Module-1-5-FDA CTD大纲

Version2.3TheComprehensiveTableofContentsHeadingsandHierarchyRevisionHistoryDateVersionSummaryofChanges2004-071.0Originalversion2005-06-161.1Correctionsandadditionstothemappingtables2005-07-061.2Correctionstotheheadings2012-06-012.0CorrectionsandadditionstothemappingtablesbasedonmajorupdatetoModule1specifications(SummaryofChangesinSectionCofAppendix2)2012-11-012.1Modifiedtheheadingfor1.16andaddedREMSandnon-REMSsub-headings(SummaryofChangesinSectionBofAppendix2)2013-08-232.2Addedtwonewattributesfor1.15.2.1(SummaryofChangesinSectionAofAppendix2)2014-02-072.3Modifiedtheheadingfor1.15.1.5(SummaryofChangesinSectionAofAppendix2)Version2.3iiTableofContentsTHECOMPREHENSIVETABLEOFCONTENTSHEADINGSANDHIERARCHY......................................................ITHECOMPREHENSIVETABLEOFCONTENTSHEADINGSANDHIERARCHY.....................................................1MODULE1ADMINISTRATIVEINFORMATION.................................................................................................1MODULE2SUMMARIES..........................................................................................................................................4MODULE3QUALITY.................................................................................................................................................5MODULE4NONCLINICALSTUDYREPORTS....................................................................................................6MODULE5CLINICALSTUDYREPORTS.............................................................................................................9APPENDIXI–MAPPINGSECTION.......................................................................................................................13APPENDIX2–MODULE1SUMMARYOFCHANGES......................................................................................39A.MODULE1SUMMARYOFCHANGES(02/07/2014,VERSION2.3).........................................................39B.MODULE1SUMMARYOFCHANGES(08/23/2013,VERSION2.2).........................................................39C.MODULE1SUMMARYOFCHANGES(11/1/2012,VERSION2.1)...........................................................39D.MODULE1SUMMARYOFCHANGES(6/1/2012,VERSION2.0).............................................................40Version2.31TheComprehensiveTableofContentsHeadingsandHierarchyModule1Administrativeinformation1.1FormsForm[form-type]1.2Coverletters1.3Administrativeinformation1.3.1Contact/sponsor/applicantinformation1.3.1.1Changeofaddressorcorporatename1.3.1.2Changeincontact/agent1.3.1.3Changeinsponsor1.3.1.4Transferofobligation1.3.1.5Changeinownershipofanapplicationorreissuanceoflicense1.3.2Fieldcopycertification1.3.3Debarmentcertification1.3.4Financialcertificationanddisclosure1.3.5Patentandexclusivity1.3.5.1Patentinformation1.3.5.2Patentcertification1.3.5.3Exclusivityclaim1.3.6Tropicaldiseasepriorityreviewvoucher1.4References1.4.1Letterofauthorization1.4.2Statementofrightofreference1.4.3Listofauthorizedpersonstoincorporatebyreference1.4.4Cross-referencetopreviouslysubmittedinformation1.5Applicationstatus1.5.1WithdrawalofanIND1.5.2Inactivationrequest1.5.3Reactivationrequest1.5.4Reinstatementrequest1.5.5WithdrawalofanunapprovedBLA,NDA,ANDA,orSupplement1.56Withdrawaloflisteddrug1.5.7Withdrawalofapprovalofanapplicationorrevocationoflicense1.6Meetings1.6.1Meetingrequest1.6.2Meetingbackgroundmaterials1.6.3Correspondenceregardingmeetings1.7Fasttrack1.7.1Fasttrackdesignationrequest1.7.2Fasttrackdesignationwithdrawalrequest1.7.3Rollingreviewrequest1.7.4Correspondenceregardingfasttrack/rollingreviewVersion2.321.8Specialprotocolassessmentrequest1.8.1Clinicalstudy1.8.2Carcinogenicitystudy1.8.3Stabilitystudy1.8.4Animalefficacystudyforapprovalundertheanimalrule1.9Pediatricadministrativeinformation1.9.1Requestforwaiverofpediatricstudies1.9.2Requestfordeferralofpediatricstudies1.9.3Requestforpediatricexclusivitydetermination1.9.4Proposedpediatricstudyrequestandamendments1.9.5Proposalforwrittenagreement(nolongerapplicable)1.9.6Othercorrespondenceregardingpediatricexclusivityorstudyplans1.10Disputeresolution1.10.1Requestfordisputeresolution1.10.2Correspondencerelatedtodisputeresolution1.11Informationamendment:Informationnotcoveredundermodules2to51.11.1Qualityinformationamendment1.11.2Nonclinicalinformationamendment1.11.3Clinicalinformationamendment1.11.4Multiplemoduleinformationamendment1.12Othercorrespondence1.12.1PreINDcorrespondence1.12.2Requesttochargeforclinicaltrial1.12.3Requesttochargeforexpandedaccess1.12.4Requestforcommentsandadvice1.12.5Requestforawaiver1.12.6Exceptionfrominformedconsentforemergencyresearch1.12.7Publicdisclosurestatementforexceptionfrominformedconsentforemergencyresearch1.12.8Correspondenceregardingexceptionfrominformedconsentforemergencyresearch1.12.9Notificationofdiscontinuationofclinicaltrial1.12.10Genericdrugenforcementactstatement1.12.11ANDAbasisforsubmissionstatement1.12.12Comparisonofgenericdrugandreferencelisteddrug1.12.13Requestforwaiverforinvivostudies1.12.14Environmentalanalysis1.12.15Requestforwaiverofinvivobioavailabilitystudies1.12.16Fieldalertreports1.12.17Orphandrugdesignation1.13Annualreport1.13.1Summaryfornonclinicalstudies1.13.2Summaryofclinicalpharmacologyinformation1.13.3Summaryofsafetyinformation1.13.4Summaryoflabelingchanges1.13.5SummaryofmanufacturingchangesVersion2.331.13.6Summaryofmicrobiologicalchanges1.13.7Summaryofothersignificantnewinformation1.13.8Individualstudyinformation1.13.9Generalinvestigationalplan1.13.10Foreignmarketing1.13.11Distributiondata1.13.12Statusofpostmarketingstudycommitmentsandrequirements1.13.13Statusofotherpostmarketingstudiesandrequirements1.13.14Logofoutstandingregulatorybusiness1.13.15Developmentsafetyupdatereport(DSUR)1.14Labeling1.14.1Draftlabeling1.14.1.1Draftcartonandcontainerlabels1.14.1.2Annotateddraftlabelingtext1.14.1.3Draftlabelingtext1.14.1.4Labelcomprehensionstudies1.14.1.5Labelinghistory1.14.2Finallabeling1.14.2.1Finalcartonorcontainerlabels1.14.2.2Finalpackageinsert(packageinserts,patientinformation,medicationguides)1.14.2.3Finallabelingtext1.14.3Listeddruglabeling1.14.3.1Annotatedcomparisonwithlisteddrug1.14.3.2Approvedlabelingtextforlisteddrug1.14.3.3Labelingtextforreferencelisteddrug1.14.4Investigationaldruglabeling1.14.4.1Investigationalbrochure1.14.4.2Investigationaldruglabeling1.14.5Foreignlabeling1.14.6Productlabelingfor2253submissions1.15Promotionalmaterial[promotional-material-audience-type]1.15.1Correspondencerelatingtopromotionalmaterials1.15.1.1Requestforadvisorycommentsonlaunchmaterials1.15.1.2Requestforadvisorycommentsonnon-launchmaterials1.15.1.3Presubmissionoflaunchpromotionalmaterialsforacceleratedapprovalproducts1.15.1.4Presubmissionofnon-launchpromotionalmaterialsforacceleratedapprovalproducts1.15.1.5Pre-disseminationreviewoftelevisionads1.15.1.6Responsetountitledletterorwarningletter1.15.1.7Responsetoinformationrequest1.15.1.8Correspondenceaccompanyingmaterialspreviouslymissingorrejected1.15.1.9WithdrawalrequestVersion2.341.15.1.10Submissionofannotatedreferences1.15.1.11Generalcorrespondence1.15.2Materialsattribute=[promotional-material-doc-type]1.15.2.1Material[promotional-material-type,material-id,issue-date]1.15.2.1.1Cleanversion1.15.2.1.2Annotatedversion1.15.2.1.3Annotatedlabelingversion1.15.2.1.4Annotatedreferences1.16Riskmanagementplan1.16.1RiskManagement(Non-REMS)1.16.2RiskEvaluationandMitigationStrategy(REMS)1.16.2.1FinalREMS1.16.2.2DraftREMS1.16.2.3REMSAssessment1.16.2.4REMSAssessmentMethodology1.16.2.5REMSCorrespondence1.16.2.6REMSModificationHistory1.17Postmarketingstudies1.17.1Correspondenceregardingpostmarketingcommitments1.17.2Correspondenceregardingpostmarketingrequirements1.18Proprietarynames1.19Pre-EUAandEUA1.20GeneralinvestigationalplanforinitialINDModule2Summaries2.2Introductiontosummary2.3Qualityoverallsummary2.4Nonclinicaloverview2.5Clinicaloverview2.6Nonclinicalwrittenandtabulatedsummaries2.6.1Introduction2.6.2Pharmacologywrittensummary2.6.3Pharmacologytabulatedsummary2.6.4Pharmacokineticwrittensummary2.6.5Pharmacokinetictabulatedsummary2.6.6Toxicologywrittensummary2.6.7Toxicologytabulatedsummary2.7Clinicalsummary2.7.1SummaryofBiopharmaceuticStudiesandAssociatedAnalyticalMethods2.7.2SummaryofClinicalPharmacologystudies2.7.3SummaryofClinicalEfficacy[indication]2.7.4SummaryofClinicalSafety2.7.5References2.7.6SynopsesofindividualstudiesVersion2.35Module3Quality3.2Bodyofdata3.2.SDrugsubstance[name,manufacturer]3.2.S.1Generalinformation3.2.S.1.1Nomenclature3.2.S.1.2Structure3.2.S.1.3Generalproperties3.2.S.2Manufacture3.2.S.2.1Manufacturer(s)3.2.S.2.2DescriptionofManufacturingProcessandProcessControls3.2.S.2.3ControlofMaterials3.2.S.2.4ControlsofCriticalStepsandIntermediates3.2.S.2.5ProcessValidationand/orEvaluation3.2.S.2.6ManufacturingProcessDevelopment3.2.S.3Characterization3.2.S.3.1ElucidationofStructureandotherCharacteristics3.2.S.3.2Impurities3.2.S.4Controlofdrugsubstance3.2.S.4.1Specification3.2.S.4.2AnalyticalProcedures3.2.S.4.3ValidationofAnalyticalProcedures3.2.S.4.4BatchAnalyses3.2.S.4.5JustificationofSpecification3.2.S.5Referencestandardsormaterials3.2.S.6Containerclosuresystems3.2.S.7Stability3.2.S.7.1StabilitySummaryandConclusions3.2.S.7.2PostApprovalStabilityProtocolandStabilityCommitment3.2.S.7.3StabilityData3.2.PDrugproduct[name,dosageform,manufacturer]3.2.P.1Descriptionandcompositionofthedrugproduct3.2.P.2Pharmaceuticaldevelopment3.2.P.3Manufacture3.2.P.3.1Manufacturer(s)3.2.P.3.2BatchFormula3.2.P.3.3DescriptionofManufacturingProcessandProcessControls3.2.P.3.4ControlsofCriticalStepsandIntermediates3.2.P.3.5ProcessValidationand/orEvaluation3.2.P.4Controlofexcipients[name]3.2.P.4.1Specification(s)3.2.P.4.2AnalyticalProcedures3.2.P.4.3ValidationofAnalyticalProcedures3.2.P.4.4JustificationofSpecifications3.2.P.4.5ExcipientsofHumanorAnimalOrigin3.2.P.4.6NovelExcipients3.2.P.5Controlofdrugproduct3.2.P.5.1Specification(s)3.2.P.5.2AnalyticalProcedures3.2.P.5.3ValidationofAnalyticalProceduresVersion2.363.2.P.5.4BatchAnalyses3.2.P.5.5CharacterizationofImpurities3.2.P.5.6JustificationofSpecification(s)3.2.P.6Referencestandardsormaterials3.2.P.7Containerclosuresystem3.2.P.8Stability3.2.P.8.1StabilitySummaryandConclusion3.2.P.8.2PostapprovalStabilityProtocolandStabilityCommitment3.2.P.8.3StabilityData3.2.AAppendices3.2.A.1FacilitiesandEquipment[name,manufacturer]3.2.A.2Adventitiousagentssafetyevaluation[name,dosageform,manufacturer]3.2.A.3Novelexcipients3.2.RRegionalinformation3.3LiteraturereferencesModule4NonclinicalStudyReports4.2Studyreports4.2.1Pharmacology4.2.1.1PrimarypharmacodynamicsStudyreport[identificationnumber]andrelatedinformationLegacystudyreportSynopsisStudyreportbodyProtocolandamendmentsSignaturesofprincipalorcoordinatinginvestigator(s)AuditcertificationsandreportsDocumentationofstatisticalmethodsandinterimanalysisplansDocumentationofinterlaboratorystandardizationmethodsofqualityassuranceproceduresifusedPublicationsbasedonthestudyImportantpublicationsreferencedinthereportComplianceand/ordrugconcentrationdataIndividualsubjectdatalistingsDatatabulationDatatabulationdatasetsDatadefinitionsDatalistingdatasetsDatalistingdatasetsDatadefinitionsAnalysisdatasetsAnalysisdatasetsAnalysisprogramsDatadefinitionsINDsafetyreports4.2.1.2SecondarypharmacodynamicsStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadingsVersion2.374.2.1.3SafetypharmacologyStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.1.4PharmacodynamicdruginteractionsStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2Pharmacokinetics4.2.2.1AnalyticalmethodsandvalidationreportsStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2.2AbsorptionStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2.3DistributionStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2.4MetabolismStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2.5ExcretionStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.2.6PharmacokineticdruginteractionsStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadingStatementofQAdifferences4.2.2.7OtherpharmacokineticstudiesStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3Toxicology4.2.3.1Singledosetoxicity[Speciesandroute]Studyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.2Repeatdosetoxicity[Species,route,duration]Studyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.3Genotoxicity4.2.3.3.1InvitroStudyreport[identificationnumber]andrelatedinformationVersion2.38SeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.3.2InvivoStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.4Carcinogenicity4.2.3.4.1Longtermstudies[Species]Studyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.4.2ShortormediumtermstudiesStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.4.3OtherstudiesStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.5Reproductiveanddevelopmentaltoxicity4.2.3.5.1FertilityandearlyembryonicdevelopmentStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.5.2EmbryofetaldevelopmentStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.5.3Prenatalandpostnataldevelopment,includingmaternalfunctionStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.5.4Studiesinwhichtheoffspring(juvenileanimals)aredosedand/orfurtherevaluatedStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.6LocaltoleranceStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7Othertoxicitystudies4.2.3.7.1AntigenicityStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.2ImmunotoxicityStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.3MechanisticstudiesStudyreport[identificationnumber]andrelatedinformationVersion2.39SeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.4DependenceStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.5MetabolitesStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.6ImpuritiesStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.2.3.7.7OtherStudyreport[identificationnumber]andrelatedinformationSeePrimarypharmacodynamicsStudyreportandrelatedinformationforheadings4.3LiteraturereferencesModule5ClinicalStudyReports5.2Tabularlistingofallclinicalstudies5.3Clinicalstudyreportsandrelatedinformation5.3.1Reportsofbiopharmaceuticstudies5.3.1.1Bioavailability(BA)StudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationLegacystudyreportSynopsis(ICHE3,section2)Studyreport(E31,3to15)Protocolandamendments(E316.1.1)Samplecasereportform(E316.1.2)ListofIECsorIRBs(E316.1.3)andconsentformsListanddescriptionofinvestigators(E316.1.4)andsitesSignaturesofprincipalorcoordinatinginvestigator(s)orsponsor’sresponsiblemedicalofficer(E316.1.5)Listingofpatientsreceivingtestdrug(s)fromspecifiedbatch(E316.1.6)Randomisationsscheme(E316.1.7)Auditcertificates(E316.1.8)andreportsDocumentationofstatisticalmethods(E316.1.9)andinterimanalysisplansDocumentationofinterlaboratorystandardizationmethodsofqualityassuranceproceduresifused(E316.1.10)Publicationsbasedonthestudy(E316.1.11)Importantpublicationsreferencedinthereport(E316.1.12)Discontinuedpatients(E316.2.1)Protocoldeviations(E316.2.2)Patientsexcludedfromtheefficacyanalysis(E316.2.3)Demographicdata(E316.2.4)Complianceand/ordrugconcentrationdata(E316.2.5)Version2.310Individualefficacyresponsedata(E316.2.6)Adverseeventlistings(E316.2.7)Listingofindividuallaboratorymeasurementsbypatient(E316.2.8)Casereportforms(E316.3)Site[identifier]Individualpatientdatalistings(E316.4)DatatabulationDatatabulationdatasetsDatadefinitionsDatalistingdatasetsDatalistingdatasetsDatadefinitionsAnalysisdatasetsAnalysisdatasetsAnalysisprogramsDatadefinitionsAnnotatedCRFAnnotatedECGwaveformdatasetsImagefilesSubjectprofilesINDsafetyreports5.3.1.2ComparativeBAandbioequivalence(BE)StudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.1.3InVitro-inVivocorrelationStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.1.4ReportsofbioanalyticalandanalyticalmethodsforhumanstudiesStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.2Reportsofstudiespertinenttopharmacokineticsusinghumanbiomaterials5.3.2.1PlasmaproteinbindingStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.2.2ReportsofhepaticmetabolismanddruginteractionstudiesStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)StudyreportsandrelatedinformationforheadingsVersion2.3115.3.2.3ReportsofstudiesusingotherhumanbiomaterialsStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.3Reportsofhumanpharmacokinetic(PK)studies5.3.3.1HealthysubjectPKandinitialtolerabilityStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.3.2PatientPKandinitialtolerabilityStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.3.3IntrinsicfactorPKStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.3.4ExtrinsicfactorStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.3.5PopulationPKStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.4Reportsofhumanpharmacodynamic(PD)studies5.3.4.1HealthysubjectPDandPK/PDStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformationSeeexampleunderbioavailability(BA)Studyreportsandrelatedinformationforheadings5.3.4.2PatientPDandPK/PDStudyreportsandrelatedinformationStudyreport[identification]andrelatedinformat