Description
Book SynopsisAuthoritative guide to the principles, characteristics, engineering aspects, economics, and applications of disposables in the manufacture of biopharmaceuticals
The revised and updated second edition of Single-Use Technology in Biopharmaceutical Manufacture offers a comprehensive examination of the most-commonly used disposables in the manufacture of biopharmaceuticals. The authorsnoted experts on the topicprovide the essential information on the principles, characteristics, engineering aspects, economics, and applications.
This authoritative guide contains the basic knowledge and information about disposable equipment. The author also discusses biopharmaceuticals' applications through the lens of case studies that clearly illustrate the role of manufacturing, quality assurance, and environmental influences. This updated second edition revises existing information with recent developments that have taken place since the first edition was published. The bo
Table of Contents
List of Contributors xvii
Preface xxi
Part I Basics 1
1 Single‐Use Equipment in Biopharmaceutical Manufacture: A Brief Introduction 3
Dieter Eibl and Regine Eibl
1.1 Background 3
1.2 Terminology and Features 3
1.3 Single‐Use Systems in Production Processes for Therapeutic Proteins such as mAbs: Product Overview and Classification 5
1.4 Single‐Use Production Facilities 7
1.5 Summary and Conclusions 7
Nomenclature 9
References 9
2 Types of Single‐Use Bag Systems and Integrity Testing Methods 13
Jens Rumsfeld and Regine Eibl
2.1 Introduction 13
2.2 Bags for Fluid and Powder Handling 13
2.3 Bag‐Handling and Container Systems 15
2.4 Single‐Use Bag Systems for Freezing and Thawing 18
2.5 Container Closure Integrity Testing 18
2.6 Summary and Conclusions 22
Nomenclature 22
References 22
3 Mixing Systems for Single‐Use 25
Sören Werner, Matthias Kraume, and Dieter Eibl
3.1 Introduction 25
3.2 The Mixing Process 25
3.3 Single‐Use Bag Mixing Systems 27
3.4 Summary and Conclusions 33
Nomenclature 33
References 33
4 Single‐Use Bioreactors – An Overview 37
Valentin Jossen, Regine Eibl, and Dieter Eibl
4.1 Introduction 37
4.2 SUB History 38
4.3 Comparison of the Current, Most Common SUB Types 40
4.4 Decision Criteria for Selection of the Most Suitable SUB Type 47
4.5 Summary and Future Trends 48
Nomenclature 48
References 48
5 Systems for Coupling and Sampling 53
Cedric Schirmer, Sebastian Rothe, Ernest Jenness, and Dieter Eibl
5.1 Introduction 53
5.2 Components of Single‐Use Transfer Lines 53
5.3 Systems for Aseptic Coupling 57
5.4 Aseptic Disconnection 62
5.5 Systems for Sampling 64
5.6 Summary and Conclusion 66
Nomenclature 66
References 66
6 Sensors for Disposable Bioreactor Systems 69
Tobias Steinwedel, Katharina Dahlmann, Dörte Solle, Thomas Scheper, Kenneth F. Reardon, and Frank Lammers
6.1 Introduction 69
6.2 Interfaces for Sensor Technology 70
6.3 Considerations of Extractables and Leachables from Integrated Sensors 71
6.4 Optical Chemosensors 72
6.5 Spectroscopic Sensors 73
6.6 Capacitance Sensors 75
6.7 Electrochemical Sensors 76
6.8 Biosensors 78
6.9 Conclusions and Outlook 78
Nomenclature 79
References 79
7 Bioinformatics and Single‐Use 83
Barbara A. Paldus
7.1 Introduction 83
7.2 Bioinformatics and Single‐Use 84
7.3 Smart Sensors 86
7.4 Intelligent Control Systems 87
7.5 Continuous Processing 88
7.6 Conclusions 92
Nomenclature 94
References 94
8 Production of Disposable Bags: A Manufacturer’s Report 95
Steven Vanhamel and Catherine Piton
8.1 Introduction 95
8.2 Materials 95
8.4 Bag Manufacturing 110
8.5 Summary and Conclusions 113
Nomenclature 115
References 116
9 Single‐Use Downstream Processing for Biopharmaceuticals: Current State and Trends 117
Britta Manser, Martin Glenz, and Marc Bisschops
9.1 Introduction 117
9.2 Single‐Use DSP Today 117
9.3 Technologies in Single-Use DSP 120
9.4 Single‐Use Continuous Downstream Processing 121
9.5 Integrated and Continuous DSP 124
9.6 Summary and Conclusions 124
Nomenclature 124
References 125
10 Application of Microporous Filtration in Single‐Use Systems 127
Christian Julien and Chuck Capron
10.1 Introduction 127
10.2 Microporous Filters 128
10.3 Filter Selection 134
10.4 Final Sterile Filtration 136
10.5 Filter Integrity Testing 138
10.6 Filter Qualification and Validation 139
10.7 Summary and Conclusions 140
Nomenclature 140
References 140
11 Extractables/Leachables from Single‐Use Equipment: Considerations from a (Bio) Pharmaceutical Manufacturer 143
Alicja Sobańtka and Christian Weiner
11.1 Introduction 143
11.2 Regulatory Environment 144
11.3 The (Bio)Pharmaceutical Manufacturer’s Approach 146
11.4 The (Bio)Pharmaceutical Manufacturer’s Challenges 153
11.5 Summary 155
11.6 Discussion and Outlook 156
Acknowledgments 156
Nomenclature 157
References 157
12 The Single‐Use Standardization 159
P.E. James Dean Vogel
12.1 Introduction 159
12.2 Alphabet Soup 159
12.3 History 161
12.4 Compare and Contrast 161
12.5 Collaboration and Alignment Lead to Standardization 162
12.6 General SUT Efforts 163
12.7 Leachables and Extractables 164
12.8 Particulates in SUT 164
12.9 Change Notification 165
12.10 SUT System Integrity 165
12.11 SUT User Requirements 165
12.12 Connectors 165
12.13 SUT Design Verification 165
12.14 Summary and Conclusions 166
Nomenclature 166
References 166
Further Reading 166
13 Environmental Impacts of Single‐Use Systems 169
William G. Whitford, Mark A. Petrich, and William P. Flanagan
13.1 Introduction 169
13.2 Sustainability 169
13.3 The Evolution of SU Technologies 169
13.4 Implications in Sustainability 172
13.5 LCA – A Holistic Methodology 172
13.6 LCA Applied to SU Technologies 173
13.7 Sustainability Efforts in the BioPharma Industry 175
13.8 End‐of‐Life (Waste) Management 177
13.9 Summary and Conclusions 178
Nomenclature 178
References 178
14 Design Considerations Towards an Intensified Single‐Use Facility 181
Gerben Zijlstra, Kai Touw, Michael Koch, and Miriam Monge
14.1 Introduction 181
14.2 Moving Towards Intensified and Continuous Processing 181
14.3 Methodologies for Continuous and Intensified Single‐Use Bioprocessing 183
14.4 Process Development for Intensified Biomanufacturing Facilities 184
14.5 The Intensified Biomanufacturing Facility 184
14.6 Process Automation for Commercial Manufacturing Facilities 187
14.7 Intensified Upstream Processing 187
14.8 Intensified Downstream Processing 189
14.9 Summary and Conclusions 191
Acknowledgments 191
Nomenclature 191
References 191
15 Single‐Use Technologies in Biopharmaceutical Manufacturing: A 10‐Year Review of Trends and the Future 193
Ronald A. Rader and Eric S. Langer
15.1 Introduction 193
15.2 Background 193
15.3 Methods 194
15.4 Results 194
15.5 Discussion 197
15.6 Conclusions 199
Nomenclature 200
References 200
Part II Application Reports and Case Studies 201
16 Single‐Use Process Platforms for Responsive and Cost‐Effective Manufacturing 203
Priyanka Gupta, Miriam Monge, Amelie Boulais, Nitin Chopra, and Nick Hutchinson
16.1 Introduction 203
16.2 Standardized Single‐Use Process Platforms for Biomanufacturing 204
16.3 Implementing Single‐Use Process Platforms 204
16.4 Economic Analysis Comparing Stainless Steel with Single‐Use Process Platforms 207
16.5 Summary and Conclusions 209
Nomenclature 209
References 210
17 Considerations on Performing Quality Risk Analysis for Production Processes with Single‐Use Systems 211
Ina Pahl, Armin Hauk, Lydia Schosser, and Sonja von Orlikowski
17.1 Introduction 211
17.2 Quality Risk Assessment 211
17.3 Terminology and Features 212
17.4 Current Industrial Approach for Leachable Assessment in Biopharmaceutical Processes 212
17.5 Holistic Approach to Predict Leachables for Quality Risk Assessment 214
17.6 Summary and Conclusions 215
Nomenclature 217
References 217
18 How to Assure Robustness, Sterility, and Performance of Single‐Use Systems: A Quality Approach from the Manufacturer’s Perspective 219
Simone Biel and Sara Bell
18.1 Introduction 219
18.2 Component Qualification 219
18.3 Validation of Product Design 220
18.4 Manufacturing and Control 224
18.5 Operator Training, Performance Culture 225
18.6 Particulate Risk Mitigation 225
18.7 Change Management 225
18.8 Summary and Conclusions 226
Nomenclature 227
References 227
19 How to Design and Qualify an Improved Film for Storage and Bioreactor Bags 229
Lucie Delaunay, Elke Jurkiewicz, Gerhard Greller, and Magali Barbaroux
19.1 Introduction229
19.2 Materials, Process, and Suppliers Selection 229
19.3 Biological Properties 229
19.4 Specifications and Process Design Space 231
19.5 Process Control Strategy 233
19.6 Summary and Conclusions 233
Nomenclature 233
References 233
20 An Approach for Rapid Manufacture and Qualification of a Single‐Use Bioreactor Prototype 235
Stephan C. Kaiser
20.1 Introduction 235
20.2 About the Development Process of a Single‐Use Bioreactor 235
20.3 Summary and Conclusions 243
Nomenclature 244
References 244
21 Single‐Use Bioreactor Platform for Microbial Fermentation 247
Parrish M. Galliher, Patrick Guertin, Ken Clapp, Colin Tuohey, Rick Damren, Yasser Kehail, Vincent Colombie, and Andreas Castan
21.1 Introduction 247
21.2 General Design Basis for Microbial SUFs 247
21.3 SUF Design Criteria and Approach – Heat Transfer 247
21.4 SUF Design Criteria and Approach – Oxygen Transfer 249
21.5 SUF Design Criteria and Approach – Mixing 251
21.6 Operational Considerations for SUFs 252
21.7 Case Studies 252
21.8 Summary and Conclusions 256
Nomenclature 257
References 258
22 Engineering Parameters in Single‐Use Bioreactors: Flow, Mixing, Aeration, and Suspension 259
Martina Micheletti and Andrea Ducci
22.1 Introduction 259
22.2 Stirred Bioreactors 259
22.3 Orbitally Shaken Bioreactors 262
22.4 Rocking Bag 267
22.5 Summary and Conclusions 268
Nomenclature 268
References 268
23 Alluvial Filtration: An Effective and Economical Solution for Midstream Application (e.g. Cell and Host Cell Protein Removal) 271
Ralph Daumke, Vasily Medvedev, Tiago Albano, and Fabien Rousset
23.1 Introduction 271
23.2 Case Study 2: Cell Removal 272
23.3 Case Study 2: HCP Removal 275
23.4 Summary and Conclusions 276
Nomenclature 277
References 277
24 Single‐Use Continuous Downstream Processing for Biopharmaceutical Products 279
Marc Bisschops, Britta Manser, and Martin Glenz
24.1 Introduction 279
24.2 Continuous Multicolumn Chromatography 279
24.3 Single‐Use Continuous Downstream Processing 280
24.4 Summary and Conclusions 283
References 283
25 Single‐Use Technology for Formulation and Filling Applications 285
Christophe Pierlot, Alain Vanhecke, Kevin Thompson, Rainer Gloeckler, and Daniel Kehl
25.1 Introduction 285
25.2 Challenges in Formulation and Filling 285
25.3 End‐User Requirements 286
25.4 Quality by Design 287
25.5 Hardware Design and Usability 288
25.6 Single‐Use Technology, Arrangement, and Operation 290
25.7 Summary and Conclusions 293
Nomenclature 294
References 294
26 Facility Design Considerations for Mammalian Cell Culture 295
Sue Walker
26.1 Introduction 295
26.2 Generic Case Study 295
26.3 Summary and Conclusions 301
Nomenclature 301
References 301
27 Progress in the Development of Single‐Use Solutions in Antibody–Drug Conjugate (ADC) Manufacturing 303
Diego R. Schmidhalter, Stephan Elzner, and Romeo Schmid
27.1 Introduction 303
27.2 Challenges for the Use of Disposables in ADC Processes 304
27.3 Key Unit Operations 306
27.4 Cysteine Conjugation Process – An ADC Production Process Case Study 308
27.5 Summary and Conclusions 309
Acknowledgment 309
Nomenclature 309
References 310
28 Single‐Use Processing as a Safe and Convenient Way to Develop and Manufacture Moss‐Derived Biopharmaceuticals 311
Holger Niederkrüger, Andreas Busch, Paulina Dabrowska‐Schlepp, Nicola Krieghoff, Andreas Schaaf, and Thomas Frischmuth
28.1 Introduction 311
28.2 Case Study 311
28.3 Summary and Outlook 317
Nomenclature 317
References 318
29 Single‐Use Technologies Used in Cell and Gene Therapy Manufacturing Need to Fulfill Higher and Novel Requirements: How Can this Challenge Be Addressed? 319
Alain Pralong and Angélique Palumbo
29.1 Introduction 319
29.2 Promise of Cell and Gene Therapy 320
29.3 Considerations for Biopharmaceutical Industry and Conclusion 322
Nomenclature 325
References 325
30 Single‐Use Bioreactors for Manufacturing of Immune Cell Therapeutics 327
Ralf Pörtner, Christian Sebald, Shreemanta K. Parida, and Hans Hoffmeister
30.1 Introduction 327
30.2 The Particular Nature of Immune Cell Therapeutics 327
30.3 Uncertain Mass Production of Immune Cells for Therapy 328
30.4 Technical Standards Required for Immune Cell ATMP Manufacturing 329
30.5 Techniques for Expansion of Immune Cells 329
30.6 Case Study ZRP System Consisting of GMP Breeder, Control Unit, and Software 330
30.7 Summary and Conclusions 330
Nomenclature 332
References 332
Index 335
