Cell Culture Engineering

178 Pages·2006·2.719 MB·English

by  Suzanne S. Farid (auth.), Wei-Shou Hu (eds.)

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
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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
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ISSN0724-6145
ISBN-103-540-34006-8SpringerBerlinHeidelbergNewYork
ISBN-13978-3-540-34006-5SpringerBerlinHeidelbergNewYork
DOI10.1007/11751571
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ChemicalEngineering
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EditorialBoard
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SectionofEnvironmentalMicrobiology DepartmentofBiochemicalEngineering
Leipzig-HalleGmbH UniversityCollegeLondon
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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
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[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
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ForschungszentrumJülichGmbH
LaboratoiredeGénieChimiqueet
52425Jülich,Germany
Biologique(LGCB),DépartmentdeChimie
[email protected]
SwissFederalInstitute
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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
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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