Bioprocessing for Cell-Based Therapies (eBook)

Che J. Connon (Herausgeber)

eBook Download: PDF

2017
John Wiley & Sons (Verlag)
978-1-118-74339-3 (ISBN)

Infos

With contributions from leading, international academics and industrial practitioners, Bioprocessing for Cell-Based Therapies explores the very latest techniques and guidelines in bioprocess production to meet safety, regulatory and ethical requirements, for the production of therapeutic cells, including stem cells.

• An authoritative, cutting-edge handbook on bioprocessing for the production of therapeutic cells with extensive illustrations in full colour throughout
• An authoritative, cutting-edge handbook on bioprocessing for the production of therapeutic cells with extensive illustrations in full colour throughout
• In depth discussion of the application of cell therapy including methods used in the delivery of cells to the patient
• Includes contributions from experts in both academia and industry, combining a practical approach with cutting edge research
• The only handbook currently available to provide a state of the art guide to Bioprocessing covering the complete range of cell-based therapies, from experts in academia and industry

Che Connon, is Professor of Tissue Engineering at the Institute of Genetic Medicine, University of Newcastle upon Tyne, UK; he is also a member of the Bioprocessing Research Industry Club (supported by the BBSRC and EPSRC). His research focuses on seeking to engineer functional replacement and temporary 'bridge' tissues using a modular approach while also developing model systems to study physiological and pathophysiological corneal tissue formation. He is the author of Corneal Regenerative Medicine (with Bernice Wright, 2013) and Hydrogels in Cell-Based Therapies (with Ian W Hamley, 2014), as well as numerous research papers.

Inhalt

Cover 1
Title Page 5
Copyright 6
Contents 7
List of Contributors 13
Preface 17
Chapter 1 Overview of the Cell Therapy Field 19
1.1 The Context of Cell Therapies and Their Manufacturing Challenges 19
1.1.1 Regulation of Cell Therapies 22
1.1.2 Manufacturing Challenges in Cell Therapy 23
1.2 The Cell Therapy Landscape 23
1.2.1 Licensed Cell Therapy Products 25
1.2.2 Companies, Clinicians, Products and Procedures 26
1.2.3 Cell Therapy Clinical Trials 26
1.3 Operations in Cell Therapy Manufacture 29
1.3.1 Cells for Cell Therapy Production 30
1.4 Upstream Processing of Cellular Therapies 31
1.4.1 Cell Separation 31
1.4.2 Cell Expansion 31
1.4.3 Tissue Expansion 33
1.4.4 Adherent Cell Expansion 33
1.4.5 Suspension Cell Expansion 36
1.4.6 Differentiation 37
1.5 Downstream Processing of Cellular Therapies 38
1.5.1 Harvest, Washing and Concentration 38
1.5.2 Separation and Purification 40
1.6 Formulation, Fill and Finish of Cellular Therapies 42
1.6.1 Formulation 43
1.6.2 Fill and Finish 43
1.6.3 Preservation and Shipment 44
1.7 Administration of the Cell Therapy to a Patient 45
1.8 Cell Therapy Manufacturing Facilities of the Future 46
1.8.1 Factory of the Future Requirements 49
1.9 Conclusion 49
References 50
Chapter 2 Structured Methodology for Process Development in Scalable Stirred Tank Bioreactors Platforms 53
2.1 Introduction 53
2.2 Understanding the Engineering of the Stirred Tank Bioreactors 54
2.2.1 Mixing Phenomena in Stirred Tank Bioreactors 55
2.2.2 Understanding Oxygen Transfer Rate (kLa) with Different Sparging Methodologies 58
2.2.3 Heat Transfer in STB (Minimum Volume, Sensor/Sensing Control) 60
2.2.4 How to Choose a Microcarrier for Adherent Cells (hMSCs) 61
2.3 Understanding the Biology of the Cells in Stirred Tank Bioreactors (STB) 63
2.3.1 Cell Types (Adherent and Suspension Cells) 63
2.3.2 Assays for Comparability, Nutrients, Senescence and Doubling Dime 64
2.4 Process Development of Adherent Cells in STB Platforms 65
2.4.1 Standard Comparison to Cell Factory 65
2.4.2 Methodology for Screening of Microcarriers 67
2.4.3 Process Development in Small?scale Bioreactors (3L) 68
2.4.4 Process Development in Medium?scale Bioreactors (50L) 73
2.4.5 Case Study for Expansion of Bone Marrow Derived MSCs in Stirred Tank Bioreactors 77
2.5 Future Directions 78
References 79
Chapter 3 The Effect of Scale-up on Cell Phenotype: Comparability Testing to Optimize Bioreactor Usage and Manufacturing Strategies 83
3.1 Introduction 83
3.1.1 Cell Characterization in the Development Path 84
3.1.2 The MultiStem® Allogeneic Cell Therapy Product: Mechanisms of Benefit and Target Cells Numbers 87
3.2 Challenges in Cell Product Development 90
3.2.1 Effect of Large-scale Expansion on Stem Cell Properties 90
3.2.2 Serum-free and Xeno-free Media Development 92
3.3 Stem Cell Characterization 93
3.3.1 ISCT Requirements 93
3.3.2 Potency Assays 95
3.3.3 Omics Screens for Therapeutic Stem Cell Characterization 96
3.4 Next-generation Stem Cell Development 98
References 101
Chapter 4 The Scale-up of Human Mesenchymal Stem Cell Expansion and Recovery 109
4.1 Introduction 109
4.2 Scale-up or Scale-out 111
4.3 Understanding the Small Scale 114
4.4 Microcarrier Screening 121
4.5 Spinner Flask Culture 126
4.6 Large-scale Expansion in Conventional Stirred Tank Bioreactors 129
4.7 Cell Recovery from Microcarriers 135
4.8 Conclusions 138
References 139
Chapter 5 Challenges of Scale-up of Cell Separation and Purification Techniques 145
5.1 Introduction 145
5.1.1 Cell Separation for Cell-based Therapeutics 145
5.1.2 Separation Methodology Design 146
5.1.3 Objective of this Chapter 146
5.2 Scalable Cell Separation for Cell Therapy 148
5.2.1 Label Requiring versus Label-free Separation 148
5.2.2 Active versus Passive Method 151
5.2.3 Isolated Purification (Including Off-the-Shelf) versus Embedded Integrated Process 151
5.2.4 Low versus High Resolution 151
5.2.5 Open versus Closed Systems 152
5.2.6 Batch versus Continuous Separation 152
5.3 Currently Developed Cell Separation Techniques 153
5.3.1 Acoustophoresis 153
5.3.2 Aqueous Two-Phase System (ATPS) 155
5.3.3 Centrifugal Techniques 156
5.3.4 Dielectrophoresis (DEP) 158
5.3.5 Deterministic Lateral Displacement (DLD) 159
5.3.6 Genetic Engineering 159
5.3.7 Hydrodynamic Filtration (HDF) 160
5.3.8 Immunoadsorption 160
5.3.9 Immunomagnetic Cell Sorting 163
5.3.10 Inertial Migration 163
5.3.11 Magnetic Cell Sorting – Label-free 165
5.3.12 Microscale Vortices 168
5.3.13 Normal Flow Filter (NFF) 168
5.3.14 Optical – Label-free 169
5.3.15 Tangential Flow Filters (TFF) 173
5.3.16 Weir and Pillar 174
5.4 Conclusion 175
Acknowledgements 177
References 177
Chapter 6 Fundamental Points to Consider in the Cryopreservation and Shipment of Cells for Human Application 185
6.1 Introduction 185
6.2 The Role of Cryoprotective Agents (CPA) 186
6.3 Vitrification versus Cryopreservation 187
6.4 Points to Consider in the Development of Cryopreservation Protocols 187
6.4.1 General Considerations 187
6.4.2 Cellular Characteristics and Selection of Appropriate CPAs and Cooling Protocols 188
6.4.3 Key Events in Cryopreservation 190
6.5 Large-volume Freezing 196
6.6 Cryopreservation as Part of Manufacturing Processes 197
6.6.1 Containers for Cryopreserved Cells 197
6.6.2 Controlled Rate Freezers and Storage Systems 197
6.6.3 The Cold-chain: Challenges and Solutions 198
6.6.4 Biobanking and Regulatory Requirements 199
6.7 Conclusions 199
Acknowledgements 200
References 200
Chapter 7 Short-term Storage of Cells for Application in Cell-based Therapies 205
7.1 Introduction 205
7.1.1 Advances in Cell-based Therapies 206
7.1.2 The Logistical Landscape for CTPs and the Requirement for Short-term Storage of Cells 206
7.2 Hypothermia and Mammalian Cell Storage 211
7.2.1 Hypothermic Storage of Mesenchymal Stem Cells (MSCs) 212
7.2.2 Optimal Temperature for Cell Storage 220
7.3 The Application of Hypothermic Storage in Cell-based Therapies 222
7.4 Concluding Remarks 223
References 223
Chapter 8 Cell Therapy in Practice 229
8.1 Introduction 229
8.2 The Classification of ATMPs 230
8.3 European Regulations 234
8.3.1 Hospital Exemption (HE) and “Specials” Manufacturing 237
8.3.2 Orphan Medicinal Product Designation 238
8.3.3 Committee for Advanced Therapies 239
8.3.4 Good Manufacturing Practice (GMP) 239
8.3.5 European Union Tissue and Cells Directives (EUTCD) 241
8.4 ATMP Case Study: Autologous Limbal Stem Cell Therapy: the Newcastle Experience 242
8.5 Conclusion 251
References 252
Index 255
EULA 273

Produkt-Details

• Erscheint lt. Verlag: 1.3.2017
• Sprache: englisch
• Themenwelt: Naturwissenschaften ► Biologie ► Mikrobiologie / Immunologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Technik ► Umwelttechnik / Biotechnologie
• Schlagworte: Bioengineering • Biomedical Science • biopharmaceuticals • Bioprocessing • Biowissenschaften • Cancer cells • Cell-based therapies • Cell Biology • Cell research • Cell Therapies & Tissue Engineering • Cell Therapy • cellular therapy • drug development • Industrial Biotechnology • Life Sciences • Medical Cell Biology • Medical Science • Medizin • Medizinische Zellbiologie • Molecular Biology • Stem Cell Bioprocessing • Stem Cells • Tissue engineering • Zelltherapien u. Tissue Engineering
• ISBN-10: 1-118-74339-3 / 1118743393
• ISBN-13: 978-1-118-74339-3 / 9781118743393