Biotechnology and biopharmaceutical manufacturing, processing, and preservation

Cover......Page 1
Title Page......Page 2
Copyright Page......Page 3
Table of Contents......Page 4
Foreword......Page 14
1. Introduction......Page 16
2. Large-Scale Freezing and Thawing of Biopharmaceutical Products......Page 22
  Thermodynamics of Protein Cold Denaturation......Page 26
  Dendritic Ice Growth......Page 28
  Concentration Phenomenon......Page 30
  Interaction of Solutes with the Ice-Liquid Interface......Page 31
 Freeze-Thaw Process Development......Page 36
  Large-Scale Freezing......Page 41
  Large-Scale Thawing......Page 42
 Formulation Issues Associated with Large-Scale Freeze-Thaw......Page 43
 Heat and Mass Transfer......Page 45
 Vessel Design......Page 49
  Design......Page 52
  Heat Exchange Media......Page 53
  Managing Moisture in the System......Page 54
  Mechanical Refrigeration Systems......Page 55
  Instrumentation and Controls......Page 57
  Liquefied Gas Refrigeration Systems......Page 59
 Product Release and Sampling......Page 60
 Stability Considerations......Page 61
 Validation of the Freezing and Thawing Processes......Page 62
  Thawing Validation......Page 63
 Summary......Page 64
 References......Page 66
3. Process Design Considerations for Large-Scale Chromatography of Biomolecules......Page 76
 Major Chromatography Techniques Used in Large-Scale Processes......Page 81
  Principles of Chromatographic Separations......Page 82
  Major Techniques......Page 83
 Process Development and Scale-Up......Page 88
  Phases in Process Development......Page 90
  Scale-Up Philosophy......Page 99
  An Extra Column Effect......Page 103
  General Requirements......Page 106
  System Components......Page 107
  Column Design......Page 108
  Pumping System Before and After the Column......Page 120
  Detection and Fraction Collection......Page 134
  Monitoring and Controls......Page 137
  System Design and Integration......Page 140
 Chromatographic Media and Their Use......Page 143
  Main Media Concepts for Liquid Chromatography......Page 144
  Media Features as a Function of Purification Steps......Page 148
  Importance of Particle Shape, Size, and Porosity......Page 152
  Resolution Versus Packing Properties......Page 154
  Media for Ion-Exchange Chromatography......Page 157
  Media for Hydrophobic Interaction Chromatography......Page 159
  Media for Affinity Chromatography......Page 160
  Media for Molecular Sieving (Gel Filtration)......Page 162
  Other Special Media Used in Bioseparation......Page 167
  Molecular Interactions......Page 170
  The Purification Plant......Page 176
  Multipurpose (Multiproduct) Unit......Page 180
  Operation Modes......Page 181
  Stationary Phase–Product Interaction and Design and Operating Parameters in Large-Scale Chromatography......Page 183
  Handling of Chromatographic Media......Page 185
 Validation......Page 186
  Systems Validation......Page 187
  Media Validation......Page 189
  Cleaning Validation......Page 190
 Summary......Page 192
 References......Page 196
4. Lyophilization of Protein Pharmaceuticals......Page 214
 Design of Freeze-Drying Cycles......Page 219
  Optimization of Formulations......Page 220
  Optimization of the Freezing Step......Page 227
  Presublimation Annealing......Page 228
  Optimization of Primary Drying......Page 229
  Optimization of Secondary Drying......Page 231
  Single-Step Freeze-Drying Cycle......Page 233
  Functional Limitations of Lyophilizers......Page 234
 Acute Stabilization of Proteins During Freezing and Drying......Page 235
  Protein Stabilization During Lyophilization/Rehydration......Page 236
  Practical Approaches to Minimizing Freezing-Induced Damage......Page 255
 Optimizing Formulations for Long-Term Storage Stability......Page 265
  Inhibition of Chemical Degradation ofLyophilized Proteins......Page 267
  Effect of Physical Factors on the Storage Stability of Dried Proteins......Page 268
 References......Page 271
5. Advances in Blow/Fill/Seal Technology: A Case Study in the Qualification of a Biopharmaceutical Product......Page 280
 Economics......Page 283
 Facility Layout and Equipment......Page 284
  Peripheral Equipment......Page 285
 Sterility Assurance......Page 287
 Process Time......Page 289
 Resin Sterilization Studies......Page 290
 Environmental Monitoring......Page 291
 Development Considerations......Page 293
 Packaging Design......Page 294
  Evaluation of Resin Containers for Extractable and Leachable Substances......Page 295
  Product Stability......Page 296
 Product Temperature......Page 297
 Operational Qualification......Page 298
 Defects......Page 299
 Steam-in-Place......Page 300
 Media Fills......Page 302
  Simulated Interventions......Page 303
 Acknowledgments......Page 306
 References......Page 307
6. Multiproduct Facility Design: An Integrated Approach......Page 308
 Multiproduct Processing Definitions......Page 310
  Airborne Contamination......Page 311
  Materials Produced by Different Biosynthetic Systems......Page 312
 FDA and Industry Views on Multiproduct Processing......Page 313
 Integrated Approach to Conceptual Multiproduct Facility Design......Page 314
  Information Gathering......Page 315
  Functional and Operational Description......Page 317
  Affinity Diagrams......Page 318
  Predesign Scope Reviews......Page 323
  Regulatory Design Guidelines......Page 324
 General Considerations for Multiprocess Facility Design Facility Design......Page 325
  Operational Efficiency......Page 326
  Validation Contingencies......Page 327
  Flow Separation......Page 328
  Personnel Access......Page 329
  Facility Finishes......Page 330
  Design Features of Process Areas......Page 332
  Design of Process Support Areas......Page 334
  Design of Utility and Mechanical Spaces......Page 336
  General Requirements for Process and Plant Utilities......Page 337
  Biohazard Considerations......Page 338
  GMP Design for a HVAC System for Multiproduct Facilities......Page 339
  Liquid Waste Containment and Treatment......Page 342
  Process Utilities......Page 343
  Sterile Piping Systems......Page 344
  FDA Reviews......Page 345
 References......Page 346
7. Economic and Cost Factors of Bioprocess Engineering......Page 348
  Time Value of Money......Page 350
  Measures of Financial Performance......Page 352
  Uncertainty and Risk......Page 354
 Development......Page 357
  Cost Drivers......Page 358
  Construction Alternatives......Page 361
  Utilities......Page 363
  Containment......Page 364
 Operations......Page 365
 Optimization......Page 367
 References......Page 368
 Name Index......Page 370
 Subject Index......Page 379
 Drug Manufacturing Technology Series: Key Concept Cross-Reference Index......Page 399