Industrial scale suspension culture of living cells:
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| Format: | Buch |
| Sprache: | English |
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Weinheim
Wiley Blackwell
2014
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| Beschreibung: | XXIX, 612 S. Ill., graph. Darst. 244 mm x 170 mm |
| ISBN: | 3527335471 9783527335473 9783527683321 |
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| 245 | 1 | 0 | |a Industrial scale suspension culture of living cells |c ed. by Hans-Peter Meyer ... |
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| 300 | |a XXIX, 612 S. |b Ill., graph. Darst. |c 244 mm x 170 mm | ||
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Datensatz im Suchindex
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I VII
CONTENTS
FOREWORD V
PREFACE
XXI
LIST OF CONTRIBUTORS XXIII
THE HISTORY AND ECONOMIC RELEVANCE OF INDUSTRIAL SCALE
SUSPENSION CULTURE OF LIVING CELLS 1
HANS-PETER MEYER AND
DIEGO R. SCHMIDHALTER
1 INTRODUCTION 2
2 A SHORT HISTORY OF SUSPENSION CULTURE (FERMENTATION) 2
2.1 ETHANOL, ORGANIC ACIDS, AND SOLVENTS, THE BEGINNING 2
2.2 VITAMINS FERMENTATION TAKES A LONG TIME TO DEVELOP 4
2.3 STEROIDS, THE FIRST LARGE-SCALE BIOCATALYSIS PROCESSES 5
2.4 ANTIBIOTICS, A US-LEAD TURNING POINT IN FERMENTATION TECHNOLOGY 5
2.5 AMINO ACIDS, A JAPANESE FERMENTATION SUCCESS STORY
8
2.6 ENZYMES, A EUROPEAN FERMENTATION SUCCESS STORY 9
2.7 SINGLE CELL PROTEINS, AN ECONOMIC FLOP 9
2.8 BIOFUELS ARE CONTROVERSIAL STORY 10
2.9 RECOMBINANT DNA TECHNOLOGY BASED PRODUCTS (MONOCLONAL
ANTIBODIES AND OTHER RECOMBINANT PROTEINS), SETTING OFF AN AVALANCHE
OF NEW PRODUCTS
11
3 THE CONTEMPORARY SITUATION 11
3.1 HOW LONG CAN THE USA KEEP ITS LEADING ROLE? 11
3.2 CHINA AND INDIA BECOME GLOBAL FORCES IN FERMENTATION 12
4 THE FUTURE OF SUSPENSION CULTURE 13
4.1 NEW FRONTIERS 14
4.2 YET "UNCULTURED" CELLS AND ORGANISMS? 15
5 ECONOMIC AND MARKET CONSIDERATIONS 16
5.1 THE PHARMACEUTICAL MARKET 19
5.2 PERSONAL CARE PRODUCTS 25
5.3 CHEMICALS, INDUSTRIAL AND TECHNICAL ENZYMES 27
5.4 FOOD, DIETARY SUPPLEMENTS (FUNCTIONAL FOOD, NUTRACEUTICALS), AND
FEED
PRODUCTS 27
HTTP://D-NB.INFO/1047121239
VIII
| CONTENTS
6 CONDUSIONS 32
REFERENCES 34
PARTI SUSPENSION CULTURE OF BACTERIA, YEASTS, AND FILAMENTOUS FUNGI 39
1 BACTERIAL SUSPENSION CULTURES 41
PATRICK
SAGMEISTER, MOHAMMADHADIJAZINI, JOACHIM KLEIN, AND
CHRISTOPH HERWIG
1.1 INTRODUCTION 41
1.2 ORGANISMS, CELLS, AND THEIR PRODUCTS 42
1.2.1 BACTERIA AS PRODUCTION PLATFORM FOR VARIOUS PRODUCTS 42
1.2.2 HISTORICAL OUTLINE FOR ESCHERICHIA COLI 44
1.2.3 INDUSTRIAL ASPECTS OF BACTERIAL EXPRESSION SYSTEMS 45
1.3 BIOPROCESS DESIGN ASPECTS FOR RECOMBINANT PRODUCTS 51
1.3.1 BACTERIAL CULTIVATION PROCESSES 51
1.3.2 GRAM NEGATIVE CELL FACTORY; CELLULAR COMPARTMENTS AND TRANSPORT
ACROSS MEMBRANES 52
1.3.3 INDUSTRIAL STRATEGIES: QUALITY, FOLDING STATE, AND LOCATION OF
RECOMBINANT PROTEIN PRODUCTS 53
1.3.4 APPROACHES TOWARDS BIOPROCESS DESIGN, OPTIMIZATION, AND
MANUFACTURING 55
1.3.5 BACTERIAL BIOPROCESS DESIGN 56
1.3.5.1 TECHNICAL AND PHYSIOLOGICAL CONSTRAINTS FOR BACTERIAL BIOPROCESS
DESIGN 56
1.3.5.2 MEDIA DESIGN 57
1.3.5.3 PRODUCT TITER IS DETERMINED BY THE BIOMASS CONCENTRATION AND THE
SPECIFIC PRODUCTIVITY Q
P
58
1.3.6 INDUSTRIAL PRODUCTION STRATEGY BY TWO-STEP CULTIVATION 59
1.3.6.1 BATCH PHASE FOR THE ACCUMULATION OF BIOMASS 60
1.3.6.2 STRUCTURED APPROACH TOWARDS BATCH DESIGN 60
1.3.6.3 FED-BATCH PHASE PROCESS DESIGN FROM SCRATCH 61
1.3.6.4 INDUCTION PHASE: PRODUCT FORMATION CHARACTERISTICS 63
1.3.6.5 PROCESS PARAMETERS IMPACTING RECOMBINANT PRODUCT FORMATION 64
1.3.6.6 CONCEPT OF TIME-SPACE YIELD 65
1.4 BASIC BIOREACTOR DESIGN ASPECTS 66
1.4.1 INTRODUCTION 66
1.4.2 VESSEL DESIGN AND CONSTRUCTION 67
1.4.3 DIMENSIONING 67
1.4.3.1 MATERIALS OF CONSTRUCTION 67
1.4.3.2 SURFACE QUALITY AND WELDING 69
1.4.3.3 NOZZLES AND PORTS 70
1.4.4 MASS TRANSFER 70
1.4.5 CLEANING IN PLACE 72
1.4.6 STEAMING IN PLACE 73
CONTENTS | IX
1.4.7 MONITORING AND CONTROL OF BIOPROCESSES 73
1.4.7.1 STANDARD INSTRUMENTATION - MEASURING AND CONTROL OF PROCESS
PARAMETERS 73
1.4.7.2 CHALLENGES WITH BIOREACTOR STANDARD SENSORS 74
1.4.7.3 ADVANCED BIOPROCESS ANALYTICS: REAL-TIME MONITORING OF PROCESS
VARIABLES 74
1.5 SINGLE USE BIOREACTORS FOR MICROBIAL CULTIVATION 76
1.5.1 MULTI-USE OR SINGLE USE? 76
1.5.2 CHALLENGES FOR THE USE OF SINGLE USE BIOREACTORS IN MICROBIAL
BIOPROCESSES 77
1.5.3 MICROBIAL BIOPROCESS DEVELOPMENT USING SINGLE USE BIOREACTORS 77
1.5.4 APPLICATIONS FOR SINGLE USE BIOREACTORS IN MICROBIAL SUSPENSION
CULTURES 79
1.6 QUALITY BY DESIGN: VISION OR THREAT FOR TWENTY-FIRST CENTURY
PHARMACEUTICAL MANUFACTURING 79
1.6.1 REGULATORY DRIVE TOWARDS THE IMPLEMENTATION OF QBD 80
1.6.2 PROCESS DEVELOPMENT ALONG QBD PRINCIPLES 82
1.6.3 ENTRY POINTS TO QBD FOR MANUFACTURERS 84
1.6.4 CHALLENGES FOR PUTTING QBD INTO PRACTICE 84
1.6.5 PROCESS UNDERSTANDING FOR BIOPHARMACEUTICAL PROCESSES 85
1.6.5.1 QUALITY BY DESIGN - OPPORTUNITY OR THREAT FOR THE PHARMACEUTICAL
INDUSTRY?
86
1.7 PROCESS ECONOMICS 87
1.7.1 OPTIMIZATION OF OVERALL PRODUCTIVITY AND CAPITAL EXPENSES OF THE
PRODUCTION FACILITY 87
1.7.2 FURTHER ECONOMIC EFFECTS BY INTRACELLULAR PRODUCT LOCATION
88
1.7.3 COMPARISON OF PRODUCT YIELDS, INTRACELLULAR VERSUS EXTRACELLULAR
88
REFERENCES 90
2 YEAST SUSPENSION CULTURE 95
DIETHARD
MATTANOVICH, CARMEN
JUNGO,JANA WENGER, MICHAL DABROS, AND
MICHAEL
MAURER
2.1 INTRODUCTION 95
2.2 YEAST SPECIES USED IN BIOTECHNOLOGY AND THEIR PRODUCTS 96
2.2.1 EXPRESSION SYSTEMS 98
2.3 BASIC PROCESS DESIGN ASPECTS 98
2.3.1 PROCESS HISTORY 98
2.3.2 YEAST FERMENTATION PROCESSES 99
2.3.3 PROCESS DESIGN FOR ETHANOL PRODUCTION 106
2.3.4 HIGH CELL DENSITY FERMENTATIONS - A DOWNSTREAM PROCESSING
CHALLENGE
AND A YIELD PROBLEM? 106
2.4 BASIC BIOREACTOR DESIGN ASPECTS 107
2.4.1 BIOREACTORS FOR YEAST CULTIVATION 107
2.4.2 METHANOL, SAFETY AND EXPLOSION-PROOF (EX-PROOF) MEASURES 108
2.4.2.1 CONCERNS REGARDING METHANOL USE 108
X | CONTENTS
2.4.2.2 SAFETY ISSUES AND EQUIPMENT DESIGN 108
2.4.2.3 RISK ASSESSMENT 109
2.4.2.4 REGULATIONS 110
2.4.3 PROCESS MONITORING AND CONTROL SOLUTIONS 111
2.4.3.1 THE CLASSICAL FOUR 111
2.4.3.2 ADVANCED BIOPROCESS MONITORING AND CONTROL 112
2.5 KEY FACTORS RELATED TO PROCESS ECONOMICS 114
2.5.1 EQUIPMENT REQUIREMENTS 114
2.5.1.1 UPSTREAM 114
2.5.1.2 PRIMARY RECOVERY 114
2.5.1.3 DOWNSTREAM PROCESSING 115
2.5.2 KEY FACTORS RELATED TO PROCESS ECONOMICS OF THE FERMENTATION
PROCESS 116
2.5.2.1 RAW MATERIALS 116
2.5.2.2 CYCLE TIME 117
2.5.2.3 FORMATION OF BY-PRODUCTS 118
2.5.3 EXPRESSION SYSTEM AND ITS IMPACT ON THE COST OF PRIMARY RECOVERY
AND
PURIFICATION 118
2.5.4 INFLUENCE OF THE EXPRESSION SYSTEM ON THE ANALYTICAL SCOPE IN THE
PRODUCTION 119
2.5.4.1 IN-PROCESS CONTROLS (IPCS) 119
2.5.4.2 FINAL RELEASE ANALYSIS 119
2.5.4.3 ADDITIONAL COSTS 119
2.5.5 ESTIMATION OF COST OF GOODS WITH MODEL SIMULATIONS 119
2.6 REGULATORY ASPECTS 120
2.6.1 FOOD INGREDIENTS 121
2.6.2 PHARMACEUTICALS 121
2.6.2.1 REGULATORY ASPECTS TO CONSIDER/GUIDELINES 122
2.6.2.2 CONSTRUCTION AND QUALITY OF CELL BANKS
(PART OF ICHQ5) 122
2.6.2.3 MANUFACTURING OF APIS BY CELL CULTURE OR MICROBIAL FERMENTATION
(ICHQ7) 124
2.6.2.4 TEST PROCEDURES AND ACCEPTANCE CRITERIA FOR BIOTECHNOLOGICAL
PRODUCTS
(PART OF ICHQ6) 125
2.6.2.5 COMPARABILITY OF BIOTECHNOLOGICAL PRODUCTS AFTER PROCESS CHANGES
(PART
OF ICHQ5) 125
2.7 SUMMARY AND OUTLOOK 126
REFERENCES 127
3 FILAMENTOUS FUNGI FERMENTATION 131
ANDERS
NERREGAARD, STUART
M. STOCKS,
JOHN M. WOODLEY, AND KRIST V. GEMAEY
3.1 INTRODUCTION 131
3.2 PRODUCTS AND ORGANISMS IN THE INDUSTRY 132
3.2.1 BACKGROUND 132
3.2.2 SECONDARY METABOLITES 133
CONTENTS I XI
3.2.3 ORGANIC ACIDS 134
3.2.4 PROTEINS 134
3.3 FILAMENTOUS FUNGI AS A PRODUCTION PLATFORM 135
3.3.1 EXPRESSION SYSTEMS 135
3.3.2 MORPHOLOGY 136
3.3.3 GENOMIC TOOLS 137
3.3.4 SEQUENCING AND GENOME ANNOTATION 13B
3.4 FERMENTATION OF FILAMENTOUS ORGANISMS 140
3.4.1 FERMENTATION PLATFORMS 140
3.4.2 REACTOR DESIGN 141
3.4.3 AGITATION AND AERATION 141
3.4.4 MASS TRANSFER 143
3.4.5 REACTOR CONTROL 146
3.4.6 RHEOLOGY 147
3.4.7 MIXING TIME AND CAVERN FORMATION 151
3.4.8 CORRELATION BETWEEN VISCOSITY AND K
L
A 151
3.5 PROCESS SCALING 152
3.5.1 DIMENSIONLESS NUMBERS 153
3.5.2 POWER DRAW 154
3.5.3 MODELING OXYGEN MASS TRANSFER 155
3.6 REGULATORY ASPECTS 156
3.7 ECONOMIC ASPECTS 157
3.8 CONCLUSIONS AND PERSPECTIVES 157
REFERENCES 158
PART II SUSPENSION CULTURE OF ALGAE AND PLANT CELLS 163
4 MICROALGAE CROWN UNDER HETEROTROPHIC AND MIXOTROPHIC CONDITIONS 165
KARIN KOVAR,
PAVEL PRIBYL,
AND MARKUS WYSS
4.1 ECO-PHYSIOLOGY AND GENETICS OF BIOTECHNOLOGICALLY RELEVANT
SPECIES 165
4.1.1 TAXONOMY 166
4.1.2 ACCESS TO AXENIC CULTURES AND SCREENING FOR BIOACTIVITIES 167
4.1.3 BIOTECHNOLOGICALLY RELEVANT SPECIES AND THEIR GENETIC
IMPROVEMENT 168
4.2 PRODUCTS FROM MICROALGAE GROWN IN THE ABSENCE OF LIGHT 172
4.3 BIOREACTOR DESIGN 174
4.4 PROCESS DESIGN: CULTURE MEDIA AND PROCESS CONTROL
STRATEGIES 174
4.5 PROCESS ECONOMICS 176
4.6 COMMERCIALIZATION OF MICROALGAE-DERIVED PRODUCTS AND REGULATORY
ASPECTS 176
REFERENCES 178
XII
| CONTENTS
5 RECOMBINANT PROTEIN PRODUCTION WITH MICROALGAE 187
ALEXANDRE
LEJEUNE, REMY
MICHEL, AND AUDE CARLIER
5.1 ORGANISMS, CELLS, EXPRESSION SYSTEMS, PRODUCTS 187
5.2 PRODUCTION OF RECOMBINANT THERAPEUTICS IN MICROALGAE: PROCESS
DESIGN ASPECTS 189
5.2.1 OVERALL PROCESS OVERVIEW FROM GENETIC TRANSFORMATION TO CELL
BANKING 18 9
5.2.2 BASIC ASPECTS OF CULTIVATION OF MICROALGAL CELLS FOR PRODUCTION OF
RECOMBINANT THERAPEUTIC PROTEINS 190
5.3 REGULATORY ASPECTS 192
5.4 SUMMARY AND OUTLOOK 194
REFERENCES 195
6 SUSPENSION CULTURE OF MICROORGANISMS (ALGAE AND CYANOBACTERIA)
UNDER PHOTOTROPHIC CONDITIONS 199
PETER BERGMANN, ASTRID
NISSEN, LARS
BEYER, PETER
RIPPLINGER,
AND WALTER TROSCH
6.1 INTRODUCTION 199
6.1.1 PHOTOSYNTHETIC MICROORGANISMS (ALGAE AND CYANOBACTERIA) IN
GENERAL 200
6.1.2 MICROALGAL EVOLUTION AND TAXONOMY 201
6.1.3 MICROALGAE IN BIOTECHNOLOGY 201
6.1.4 INDUSTRIAL MICROALGAE BIOTECHNOLOGY - A BRIEF HISTORY 202
6.2 BASIC PROCESS DESIGN ASPECTS 203
6.3 LARGE-SCALE CULTIVATION SYSTEMS 206
6.3.1 OPEN PONDS - TECHNOLOGY OVERVIEW 207
6.3.2 OPEN PONDS - PRODUCTION SITES 208
6.3.3 OPEN PONDS - PERFORMANCE 209
6.3.4 OPEN PONDS - ENERGY CONSUMPTION 210
6.4 PHOTOBIOREACTORS - TECHNOLOGY OVERVIEW 211
6.4.1 PHOTOBIOREACTORS - TUBULAR 212
6.4.1.1 TUBULAR PHOTOBIOREACTORS - PRODUCTION SITES 213
6.4.1.2 TUBULAR PHOTOBIOREACTORS - PERFORMANCE 213
6.4.1.3 TUBULAR PHOTOBIOREACTORS - ENERGY CONSUMPTION 214
6.4.2 PHOTOBIOREACTORS - FLAT-PLATE 215
6.4.2.1 FLAT-PLATE PHOTOBIOREACTORS - PRODUCTION SITES 217
6.4.2.2 FLAT-PLATE PHOTOBIOREACTORS - PERFORMANCE 217
6.4.2.3 FLAT-PLATE PHOTOBIOREACTORS - ENERGY CONSUMPTION 217
6.5 CONCLUSION/OUTLOOK 218
REFERENCES 219
7 SUSPENSION CULTURE OF PLANT CELLS UNDER HETEROTROPHIC CONDITIONS 225
NICOLE
IMSENG, STEFAN SCHILLBERG, CORNELIA
SCHURCH, DANIEL
SCHMID,
KAI SCHUTTE, GILBERT CORR,
DIETER EIBL, AND
REGINE
EIBL
7.1 INTRODUCTION 225
CONTENTS
7.2 IN VITRO
INITIATION AND MAINTENANCE OF PLANT CELL SUSPENSION
CULTURES 229
7.2.1 GENERAL PROCEDURE 229
7.2.2 PLANT STEM CELLS 231
7.2.3 NON-TRANSFORMED AND GENETICALLY MODIFIED PLANT CELL
SUSPENSIONS 233
7.3 CHARACTERISTICS OF HETEROTROPHIC PLANT SUSPENSION CELLS AND
RESULTING
PROCESS DESIGN 235
7.3.1 CULTURE CHARACTERISTICS AND TYPICAL CULTIVATION PARAMETERS 235
7.3.2 PRIMARY CELL METABOLISM AND CULTURE MEDIA 236
7.3.3 PROCESS MODE 237
7.4 SUITABLE BIOREACTORS 238
7.4.1 CATEGORIZATION APPROACH 238
7.4.2 MOST OFTEN USED BIOREACTORS TYPES 240
7.5 COMMERCIAL MANUFACTURE OF PLANT CELL-DERIVED COSMETICS AND
THERAPEUTICS UNDER ADDITIONAL CONSIDERATION OF ECONOMIC AND
REGULATORY ASPECTS 243
7.5.1 CASE STUDY: PHYTOCEUTEC* MALUS DOMESTICA 243
7.5.1.1 PRODUCTION PROCESS 243
7.5.1.2 EFFECTIVENESS OF THE BIOACTIVE INGREDIENTS PRODUCED IN VITRO 244
7.5.2 CASE STUDY: PACLITAXEL 248
7.5.2.1 INTRODUCTION 248
7.5.2.2 CELL LINE DEVELOPMENT AND CRYOPRESERVATION 249
7.5.2.3 PCF* PROCESS CONDITIONS 250
7.5.2.4 SUMMARY 252
7.6 CONCLUSION 252
REFERENCES 252
8 SUSPENSION CULTURE OF PLANT CELLS UNDER PHOTOTROPHIC CONDITIONS 261
HOLGER NIEDERKR'UGER,
PAULINA DABROWSKA-SCMEPP, AND
ANDREAS SCHAAF
8.1 INTRODUCTION 261
8.2 BRYOTECHNOLOGY*: PRODUCTION OF BIOLOGIES WITH MOSS
(PHYSCOMITRELLA PATENS) 262
8.2.1 CHARACTERISTICS OF BRYOTECHNOLOGY* 262
8.2.1.1 MOSS TAXONOMY AND NATURAL HABITATS 262
8.2.1.2 LIFE CYCLE AND PHYSIOLOGY 262
8.2.1.3 HOMOLOGOUS RECOMBINATION 263
8.2.1.4 RECOMBINANT PROTEIN PRODUCTION 265
8.2.2 BASIC PROCESS DESIGN ASPECTS 265
8.2.2.1 TRANSFORMATION 265
8.2.2.2 EXPRESSION VECTORS 266
8.2.2.3 STRAIN DEVELOPMENT 266
8.2.2.4 CELL BANKING 267
8.2.2.5 UPSTREAM PROCESS 267
8.2.2.6 HARVEST 269
XIV
| CONTENTS
8.2.2.7 DOWNSTREAM 271
8.2.2.8 TIMELINES OF PROCESS DEVELOPMENT 272
8.2.3 BASIC BIOREACTOR DESIGN ASPECTS 272
8.2.3.1 ILLUMINATION 275
8.2.3.2 BIOMASS HANDLING 275
8.2.3.3 IPC 276
8.2.3.4 PROCESS SCALE-UP 276
8.2.3.5 CURRENT LIMITATIONS 277
8.2.4 SUMMARY AND OUTLOOK 279
8.3 THE LEX-SYSTEM: PRODUCTION OF BIOLOGIES WITH DUCKWEED
(LEMNA MINOR) 280
8.3.1 CHARACTERISTICS OF THE LEX-SYSTEM 280
8.3.1.1 DUCKWEED TAXONOMY, PHYSIOLOGY AND MORPHOLOGY 280
8.3.1.2 BIOTECHNOLOGICAL ASPECTS OF DUCKWEED 280
8.3.1.3 TIMELINES OF PROCESS DEVELOPMENT 281
8.3.2 BASIC PROCESS DESIGN ASPECTS 281
8.3.2.1 EXPRESSION VECTORS 281
8.3.2.2 STRAIN DEVELOPMENT 282
8.3.2.3 MASTER-PLANT BANKING 282
8.3.2.4 UPSTREAM PROCESS 282
8.3.2.5 DOWNSTREAM 283
8.3.3 BASIC BIOREACTOR DESIGN ASPECTS 284
8.3.4 SUMMARY AND OUTLOOK 285
8.4 KEY FACTORS RELATED TO PROCESS ECONOMICS 285
8.5 REGULATORY ASPECTS 286
REFERENCES 288
PART III SUSPENSION CULTURE OF PROTOZOA, INSECT CELLS, AVIAN CELLS,
AND MAMMALIAN CELLS 293
9 SUSPENSION CULTURE OF PROTOZOAN ORGANISMS 295
MARCUS W.W. HARTMANN AND REINHARD BREITLING
9.1 INTRODUCTION 295
9.2 CILIATES 296
9.2.1 SPECIFIC FEATURES OF CILIATES 296
9.2.2 SUSPENSION CULTURE OF CILIATES 299
9.2.3 STRENGTHS OF THE CILIATE TETRAHYMENA THERMOPHILA 304
9.2.3.1 MASS CULTIVATION, SCALABILITY, AND USABILITY OF MARKET STANDARD
FERMENTATION EQUIPMENT 304
9.2.3.2 RELIABLE HIGH-EFFICIENCY TRANSFORMATION PROTOCOLS 305
9.2.3.3 ESTABLISHED EXPRESSION VECTORS 305
9.2.3.4 SERUM-FREE COMPLEX- AND CHEMICALLY-DEFINED MEDIA 307
9.2.3.5 CONSISTENT AND ADVANTAGEOUS N-GLYCOSYLATION WITH LACK OF FUCOSE
309
CONTENTS I XV
9.2.4 CHALLENGES FOR USING TETRAHYMENA IN PRODUCTION OF RECOMBINANT
PROTEINS 310
9.2.4.1 LACK OF TERMINAL SIALYLATION AND -Y-CARBOXYLATION AS
POST-TRANSLATIONAL
MODIFICATIONS 310
9.2.5 BIG LINES TO CLASSES OF PRODUCTS AND MAIN MARKETS 311
9.2.5.1 TETRAHYMENA AS NEW PRODUCTION PLATFORM TECHNOLOGY 311
9.2.6 BASIC PROCESS DESIGN ASPECTS FOR TETRAHYMENA SUSPENSION CULTURE
313
9.2.6.1 PRINCIPAL BIOREACTOR SET UP FOR TETRAHYMENA SUSPENSION CULTURE
313
9.2.6.2 INOCULATION TITER, CELL COUNTING AND DRY MASS 314
9.2.6.3 AGITATION RATE AND SHEAR STRESS 315
9.2.6.4 AERATION, DISSOLVED OXYGEN CONCENTRATION, AND ANTIFOAM
REAGENTS 315
9.2.6.5 MUCOCYST MATERIAL 316
9.2.7 BASIC BIOREACTOR DESIGN ASPECTS FOR TETRAHYMENA SUSPENSION
CULTURE 316
9.2.8 KEY FACTORS IN PROCESS ECONOMICS 317
9.2.8.1 INVESTMENT COSTS 317
9.2.8.2 COST OF GOODS FOR FERMENTATION 318
9.2.8.3 OTHER COSTS 318
9.3 FLAGELLATES 319
9.3.1 SPECIFIC FEATURES OF FLAGELLATES 319
9.3.2 SUSPENSION CULTURE OF HEMOFLAGELLATES 322
9.3.3 STRENGTHS OF THE HEMOFLAGELLATE LEISHMANIA TARENTOLAE 324
9.3.4 CHALLENGES FOR THE APPLICATION OF THE HEMOFLAGELLATE
LEISHMANIA TARENTOLAE 326
9.3.5 BIG LINES TO CLASSES OF PRODUCTS AND MAIN MARKETS 327
9.3.6 BASIC PROCESS DESIGN ASPECTS FOR LEISHMANIA SUSPENSION CULTURE 328
9.3.7 BASIC BIOREACTOR DESIGN ASPECTS FOR LEISHMANIA SUSPENSION
CULTURE 331
9.3.8 KEY FACTORS FOR PROCESS ECONOMICS 332
9.4 REGULATORY ASPECTS OF PROTOZOAN PRODUCTION ORGANISM 334
9.5 SUMMARY AND OUTLOOK 335
REFERENCES 336
10 INDUSTRIAL LARGE SCALE OF SUSPENSION CULTURE OF INSECT CELLS 349
ANTONIO ROLDAO,
MARION COX, PAULA ABES,
MANUEL CARRONDO,
AND TIAGO VICENTE
10.1 HISTORY 349
10.2 CONCEPTS IN INSECT CELL CULTURE 351
10.2.1 CELL TYPES, EXPRESSION SYSTEMS, AND PRODUCTS 351
10.2.2 MAINTAINING INSECT CELLS IN CULTURE - REQUIREMENTS OF THE
BIOREACTOR
DESIGN 358
10.2.3 INSECT CELL METABOLISM: A BRIEF OVERVIEW 364
10.2.4 A BOTTOM-UP APPROACH FOR INDUSTRIAL INSECT CELL-BASED CULTURES
366
10.2.4.1 UPSTREAM PROCESS DEVELOPMENT STRATEGIES 367
CONTENTS
10.2.4.2 DOWNSTREAM PROCESS DEVELOPMENT STRATEGIES 370
10.3 REGULATORY HURDLES FOR INSECT DERIVED HUMAN PRODUCTS 374
10.3.1 CASE STUDY; FLUBLOK REGULATORY HISTORY 376
10.4 WHAT COMES NEXT? 377
10.4.1 IMPROVEMENTS IN PRODUCTION CYCLE AND YIELDS 377
REFERENCES 378
71
AVIAN SUSPENSION CULTURE CELL LINES FOR PRODUCTION OF VACCINES AND
OTHER
BIOLOGICALS 391
MANFRED
REITER,
DANIEL
PORTSMOUTH, AND P. NOEL BARRETT
11.1 DEVELOPMENT OF CELL CULTURE FOR THE PRODUCTION OF VACCINES AND
BIOLOGICALS 391
11.2 AVIAN CELL LINES 393
11.3 POTENTIAL OF AVIAN CELL LINES FOR THE MANUFACTURE OF VACCINES AND
BIOLOGICALS 394
11.3.1 MODIFIED VACCINIA VIRUS ANKARA (MVA) VACCINES 394
11.3.2 YELLOW FEVER VACCINES 3 94
11.3.3 TBEV VACCINES 395
11.3.4 INFLUENZA VACCINES 395
11.3.5 MONOCLONAL ANTIBODIES 397
11.4 DEVELOPMENT OF AVIAN CELL LINES 397
11.4.1 EB66 (VIVALIS) 398
11.4.2 AGE1.CR (PROBIOGEN) 399
11.4.3 QOR2/2E11 (BAXTER) 400
11.4.3.1 ESTABLISHMENT OF QOR2/2E11 400
11.4.3.2 CHARACTERIZATION AND GMP QUALIFICATION 401
11.4.3.3 VIRUS GROWTH IN QOR2/2E11 CELLS 401
11.4.3.4 MVA VIRUS REPLICATION ON QOR2/2E11 CELLS AT DIFFERENT MOIS
AND TEMPERATURE 403
11.4.4 CHICKEN EMBRYO CELL LINE PBS-12SF
(MICHIGAN STATE UNIVERSITY, USA) 405
11.5 BASIC PROCESS DESIGN ASPECTS 405
11.6 BASIC BIOREACTOR DESIGN ASPECTS 405
11.7 KEY FACTORS RELATED TO PROCESS ECONOMICS 405
11.8 REGULATORY ASPECTS 406
11.9 SUMMARY AND OUTLOOK 406
REFERENCES 407
12 LARGE SCALE
SUSPENSION CULTURE OF MAMMALIAN CELLS 411
RICHARD
M. ALLDREAD,
JOHN R. BIRCH,
HILARY K. METCALFE, SUZANNE FARID,
ANDREW
J. RACHER, ROBERT J. YOUNG AND
MOHSAN KHAN
12.1 INTRODUCTION TO MAMMALIAN CELL CULTURE 412
12.1.1 BRIEF HISTORY OF THE USE OF MAMMALIAN CELL CULTURE 412
12.1.2 WHY MAMMALIAN CELLS FOR PROTEIN PRODUCTION? 413
12.1.3 COMMERCIAL IMPORTANCE OF MAMMALIAN CELL CULTURE 414
CONTENTS | XVII
12.1.4 MAMMALIAN CELL CULTURE INDUSTRY 415
12.2 CELL LINES AND EXPRESSION TECHNOLOGIES 417
12.2.1 INTRODUCTION 417
12.2.2 HOST CELL LINES FOR MANUFACTURING THERAPEUTIC PROTEINS 419
12.2.2.1 REGULATORY ACCEPTANCE 419
12.2.2.2 PRODUCTIVITY OF CHO CELL LINES 419
12.2.2.3 CELL LINE DEVELOPMENT TIMELINE 420
12.2.2.4 PRODUCT CHARACTERISTICS 420
12.2.2.5 CURRENT STATUS AND FUTURE DEVELOPMENTS 420
12.2.3 SELECTING HIGHLY PRODUCTIVE CELL LINES 421
12.2.4 EXPRESSION VECTOR ARCHITECTURE 421
12.2.4.1 INSULATOR AND CHROMATIN OPENING SEQUENCES 423
12.2.5 SELECTION MARKERS 424
12.2.6 TARGETED INTEGRATION 425
12.3 BIOREACTOR DESIGN 427
12.3.1 INTRODUCTION 427
12.3.2 TYPES OF MAMMALIAN CELL CULTURE BIOREACTORS 428
12.3.2.1 STIRRED-TANK BIOREACTOR 428
12.3.2.2 AIRLIFT BIOREACTOR 429
12.3.2.3 WAVE-BASED BIOREACTOR 430
12.3.3 SCALE UP CONSIDERATIONS 431
12.3.3.1 MIXING 431
12.3.3.2 MASS TRANSFER 432
12.3.3.3 SHEAR 432
12.3.3.4 PRESSURE 432
12.3.3.5 SCALE UP STRATEGY 433
12.3.4 STERILIZATION AND CLEANING 433
12.3.5 SINGLE USE BIOREACTOR SYSTEMS 435
12.4 PROCESS OPERATION 436
12.4.1 BATCH AND FED-BATCH CULTURE 436
12.4.2 PERFUSION CULTURE 438
12.4.3 CULTURE MEDIA AND FEEDS 439
12.4.4 NON-NUTRIENT ADDITIONS 439
12.4.5 CONTROL PARAMETERS 440
12.4.5.1 TEMPERATURE 440
12.4.5.2 PH 441
12.4.5.3 DISSOLVED OXYGEN CONCENTRATION 442
12.4.5.4 CARBON DIOXIDE CONCENTRATION 442
12.4.5.5 OSMOLARITY 443
12.5 PROCESS ECONOMICS OF MAMMALIAN CELL CULTURE 443
12.5.1 PROCESS ECONOMIC CHALLENGES 443
12.5.2 PROCESS ECONOMIC DRIVERS 444
12.5.3 ANTIBODY PROCESS ECONOMICS CASE STUDIES 447
12.5.3.1 STAINLESS STEEL VERSUS SINGLE USE DECISIONS 447
12.5.3.2 FED-BATCH VERSUS PERFUSION DECISIONS 448
XVIII
| CONTENTS
12.5.3.3 ROBUSTNESS OF LEGACY PURIFICATION FACILITIES TO HIGHER TITER
PROCESSES 450
12.6 REGULATORY ASPECTS 450
12.6.1 SOURCE, HISTORY, AND GENERATION OF THE CELL SUBSTRATE 451
12.6.2 CELL BANKS 452
12.6.3 CELL SUBSTRATE STABILITY 452
12.6.4 EXPRESSION VECTOR 452
12.6.5 CHARACTERIZATION OF CELL BANKS 452
12.6.6 QUALITY BY DESIGN (QBD) 453
12.7 SUMMARY AND OUTLOOK 453
REFERENCES 455
PART IV SUSPENSION CULTURE FOR SPECIAL PRODUCTS 463
13 PILLARS OF REGENERATIVE MEDICINE: THERAPEUTIC HUMAN CELLS AND THEIR
MANUFACTURE 465
CHRISTIAN VAN DEN BOS,
ROBERT
KEEFE, CARMEN SCHIRMAIER,
AND MICHAEL MCCAMAN
13.1 INTRODUCTION 465
13.1.1 REGENERATION 465
13.1.2 THERAPEUTICALLY VALUABLE CELLS 466
13.2 AUTOLOGOUS THERAPIES 468
13.2.1 T-CELLS 470
13.2.2 DENDRITIC CELLS 473
13.2.3 NATURAL KILLER CELLS 474
13.2.4 HEMATOPOIETIC STEM CELLS 475
13.3 ALLOGENEIC THERAPIES 476
13.3.1 BACKGROUND 476
13.3.2 CURRENT DEFINITION 477
13.3.3 ACTIVITY 477
13.3.4 ANIMAL MODELS 478
13.3.5 SAFETY 479
13.3.6 LACK OF REJECTION 479
13.3.7 IMMUNITY AND MANUFACTURING 480
13.3.8 MANUFACTURING AND TECHNOLOGY TRANSITIONS 480
13.3.9 CHALLENGES TO MANUFACTURING 480
13.3.9.1 DOSING 481
13.3.9.2 BIOLOGICAL LIMITATIONS TO CULTURE EXPANSION YIELDS 482
13.3.9.3 REGULATORY EXPECTATIONS 482
13.3.10 MARKERS VERSUS PROCESS 483
13.3.11 CURRENT SOLUTIONS 483
13.3.12 FORTHCOMING SOLUTIONS, LESSONS FROM BIOPRODUCTION VERSUS MSC
BIOLOGY 484
CONTENTS | XIX
13.3.13 ADAPTATION/DIRECTED EVOLUTION OF INDUSTRIAL CELL
LINES 486
13.3.14 THERAPEUTIC CELLS SHOULD NOT BE ADAPTED 486
13.3.15 PROVIDING SCALABLE ADHESION SURFACES IN STIRRED-TANK
BIOREACTORS:
MICROCARRIER BASED BIOREACTOR PROCESSES 487
13.3.15.1 EXPANDING ADULT SOMATIC STEM CELLS: A MEDIUM SCALE BIOREACTOR
EXAMPLE 488
13.3.16 CRITICAL QUALITY ATTRIBUTES (CQAS) FOR THERAPEUTIC CELLS 488
13.3.17 POTENCY 490
13.3.18 PRACTICAL CHALLENGES 493
13.3.19 FUTURE DIRECTIONS FOR CELL TESTING 493
13.4 DOWNSTREAM PROCESSING 494
13.5 KEY FACTORS TOWARDS ECONOMIC SUCCESS 496
13.6 REGULATORY CONSIDERATIONS 497
13.7 SUMMARY AND OUTLOOK 497
REFERENCES 498
14 VIRUS PRODUCTION UNDER SUSPENSION CONDITIONS 503
OTTO-WILHELM MERTEN, WILFRIED AM. BAKKER,
J'IIRGEN VORLOP,
MANFRED
REITER, GABRIEL VISNOVSKY, VOLKERJ'AGER, MAIA MERABISHVILI,
AND UDO REICHL
14.1 INTRODUCTION 503
14.2 ADHERENT VERSUS SUSPENSION CULTURE FOR VIRUS PRODUCTION 504
14.2.1 VIRAL VACCINES FOR HUMAN USE PRODUCED WITH MICROCARRIER BASED
MANUFACTURING PROCESSES 506
14.2.2 TOWARDS SINGLE CELL SUSPENSION PROCESSES FOR VIRUS PRODUCTION 506
14.3 POLIO VIRUS/VACCINES 508
14.3.1 INTRODUCTION 508
14.3.2 LARGE-SCALE IPV MANUFACTURING USING VERO CELLS GROWN ON
MICROCARRIERS 509
14.3.3 PER.C6 AND OTHER CELL LINES FOR FUTURE POLIO VACCINE PRODUCTION
509
14.3.4 FUTURE PERSPECTIVES IN IPV MANUFACTURING 511
14.4 INFLUENZA VIRUS/VACCINES 512
14.4.1 INTRODUCTION 512
14.4.2 USE OF ANCHORAGE DEPENDENT CELL LINES - DEVELOPMENT OF
MICROCARRIER
BASED SUSPENSION PROCESSES 512
14.4.3 USE OF CELL LINES ADAPTED TO SUSPENSION GROWTH 514
14.5 MODIFIED VACCINIA ANKARA (MVA) PRODUCTION IN SUSPENSION
CELL LINES 517
14.6 PRODUCTION OF VIRUSES FOR GENE THERAPY PURPOSE 519
14.6.1 LARGE SCALE ADENOVIRUS PRODUCTION USING SUSPENSION CULTURE
PROCESSES 520
14.6.2 LARGE SCALE AAV PRODUCTION USING SUSPENSION CULTURE PROCESSES -
COMPARISON OF DIFFERENT PRODUCTION SYSTEMS 523
14.6.3 LV VECTOR PRODUCTION - TOWARDS THE USE OF SUSPENSION PROCESS FOR
TRANSIENT VECTOR PRODUCTION 527
XX | CONTENTS
14.7 OTHER VIRUSES 532
14.7.1 PRODUCTION OF VIRUSES FOR VETERINARY VACCINES 532
14.7.2 PRODUCTION OF BIO-PESTICIDES USING THE INSECT CELL/BACULOVIRUS
SYSTEM 533
14.7.3 PRODUCTION OF BACTERIOPHAGES USING BACTERIAL SUSPENSION CULTURES
FOR
PHAGE-THERAPY 537
14.7.3.1 INTRODUCTION 537
14.7.3.2 BACTERIAL STRAINS - SELECTION FOR BACTERIOPHAGE GENERATION 538
14.7.3.3 BACTERIOPHAGES - ISOLATION 539
14.7.3.4 BACTERIOPHAGES - PRODUCTION 540
14.7.3.5 LARGE SCALE PRODUCTION OF PHAGES 540
14.8 CONCLUDING REMARKS 542
REFERENCES 543
15 CULTIVABLE MARINE ORGANISMS AS A SOURCE OF NEW PRODUCTS 555
JEAN-MICHEL KOMPROBST
15.1 INTRODUCTION 555
15.2 SUBSTANCES OF INTEREST ISOLATED FROM ARCHAEA AND PROKARYOTES 557
15.2.1 ARCHAEA 557
15.2.2 NON-PHOTOSYNTHETIC BACTERIA 558
15.2.3 CYANOBACTERIA 560
15.3 SUBSTANCES OF INTEREST ISOLATED FROM UNICELLULAR EUKARYOTES 560
15.3.1 UNICELLULAR CHLOROPHYTA AND RHODOPHYTA 563
15.3.2 DIATOMS, CHRYSOPHYCEAE, RAPHIDOPHYCEAE, AND
EUSTIGMATOPHYCEAE 564
15.3.3 HAPTOPHYCEAE (= PRYMNESIOPHYCEAE) 565
15.3.4 FUNGI AND THRAUSTOCHYTRIDS 565
15.3.5 DINOFLAGELLATES 567
15.4 SUBSTANCES OF INTEREST ISOLATED FROM MICROORGANISMS ASSOCIATED WITH
PLURICELLULAR ORGANISMS 570
15.4.1 BACTERIA AND SPONGES 570
15.4.2 BACTERIA AND BRYOZOANS 572
15.4.3 BACTERIA, PROCHLOROPHYTA, AND DIDEMNIDAE 572
15.4.4 DINOFLAGELLATES AND CNIDARIA 573
15.4.5 DINOFLAGELLATES AND PLATYHELMINTHES (FLAT WORMS) 575
15.5 SUBSTANCES OF INTEREST PRODUCED BY SPONGE CELL CULTURE 575
15.6 SUBSTANCES OF INTEREST ISOLATED BY CULTURE OF MACROORGANISMS 575
15.6.1 RED ALGAE AND MARINE SPERMATOPHYTA 578
15.6.2 GREEN ALGAE AND MOLLUSCS 579
15.7 CONCLUSION AND FUTURE PROSPECTS 579
REFERENCES 584
INDEX 593 |
| any_adam_object | 1 |
| author2 | Meyer, Hans-Peter 195X- |
| author2_role | edt |
| author2_variant | h p m hpm |
| author_GND | (DE-588)1053308264 |
| author_facet | Meyer, Hans-Peter 195X- |
| building | Verbundindex |
| bvnumber | BV041896172 |
| classification_rvk | WF 9735 |
| classification_tum | CIT 940f |
| ctrlnum | (OCoLC)870543636 (DE-599)DNB1047121239 |
| dewey-full | 660.62 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 660 - Chemical engineering |
| dewey-raw | 660.62 |
| dewey-search | 660.62 |
| dewey-sort | 3660.62 |
| dewey-tens | 660 - Chemical engineering |
| discipline | Chemie / Pharmazie Biologie Chemie-Ingenieurwesen Biotechnologie |
| format | Book |
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| id | DE-604.BV041896172 |
| illustrated | Illustrated |
| indexdate | 2024-09-10T01:16:12Z |
| institution | BVB |
| isbn | 3527335471 9783527335473 9783527683321 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027339995 |
| oclc_num | 870543636 |
| open_access_boolean | |
| owner | DE-29T DE-91G DE-BY-TUM DE-83 |
| owner_facet | DE-29T DE-91G DE-BY-TUM DE-83 |
| physical | XXIX, 612 S. Ill., graph. Darst. 244 mm x 170 mm |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| publisher | Wiley Blackwell |
| record_format | marc |
| spelling | Industrial scale suspension culture of living cells ed. by Hans-Peter Meyer ... Weinheim Wiley Blackwell 2014 XXIX, 612 S. Ill., graph. Darst. 244 mm x 170 mm txt rdacontent n rdamedia nc rdacarrier Zellkultur (DE-588)4067547-6 gnd rswk-swf Submerskultur (DE-588)4417433-0 gnd rswk-swf Suspensionskultur (DE-588)4272660-8 gnd rswk-swf Suspensionskultur (DE-588)4272660-8 s Submerskultur (DE-588)4417433-0 s Zellkultur (DE-588)4067547-6 s DE-604 Meyer, Hans-Peter 195X- (DE-588)1053308264 edt Erscheint auch als Online-Ausgabe, EPUB 978-3-527-68335-2 Erscheint auch als Online-Ausgabe, MOBI 978-3-527-68333-8 Erscheint auch als Online-Ausgabe, PDF 978-3-527-68334-5 X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=4583959&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027339995&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Industrial scale suspension culture of living cells Zellkultur (DE-588)4067547-6 gnd Submerskultur (DE-588)4417433-0 gnd Suspensionskultur (DE-588)4272660-8 gnd |
| subject_GND | (DE-588)4067547-6 (DE-588)4417433-0 (DE-588)4272660-8 |
| title | Industrial scale suspension culture of living cells |
| title_auth | Industrial scale suspension culture of living cells |
| title_exact_search | Industrial scale suspension culture of living cells |
| title_full | Industrial scale suspension culture of living cells ed. by Hans-Peter Meyer ... |
| title_fullStr | Industrial scale suspension culture of living cells ed. by Hans-Peter Meyer ... |
| title_full_unstemmed | Industrial scale suspension culture of living cells ed. by Hans-Peter Meyer ... |
| title_short | Industrial scale suspension culture of living cells |
| title_sort | industrial scale suspension culture of living cells |
| topic | Zellkultur (DE-588)4067547-6 gnd Submerskultur (DE-588)4417433-0 gnd Suspensionskultur (DE-588)4272660-8 gnd |
| topic_facet | Zellkultur Submerskultur Suspensionskultur |
| url | http://deposit.dnb.de/cgi-bin/dokserv?id=4583959&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027339995&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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