Bioprocessing technology for production of biopharmaceuticals and bioproducts

290 Pages·2019·4.668 MB·English

by  Komives, Claire, Zhou, Weichang

BioprocessingTechnologyforProductionof
BiopharmaceuticalsandBioproducts
WileySeriesinBiotechnologyandBioengineering
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titioners both in academia and industry. Authors and editors were carefully
selected for their recognized expertise and their contributions to the various
andfar-reachingfieldsofbiotechnology.
BioprocessingTechnologyforProductionofBiopharmaceuticals
andBioproducts
byClaireKomives(Editor),WeichangZhou(Editor)
PreparativeChromatographyforSeparationofProteins
byArneStaby,AnuragS.Rathore,Satinder(Sut)Ahuja
VaccineDevelopmentandManufacturing
byEmilyP.Wen(Editor),RonaldEllis(Editor),NarahariS.Pujar(Editor)
RiskManagementApplicationsinPharmaceuticalandBiopharmaceutical
Manufacturing
byHamidMollah(Editor),HaroldBaseman(Editor),MikeLong(Editor)
Emerging Cancer Therapy: Microbial Approaches and Biotechnological
Tools
byArsenioFialho(Editor),AnandaChakrabarty(Editor)
QualitybyDesignforBiopharmaceuticals:PrinciplesandCaseStudies
byAnuragS.Rathore(Editor),RohinMhatre(Editor)
Bioprocessing Technology for Production of
Biopharmaceuticals and Bioproducts
Editedby
ClaireKomives
SanJoseStateUniversity
SanJose,CA,US
WeichangZhou
WuXiBiologics
Shanghai,China
Thiseditionfirstpublished2019
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LibraryofCongressCataloging-in-PublicationData
Names:Komives,Claire,editor.|Zhou,Weichang,1963-editor.
Title:Bioprocessingtechnologyforproductionofbiopharmaceuticalsand
bioproducts/editedbyClaireKomives,WeichangZhou.
Description:Firstedition.|Hoboken,NJ:JohnWiley&Sons,Inc.,2019.|
Series:Wileyseriesinbiotechnologyandbioengineering|Includes
bibliographicalreferencesandindex.|
Identifiers:LCCN2018036496(print)|LCCN2018037472(ebook)|ISBN
9781119378280(AdobePDF)|ISBN9781119378303(ePub)|ISBN9781118361986
(hardback)
Subjects:|MESH:BiologicalProducts–chemistry|DrugCompounding|
Technology,Pharmaceutical|Bioreactors
Classification:LCCRM301.25(ebook)|LCCRM301.25(print)|NLMQV241|
DDC615.1/9–dc23
LCrecordavailableathttps://lccn.loc.gov/2018036496
CoverdesignbyWiley
Coverimage:©iStock.com/MiljaPhoto
Setin10/12ptWarnockProbySPiGlobal,Chennai,India
PrintedintheUnitedStatesofAmerica
10 9 8 7 6 5 4 3 2 1
v
Contents
ListofContributors xi
PartI CaseStudy 1
1 BacillusandtheStoryofProteinSecretionandProduction 3
GiuliaBarbieri,AnthonyCalabria,GopalChotani,andEugenioFerrari
1.1 BacillusasaProductionHost:IntroductionandHistorical
Account 3
1.2 TheBuildingofaProductionStrain:GeneticToolsforB.subtilis
Manipulation 5
1.2.1 Promoters 5
1.2.2 VectorsforBuildingaProductionStrain 6
1.2.3 B.subtilisCompetentCellTransformation 7
1.2.4 Protoplasts-MediatedManipulations 9
1.2.5 GeneticsbyElectroporation 9
1.3 B.subtilisSecretionSystemandHeterologousProteinProduction 9
1.3.1 BacillusFermentationandRecoveryofIndustrialEnzyme 11
1.3.2 FermentationStoichiometry 12
1.3.3 FermentorKineticsandOutputs 14
1.3.4 DownstreamProcessing 17
1.4 Summary 21
References 21
2 NewExpressionSystemsforGPCRs 29
DimitraGialama,FragiskosN.Kolisis,andGeorgiosSkretas
2.1 Introduction 29
2.2 RecombinantGPCRProduction–TraditionalApproachesfor
AchievingHigh-LevelProduction 39
2.3 EngineeredExpressionSystemsforGPCRProduction 42
2.3.1 Bacteria 42
vi Contents
2.3.2 Yeasts 48
2.3.3 InsectCells 51
2.3.4 MammalianCells 54
2.3.5 TransgenicAnimals 54
2.3.6 Cell-FreeSystems 56
2.4 Conclusion 57
References 58
3 Glycosylation 71
MaureenSpearman,ErikaLattová,HélènePerreault,andMichaelButler
3.1 Introduction 71
3.2 TypesofGlycosylation 72
3.2.1 N-linkedGlycans 72
3.2.2 O-linkedGlycans 74
3.3 FactorsAffectingGlycosylation 76
3.3.1 NutrientDepletion 76
3.3.2 Fed-batchCulturesandSupplements 79
3.3.3 SpecificCultureSupplements 80
3.3.4 Ammonia 82
3.3.5 pH 82
3.3.6 Oxygen 83
3.3.7 HostCellSystems 83
3.3.8 OtherFactors 85
3.4 ModificationofGlycosylation 86
3.4.1 siRNAandGeneKnockout/Knockin 86
3.4.2 GlycoproteinProcessingInhibitorsandInVitroModificationof
Glycans 88
3.5 GlycosylationAnalysis 89
3.5.1 ReleaseofGlycansfromGlycoproteins 90
3.5.2 DerivatizationofGlycans 91
3.6 MethodsofAnalysis 91
3.6.1 LectinArrays 91
3.6.2 LiquidChromatography 93
3.6.2.1 HILICAnalysis 93
3.6.2.2 ReversedPhase(RP)andPorousGraphiticCarbon(PGC)
Chromatography 95
3.6.2.3 WeakAnionExchange(WAX)HPLCAnalysis 96
3.6.2.4 HighpHAnionExchangeChromatographywithPulsed
AmperometricDetection(HPAEC-PAD) 96
3.6.3 CapillaryElectrophoresis(CE) 97
3.6.4 Fluorophore-assistedCarbohydrateElectrophoresis(FACE)and
CGE-LIF 99
Contents vii
3.6.5 MassSpectrometry(MS) 100
3.6.5.1 Ionization 100
3.6.5.2 DerivatizationTechniquesUsedforMSAnalysisof
Glycans 102
3.6.5.3 FragmentationofCarbohydrates 103
3.7 Conclusion 109
References 109
PartII Bioreactors 131
4 BioreactorsforStemCellandMammalianCell
Cultivation 133
AnaFernandes-Platzgummer,SaraM.Badenes,CláudiaL.daSilva,and
JoaquimM.S.Cabral
4.1 Overviewof(MammalianandStem)CellCultureEngineering 133
4.1.1 CellProductsforTherapeutics 134
4.1.2 CellasaProduct:StemCells 136
4.2 BioprocessCharacterization 140
4.2.1 CellCultivationMethods 140
4.2.2 CellMetabolism 141
4.2.3 CultureMediumDesign 143
4.2.4 CultureParameters 144
4.2.5 CultureModes 145
4.3 CellCultureSystems 147
4.3.1 StaticCultureSystems 147
4.3.2 RollerBottles 150
4.3.3 SpinnerFlask 150
4.3.4 AirliftBioreactor 151
4.3.5 Fixed/Fluidized-BedBioreactor 152
4.3.6 WaveBioreactor 152
4.3.7 Rotating-WallVesselBioreactor 154
4.3.8 StirredTankBioreactor 155
4.3.8.1 Agitation/ShearStress 156
4.4 CellCultureModeling 157
4.5 CaseStudies 159
4.5.1 AntibodyProductioninBioreactorSystems 159
4.5.2 mESCExpansiononMicrocarriersinaStirredTank
Bioreactor 161
4.6 ConcludingRemarks 162
ListofSymbols 163
References 164
viii Contents
5 Model-BasedTechnologiesEnablingOptimalBioreactor
Performance 175
RimvydasSimutis,MarcoJenzsch,andAndreasLübbert
5.1 Introduction 175
5.2 Basics 176
5.2.1 Balances 176
5.2.2 ModelIdentification 177
5.2.3 Model-BasedProcessOptimization 178
5.3 Examples 180
5.3.1 Model-BasedStateEstimation 180
5.3.1.1 StaticModelApproach 180
5.3.1.2 DynamicAlternatives 183
5.3.2 OptimizingOpenLoop-ControlledCultivations 184
5.3.2.1 RobustCultivationProfiles 184
5.3.2.2 EvolutionaryModelingApproach 188
5.3.3 OptimizationbyModel-AidedFeedbackControl 190
5.3.3.1 ImprovingtheBasicControl 190
5.3.3.2 OptimizingtheAmountofSolubleProduct 190
5.3.4 CO -RemovalinLarge-ScaleCellCultures 194
2
5.4 Conclusion 197
References 198
6 MonitoringandControlofBioreactor:BasicConceptsand
RecentAdvances 201
JamesGomes,VikiChopda,andAnuragS.Rathore
6.1 Introduction 201
6.2 ChallengesinBioprocessControl 202
6.2.1 ProcessDynamicsandModeling 202
6.2.2 LimitsofHardwareandSoftwareandTheirIntegration 203
6.2.3 RegulatoryAspects 204
6.3 BasicElementsofBioprocessControl 205
6.3.1 BioprocessMonitoring 205
6.3.2 ParameterEstimators 205
6.3.3 BioprocessModeling 206
6.4 CurrentPracticesinBioprocessControl 208
6.4.1 PIDControl 208
6.4.2 Model-BasedControl 209
6.4.3 AdaptiveControl 211
6.4.4 NonlinearControl 214
6.5 IntelligentControlSystems 217
6.5.1 FuzzyControl 217
6.5.2 NeuralControl 219