生物等效性豁免指南中英对照

GUIDANCEFORINDUSTRY1WaiverofInVivoBioavailabilityandBioequivalenceStudiesforImmediate-ReleaseSolidOralDosageFormsBasedonaBiopharmaceuticsClassificationSystem基于生物制剂分类系统的速释固体口服制剂体内生物利用度和生物等效性研究豁免指南目录I.INTRODUCTION引言..............................................................................................................................3II.THEBIOPHARMACEUTICSCLASSIFICATIONSYSTEM生物制剂分类系统...............................3A.Solubility溶解..................................................................................................................................4B.Permeability渗透..............................................................................................................................4C.Dissolution分解................................................................................................................................5III.METHODOLOGYFORCLASSIFYINGADRUGSUBSTANCEANDFORDETERMININGTHEDISSOLUTIONCHARACTERISTICSOFADRUGPRODUCT药物分类和制剂溶解特性测定方法..........................................................................................................................................................5A.DeterminingDrugSubstanceSolubilityClass判定原料药的溶解度分类.....................................5B.DeterminingDrugSubstancePermeabilityClass判定原料药渗透性分类.....................................61.PharmacokineticStudiesinHumans人体内药代动力学研究.................................................72.IntestinalPermeabilityMethods肠道通透性检测方法............................................................73.InstabilityintheGastrointestinalTract胃肠道稳定性研究...................................................10C.DeterminingDrugProductDissolutionCharacteristicsandDissolutionProfileSimilarity测定药物的溶解特性和溶解相似性................................................................................................................11IV.ADDITIONALCONSIDERATIONSFORREQUESTINGABIOWAIVER生物豁免请求其他注意事项........................................................................................................................................................12A.Excipients辅料...............................................................................................................................12B.Prodrugs药物前体..........................................................................................................................13C.Exceptions不适用情况...................................................................................................................131.NarrowTherapeuticRangeDrugs治疗范围狭窄的药品........................................................132.ProductsDesignedtobeAbsorbedintheOralCavity口腔吸收制剂....................................13V.REGULATORYAPPLICATIONSOFTHEBCSBCS的申请............................................................13A.INDs/NDAs.......................................................................................................................................13B.ANDAs..............................................................................................................................................14C.PostapprovalChanges批准后变更.................................................................................................14VI.DATATOSUPPORTAREQUESTFORBIOWAIVERS生物豁免请求支持数据.........................15A.DataSupportingHighSolubility支持高溶解度的数据................................................................15B.DataSupportingHighPermeability高渗透性支持数据................................................................15C.DataSupportingRapidandSimilarDissolution快速及相似溶出支持数据.................................16D.AdditionalInformation其他信息...................................................................................................17ATTACHMENTA附录A............................................................................................................................18I.INTRODUCTION引言Thisguidanceprovidesrecommendationsforsponsorsofinvestigationalnewdrugapplications(INDs),newdrugapplications(NDAs),abbreviatednewdrugapplications(ANDAs),andsupplementstotheseapplicationswhowishtorequestawaiverofinvivobioavailability(BA)and/orbioequivalence(BE)studiesforimmediaterelease(IR)solidoraldosageforms.Thesewaiversareintendedtoapplyto(1)subsequentinvivoBAorBEstudiesofformulationsaftertheinitialestablishmentoftheinvivoBAofIRdosageformsduringtheINDperiod,and(2)invivoBEstudiesofIRdosageformsinANDAs.Regulationsat21CFRpart320addresstherequirementsforbioavailability(BA)andBEdataforapprovalofdrugapplicationsandsupplementalapplications.ProvisionforwaiversofinvivoBA/BEstudies(biowaivers)undercertainconditionsisprovidedat21CFR320.22.ThisguidanceexplainswhenbiowaiverscanberequestedforIRsolidoraldosageformsbasedonanapproachtermedtheBiopharmaceuticsClassificationSystem(BCS).本指南给INDs、MDAs、ANDAs和增补申请主办方为速释固体口服制剂请求获得生物利用度和/或生物等效性研究豁免提供建议。该豁免适用于：1：IND研究期间，起始建立的IR剂型体内生物利用度研究的后续配方体内生物利用度或生物等效性研究；2：ANDAs的IR剂型体内生物等效性研究。21CFR302部分的规定声明了通过药物申请和增补申请的BA、BE数据的要求。特定情况下的体内BA/BE研究规定在21CFR320.22部分提供。本指南解释了何时IR口服剂型能够按照术语是生物药剂分类系统这种途径来请求豁免的情况。II.THEBIOPHARMACEUTICSCLASSIFICATIONSYSTEM生物药剂分类系统TheBCS