DMF简介

DMF知识简介12020/1/2922020/1/29DMF制度背景32020/1/29Content•DMF定义•DMF类型•DMF状态•DMF递交•DMF审评•DMF费用42020/1/29DMF定义•ADrugMasterFile(DMF)isasubmissiontotheFoodandDrugAdministration(FDA)thatmaybeusedtoprovideconfidentialdetailedinformationaboutfacilities,processes,orarticlesusedinthemanufacturing,processing,packaging,andstoringofoneormorehumandrugs.•ThesubmissionofaDMFisnotrequiredbylaworFDAregulation.ADMFissubmittedsolelyatthediscretionoftheholder.•TheinformationcontainedintheDMFmaybeusedtosupportanInvestigationalNewDrugApplication(IND),aNewDrugApplication(NDA),anAbbreviatedNewDrugApplication(ANDA),anotherDMF,anExportApplication,oramendmentsandsupplementstoanyofthese.•ADMFisNOTasubstituteforanIND,NDA,ANDA,orExportApplication.Itisnotapprovedordisapproved.TechnicalcontentsofaDMFarereviewedonlyinconnectionwiththereviewofanIND,NDA,ANDA,oranExportApplication.52020/1/2962020/1/29五种类型•TypeIManufacturingSite,Facilities,OperatingProcedures,andPersonnel(nolongerapplicable)•TypeIIDrugSubstance,DrugSubstanceIntermediate,andMaterialUsedinTheirPreparation,orDrugProduct•TypeIIIPackagingMaterial•TypeIVExcipient,Colorant,Flavor,Essence,orMaterialUsedinTheirPreparation•TypeVFDAAcceptedReferenceInformation72020/1/29两种状态STATUSOFDMFs•“A”=Active.ThismeansthattheDMFwasfoundacceptableforfiling,administratively,andhasnotbeenclosed.•“I”=Inactive.ThismeansaDMFthathasbeenclosed,eitherbytheholderorbytheFDA.82020/1/2992020/1/29DMF递交•atransmittalletter•administrativeinformationaboutthesubmission•thespecificinformationtobeincludedintheDMF文件内容，纸张大小排版，文件格式…..GuidelineforDrugMasterFiles(September1989)(DMFGuidance).102020/1/29DMF递交•FoodandDrugAdministrationCenterforDrugEvaluationandResearchCentralDocumentRoom5901-BAmmendaleRoadDrugMasterFileStaffBeltsvilleMD20705-1266•AllsubmissionstoanexistingDMFthatisinpapermustbesubmittedintwocopiesinpapertotheaddressabove.Submissionsviae-mailarenotaccepted.112020/1/29DMF递交Currently,thereisnorequirementtosubmitorresubmitDMFsinanelectronicformat.However,beginningonMay5,2017,newDMFsaswellasamendmentstopreviouslysubmittedDMFs(i.e.,amendments)mustbesubmittedinanelectronicformatGuidanceforIndustry:ProvidingRegulatorySubmissionsinElectronicFormat—CertainHumanPharmaceuticalProductApplicationsandRelatedSubmissionsUsingtheeCTDSpecifications”(PDF)(May2015)122020/1/29DMF审评AdministrativeReview•TheFDAdoesnotsendanotificationtothesubmitterwhenanysubmission,includingaDMF,isreceivedbythedocumentroom.•Afterreceipt,theoriginalDMFundergoesanadministrativereviewtodeterminewhetheritisadministrativelycomplete.Thisadministrativereviewmaytake2-3weeks.•IftheDMFisacceptablefromanadministrativepointofview,anAcknowledgementLetterwillbeissued,notifyingtheholderoftheDMFnumber.AtthispointtheDMFisACTIVE.•Ifitisnotacceptablefromanadministrativepointofview,theholderwillbenotifiedofwhatdeficienciesneedtobecorrectedinordertomaketheDMFActive.132020/1/29DMF审评TechnicalReviewDMFsaresubjecttoacompletereviewfortechnicalinformationonlyunderthefollowingcircumstances:TheDMFisACTIVE.TheDMFholdersubmitsaLetterofAuthorization(LOA)intwocopies(ifapapersubmission)totheDMF.IftheDMFisinCTDformat,whetherelectronicorpaper,theLOAshouldbesubmittedinSection1.4.1.ThisLOAshouldcontaintheDMFnumber.TheholdersendsacopyoftheLOAtotheauthorizedparty(customer).ThecustomersubmitsanapplicationtotheFDAthatcontainsacopyoftheLOA.ThecopyoftheLOAshouldbesubmittedinSection1.4.2.142020/1/29DMF审评completenessassessment(CA)UnderGDUFA,beginningOctober1,2012,theholderofaTypeIIAPIDMFmustpayaone-timeDMFfeewhentheDMFisfirstreferencedinagenericdrugsubmissionsubmittedtoFDAonthebasisofaletterofauthorization(LOA)fromtheDMFholder.TheCAdoesnotreplacethefullscientificreview,whichdetermineswhethertheinformationcontainedintheDMFisadequatetosupportanANDAregulatoryaction.FDAwillconducttheCAbydeterminingtheanswerstoaseriesofquestionslistedintheCAChecklist152020/1/29DMF审评completenessassessment(CA)FDAwillundertakeaCAtodeterminethefollowing:•IstheDMFactive?•Hasthefeebeenpaid?•HastheDMFbeenpreviouslyreviewed?•DoestheDMFpertaintoasingleAPI?•DoestheDMFcontaincertainadministrativeinformation?•DoestheDMFcontainalltheinformationnecessarytoenableascientificreview?•IstheDMFwritteninEnglish?DMFsforwhichthefeehasbeenpaidandwhichhavebeenfoundcompleteinaccordancewiththecriteriaforaCAsetoutintheCAChecklistwillbeidentifiedonFDA’spublicWebsiteasavailableforreferenceinsupportofagenericdrugsubmission.DraftGuidanceforIndustryInitialCompletenessAssessmentsforTypeIIAPIDMFsUnderGDUFA162020/1/29DMF审评172020/1/29DMF费用TheFY（fiscalyear）2016DMFfeeis$42,170.182020/1/29DMF费用•EachpersonthatownsaTypeIIAPIDMF(DMFholder)thatisreferencedonorafterOctober1,2012,inagenericdrugsubmissionbyanyinitialletterofauthorizationshallbesubjecttoaDMFfee.•TheDMFfeeisaone-timefee,incurredonfirstreferenceoftheDMFonorafterOctober1,2012.ThisfeeisnotincurredeverytimeaDMFisreferenced.•FeeswillbedueonthedatethefirstgenericdrugsubmissionissubmittedthatreferencestheassociatedtypeIIAPIDMF.•AnyoneoranyentitycanpaytheDMFfee.192020/1/29DMF费用DMFholdersmayalsopaythefeeinadvanc