REGINE EIBL, PHD, is a professor at the Zurich University of Applied Sciences (Switzerland), where she lectures in biotechnology and cell cultivation techniques.

DIETER EIBL, PHD, is a professor at the Zurich University of Applied Sciences, where he lectures in biochemical engineering and the planning of biotechnological production facilities.

List of Contributors xvii Preface xxi Part I Basics 1 1 Single¿Use Equipment in Biopharmaceutical Manufacture: A Brief Introduction 3Dieter 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 13Jens 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 25Sören 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 37Valentin 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 53Cedric 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 69Tobias 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 83Barbara 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 95Steven 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 117Britta 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 127Christian 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 143Alicja Sobätka 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 159P.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 169William 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 181Gerben 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 193Ronald 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 203Priyanka 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 211Ina 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 219Simone 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 229Lucie 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 235Stephan 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 247Parrish 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 259Martina 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) 271Ralph 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 279Marc 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 285Christophe 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 295Sue Walker 26.1 Introduction 295 26.2 Generic Case Study 295 26.3 Summary and Conclusions 301...