对生物类似药研发中临床研究的思考

“”2015ZX09501008*[e-mail]*100038。。。、、。、、。doi10.11669/cpj.2015.06.006Ｒ915A1001－2494201506－0494－03ConsiderationsonClinicalStudyofBiosimilarsGAOChen-yanXIESong-meiBAIYuWANGHai-xueWANGTaoWANGQing-liLUOJian-huiYINHong-hangYANGZhi-min*CenterforDrugEvaluationChinaFoodandDrugAdministrationBeijing100038ChinaABSTＲACTOBJECTIVEToevaluatethesimilarityofbiosimilarsinclinicalsafetyandefficacybetweenthecandidateandrefer-enceproducts．Thisevaluationrequiresdesigningandconductingscientificandreasonableclinicaltrials．Thisreportaimsatraisingkeyissuesinclinicalstudyforbiosimilarsandgivingsolutionstotherespectiveproblems．METHODSTheprincipleofclinicalstudyofbiosimilarswasestablishedbasedonthecurrentdevelopmentofbiosimilarproductsandtheguidancesonbiosimilarsevaluationofmultiplecountries．ＲESULTSANDCONCLUSIONAgoodclinicalstudyforbiosimilarsshouldbedesignedbasedonthefeatureoftheoriginalproductandtheresultsofthechemistrymanufacturingandcontrolsCMCandnon-clinicalstudies．Withsomesimplifiedbuthigh-qualitystudiestoprovetheequivalenceofthecandidatesandreferenceproductthesafetyandefficacyoftheoriginalproductcouldbridgethebiosimilarproduct．Intheclinicaltrialdesignaccurateindicationssensitivesubjectsandappropriateendpointareessentialtoprovidevaluabledataandsolidevidenceforthefinalevaluationofsimilarity．KEYWOＲDSbiosimilarclinicalstudyevaluationbiosimi-lar。“”、“”。。1similarbiotherapeuticprod-ucts1biosimilarbiosimilarity2similarbiologicalmedicinalproductsbiosimilars3subsequententrybiologic4。5。①。②“”。③、。·494·ChinPharmJ2015MarchVol.50No.6201535061-8。2。2．1。。。。“”。。2．2。。、、PKcmax-AUC。。、、。。、、PD/1-5。2.3“”①②③④PK⑤PD⑥PK。1-8。BEPD/。。3。。3.1。、。H0①②。H0。。。3.2。。。。3.3·594·20153506ChinPharmJ2015MarchVol.50No.6。。。。。3.4。、。。。3.5。。。、overallsurvivalOS、。。internationalnormalizedratioINＲINＲ。。3.6PK、PD。。CMC、。。3.7。。、。、、、、。。。4、。。、、。ＲEFEＲENCES1WHO．GuidelinesonevaluationofsimilarbiotherapeuticproductsSBPsS．2010．2FDA．DraftguidanceforIndustry-scientificconsiderationsindem-onstratingbiosimilaritytoareferenceProductS．2012．3EMA．GuidelineonsimilarbiologicalmedicinalproductsS．2006．4HPFB．GuidanceforsponsorsInformationandsubmissionrequire-mentsforsubsequententrybiologicsSEBsS．2010．5CFDA．GuidelineonDevelopmentandEvaluationofBiosimilars2015．S．2015．6KFDA．GuidelinesontheevaluationofbiosimilarproductsS．2010．7MHLWGuidelineforensuringqualitysafetyandefficacyofbio-similarproductsS．2009．8DCGI．GuidelinesonSimilarBiologicsＲegulatoryＲequirementsforMarketingAuthorizationinIndiaS．2012．2015-01-28·694·ChinPharmJ2015MarchVol.50No.620153506