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1、Biologicals(1999)27,203215ArticleNo.biol.1999.0179,availableonlineathttp://www.idealibrary.comonComparabilityTestingofaHumanizedMonoclonal®Antibody(Synagis)toSupportCellLineStability,ProcessValidation,andScale-UpforManufacturingMarkA.Schenerman*,JohnN.Hop
2、e,CathyKletke,JuspreetK.Singh,RoyKimura,EricI.TsaoandGailFolena-WassermanMedImmune,Inc.,35W.WatkinsMillRd.,Gaithersburg,MD,20878,U.S.A.Abstract.Biochemicalandfunctionaltestingofahumanizedmonoclonalantibodydirectedagainst®RespiratorySyncytialVirus(Synagis)
3、hasbeenperformedtoevaluatecelllinestability,supportprocessvalidation,andtodemonstrate‘‘comparability’’duringthecourseofprocessdevelopment.Usingavarietyofanalyticalmethods,productmanufacturedatdifferentsitesandinbioreactorsfrom20litresto10000litreswasshown
4、tobebiochemicallyandfunctionallyequivalent.Thebiochemicaltestingformicrohetero-®geneityfoundonSynagisincludedevaluationofchangesinpost-translationalmodificationssuchasdeamidation,truncation,andcarbohydratestructure.Studieswerealsoperformedtosupportcelllin
5、estabilityassessmentandcellcultureprocessvalidation.Cellcultureconditionsweredeliberatelyvariedinanattempttodetermineifthiswouldhaveanimpactonthemicroheterogeneityoftheproduct.Inthese®studiesSynagiswasproducedfromcellsculturedbeyondthepopulationdoublingsa
6、chievedatthemaximummanufacturingscale,underconditionsoflowglucose,andusingharvesttimesoutsideofthehistoricalmanufacturingoperatingrange.Resultsshowedthattherewasadifferentpatternofglycosylationduringtheearlystagesofbioreactorculture.Nootherchangesinmicroh
7、eterogeneitywereapparentforthe®othercultureconditionsstudied.Insummary,comparabilityassessmentdemonstratedthattheSynagismanufacturingprocessisrobustandconsistentresultinginapredictableandreproduciblemonoclonalantibodyproduct.©1999TheInternationalAssociati
8、onforBiologicalsIntroductionrabilitycanbedemonstratedbycomparingnewlymanufacturedmaterialtoapreviouslytestedandTherecentpublicationofFoodandDrugAdmin-qualifiedReferenceStandard(RS).Forexample,istrationregulationsforr
