Cell Culture Engineering (eBook)

Preface 10
Contents 12
Established Bioprocesses for Producing Antibodies as a Basis for Future Planning 13
Introduction 14
Antibody Engineering Efforts 15
Investigating Marketed Monoclonal Antibodies 16
Generic Antibody Production Processes 36
Dose and Market Potential as Drivers of Quantities Needed 39
Future Trends in Antibody Manufacture 40
Conclusions 50
References 51
Fedbatch Culture and Dynamic Nutrient Feeding 55
Different Forms of Fedbatch Culture 57
Designing Feed Medium for Fedbatch Cultures 62
Control Strategies for Fedbatch Cultures 70
On-line Estimation for Control of Stoichiometric Feeding 77
Factors Limiting Cell Concentration and Productivity in Fedbatch Cultures 80
Concluding Remarks 84
References 84
The “Push-to-Low” Approach for Optimization of High- Density Perfusion Cultures of Animal Cells 87
Introduction 89
Materials and Methods 90
Conceptual Framework for Optimization of Perfusion Cultures 93
Results and Discussion 104
Conclusions 108
References 110
Towards Industrial Application of Quasi Real-Time Metabolic Flux Analysis for Mammalian Cell Culture 111
Introduction 112
Framework for Quasi Real-Time MFA 113
Materials and Methods 115
Results 118
Discussion 123
Conclusions 128
References 129
Engineering Cells for Cell Culture Bioprocessing – Physiological Fundamentals 131
Introduction 132
Cell Line Development for Recombinant Protein Therapeutics 134
Cellular Pathways Associated with Superior Growth and Production Characteristics 135
Prospect of Cell Engineering for Bioprocessing 168
References 170
Subject Index 178
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