Spier / Griffiths / Meignier Production of Biologicals from Animal Cells in Culture

1. Auflage 2013
ISBN: 978-1-4831-6515-8
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 852 Seiten, Web PDF

Production of Biologicals from Animal Cells in Culture reviews the state of the art in animal cell biotechnology, with emphasis on the sequence of events that occur when generating a biological from animal cells in culture. Methods that enable adjustment of nutrient feed streams into perfusion bioreactors so as to increase productivity are described. A number of issues are also addressed, such as the usefulness of the fingerprint method for cell characterization. Comprised of 135 chapters, this book begins with an overview of the problems and benefits of animal cell culture, followed by a discussion on the isolation of immortal murine macrophage cell lines. The reader is systematically introduced to the use of DNA fingerprinting to characterize cell banks; immortalization of cells with oncogenes; lipid metabolism of animal cells in culture; and energetics of glutaminolysis. Subsequent chapters explore serum-free and protein-free media; the physiology of animal cells; gene expression in animal cell systems; and animal cell bioreactors. The monitoring and assay of animal cell parameters are also considered, along with downstream processing and regulatory issues. This monograph will be of interest to students, practitioners, and investigators in the fields of microbiology and biotechnology.

Autoren/Hrsg.

Spier, R. E.

Griffiths, J. B.

Meignier, B.

Inhaltsverzeichnis

1;Front Cover;1
2;Production of Biologicals from Animal Cells in Culture;4
3;Copyright Page;5
4;Table of Contents;14
5;Hyclone Award Lecture;28
6;Chapter 1. Animal cell culture: the problems and rewards;30
7;Section 1: Cell lines and their characterization;40
7.1;Chapter 2. The isolation of immortal murine macrophage cell lines;42
7.1.1;ABSTRACT;42
7.1.2;INTRODUCTION;42
7.1.3;MATERIALS AND METHODS;42
7.1.4;RESULTS AND DISCUSSION;43
7.1.5;ACKNOWLEDGEMENTS;44
7.1.6;REFERENCES;44
7.2;Chapter 3. Propagation of human CD4-immunoglobulin producing cell lines;45
7.2.1;Abstract;45
7.2.2;Introduction;45
7.2.3;Materials and Methods;46
7.2.4;Results and Discussions;46
7.2.5;References;52
7.2.6;Paper of Schlaeger;53
7.3;Chapter 4. Characterisation of cell banks by DNA fingerprinting;55
7.3.1;INTRODUCTION;55
7.3.2;MATERIALS AND METHODS;55
7.3.3;RESULTS;55
7.3.4;CONCLUSIONS;56
7.3.5;REFERENCES;56
7.3.6;Paper of Stacey ;58
7.4;Chapter 5. Evaluating the safety of murine and human hybridomas: new problems and new

techniques;61
7.4.1;David Onions1 and Gillian Lees2;61
7.4.2;ABSTRACT AND INTRODUCTION;61
7.4.3;SCREENING FOR MURINE RETROVIRUSES;61
7.4.4;HUMAN RETROVIRUSES;63
7.4.5;HERPESVIRUS SCREENING;63
7.4.6;PCR BASED TECHNIQUES;63
7.4.7;SUMMARY;65
7.4.8;REFERENCES;65
7.5;Chapter 6. Defective endogenous retroviruslike particles of Chinese hamster ovary cells;66
7.5.1;ABSTRACT;66
7.5.2;INTRODUCTION;67
7.5.3;MATERIALS AND METHODS;67
7.5.4;RESULTS;68
7.5.5;DISCUSSION;70
7.5.6;ACKNOWLEDGEMENTS;71
7.5.7;REFERENCES;71
7.5.8;Paper of Anderson;72
7.6;Chapter 7. Reference cell lines;73
7.6.1;BACKGROUND;73
7.6.2;PROPOSAL;73
7.6.3;ACTION;74
7.6.4;REFERENCES;74
7.7;Chapter 8. A European database for animal cell lines;75
7.7.1;A Doyle*, J B Griffiths+ and C Caulcott;75
7.7.2;ABSTRACT;75
7.8;Chapter 9. Cell line data base: an on-line data bank where industry meets researchers;76
7.8.1;ABSTRACT;76
7.8.2;INTRODUCTION;76
7.8.3;TECHNICAL DESCRIPTION;77
7.8.4;CELL LINE DATA BASE;77
7.8.5;ACKNOWLEDGEMENTS;78
7.8.6;REFERENCES;78
7.9;Chapter 10. Adhesion and motility of embryonic and cancer cells;79
7.9.1;Paper of Thiery;80
7.10;Chapter 11. Immortalization of cells with oncogenes;82
7.10.1;Paper of Samarut;83
8;Section 2: Nutrient media with special supplements;86
8.1;Chapter 12. Lipid metabolism of animal cells in culture - a review;88
8.1.1;ABSTRACT;88
8.1.2;BACKGROUND;88
8.1.3;UTILIZATION OF EXTRACELLULAR LIPIDS;89
8.1.4;TURNOVER AND MODIFICATIONS OF CELL LIPID COMPOSITION;89
8.1.5;INFLUENCE OF LIPIDIC SUPPLEMENTS ON CELL GROWTH RATES;89
8.1.6;POTENTIAL IMPACT ON LARGE-SCALE MAMMALIAN CELL CULTURE;90
8.1.7;REFERENCES;90
8.1.8;Paper of Schmidt;92
8.2;Chapter 13. Lipoprotein requirements of cultured mammalian cells;94
8.2.1;ABSTRACT;94
8.2.2;INTRODUCTION;94
8.2.3;MATERIALS AND METHODS;94
8.2.4;RESULTS AND DISCUSSION;95
8.2.5;CONCLUSION;96
8.2.6;REFERENCE;96
8.3;Chapter 14. Effect of nutrients and waste metabolites on growth, metabolism and protein synthesis in hybridoma;97
8.3.1;ABSTRACT;97
8.3.2;KEYWORDS ;97
8.3.3;INTRODUCTION;97
8.3.4;MATERIALS AND METHODS;97
8.3.5;RESULTS AND DISCUSSION;98
8.3.6;REFERENCES;98
8.4;Chapter 15. Hybridoma growth, metabolism, and product formation in hepes–buffered medium: effect of passage number and pH
;100
8.4.1;ABSTRACT;100
8.4.2;INTRODUCTION;100
8.4.3;MATERIALS AND METHODS;100
8.4.4;RESULTS AND DISCUSSION;100
8.4.5;ACKNOWLEDGEMENTS;102
8.4.6;REFERENCES;102
8.5;Chapter 16. A screening experiment of media supplements on CHO cells;103
8.5.1;INTRODUCTION;103
8.5.2;EXPERIMENTAL DESIGN;103
8.5.3;MATERIALS AND METHODS;103
8.5.4;RESULTS AND DISCUSSION;104
8.5.5;CONCLUSION;105
8.5.6;ACKNOWLEDGEMENTS;105
8.5.7;REFERENCES;105
8.6;Chapter 17. Energetics of glutaminolysis - a theoretical evaluation;106
8.6.1;ABSTRACT;106
8.6.2;INTRODUCTION;106
8.6.3;RESULTS;106
8.6.4;DISCUSSION;108
8.6.5;REFERENCES;108
8.7;Chapter 18. Degrading effect of light on cell culture media;109
8.7.1;ABSTRACT;109
8.7.2;INTRODUCTION;109
8.7.3;MATERIALS AND METHODS;109
8.7.4;RESULTS AND DISCUSSION;110
8.7.5;ACKNOWLEDGEMENTS;111
8.7.6;REFERENCES;111
8.8;Chapter 19. Culture of hybridoma in dialysed media;112
8.8.1;ABSTRACT;112
8.8.2;INTRODUCTION;112
8.8.3;MATERIAL AND METHODS;113
8.8.4;RESULTS AND DISCUSSION;113
8.8.5;CONCLUSION;116
8.8.6;REFERENCES;116
8.9;Chapter 20. Evaluation of fetal bovine serum substitutes on cell growth and recombinant protein production;117
8.9.1;ABSTRACT;117
8.9.2;INTRODUCTION;117
8.9.3;MATERIALS AND METHODS;117
8.9.4;RESULTS;118
8.9.5;DISCUSSION;121
8.9.6;REFERENCES;121
8.10;Chapter 21. Cell growth activators (CGA) and cell function modulators (CFM) of blood: effect on cell replication and protein expression;122
8.10.1;ABSTRACT;122
8.10.2;INTRODUCTION;122
8.10.3;MATERIALS AND METHODS;123
8.10.4;CONCLUSION;130
8.10.5;ACKNOWLEDGEMENTS;130
8.10.6;REFERENCES;130
8.11;Chapter 22. Increased expression of factor VIII by butyrate in Chinese hamster ovary cells;131
8.11.1;INTRIDUCATION;131
8.11.2;MATERIALS AND METHODS;131
8.11.3;RESULTS;131
8.11.4;DISCUSSION;132
8.11.5;REFERENCES;133
8.12;Chapter 23. Polyamine enhanced product expression from transformed and recombinant cell lines;134
8.12.1;ABSTRACT;134
8.12.2;KEY WORDS;134
8.12.3;INTRODUCTION;134
8.12.4;MATERIALS AND METHODS;135
8.12.5;RESULTS;135
8.12.6;REFERENCES;136
8.13;Chapter 24. The development of a process for the production of HIV1 GP120 from recombinant cell lines;137
8.13.1;ABSTRACT;137
8.13.2;KEY WORDS;137
8.13.3;INTRODUCTION;137
8.13.4;MATERIALS AND METHODS;138
8.13.5;RESULTS AND DISCUSSION;138
8.13.6;ACKNOWLEDGEMENTS;141
8.13.7;REFERENCES;142
8.13.8;Paper of Froud;143
8.14;Chapter 25. 'Safe' animal derived medium supplements for cell cultures;144
8.14.1;ABSTRACT;144
8.14.2;INTRODUCTIONS;144
8.14.3;MATERIALS AND METHODS;145
8.14.4;RESULTS AND DISCUSSION;145
8.14.5;CONCLUSION;150
8.14.6;ACKNOWLEDGEMENTS;150
8.14.7;Paper of Seefried;151
8.15;26. Effect of desferrioxamine on transferrin receptor expression, growth and IgG production of the rat hybridoma MA C57;152
8.15.1;ABSTRACT;152
8.15.2;INTRODUCTION;152
8.15.3;MATERIALS AND METHODS;152
8.15.4;RESULTS AND DISCUSSION;153
8.15.5;ACKNOWLEDGEMENTS;155
8.15.6;REFERENCES;155
8.15.7;Paper of Tomlinson;156
9;Section 3: Serum-free and protein-free media;158
9.1;Chapter 27. Development of serum-free media for mammalian cell culture;160
9.1.1;ABSTRACT;160
9.1.2;INTRODUCTION;160
9.1.3;MATERIALS AND METHODS;161
9.1.4;RESULTS;161
9.1.5;CONCLUSION;162
9.1.6;ACKNOWLEDGEMENTS;162
9.1.7;REFERENCES;162
9.2;Chapter 28. Concept and strategy for the development of a general purpose serum-free medium for anchorage-dependent cells;164
9.2.1;ABSTRACT;164
9.2.2;INTRODUCTION;164
9.2.3;MATERIALS AND METHODS;164
9.2.4;RESULTS;164
9.2.5;DISCUSSION;166
9.2.6;ACKNOWLEDGEMENTS;166
9.2.7;REFERENCES;166
9.3;Chapter 29. Growth of mammalian cell lines under serum-free conditions;167
9.3.1;ABSTRACT;167
9.3.2;INTRODUCTION;167
9.3.3;MATERIALS AND METHODS;167
9.3.4;RESULTS AND DISCUSSION;168
9.3.5;REFERENCES;170
9.4;Chapter 30. Development of a low-serum growth medium for production of a human glycoprotein by recombinant BHK cells;171
9.4.1;ABSTRACT;171
9.4.2;INTRODUCTION;171
9.4.3;MATERIALS AND METHODS;171
9.4.4;RESULTS AND DISCUSSION;174
9.4.5;ACKNOWLEDGEMENTS;174
9.4.6;REFERENCES;174
9.5;Chapter 31. Optimalisation of a serum free medium for large scale continuous growth and immunoglobulin production by a mouse hybridoma;175
9.6;Chapter 32. Longterm serum-free culture of murine hybridomas;176
9.6.1;Abstract;176
9.6.2;Introduction;176
9.6.3;Methods;176
9.6.4;Results;178
9.6.5;Discussion;180
9.6.6;Acknowledgements;180
9.6.7;References;181
9.7;Chapter 33. Serum-free media suitable for upstream and downstream processing;182
9.7.1;Abstract;182
9.7.2;Supplements for serum-free media;182
9.7.3;Media requirements for production andgenomic stability;186
9.7.4;Strategies for reduction of media costs;186
9.7.5;Media requirements for downstream processing and strategies to optimize product quality;188
9.7.6;References;189
9.7.7;Paper of Jaqer:;192
9.8;Chapter 34. Production of human fibronectin from serum-free continuous cultured human hepatoblastoma line HUH-6;194
9.8.1;ABSTRACT;194
9.8.2;INTRODUCTION;194
9.8.3;MATERIALS AND METHODS;194
9.8.4;RESULTS;195
9.8.5;DISCUSSION;196
9.8.6;REFERENCES;196
9.9;Chapter 35. Development of a protein-free medium for bioreactor cultures of hybridoma cell lines;197
9.9.1;ABSTRACT;197
9.9.2;INTRODUCTION;197
9.9.3;MATERIAL AND METHODS;198
9.9.4;RESULTS;199
9.9.5;DISCUSSION;202
9.9.6;REFERENCES;206
9.10;Chapter 36. Conditions for the production of recombinant IL-2 in stirred suspension culture using a protein-free medium;207
9.10.1;ABSTRACT;207
9.10.2;INTRODUCTION;207
9.10.3;MATERIALS AND METHODS;207
9.10.4;RESULTS AND DISCUSSION;208
9.10.5;REFERENCES;211
9.10.6;Paper of Wagner
;213
9.11;Chapter 37. A protein-free serum replacement (SSR) for cell culture;214
9.11.1;ABSTRACT;214
9.11.2;INTRODUCTION;214
9.11.3;MATERIALS AND METHODS;214
9.11.4;RESULTS AND DISCUSSION;215
9.12;Chapter 38. Adaptation and characterization of hybridomas growing in low protein and protein-free medium;217
9.12.1;Abstract:;217
9.12.2;Introduction:;217
9.12.3;Materials & Methods:;217
9.12.4;Results & Discussion;218
9.12.5;References;222
9.13;Chapter 39. Characterization of protease activity in serum-free culture supernatants of hybridomas and recombinant mammalian cells;223
9.13.1;ABSTRACT;223
9.13.2;INTRODUCTION;223
9.13.3;MATERIAL AND METHODS;223
9.13.4;RESULTS AND DISCUSSION;225
9.13.5;REFERENCES;228
9.13.6;Paper of Lund:;230
10;Section 4: Cell physiology;232
10.1;Chapter 40. Animal cells in culture make secondary metabolites too;234
10.1.1;1. Objectives of this paper
;234
10.1.2;2. What are Secondary Metabolites;235
10.1.3;3. The Physiology of the production of Secondary Metabolites in non-animal cell
;237
10.1.4;4. The Physiology of the Production of Secondary Metabolites from Animal Cells in Culture
;239
10.1.5;5. References;240
10.1.6;Paper of Spier;243
10.2;Chapter 41. Removal of inhibitory factors from hybridoma cell cultures by gel filtration;245
10.2.1;ABSTRACT;245
10.2.2;INTRODUCTION;245
10.2.3;MATERIALS AND METHODS;246
10.2.4;RESULTS AND DISCUSSION;246
10.2.5;AKNOWLEDGEMENT;250
10.2.6;REFERENCES;250
10.2.7;Paper of Ronning;251
10.3;Chapter 42. The effect of metabolic by-products on animal cells in culture;253
10.3.1;ABSTRACT;253
10.3.2;INTRODUCTION;253
10.3.3;MATERIALS and METHODS;253
10.3.4;RESULTS and DISCUSSION;253
10.3.5;REFERENCES;255
10.4;Chapter 43. Cytoskeletal microfilament network and energy metabolism affect ability of animal cells to resist shear injury;256
10.4.1;INTRODUCTION;256
10.4.2;MATERIALS AND METHODS;257
10.4.3;RESULTS;258
10.4.4;DISCUSSION;259
10.4.5;ACKNOWLEDGEMENTS.;259
10.4.6;REFERENCES;259
10.4.7;Paper of Papoutsakis:;262
10.5;Chapter 44. Intracellular concentration of ATP and other nucleotides during continuous cultivation of hybridoma cells;263
10.5.1;Abstract;263
10.5.2;Introduction;263
10.5.3;Material and Methods;264
10.5.4;Results and Discussion;265
10.5.5;References;268
10.5.6;Paper of Ryll;270
10.6;Chapter 45. Determination of the 'critical shear stress level' for adherent BHK cells;271
10.6.1;ABSTRACT;271
10.6.2;INTRODUCTION;271
10.6.3;METHODS;271
10.6.4;RESULTS;272
10.6.5;DISCUSSION;273
10.6.6;REFERENCES;273
10.7;Chapter 46. Effects of dissolved oxygen supply and glucose concentration on human lymphoblastoid cell growth and metabolism in continuous culture;274
10.7.1;ABSTRACT;274
10.7.2;INTRODUCTION;274
10.7.3;MATERIALS AND METHODS;275
10.7.4;RESULTS AND DISCUSSION;275
10.7.5;CONCLUSION;280
10.7.6;ACKNOWLEDGEMENT;280
10.7.7;REFERENCES;280
10.7.8;Paper of Deramoudt;282
10.8;Chapter 47. The role of dissolved oxygen in growth of animal cells;283
10.8.1;ABSTRACT;283
10.8.2;INTRODUCTION;283
10.8.3;MATERIALS AND METHODS;283
10.8.4;RESULTS AND DISCUSSION;284
10.8.5;REFERENCES;285
10.9;Chapter 48. The effect of osmolarity on hybridoma cell growth and antibody production in serum-free media;286
10.9.1;ABSTRACT;286
10.9.2;INTRODUCTION;286
10.9.3;MATERIALS AND METHODS;286
10.9.4;RESULTS;286
10.9.5;DISCUSSION;288
10.9.6;REFERENCES;288
10.10;Chapter 49. Physiological investigations in high density perfusion culture of free suspended animal cells;289
10.10.1;ABSTRACT;289
10.10.2;INTRODUCTION;289
10.10.3;MATERIALS AND METHODS;289
10.10.4;RESULTS AND DISCUSSION;290
10.10.5;REFERENCES;292
10.11;Chapter 50. Factors affecting hybridoma cell attachment to derivatized polyacrylamide beads;293
10.11.1;ABSTRACT;293
10.11.2;INTRODUCTION;293
10.11.3;MATERIALS AND METHODS;294
10.11.4;RESULTS AND DISCUSSION;294
10.11.5;IN CONCLUSION:;299
10.11.6;REFERENCES;299
10.11.7;Paper of Reuveny;301
10.12;Chapter 51. Adaption of anchorage-dependent cells to glutamine-free medium;303
10.12.1;ABSTRACT;303
10.12.2;INTRODUCTION;303
10.12.3;MATERIALS AND METHODS;303
10.12.4;RESULTS AND DISCUSSION;304
10.12.5;ACKNOWLEDGEMENTS;305
10.12.6;REFERENCES;305
10.13;Chapter 52. The 2'5'oligoadenylate synthetase, a multienzyme system involved in the growth properties and the sensitivity to viruses of mammalian cells: selection of antibodies in order to investigate their specific biological roles;306
10.13.1;Abstract;306
10.13.2;Introduction;306
10.13.3;Materials and methods;307
10.13.4;Results and discussion;308
10.13.5;References;310
10.13.6;Acknowledgments;311
11;Section 5: Gene expression in animal cell systems;312
11.1;Chapter 53. Recent developments in mammalian expression systems;314
11.1.1;Promoters;314
11.1.2;Gene source;314
11.1.3;Mammalian selectable markers;315
11.1.4;Transfeetion methods;316
11.1.5;Transient expression systems;316
11.1.6;Stable expression systems;318
11.1.7;Amplification systems;320
11.1.8;Future mammalian cell expression vectors;321
11.1.9;Dominant control regions;322
11.1.10;REFERENCES;323
11.1.11;Paper of Hentschel;329
11.2;Chapter 54. Genetic engineering of cellular physiology;331
11.2.1;ABSTRACT;331
11.2.2;INTRODUCTION;331
11.2.3;RESULTS;331
11.2.4;ACKNOWLEDGEMENTS;333
11.2.5;REFERENCES;333
11.2.6;Papers of Scott and Bell;334
11.3;Chapter 55. Stability of amplified DNA in Chinese hamster ovary cells;336
11.3.1;ABSTRACT;336
11.3.2;INTRODUCTION;336
11.3.3;MATERIALS AND METHODS;337
11.3.4;RESULTS & DISCUSSION;339
11.3.5;ACKNOWLEDGEMENTS;340
11.3.6;REFERENCES;340
11.3.7;Paper of Cassons;342
11.4;Chapter 56. Methotrexate and CHO cells: productivity and genetics of amplified expression vector sequences;343
11.4.1;ABSTRACT;343
11.4.2;INTRODUCTION;343
11.4.3;RESULTS AND DISCUSSION;344
11.4.4;SUMMARY;347
11.4.5;LITERATURE;349
11.4.6;Paper of Wurm;351
11.5;Chapter 57. The stability of expression of hybridoma cells in homogeneous continuous culture systems;354
11.5.1;ABSTRACT;354
11.5.2;INTRODUCTION;354
11.5.3;MATERIALS AND METHODS;355
11.5.4;RESULTS AND DISCUSSION;356
11.5.5;CONCLUSION;360
11.5.6;REFERENCES;360
11.5.7;Paper of van der Gelden de Groot;361
11.6;Chapter 58. Cloning and expression of a bovine anti-testosterone monoclonal antibody;362
11.6.1;ABSTRACT;362
11.6.2;INTRODUCTION;362
11.6.3;METHODS;362
11.6.4;RESULTS;362
11.6.5;DISCUSSION;363
11.6.6;ACKNOWLEDGEMENTS;363
11.6.7;REFERENCES;364
11.7;Chapter 59. Use of dicistronic transcription units for the correlated expression of two genes in mammalian cells;365
11.7.1;ABSTRACT;365
11.7.2;KEYWORDS;365
11.7.3;INTRODUCTION;365
11.7.4;MATERIALS AND METHODS;366
11.7.5;RESULTS AND DISCUSSION;366
11.7.6;ACKNOWLEDGEMENT;369
11.7.7;REFERENCES;369
11.7.8;Paper of Wirth;371
11.8;Chapter 60. Large-scale recombinant protein production using the insect cell-baculovirus expression system: antistatsin and ß-adrenergic receptor;372
11.8.1;ABSTRACT;372
11.8.2;INTRODUCTION;372
11.8.3;MATERIALS AND METHODS;373
11.8.4;RESULTS;373
11.8.5;DISCUSSION;376
11.8.6;ACKNOWLEDGEMENTS;377
11.8.7;REFERENCES;377
11.8.8;Paper of Jain;378
11.9;Chapter 61. Quantitation of mRNA specific for heavy and light chains of IgG in hybridomas during different phases of batch culture;379
11.9.1;ABSTRACT;379
11.9.2;INTRODUCTION;379
11.9.3;MATERIALS AND METHODS;380
11.9.4;RESULTS;381
11.9.5;DISCUSSION;382
11.9.6;REFERENCES;384
12;Section 6.1 Bioreactors: overview;388
12.1;Chapter 62. Development of mammalian cell manufacturing processes;390
12.1.1;ABSTRACT;390
12.1.2;INTRODUCTION;390
12.1.3;INITIAL PROCESS DEVELOPMENT;391
12.1.4;PROCESS OPTIMIZATION IN MODEL BIOREACTOR SYSTEMS (NON-CLINICAL);392
12.1.5;PILOT PRODUCTION RUN (PRE-CLINICAL SUPPLIES);393
12.1.6;CONTINUED PROCESS DEVELOPMENT DURING CLINICAL PRODUCTION;394
12.1.7;CONCLUSION;395
12.1.8;Paper of Tolbert;396
12.2;Chapter 63. A new look at animal cell bioreactor development;397
12.2.1;INTRODUCTION;397
12.2.2;ROTATING WIRE-CAGE BIOREACTOR;397
12.2.3;A NEW CELL ENTRAPMENT BIOREACTOR;401
12.2.4;PERFUSION RATE IN CELL RETENTION CULTURE;403
12.2.5;CONCLUDING REMARKS;405
12.2.6;ACKNOWLEDGEMENTS;405
12.2.7;REFERENCES;405
12.2.8;Paper of Shou-Hu;406
12.3;Chapter 64. Mammalian cell fermentation: are

specialized bioreactors a necessity?;408
12.3.1;INTRODUCTION;408
12.3.2;MATERIALS & METHODS:;408
12.3.3;RESULTS
;409
12.3.4;DISCUSSION;411
12.3.5;REFERENCES
;411
13;Section 6.2: Bioreactors: hardware;412
14;Chapter 65. Engineering for sterility and containment: design of a 225 L "polymodal" fermenter for the

containment of P3 pathogens;414
14.1;ABSTRACT;414
14.2;INTRODUCTION;414
14.3;DESIGN CONSIDERATIONS;414
14.4;DESGIN SOLUTIONS;414
15;Chapter 66. Monoclonal antibody production using an airlift fermentation system consisting of a continuous seed fermenter and a fed batch production fermenter;417
15.1;INTRODUCTION;417
15.2;MATERIALS AND METHODS;417
15.3;RESULTS;417
15.4;CONCLUSION;420
15.5;REFERENCES;420
16;Chapter 67. Bleeding out dead cells from fermentation systems;421
16.1;ABSTRACT;421
16.2;INTRODUCTION;421
16.3;MATERIALS AND METHODS;422
16.4;RESULTS;422
16.5;DISCUSSION;424
16.6;ACKNOWLEDGEMENT;424
16.7;Paper of Bjorling;425
17;Chapter 68. High intensity growth of adherent cells on a porous ceramic matrix;427
17.1;ABSTRACT;427
17.2;INTRODUCTION;427
17.3;MATERIALS AND METHODS;427
17.4;RESULTS;429
17.5;DISCUSSION;431
17.6;ACKNOWLEDGEMENTS;431
17.7;REFERENCES;431
17.8;Paper of Kilburn;433
18;Chapter 69. Considerations in the design, development and scale-up of glass bead packed reactors;434
18.1;Keywords;434
18.2;REFERENCES;436
18.3;Paper of Bliem;441
19;Chapter 70. On-line removal of cells from continuous suspension cultures;443
19.1;ABSTRACT;443
19.2;INTRODUCTION;443
19.3;MATERIALS AND METHODS;443
19.4;RESULTS;444
19.5;DISCUSSION;446
19.6;REFERENCES;447
20;Section 6.3: Bioreactors: particles;448
20.1;Chapter 71. Microsphere-induced aggregate culture of animal cells;450
20.1.1;ABSTRACT;450
20.1.2;INTRODUCTION;450
20.1.3;MATERIALS AND METHODS;451
20.1.4;RESULTS AND DISCUSSION;451
20.1.5;ACKNOWLEDGEMENT;454
20.1.6;REFERENCES;454
20.1.7;Paper of .µ;455
20.2;Chapter 72. The growth of CHO and BHK cells as suspended aggregates in serum-free medium;456
20.2.1;ABSTRACT;456
20.2.2;KEY WORDS;456
20.2.3;INTRODUCTION;456
20.2.4;MATERIAL AND METHODS;456
20.2.5;RESULTS AND DISCUSSION;457
20.2.6;ACKNOWLEDGEMENTS;459
20.2.7;REFERENCES;459
20.3;Chapter 73. CultiSpher - macroporous gelatin microcarrier - new applications;461
20.3.1;ABSTRACT;461
20.3.2;INTRODUCTION;461
20.3.3;REFERENCES;465
20.4;Chapter 74. Cultivation of CHO-cells on microcarriers Dormacell;466
20.4.1;ABSTRACT;466
20.4.2;KEYWORDS;466
20.4.3;INTRODUCTION;466
20.4.4;RESULTS AND DISCUSSION;466
20.4.5;CONCLUSION;469
20.4.6;REFERENCES;469
21;Section 6.4: Bioreactors: membranes and perfusion;470
21.1;Chapter 75. Fermentation of AT III producing BHK cells in a double membrane perfusion bioreactor;472
21.1.1;Abstract;472
21.1.2;Introduction;472
21.1.3;Material and Methods;473
21.1.4;Results and Discussion;473
21.1.5;References;477
21.2;Chapter 76. Oxygen transfer characteristics in cell culture fermenters: direct spargingmembrane oxygenation-bubble-free aeration through a rotating sieve;478
21.2.1;ABSTRACT;478
21.2.2;KEYWORDS;478
21.2.3;INTRODUCTION;478
21.2.4;MATERIALS AND METHODS;478
21.2.5;RESULTS AND DISCUSSION;479
21.2.6;REFERENCES;480
21.3;Chapter 77. Hybridoma culture in a membrane system: the influence of oxygen on a reactor's performance and on the evaluation of cellular density;481
21.3.1;ABSTRACT;481
21.3.2;INTRODUCTION;481
21.3.3;MATERIAL AND METHODS;481
21.3.4;RESULTS AND DISCUSSION;482
21.3.5;REFERENCES;483
21.4;Chapter 78. Hybridoma, antibody and growth factor distributions in the shell–side of ultrafiltration hollow fiber bioreactors;484
21.4.1;ABSTRACT;484
21.4.2;INTRODUCTION;484
21.4.3;MATERIALS AND METHODS;484
21.4.4;RESULTS;485
21.4.5;DISCUSSION;486
21.4.6;ACKNOWLEDGEMENTS;486
21.4.7;REFERENCES;486
21.5;Chapter 79. Cultivation of insect cell lines in stirred membrane reactors;487
21.5.1;ABSTRACT;487
21.5.2;KEYWORDS;487
21.5.3;INTRODUCTION;487
21.5.4;MATERIAL AND METHODS;488
21.5.5;RESULTS AND DISCUSSION;489
21.5.6;ACKNOWLEDGEMENTS;491
21.5.7;REFERENCES;491
21.5.8;Paper of Schutz;493
21.6;Chapter 80. High density culture of hybridoma cells using a perfusion culture apparatus with multi-settling zones;494
21.6.1;ABSTRACT;494
21.6.2;INTRODUCTION;494
21.6.3;MATERIALS AND METHODS;494
21.6.4;RESULTS AND DISCUSSION;495
21.6.5;References;496
21.7;Chapter 81. High cell density perfusion culutre of insect cells for production of baculovirus and recombinant protein;497
21.7.1;ABSTRACT;497
21.7.2;INTRODUCTION;497
21.7.3;MATERIALS AND METHODS;498
21.7.4;RESULTS;499
21.7.5;DISCUSSION;501
21.7.6;ACKNOWLEDGEMENT;502
21.7.7;REFERENCES;502
21.7.8;Paper of Kloppinger;503
22;Section 6.5: Bioreactors: optimization via metabolism;504
22.1;Chapter 82. Metabolite parameters modulating monoclonal antibody production by hybridoma cells in flask and macroporous glass sphere culture;506
22.1.1;ABSTRACT;506
22.1.2;INTRODUCTION;506
22.1.3;MATERIALS AND METHODS;506
22.1.4;RESULTS;507
22.1.5;DISCUSSION;512
22.1.6;ACKNOWLEDGEMENTS;512
22.1.7;REFERENCES;512
22.2;Chapter 83. Optimization of OKT3 hybridoma cultures in a perfusion stirred reactor;513
22.2.1;ABSTRACT;513
22.2.2;KEY WORDS;513
22.2.3;INTRODUCTION;513
22.2.4;MATERIAL AND METHODS;513
22.2.5;RESULTS AND DISCUSSION;514
22.2.6;REFERENCES;515
22.3;Chapter 84. Biochemical control of monoclonal antibody secretion in hollow fibre reactors;516
22.3.1;ABSTRACT;516
22.3.2;INTRODUCTION;516
22.3.3;MATERIALS AND METHODS;517
22.3.4;RESULTS;518
22.3.5;DISCUSSION AND CONCLUSIONS;519
22.3.6;REFERENCES;519
22.3.7;Paper of Handa-Corrigan;521
22.4;Chapter 85. Optimization of human anti-rhesus IgG production using hollow fiber technology;522
22.4.1;ABSTRACT;522
22.4.2;INTRODUCTION;522
22.4.3;MATERIALS AND METHODS;522
22.4.4;RESULTS AND DISCUSSION;523
22.4.5;CONCLUSION;524
22.4.6;REFERENCES;524
22.5;Chapter 86. Parameters for optimization of fermentation of an AT III producing cell line;525
22.5.1;INTRODUCTION;525
22.5.2;MATERIALS AND METHODS;525
22.5.3;RESULTS;526
22.5.4;DISCUSSION;528
22.6;Chapter 87. Enhanced productivity of hybridoma and recombinant CHO cell cultures by pluronic F-68 and other medium components, and by increased perfusion rates, in fluidized-bed bioreactors;529
22.6.1;ABSTRACT;529
22.6.2;INTRODUCTION;529
22.6.3;MATERIALS AND METHODS;530
22.6.4;RESULTS AND DISCUSSION;531
22.6.5;CONCLUSIONS;536
22.6.6;REFERENCES;537
22.6.7;Paper of Vournakis;539
22.7;Chapter 88. Improved performance of the fluidized bed reactor for the cultivation of animal cells;540
22.7.1;Abstract;540
22.7.2;Introduction;540
22.7.3;Materials and Methods;540
22.7.4;Conclusions;542
22.7.5;Acknowledgement;542
22.7.6;Reference;542
23;Section 6.6: Bioreactors: comparative studies;544
23.1;Chapter 89. Bioreactors for production of HIV - a comparative evaluation of flask, suspension and fixed bed cultures;546
23.1.1;ABSTRACT;546
23.1.2;INTRODUCTION;546
23.1.3;METHODS;547
23.1.4;RESULTS;547
23.1.5;DISCUSSION;549
23.1.6;REFERENCES;549
23.2;Chapter 90. Comparison of semicontinuous culture and perfusion culture in a 75 L bioreactor;550
23.2.1;Summary;550
23.2.2;Materials and methods;550
23.2.3;Results;551
23.2.4;Discussion;551
23.3;Chapter 91. Comparison of two systems based on porous beads for the production of recombinant von Willebrand factor by CHO cells;552
23.3.1;ABSTRACT;552
23.3.2;INTRODUCTION;552
23.3.3;RESULTS;554
23.3.4;CONCLUSIONS;554
23.3.5;REFERENCES;554
23.4;Chapter 92. Comparison of the production efficiency of mammalian cells grown in a fluidized bed and in a stirred tank reactor;555
23.4.1;Abstract;555
23.4.2;Introduction;555
23.4.3;Materials and Methods;556
23.4.4;Results;557
23.4.5;Conclusion;559
23.4.6;References;559
23.5;Chapter 93. Monoclonal antibody production of three different hollow fibre bioreactor configurations;560
23.5.1;ABSTRACT;560
23.5.2;INTRODUCTION;560
23.5.3;MATERIALS AND METHODS;562
23.5.4;DISCUSSION AND CONCLUSION;563
23.5.5;REFERENCES;563
23.6;Chapter 94. A comparison of two reactors for cell cultivation;564
23.6.1;1 Indroduction;564
23.6.2;2 Dynamic k-ja Determination;564
23.6.3;3 Fermentation;564
23.6.4;References;566
24;Section 7: Monitoring and assay of animal cell parameters;568
24.1;Chapter 95. Staining of Chinese hamster ovary cells on macroporous matrices;570
24.1.1;ABSTRACT;570
24.1.2;INTRODUCTION;570
24.1.3;MATERIALS AND METHODS;570
24.1.4;RESULTS;571
24.1.5;DISCUSSION;574
24.1.6;REFERENCES;574
24.2;Chapter 96. The role of oxidation-reduction potential in monitoring growth of cultured mammalian cells;575
24.2.1;ABSTRACT;575
24.2.2;INTRODUCTION;575
24.2.3;MATERIALS AND METHODS;578
24.2.4;RESULTS AND DISCUSSION;581
24.2.5;SUMMARY;591
24.2.6;ACKNOWLEDGEMENT;591
24.2.7;REFERENCES;592
24.2.8;Paper of H w m;595
24.3;Chapter 97. Potential and pitfalls of using LDH release for the evaluation of animal cell death kinetics;596
24.3.1;ABSTRACT;596
24.3.2;KEY WORDS;596
24.3.3;INTRODUCTION;596
24.3.4;RESULTS AND DISCUSSION;597
24.3.5;CONCLUSIONS;599
24.3.6;ACKNOWLEDGEMENTS;600
24.3.7;REFERENCES;601
24.3.8;Paper of Enqasser;602
24.4;Chapter 98. Flow cytometric (FCM) analysis on the genetic stability of continuous cell lines;603
24.4.1;INTRODUCTION;603
24.4.2;MATERIALS AND METHODS;603
24.4.3;RESULTS;604
24.4.4;CONCLUSIONS;604
24.4.5;REFERENCES;605
24.5;Chapter 99. Biomass estimation in anchorage-dependent animal cell cultures;607
24.5.1;ABSTRACT;607
24.5.2;INTRODUCTION;607
24.5.3;MATERIAL AND METHODS;608
24.5.4;RESULTS;608
24.5.5;CONCLUSION;611
24.5.6;ACKNOWLEDGMENTS;612
24.5.7;REFERENCES;612
24.5.8;Paper of Chotteau;613
24.6;Chapter 100. Dynamic assay of synthetic activities in single hybridoma cells;614
24.6.1;ABSTRACT ;614
24.6.2;KEYWORDS;614
24.6.3;INTRODUCTION ;614
24.6.4;MATERIALS AND METHODS;615
24.6.5;RESULTS AND DISCUSSION;616
24.6.6;ACKNOWLEDGEMENTS;617
24.6.7;REFERENCES;617
24.6.8;Paper of Al-Rubeai;620
24.7;Chapter 101. Rapid monitoring of monoclonal antibodies in cell culture media by high performance liquid affinity chromatography (HPLAC);621
24.7.1;ABSTRACT;621
24.7.2;INTRODUCTION;621
24.7.3;MONITORING DURING PRODUCTION AND DOWNSTREAM PROCESSING;622
24.7.4;CONCLUSIONS;623
24.7.5;REFERENCES;623
24.8;Chapter 102. Application of the PCFIA to rapid off-line process monitoring;624
24.8.1;ABSTRACT;624
24.8.2;INTRODUCTION;624
24.8.3;METHODS AND MATERIALS;624
24.8.4;RESULTS AND DISCUSSION;625
24.8.5;CONCLUSION;626
24.8.6;ACKNOWLEDGEMENTS;626
24.8.7;REFERENCES;626
25;Section 8: Kinetics and modelling;628
25.1;Chapter 103. Mathematical estimator for the evaluation of cell density and medium composition in hybridoma cultures;630
25.1.1;ABSTRACT;630
25.1.2;INTRODUCTION;630
25.1.3;MATERIAL AND METHODS;630
25.1.4;RESULTS AND DISCUSSION;631
25.1.5;REFERENCES;632
25.2;Chapter 104. Kinetic effect of growth factors on batch and continuous hybridoma cultures;633
25.2.1;ABSTRACT;633
25.2.2;INTRODUCTION;633
25.2.3;MATERIAL AND METHODS;633
25.2.4;RESULTS AND DISCUSSION;634
25.2.5;ACKNOWLEDGEMENTS;635
25.2.6;REFERENCES;635
25.3;Chapter 105. Batch production kinetics of hybridomas: pulse experiments;636
25.3.1;Abstract;636
25.3.2;Introduction;636
25.3.3;Materials and Methods;637
25.3.4;Results and Discussion;638
25.3.5;In conclusion;641
25.3.6;References;641
25.4;Chapter 106. Analysis of hybridoma growth, metabolism and product formation in continuous suspension culture;643
25.4.1;ABSTRACT;643
25.4.2;INTRODUCTION;643
25.4.3;MATERIALS AND METHODS;643
25.4.4;RESULTS AND DISCUSSION;644
25.4.5;ACKNOWLEDGEMENTS;648
25.4.6;REFERENCES;648
25.5;Chapter 107. Kinetics of nutrient utilization in a hybridoma batch culture;649
25.5.1;INTRODUCTION;649
25.5.2;MATERIALS AND METHODS;649
25.5.3;RESULTS AND DISCUSSION;650
25.6;Chapter 108. Modelling growth of and antibody production by hybridomas in glutamine limited suspension cultures;652
25.6.1;ABSTRACT;652
25.6.2;INTRODUCTION;652
25.6.3;THEORY;652
25.6.4;MATERIALS AND METHODS;655
25.6.5;RESULTS AND DISCUSSION;655
25.6.6;NOMENCLATURE;657
25.6.7;REFERENCES;657
25.7;Chapter 109. A computer simulation of the kinetics and energetics of hybridoma cell growth and antibody production;658
25.7.1;ABSTRACT;658
25.7.2;MODEL AIMS;658
25.7.3;MODEL DEVELOPMENT;659
25.7.4;RESULTS;659
25.7.5;DISCUSSION;660
25.7.6;REFERENCES;660
25.8;Chapter 110. A kinetic model for the influence of serum in batch and continuous hybridoma cultures;661
25.8.1;ABSTRACT;661
25.8.2;KEY WORDS;661
25.8.3;INTRODUCTION;661
25.8.4;MATERIAL AND METHODS;661
25.8.5;RESULTS AND DISCUSSION;661
25.8.6;REFERENCES;663
26;Section 9: Downstream processing;664
26.1;Chapter 111. Isolation of biologicals: leachables and cleaning in place become a crucial issue in liquid chromatography;666
26.1.1;ABSTRACT;666
26.1.2;INTRODUCTION;666
26.1.3;CLEANING IN PLACE OF SEPARATION TOOLS;670
26.1.4;LEACHABLES : DETECTION AND ELIMINATION;672
26.1.5;CONCLUSION;676
26.1.6;Paper of Boschetti;677
26.2;Chapter 112. Composite high flow rate ion exchangers for economical scale-up;678
26.2.1;ABSTRACT;678
26.2.2;INTRODUCTION;678
26.2.3;A NEW COMPOSITE ION EXCHANGER;678
26.2.4;FRACTIONATION OF BOVINE PLASMA;680
26.2.5;COST ANALYSIS;682
26.2.6;CLEANING;682
26.2.7;REFERENCES;683
26.2.8;Paper of Glad;684
26.3;Chapter 113. Serum free media (SFM) and serum substitutes (SS) in animal cell culture: downstream considerations;685
26.3.1;ABSTRACT;685
26.3.2;INTRODUCTION;685
26.3.3;MATERIALS AND METHODS;685
26.3.4;RESULTS;686
26.3.5;CONCLUSIONS;687
26.3.6;REFERENCES;688
26.4;Chapter 114. The use of affinity chromatography for the purification of monoclonal antibodies;689
26.4.1;INTRODUCTION;689
26.4.2;MATERIALS AND METHODS;689
26.4.3;RESULTS AND DISCUSSION;690
26.4.4;LITERATURE;692
27;Section 10: Products;694
27.1;Chapter 115. Production of a pharmaceutical enzyme: animal cells or E.coli?;696
27.1.1;Introduction;696
27.1.2;Choice of production system;697
27.1.3;tPA production by E. coli;699
27.1.4;tPA production in CHO cells;702
27.1.5;tPA production by hybridomes;704
27.1.6;Down stream processing;707
27.1.7;Relative production costs of tPA in animal cells and in E.coli;712
27.1.8;Purity and quality of the tPA produced;713
27.1.9;Biological activity of animal cell and E.coli derived tPA;715
27.1.10;Conclusions;716
27.1.11;References;718
27.1.12;Paper of Cartwright;721
27.2;Chapter 116. Oral polio vaccine (Sabin) produced on large-scale vero cell culture;722
27.2.1;ABSTRACT;722
27.2.2;INTRODUCTION;722
27.2.3;MATERIAL AND METHODS
;722
27.2.4;RESULTS;723
27.2.5;DISCUSSION;724
27.2.6;ACKNOWLEDGEMENTS;724
27.2.7;REFERENCE;725
27.2.8;Paper of flontagnon;732
27.3;Chapter 117. Strategies for improved production of Epstein-Barr virus;733
27.3.1;ABSTRACT;733
27.3.2;KEYWORDS;733
27.3.3;INTRODUCTION;733
27.3.4;CULTURE OF EBV-INFECTED CELLS IN A BIOREACTOR;733
27.3.5;INDUCTION OF EBV IN MARMOSET B95-8 CELLS;734
27.3.6;PURIFICATION OF EBV USING TANGENTIAL FLOW FILTRATION;734
27.3.7;CONTROL OF EPSTEIN-BARR VIRUS INFECTION;734
27.3.8;ACKNOWLEDGMENTS ;734
27.4;Chapter 118. Optimal conditions for the growth of pig kidney endothelial cells (SK) proliferated on microcarriers and production of pig parvovirus (PPV) vaccine;736
27.4.1;ABSTRACT;736
27.4.2;INTRODUCTION;736
27.4.3;MATERIAL AND METHODS;736
27.4.4;RESULTS;736
27.4.5;DISCUSSION;738
27.5;Chapter 119. Continuous production of a novel thrombolytic from 50/100 litre perfused microcarrier cultures;739
27.5.1;ABSTRACT;739
27.5.2;KEYWORDS;739
27.5.3;INTRODUCTION;739
27.5.4;MATERIALS AND METHODS;739
27.5.5;RESULTS AND DISCUSSION;741
27.5.6;REFERENCES;741
27.6;Chapter 120. Production of recombinant human thyrotropin and its incomplete processing in CHO cells;742
27.6.1;ABSTRACT;742
27.6.2;INTRODUCTON;742
27.6.3;MATERIALS AND METHODS;742
27.6.4;RESULTS AND DISCUSSION;742
27.6.5;ACKNOWLEDGMENTS;744
27.6.6;REFERENCES;744
27.7;Chapter 121. Production of a monoclonal antibody against gelsolin;745
27.7.1;Introduction;745
27.7.2;Materials and methods;745
27.7.3;Results;746
27.7.4;Discussion;748
27.8;Chapter 122. Appearance of nonspecific amounts of monoclonal antibody during fermentation caused by decreased cell viability;749
27.8.1;ABSTRACT;749
27.8.2;INTRODUCTION;749
27.8.3;MATERIALS AND METHODS;749
27.8.4;RESULTS AND DISCUSSION;750
27.8.5;REFERENCES;752
27.9;Chapter 123. Production of biologically active insulin-like growth factor by cells transfected with a recombinant retroviral vector encoding IGF-1;753
27.9.1;ABSTRACT;753
27.9.2;INTRODUCTION;753
27.9.3;MATERIALS AND METHODS;754
27.9.4;RESULTS AND DISCUSSION;755
27.9.5;SUMMARY;757
27.9.6;ACKNOWLEDGEMENTS;757
27.9.7;REFERENCES;758
27.10;Chapter 124. In vitro production of growth regulators for human epithelial cells;759
27.10.1;ABSTRACT;759
27.10.2;INTRODUCTION;759
27.10.3;MATERIALS AND METHODS;759
27.10.4;RESULTS AND DISCUSSION;759
27.10.5;REFERENCES;761
27.11;Chapter 125. Purification and characterization of immunoglobulin production stimulating factor IIa derived from Namalwa cells;762
27.11.1;ABSTRACT;762
27.11.2;INTRODUCTION;762
27.11.3;MATERIALS AND METHODS;763
27.11.4;RESULTS;763
27.11.5;DISCUSSION;766
27.11.6;REFERENCES;767
27.11.7;Paper of Murakami;768
27.12;Chapter 126. Production of a chimeric antibody from tumour imaging and therapy from Chinese hamster ovary (CHO) and myeloma cells;769
27.12.1;ABSTRACT;769
27.12.2;INTRODUCTION;769
27.12.3;EXPRESSION OF CHIMERIC B723 ANTIBODY IN CHO CELLS;769
27.12.4;EXPRESSION OF CHIMERIC B723 IN MYELOMA CELLS;771
27.12.5;CONCLUSIONS;771
27.13;Chapter 127. Optimization of tPA production in a 3L continuous perfusion bioreact;772
27.13.1;SUMMARY;772
27.13.2;INTRODUCTION;772
27.13.3;MATERIALS AND METHODS;772
27.13.4;RESULTS AND DISCUSSION;773
27.13.5;CONCLUSIONS;774
27.13.6;REFERENCES;774
27.14;Chapter 128. The production and assay of tPA from mammalian cells;775
27.14.1;ABSTRACT;775
27.14.2;INTRODUCTION;775
27.14.3;METHODS;775
27.14.4;RESULTS;776
27.14.5;ACKNOWLEDGEMENTS;777
27.14.6;REFERENCES;777
27.15;Chapter 129. Constitutive secretion of soluble CD23 receptors in hollow fiber rea;778
27.15.1;ABSTRACT;778
27.15.2;INTRODUCTION;778
27.15.3;MATERIALS AND METHODS;778
27.15.4;RESULTS;779
27.15.5;CONCLUSIONS;780
27.15.6;REFERENCES;780
27.16;130. Production of proteins from cell nuclei by cyclic continuous fermentation;781
27.16.1;Introduction;781
27.16.2;Experimental;781
27.16.3;Results;781
27.16.4;References;783
28;Section 11: Regulatory issues;784
29;Chapter 131. Biologicals and regulatory aspects in the EEC;786
29.1;Paper of Horaud;794
29.2;Workshop of Regulatory Matters;795
30;Chapter 132. Mapping of N-linked oligosaccharides from human recombinant glycoproteins: quality control of glycosylated therapeutic polypeptides;802
30.1;ABSTRACT;802
30.2;INTRODUCTION;802
30.3;MATERIALS AND METHODS;803
30.4;RESULTS AND DISCUSSION;804
30.5;References;808
30.6;Paper of Conradt;809
31;Chapter 133. Validation of downstream processing;810
31.1;ABSTRACT AND INTRODUCTION;810
31.2;BASIC PRINCIPLES OF A VALIDATION DESIGN;810
31.3;VIRUSES IN VALIDATIONS;812
31.4;PPORT-FMS IN EVALUATING VALIDATIONS;812
31.5;INACTIVATION VERSUS CLEARANCE;815
32;Chapter 134. The culture environment affects recombinant protein processing in CHO
cells;816
32.1;ABSTRACT;816
32.2;INTRODUCTION;816
32.3;MATERIALS AND METHODS;816
32.4;RESULTS AND DISCUSSION;817
32.5;ACKNOWLEDGEMENTS;819
32.6;REFERENCES;821
32.7;Paper of Hayter;822
33;Chapter 135. The Medi-Cult Hybritest - a new test for in vitro toxicology;823
33.1;ABSTRACT;823
33.2;INTRODUCTION;823
33.3;MATERIALS AND METHODS;823
33.4;RESULTS AND DISCUSSION;824
33.5;ACKNOWLEDGEMENTS;825
33.6;REFERENCES;825
34;List of exhibitors;826
35;List of participants;828
36;Subject index;838
37;Author index;850