资源描述：
《生物类似药的注册法规思考Regulatory Considerations for the Development of Novel Antibody》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。
1、RegulatoryConsiderationsfortheDevelopmentofNovelAntibody-RelatedProductsQingZhou,PhDMarjorieShapiro,PhDFDAAbstractMonoclonalantibodies(mAbs)arewidelyrecognizedasinvaluablebiologictoolsfordiagnosticandresearchinvestigationsandhavealsobecomealeadingclassoftherapeuticmolec
2、ules.Tremendouseffortshavebeenmadetoimprovethesafetyandefficacyofantibodybasedtherapeuticsbyobtainingabetterunderstandingofthemolecularbasisofdiseasesandselectingappropriatetargets,aswellasdevelopingnovelantibodyrelatedproductsasnewoptionsforclinicalapplications.Althoug
3、hagreatamountofknowledgeregardingthequalityattributes,manufactureandcontrolstrategiesforantibodyproductsisgainedasaresultoftheseefforts,theregulationoftherapeuticantibodyrelatedproductscontinuestobechallengingforboththepharmaceuticalindustryandregulatoryauthorities.This
4、articleprovidesanoverviewofthegeneralregulatoryconsiderationsfromaqualityperspectiveformAbproducts,andoutlinesthecurrentthinkingregardingspecialconsiderationsforseveraltypesofnovelantibodyrelatedproducts.IntroductionSincethedevelopmentofanti-diphtheriaantitoxinsinthe19t
5、hcentury,researchersandphysicianshaveinvestigatedantibodiesduetotheirremarkablecharacteristicsandgreatpotentialforclinicalapplications.Afterhybridomatechnologywasintroducedinthe1970’s,thefirsttherapeuticusesofhybridoma-derivedmAbsinthe1980’sshowedsporadicpromise,butover
6、allresultedindisappointment.ThefirstmAb,Orthoclone,approvedintheUSin1986,wasamurinemAb.AlthoughOrthoclonehasbeenwithdrawnfromthemarket,itsapprovalrepresentsthebeginningofanerainthedevelopmentofanewclassoftherapeuticproteinsforclinicalapplications.EarlytherapeuticmAbsder
7、ivedfromrodentswerelargelyunsuccessfulbecausetheywereimmunogenic,hadashorthalf-lifeandwerepooratinducingeffectorfunctionsinhumans.Inaddition,inadequatepreclinicalandclinicalproductdevelopmentcontributedtothesefailures.Despitethesedisappointingclinicaloutcomes,whatwaslea
8、rnedfromthesefailureswasusedtodevelopchimeric,humanizedandhumanantibodies,whichreducedimmunogenicity,ledtoadeq
