Cell Culture Engineering PDF
Preview Cell Culture Engineering
101 Advances in Biochemical Engineering/Biotechnology SeriesEditor:T.Scheper EditorialBoard: W.Babel·I.Endo·S.-O.Enfors·A.Fiechter·M.Hoare·W.-S.Hu B.Mattiasson·J.Nielsen·H.Sahm·K.Schügerl·G.Stephanopoulos U.vonStockar·G.T.Tsao·C.Wandrey·J.-J.Zhong AdvancesinBiochemicalEngineering/Biotechnology SeriesEditor:T.Scheper RecentlyPublishedandForthcoming Volumes TissueEngineeringII RegenerativeMedicineI BasicsofTissueEngineeringandTissue Theories,ModelsandMethods Applications VolumeEditor:Yannas,I.V. VolumeEditors:Lee,K.,Kaplan,D. Vol.93,2005 Vol.103,2006 TechnologyTransferinBiotechnology TissueEngineeringI VolumeEditor:Kragl,U. ScaffoldSystemsforTissueEngineering Vol.92,2005 VolumeEditors:Lee,K.,Kaplan,D. Vol.102,2006 RecentProgressofBiochemicalandBiomedical EngineeringinJapanII CellCultureEngineering VolumeEditor:Kobayashi,T. VolumeEditor:Hu,W.-S. Vol.91,2004 Vol.101,2006 RecentProgressofBiochemicalandBiomedical BiotechnologyfortheFuture EngineeringinJapanI VolumeEditor:Nielsen,J. 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Vol.94,2005 Vol.84,2003 Cell Culture Engineering Volume Editor: Wei-Shou Hu Withcontributionsby R.Biener·S.Chuppa·S.S.Farid·C.Goudar·P.Hossler W.-S.Hu·K.Konstantinov·C.Matanguihan·R.Meneses J.Michaels·D.Naveh·M.Ng·J.Piret·G.Seth·J.Thrift K.F.Wlaschin·J.C.Yee·C.Zhang 123 AdvancesinBiochemicalEngineering/Biotechnologyreviewsactualtrendsinmodernbiotechnology. Itsaim isto coverallaspects ofthisinterdisciplinary technologywhereknowledge, methodsand expertisearerequiredforchemistry,biochemistry,micro-biology,genetics,chemicalengineeringand computerscience.Specialvolumesarededicatedtoselectedtopicswhichfocusonnewbiotechnological productsandnew processes for their synthesis and purification.They give the state-of-the-art of atopicinacomprehensivewaythusbeingavaluablesourceforthenext3–5years.Italsodiscusses newdiscoveriesandapplications.Specialvolumesareeditedbywellknownguesteditorswhoinvite reputedauthorsforthereviewarticlesintheirvolumes. In references Advances in Biochemical Engineering/Biotechnologyis abbeviated Adv Biochem En- gin/Biotechnolandiscitedasajournal. SpringerWWWhomepage:springer.com VisittheABEcontentatspringerlink.com LibraryofCongressControlNumber:2006930118 ISSN0724-6145 ISBN-103-540-34006-8SpringerBerlinHeidelbergNewYork ISBN-13978-3-540-34006-5SpringerBerlinHeidelbergNewYork DOI10.1007/11751571 Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerial isconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broad- casting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Duplicationof thispublicationorpartsthereofispermittedonlyundertheprovisionsoftheGermanCopyrightLaw ofSeptember9,1965,initscurrentversion,andpermissionforusemustalwaysbeobtainedfrom Springer.ViolationsareliableforprosecutionundertheGermanCopyrightLaw. 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Coverdesign:WMXDesignGmbH,Heidelberg TypesettingandProduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig Printedonacid-freepaper 02/3141YL–543210 SeriesEditor Prof.Dr.T.Scheper InstituteofTechnicalChemistry UniversityofHannover Callinstraße3 30167Hannover,Germany [email protected] VolumeEditor Prof.Wei-ShouHu ChemicalEngineering andMaterialsScience UniversityofMinnesota 421WashingtonAvenueSE Minneapolis,MN55455-0132,USA [email protected] EditorialBoard Prof.Dr.W.Babel Prof.Dr.M.Hoare SectionofEnvironmentalMicrobiology DepartmentofBiochemicalEngineering Leipzig-HalleGmbH UniversityCollegeLondon Permoserstraße15 TorringtonPlace 04318Leipzig,Germany London,WC1E7JE,UK [email protected] [email protected] Prof.Dr.S.-O.Enfors Prof.Dr.I.Endo DepartmentofBiochemistryand ExecutiveDirector Biotechnology SaitamaIndustrialTechnologyCenter RoyalInstituteofTechnology 3-12-18,KamiaokiKawaguchi-shi Teknikringen34, Saitama,333-0844,Japan 10044Stockholm,Sweden [email protected] [email protected] VI EditorialBoard Prof.Dr.A.Fiechter Prof.Dr.J.-J.Zhong InstituteofBiotechnology StateKeyLaboratory EidgenössischeTechnischeHochschule ofBioreactorEngineering ETH-Hönggerberg EastChinaUniversityofScience 8093Zürich,Switzerland andTechnology ae.fi[email protected] 130MeilongRoad Shanghai200237,China Prof.W.-S.Hu [email protected] ChemicalEngineering Prof.J.Nielsen andMaterialsScience UniversityofMinnesota CenterforProcessBiotechnology 421WashingtonAvenueSE TechnicalUniversityofDenmark Minneapolis,MN55455-0132,USA Building223 [email protected] 2800Lyngby,Denmark [email protected] Prof.Dr.B.Mattiasson Prof.Dr.K.Schügerl DepartmentofBiotechnology ChemicalCenter,LundUniversity InstituteofTechnicalChemistry P.O.Box124,22100Lund,Sweden UniversityofHannover,Callinstraße3 [email protected] 30167Hannover,Germany [email protected] Prof.Dr.H.Sahm InstituteofBiotechnolgy Prof.Dr.U.vonStockar ForschungszentrumJülichGmbH LaboratoiredeGénieChimiqueet 52425Jülich,Germany Biologique(LGCB),DépartmentdeChimie [email protected] SwissFederalInstitute ofTechnologyLausanne Prof.Dr.G.Stephanopoulos 1015Lausanne,Switzerland urs.vonstockar@epfl.ch DepartmentofChemicalEngineering MassachusettsInstituteofTechnology Cambridge,MA02139-4307,USA Prof.Dr.C.Wandrey [email protected] InstituteofBiotechnology ForschungszentrumJülichGmbH Prof.Dr.G.T.Tsao 52425Jülich,Germany [email protected] ProfessorEmeritus PurdueUniversity WestLafayette,IN47907,USA [email protected] AdvancesinBiochemicalEngineering/Biotechnology AlsoAvailableElectronically For all customers who have a standing order to Advances in Biochemical Engineering/Biotechnology, we offerthe electronic version via SpringerLink freeofcharge.Pleasecontactyourlibrarianwhocanreceiveapasswordorfree accesstothefullarticlesbyregisteringat: springerlink.com Ifyoudonothaveasubscription,youcanstillviewthetablesofcontentsofthe volumesandtheabstractofeacharticlebygoingtotheSpringerLinkHome- page,clickingon“BrowsebyOnlineLibraries”,then“ChemicalSciences”,and finallychooseAdvancesinBiochemicalEngineering/Biotechnology. Youwillfindinformationaboutthe – EditorialBoard – AimsandScope – InstructionsforAuthors – SampleContribution atspringer.comusingthesearchfunction. AttentionallUsers ofthe“SpringerHandbookofEnzymes” Informationonthishandbookcanbefoundontheinternetat springeronline.com AcompletelistofallenzymeentrieseitherasanalphabeticalNameIndexor as the EC-Number Index is available at the above mentioned URL. You can downloadandprintthemfreeofcharge. Acompletelistofallsynonyms(morethan25,000entries)usedfortheenzymes isavailableinprintform(ISBN3-540-41830-X). Save 15% We recommend a standing order for the series to ensure you automatically receiveallvolumesandallsupplementsandsave15%onthelistprice. Preface Since the introduction of recombinant human growth hormone and insulin a quarter century ago, protein therapeutics has greatly broadened the hori- zon of health care. Many patients suffering with life-threatening diseases or chronicdysfunctions,whichweremedicallyuntreatablenotlongago,canattest tothewonderthesedrugshaveachieved.Althoughthefirstgenerationofpro- tein therapeutics was produced in recombinant Escherichia coli, most recent productsusemammaliancellsasproductionhosts.Notlongafterthefirstpro- ductionofrecombinantproteinsinE.coli,itwasrealizedthatthecomplextasks ofmostpost-translationalmodificationsonproteinscouldonlybeefficiently carriedoutinmammaliancells.Inthe1990s,wewitnessedarapidexpansion ofmammalian-cell-derivedproteintherapeutics,chieflyantibodies.Infact,it has been nearly a decade since the market value of mammalian-cell-derived proteintherapeuticssurpassedthatofthoseproducedfromE.coli.Acommon characteristicofrecentantibodyproductsistherelativelylargedoserequired foreffectivetherapy,demandinglargerquantitiesforthetreatmentofagiven disease. This, coupled with the broadening repertoire of protein drugs, has rapidlyexpandedthequantityneededforclinicalapplications.Theincreasing demandforproteintherapeuticshasnotbeenmetexclusivelybyconstruction ofnewmanufacturing plantsandincreasingtotalvolumecapacity.Moreim- portantly the productivity of cell culture processes has been driven upward byanorderofmagnitudeinthepastdecade.Forthebiochemicalengineering community, especially the researchers and bioprocess professionals engaged incellcultureengineering,thistechnologicaladvancementisacauseforcele- bration. Althoughtheemergenceofcellcultureengineeringisrelativelyrecent,the demand for a robust manufacturing platformhas propelled tremendous ad- vances in ashort decade. In thecourse oftransformingfroman exploratory technologytoarobustinstrumentgeneratinglife-savingmedicines,cellculture processeshaveevolvedtoalmostuniformlyemployedstirredtankbioreactors for large-scale operations. Batch and simple continuous cultures are seldom employed,except onresearchscales.Fed-batchculturesandcontinuouspro- cesseswithcellretention,alsocommonlyreferredtoasperfusionculture,have becomethenorm.Tocapturetheessence ofthoseadvancesandtohighlight products that have been the driving force for the expansion of cell culture X Preface processes,threechaptersinthisvolumearedevotedtothosetopics:antibody products,fed-batchculturesandperfusionprocesses. In thepast decade, we haveseen thespecific productivityofrecombinant antibodiesbyhigh-producingcellsapproachthatofnaturalantibodysecreting cellsinvivo.Thishasbeenlargelyaccomplishedthroughrandomscreeningof cloneswithhigherproductivities.Aswestrivetogeneratehyper-producingcell linesthatexceedtheproductioncapabilitiesofnativeantibodysecretorsinour bodies,screeningprocesseswilllikelyincorporatemorerationalapproaches. Useoftargetedmarkers,knowntoconferhyper-productivitytraitswilllikely prevail.Thecomplextraitofhyper-productivityismostprobablyacomposite ofmanyphysiologicalcharacteristics,includingrobustgrowth,efficientenergy generation, reduced susceptibility to reactive oxygen species, and enhanced protein processing and secretion machinery. Identifying the potential target genes for desired traits is a key to cell engineering. This issue also includes a chapter that gives a comprehensive review of the current state and future prospectofmetabolicengineeringofmammaliancells. Lookingtothefutureofcellcultureengineering,weanticipatetheproduc- tivitytocontinuetoswingupwardatapacegreatlyexceeding theincreasing demand to reduce the cost of goods. We are likely to see the next phase of processenhancementintegraterenovationsinprocessengineeringwithinno- vationsincellularengineering.Processrenovationswillcontinuetodrawout thefullcapacityoffed-batchandperfusionprocesses.Withimagination,one mayseecellengineeringeffortsinducerevolutionizingchangesincellculture processes.Asgenomicandproteomictoolsbecomemorereadilyavailablefor cellcultureengineering researchandourunderstanding ofthephysiological basis of hyper-productivity further advances, such imagination will become closertoreality. Minneapolis,July2006 Wei-ShouHu
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