Handbook of Process Chromatography (eBook)

Cover 1
Contents 4
Preface 14
Acknowledgements 16
Chapter 1. Biopharmaceuticals Today 18
1.1 Industrial Context 18
1.2 Overview of Biopharmaceutical History 19
1.3 Biopharma Business Environment 23
1.4 Key Business Issues 27
1.5 Process Chromatography Within an Industrial Context 33
1.6 Summary 37
References 38
Chapter 2. Process Capability and Production Scenarios 40
2.1 Process Capability 40
2.2 Production Setups 44
2.3 Process Capability Conclusions 54
References 56
Chapter 3. Process-Design Concepts 58
3.1 Typical Process Design for Biopharmaceuticals 58
3.2 Management Framework for Process Design 60
3.3 Production Cells and Typical Product Characteristics 64
3.4 Risk Analysis and Risk Mitigation 72
3.5 Downstream Processing 77
3.6 Selected Downstream Processing Platform Examples 86
3.7 Characterizing the Process, Process Understanding 90
References 95
Chapter 4. Separation Technologies 98
4.1 Introduction 98
4.2 Recovery 98
4.3 Purification 103
4.4 Equipment 138
4.5 Selecting Tools from R& D to Production
References 139
Chapter 5. Analysis 144
5.1 Introduction 144
5.2 Proteins 144
5.3 Nucleic Acid Products 153
5.4 Comparability 157
5.5 Setting Specifications and Reference Standards 157
5.6 Method Validation 158
5.7 Process Analytical Technologies (PAT) 158
References 159
Chapter 6. Cleaning and Sanitization 164
6.1 Introduction 164
6.2 Cleaning 164
6.3 Decontamination of Transmissible Spongiform Encephalopathy Agents 170
6.4 Sanitization 171
References 175
Chapter 7. Validation 178
7.1 Introduction 178
7.2 What to do When? 179
7.3 Validation of Downstream Processes 181
7.4 Making Changes 201
7.5 Summary 202
Acknowledgements 202
References 203
Chapter 8. Economics 206
8.1 Economics: An Educational Excursion 207
8.2 LEAN Manufacturing, Removal of Unproductive Activities 214
8.3 Cost Model: Monoclonal Antibody Downstream Process 216
8.4 Cost Improvement Options 219
8.5 Impact from R& D, Platform Strategies and Technology Outlook
8.6 Conclusions, the Improvement Hierarchy 232
References 233
Chapter 9. Basic Properties of Peptides, Proteins, Nucleic Acids and Virus Particles 236
9.1 Introduction 236
9.2 Peptides 236
9.3 Proteins 239
9.4 Nucleic Acids 245
9.5 Viruses 248
References 251
Chapter 10. Optimization of Chromatographic Separations 254
10.1 Introduction 254
10.2 Basic Relationships 255
10.3 Purification Principles 262
10.4 Adsorption 284
10.5 Elution Modes 289
10.6 Bed Configuration 291
10.7 Experimental Determination of Basic Parameters 293
10.8 Modelling of Chromatographic Purifications 301
10.9 Simulation of Separations 308
References 309
Chapter 11. Equipment 316
11.1 Guidelines for Selecting Pilot Plant and Production Chromatography Equipment 316
11.2 Selection of Components 323
11.3. Automation 331
References 336
Chapter 12. Column Packing 338
12.1 Introduction 338
12.2 Theory 338
12.3 Preparation of Column and System 340
12.4 Packing the Column 341
12.5 Evaluating Column Packing Quality 343
12.6 Scale up 346
References 347
Appendix A: Symbols and Definitions in Liquid Chromatography 348
A.1 Introduction 348
A.2 Symbols Used in Liquid Chromatography 348
A.3 Definitions of Chromatographic Parameters and Equations 350
References 353
Appendix B: Dimensionless Numbers 354
B.1 Introduction 354
References 356
Appendix C: Activities for Biopharmaceutical Production from Genetically Engineered Mammalian Cells 358
C.1 Introduction 358
C.2 Activities Chart from Toxicology to License Application 358
Appendix D: Simulations Using the Supplied Software 362
D.1 Introduction 362
D.2 How to Use the Software? 362
D.3 Pressure Drop 363
D.4 Sample Volume 364
D.5 Resolution in SEC 365
D.6 Resolution in IEC, RPC and HIC 365
D.7 Isocratic Separation 366
D.8 Yield and Purity 367
D.9 Langmuir Isotherm 367
D.10 About this Software 368
Subject Index 370