FDA生物等效豁免原则

DraftGuidanceTemp05/04/15WaiverofInVivoBioavailabilityandBioequivalenceStudiesforImmediate-ReleaseSolidOralDosageFormsBasedonaBiopharmaceuticsClassificationSystemGuidanceforIndustryDRAFTGUIDANCEThisguidancedocumentisbeingdistributedforcommentpurposesonly.Commentsandsuggestionsregardingthisdraftdocumentshouldbesubmittedwithin60daysofpublicationintheFederalRegisterofthenoticeannouncingtheavailabilityofthedraftguidance.Submitelectroniccommentsto(HFA-305),FoodandDrugAdministration,5630FishersLane,rm.1061,Rockville,MD20852.AllcommentsshouldbeidentifiedwiththedocketnumberlistedinthenoticeofavailabilitythatpublishesintheFederalRegister.Forquestionsregardingthisdraftdocumentcontact(CDER)MehulMehta301-796-1573.U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)May2015BiopharmaceuticsRevision1DraftGuidanceTemp05/04/15WaiverofInVivoBioavailabilityandBioequivalenceStudiesforImmediate-ReleaseSolidOralDosageFormsBasedonaBiopharmaceuticsClassificationSystemGuidanceforIndustryAdditionalcopiesareavailablefrom:OfficeofCommunications,DivisionofDrugInformationCenterforDrugEvaluationandResearchFoodandDrugAdministration10001NewHampshireAve.,HillandaleBldg.,4thFloorSilverSpring,MD20993-0002Phone:[phone]or301-796-3400;Fax:[phone]Email:[e-mail](CDER)May2015BiopharmaceuticsRevision1ContainsNonbindingRecommendationsDraft—NotforImplementationDraftGuidanceTemp05/04/15TABLEOFCONTENTSI.INTRODUCTION.............................................................................................................1II.THEBIOPHARMACEUTICSCLASSIFICATIONSYSTEM...................................2A.Solubility.........................................................................................................................................3B.Permeability...................................................................................................................................3C.Dissolution......................................................................................................................................3III.RECOMMENDEDMETHODOLOGYFORCLASSIFYINGADRUGSUBSTANCEANDFORDETERMININGTHEDISSOLUTIONCHARACTERISTICSOFADRUGPRODUCT.........................................................................................................................3A.DeterminingDrugSubstanceSolubilityClass............................................................................3B.DeterminingDrugSubstancePermeabilityClass.......................................................................41.PharmacokineticStudiesinHumans..................................................................................42.IntestinalPermeabilityMethods.........................................................................................53.InstabilityintheGastrointestinalTract..............................................................................7C.DeterminingDrugProductDissolutionCharacteristicsandDissolutionProfileSimilarity..7IV.BIOWAIVERSBASEDONBCS....................................................................................8V.ADDITIONALCONSIDERATIONSFORREQUESTINGABIOWAIVER...........9A.Excipients........................................................................................................................................9B.Prodrugs.........................................................................................................................................9C.FixedDoseCombinations............................................................................................................10D.Exceptions.....................................................................................................................................101.NarrowTherapeuticRangeDrugs....................................................................................102.ProductsDesignedtobeAbsorbedintheOralCavity.....................................................10VI.REGULATORYAPPLICATIONSOFTHEBCS......................................................11A.INDs/NDASs.................................................................................................................................11B.ANDAs..........................................................................................................................................11C.SupplementalNDAs/ANDAs(PostapprovalChanges).............................................................11VII.DATATOSUPPORTAREQUESTFORBIOWAIVERS........................................12A.DataSupportingHighSolubility................................................................................................12B.DataSupportingHighPermeability..............................................