47.5.6 Feasibility of In-Line/At-Line Monitoring and Real Time Control 1042
47.6 Cost of Operating a Modern, HighThroughput Analytical Laboratory 1043
47.6.1 Typical Cost of Automated/ High Resolution Analytical Instrumentation 1043
47.6.2 Typical Cost of Analytical Full Time Employees (FTE) 1045
47.6.3 Estimated Cost of Performing Analytics for Drug Substance/ Drug Product Manufacturing Support 1045 References 1047
48. Implementation of QbD for Manufacturing of Biologics—Has It Met the Expectations?
Anurag S. Rathore, Sumit K. Singh, Jashwant Kumar, Gautam Kapoor
48.1 Introduction 1052
48.2 What is QbD? 1052
48.3 Framework for Assessing the Benefits of QbD Application in Manufacturing of Biologics 1053
48.4 Impact of QbD on Biopharmaceutical Life Cycle 1054
48.4.1 Molecule Selection 1054
48.4.2 Process Development and Characterization 1056
48.4.3 Evaluation of Safety and Efficacy of a Biologic 1062
48.4.4 Technology Transfer 1066
48.4.5 Marketing Application and Commercial Production 1067
48.4.6 Role of Knowledge Management in QbD Implementation 1067
48.5 Summary 1068 Acknowledgments 1069 References 1069 Further Reading 1073
49. Pathogen Safety
Albrecht Gröner
49.1 Introduction 1075
49.2 Raw Material 1077
49.2.1 Selection and Testing of Raw Material 1078
49.3 Starting Material 1078
49.3.1 Testing and Release of Starting Material 1078
49.3.2 Human Derived Starting Material 1079
49.3.3 Cell Culture 1080
49.3.4 Animal Derived Material 1084
49.4 Capacity of the Manufacturing Process to Inactivate and Remove Pathogens 1084
49.4.1 Principle of Virus Validation 1085
49.4.2 Product Specific Requirements Regarding Virus Validation 1088
49.4.3 Advanced Therapy Medicinal Products 1092
49.5 Transmissible Spongiform Encephalopathy 1093
49.5.1 TSE and Starting/Raw Materials 1093
49.5.2 Removal and Inactivation of TSE Agent by the Manufacturing Process of Biologicals 1094
49.6 Cleaning and Sanitization of Equipment and Material 1094
49.7 Assessment of Risk of Virus Transmission 1095
49.8 Conclusion 1097 Glossary 1100 References 1101
50. Chemistry, Manufacture and Control
Kim R. Hejnaes, Tom C. Ransohoff
50.1 Introduction 1105
50.2 Part A: Planning 1106
50.2.1 Introduction 1106
50.2.2 Target Product Profile 1107
50.2.3 Drug Product Profile 1107
50.2.4 Drug Substance Profile 1107
50.2.5 Target Protein Profile 1107
50.2.6 Expression Systems 1108
50.2.7 Process Design 1110
50.2.8 Quality 1111
50.2.9 Safety 1115
50.2.10 Freedom to Operate 1115
50.2.11 Timelines 1115
50.2.12 Project Plan 1116
50.2.13 Master Validation Plan 1116
50.2.14 Cost of Goods Sold 1116
50.3 Part B: Tech Transfer 1116
50.3.1 Description 1116
50.3.2 GAP Analysis 1117
50.3.3 Risk Profile for Project Execution 1117
50.4 Part C: Execution 1118
50.4.1 Introduction 1118
50.4.2 Specifications 1119
50.4.3 Analytical Support and Validation 1120
50.4.4 Reference Standards 1120
50.4.5 Cell Line Development 1122
50.4.6 Cell Banks 1122
50.4.7 Process Development 1123
50.4.8 Formulation Development 1124
50.4.9 Scale-Up 1125
50.4.10 GMP Manufacture 1127
50.4.11 Quality Control 1128
50.4.12 Stability Studies 1129
50.4.13 Virus Reduction 1129
50.4.14 Validation 1130
50.4.15 Documentation 1131
50.5 Part D: Common Technical Document 1133 Glossary 1134 References 1135
51. Post-Licensure Purification Process Improvements for Therapeutic Antibodies: Current and Future States
Brian D. Kelley, Annika Kleinjans, Philip Lester
51.1 Introduction 1137
51.2 History and Current Status of Therapeutic mAb Production and Purification 1137
51.2.1 Cohn Fractionation for IgIV 1137
51.2.2 First Generation Processes for mAbs 1138
51.2.3 Platform Processing Evolution and Current Status 1138
51.3 Strategies of Post-Licensure Changes 1138
51.3.1 Examples of Drivers for PostLicensure Changes 1138
51.3.2 Regulatory Considerations 1139
51.3.3 Platform Evolution 1140
51.3.4 Virus Removal and Inactivation 1140
51.3.5 Costs 1141
51.4 Case Studies 1142
51.4.1 Genentech mAbs (Licensed Before 2005): Rituxan, Herceptin, Xolair, Raptiva, Avastin 1142
51.4.2 Remicade 1144
51.4.3 Enbrel 1144
51.4.4 Humira 1144
51.4.5 Gazyva 1145
51.5 Future Embodiments and Options 1145
51.5.1 New Platforms: Evolution or Revolution? 1145
51.5.2 Detergent Inactivation 1146
51.5.3 Dual-Sourced Resins & Membranes 1146
51.5.4 Unrealized Potential: Precipitation, Crystallization, Membrane Adsorbers 1146
51.5.5 Factories of the Future 1147
51.5.6 Continuous Processing 1147
51.6 Conclusions 1148 Acknowledgments 1148 References 1148
52. Navigating the Regulatory Maze Upon Process Changes
E. Morrey Atkinson, Michael A. Rubacha
52.1 Introduction: What is Fragmentation? 1151
52.2 Why Changes Happen: The Business Case for Changes to Approved Processes 1151
52.3 Lack of Common Practice: Impact of Divergent Regulations 1153
52.4 A Call to Action: Against Future Fragmentation 1155 References 1156 Further Reading 1157
53. Security of Bioprocess Consumables Supply
Jeffrey R. Carter, Daniel Nelson, David G. Westman
53.1 Introduction 1159
53.2 Material and Product Selection 1160
53.3 Supplier Selection 1160
53.4 Risk Management 1163
53.4.1 Supplier Auditing 1163
53.4.2 Multi-Sourcing 1163
53.4.3 Manufacturing Facility Risk 1165
53.4.4 Supplier Agreements 1167
53.5 Communication 1167
53.6 Conclusion 1168 References 1168
Section IX
Financial Management and Process Economics
54. Basics of Financial Management
Brian Montgomery
54.1 Finance Management Principles & Terminology 1171
54.2 Financial Goals and Objectives of Business Enterprises 1171
Rolf A. Hjorth (269,675), CERVUS Biotech Consulting, Uppsala, Sweden; rolf@cervusbiotech.se
Geoff Hodge (987), Unum Therapeutics, Cambridge, MA, United States; geoff.hodge@unumrx.com
Matt H. Hutchinson (813), Genentech Inc., South San Francisco, CA, United States; hutchinson.matthew@ gene.com
Günter Jagschies (3,33,59,73,207,221,241,477,513,527,1191, 1227,1233,1237), GE Healthcare Life Sciences, Freiburg im Breisgau, Germany; jagschies@gmail.com
Michael J. Jenkins (899), University College London, London, United Kingdom; michael.jenkins@ucl.ac.uk
Mikael I. Johansson (477), GE Healthcare Life Sciences, Uppsala, Sweden; mikael.i.johansson@ge.com
John Joseph (637,933), GE Healthcare Lifesciences, Amersham; GE Healthcare, Little Chalfond, United Kingdom; johnjoseph@ge.com
Oliver Kaltenbrunner (741), Amgen, Thousand Oaks, CA, United States; oliverk@amgen.com
Gautam Kapoor (1051), Indian Institute of Technology, New Delhi, India
Tomas M. Karlsson (513), GE Healthcare Life Sciences, Uppsala, Sweden; tomas.m.karlsson@ge.com
Brian D. Kelley (1137), Genentech, South San Francisco, CA, United States; bkelley@vir.bio
Annika Kleinjans (1137), Roche, Penzberg, Germany; annika.kleinjans@roche.com
Jashwant Kumar (1051), Indian Institute of Technology, New Delhi, India
Karol M. Łącki (73,207,221,241,319,637), VP Technology Development, Avitide, Inc., United States (formerly at Karol Lacki Consulting AB, Höllviken, Sweden); k.lacki@icloud.com
Philip Lester (1137), Genentech, South San Francisco, CA, United States; lester.phillip@gene.com
Jakob Liderfelt (279,295,441), GE Healthcare Life Sciences, Uppsala, Sweden; jakob.liderfelt@ge.com
Xin Xin Lin (813), Genentech Inc., South San Francisco, CA, United States; lin.xin-xin@gene.com
Eva K. Lindskog (97,111,457,625), Lonza Pharma & Biotech, Basel, Switzerland; eva.lindskog@lonza.com
Mats Lundgren (147,877), GE Healthcare, Life Sciences, Uppsala, Sweden; MatsLundgren@ge.com
Ratish Mangalath-Illam (769), Pfizer Inc., Chesterfield, MO, United States; ratish.krishnan@pfizer.com
Trevor J. Marshall (579), Zenith Technologies, Dublin, Ireland; Trevor.Marshall@zenithtechnologies.com
Joseph P. Martin (769), Pfizer Inc., Chesterfield, MO, United States; joseph.p.martin@pfizer.com
Krunal K. Mehta (793), Bioprocess Sciences and Technology, Amgen, Cambridge, MA, United States; kmehta@amgen.com
Brian Montgomery (1171), GE Healthcare, Chicago, IL, United States; brian.c.montgomery@ge.com
Daniel Nelson (1159), GE Healthcare Life Sciences, Marlborough, MA, United States; daniel.nelson@ge.com
Roger Nordberg (513), GE Healthcare Life Sciences, Uppsala, Sweden; roger.nordberg@ge.com
Dana A. Olsson (813), Genentech Inc., South San Francisco, CA, United States; olson.dana@gene.com
Martin Östling (477), Martin Östling Konsult AB, Uppsala, Sweden; jagschies@gmail.com
John P. Pieracci (165), Biogen Inc., Cambridge; Visterra Inc., Cambridge, MA, United States; john.pierracci@ biogen.com
David J. Pollard (721), Merck & Co., Inc., Kenilworth, NJ, United States; david_pollard@merck.com
Alain Pralong (721), Pharma-Consulting ENABLE GmbH, Solothurn, Switzerland; alain.pralong@yahoo.com
Hari Pujar (877), Moderna Therapeutics, Cambridge, MA, United States; hari.pujar@modernatx.com
Joost P. Quaadgras (769), Pfizer Inc., Chesterfield, MO, United States; joost.p.quaadgras@pfizer.com
Tom C. Ransohoff (1105), BioProcess Technology Consultants, Inc., Woburn, MA, United States; transohoff@bptc.com
Anurag S. Rathore (1051), Indian Institute of Technology, New Delhi, India; asrathore@biotechcmz.com
Craig Robinson (295), GE Healthcare Life Sciences, Westborough MA, United States; jagschies@gmail.com
Jonathan Royce (279,295,441), GE Healthcare Life Sciences, Uppsala, Sweden; jonathan.royce@ge.com
Michael A. Rubacha (1151), Bristol-Myers Squibb, East Syracuse, NY, United States; michael.rubacha@bms.com
Henrik Sandegren (513), GE Healthcare Life Sciences, Uppsala, Sweden; henrik.sandegren@ge.com
Andreas Schaubmar (837), Large Molecule Research, Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany; andreas.schaubmar@roche.com
Patrick Schulz (111,131), Boehringer Ingelheim, Biberach, Germany; patrick_1.schulz@boehringeringelheim.com
Sumit K. Singh (1051), Indian Institute of Technology, New Delhi, India
Stephen E. Sobacke (769), Pfizer Inc., Chesterfield, MO, United States; stephen.e.sobacke@pfizer.com
Sriram Srinivasan (769), Pfizer Inc., Chesterfield, MO, United States; sriram.srinivasan@pfizer.com
Matthew J. Stork (769), Pfizer Inc., Chesterfield, MO, United States; Matthew.Stork@pfizer.com
Bruce S. Tangarone (1001), Shire, Lexington, MA, United States; btangarone@shire.com
Jorg Thommes (165), Biogen Inc., Cambridge; Visterra Inc., Cambridge, MA, United States; jthommes@ VISTERRAINC.COM
Matthew J. Traylor (1001), Shire, Lexington, MA, United States; mtraylor@shire.com
Johan Tschöp (493), GE Healthcare Life Sciences, Uppsala, Sweden; johan.tschop@ge.com
James M. Van Alstine (207,221,241), JMVA Biotech AB; Royal Institute of Technology, Stockholm, Sweden; jim. vanalstine@telia.com
Johnson Varghese (1001), Shire, Lexington, MA; Celgene, Summit, NJ, United States; jsvarg@gmail.com
Ganesh Vedantham (793), Drug Substance Process Development, Amgen Manufacturing Ltd., Juncos, Puerto Rico; vedanthg@amgen.com
Thomas von Hirschheydt (837), Large Molecule Research, Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany
William B. Wellborn (769), Pfizer Inc., Chesterfield, MO, United States; william.wellborn@pfizer.com
Till Wenger (111,131), Boehringer Ingelheim, Biberach, Germany; till.wenger@boehringer-ingelheim.com
Susanne Westin (513), GE Healthcare Life Sciences, Uppsala, Sweden; susanne.westin@ge.com
David G. Westman (1159), GE Healthcare Life Sciences, Uppsala, Sweden; David.Westman@ge.com
Matthew Westoby (165), Biogen Inc., Cambridge; Visterra Inc., Cambridge, MA, United States; matthew. westoby@biogen.com
William G. Whitford (147), GE Healthcare, Bioprocess, Logan, UT, United States; Bill.Whitford@ge.com
Ambrose J. Williams (837), Purification Development, Pharma Technical Development, Genentech (Roche), South San Francisco, CA, United States; williams. ambrose@gene.com
John M. Woodgate (755), GE Healthcare Life Sciences, Marlborough, MA, USA; john.woodgate@ge.com
