6-FDA细胞与基因治疗制品早期临床试验设计考量行业指南

GuidanceforIndustryConsiderationsfortheDesignofEarly-PhaseClinicalTrialsofCellularandGeneTherapyProductsDRAFTGUIDANCEThisguidancedocumentisforcommentpurposesonly.SubmitonesetofeitherelectronicorwrittencommentsonthisdraftguidancebythedateprovidedintheFederalRegisternoticeannouncingtheavailabilityofthedraftguidance.Submitelectroniccommentsto(HFA-305),FoodandDrugAdministration,5630FishersLane,Rm.1061,Rockville,MD20852.YoushouldidentifyallcommentswiththedocketnumberlistedinthenoticeofavailabilitythatpublishesintheFederalRegister.AdditionalcopiesofthisguidanceareavailablefromtheOfficeofCommunication,OutreachandDevelopment(OCOD),(HFM-40),1401RockvillePike,Suite200N,Rockville,MD20852-1448,orbycalling1-800-835-4709or301-827-1800,[e-mail],orfromtheInternetat–NotforImplementationiTableofContentsI.INTRODUCTION.............................................................................................................1II.BACKGROUND...............................................................................................................2III.FEATURESOFCGTPRODUCTSTHATINFLUENCECLINICALTRIALDESIGN.............................................................................................................................3A.ProductCharacteristics........................................................................................3B.ManufacturingConsiderations............................................................................5C.PreclinicalConsiderations....................................................................................5IV.CLINICALTRIALDESIGN..........................................................................................6A.Early-PhaseTrialObjectives...............................................................................6B.ChoosingaStudyPopulation...............................................................................7C.ControlGroupandBlinding..............................................................................10D.DoseSelection......................................................................................................11E.TreatmentPlan....................................................................................................12F.MonitoringandFollow-up.................................................................................14V.MEETINGSWITHOCTGT.........................................................................................18VI.GUIDANCEONSUBMITTINGANIND....................................................................18V.REFERENCES................................................................................................................21ContainsNonbindingRecommendationsDraft–NotforImplementation1GuidanceforIndustryConsiderationsfortheDesignofEarly-PhaseClinicalTrialsofCellularandGeneTherapyProductsThisdraftguidance,whenfinalized,willrepresenttheFoodandDrugAdministration’s(FDA’s)currentthinkingonthistopic.ItdoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAorthepublic.Youcanuseanalternativeapproachiftheapproachsatisfiestherequirementsoftheapplicablestatutesandregulations.Ifyouwanttodiscussanalternativeapproach,contacttheappropriateFDAstaff.IfyoucannotidentifytheappropriateFDAstaff,calltheappropriatenumberlistedonthetitlepageofthisguidance.I.INTRODUCTIONTheCenterforBiologicsEvaluationandResearch(CBER)/OfficeofCellular,Tissue,andGeneTherapies(OCTGT)isissuingthisguidancetoassistsponsorsofInvestigationalNewDrugApplications(INDs)forcellulartherapy(CT)andgenetherapy(GT)products.CTandGTproductswillbereferredtocollectivelyasCGTproducts.Thisguidanceprovidesrecommendationstoassistindesigningearly-phaseclinicaltrialsofCGTproducts.Whenthisguidanceisfinalized,webelieveitwillclarifyOCTGT’scurrentexpectationsregardingclinicaltrialsinwhichtheprimaryobjectivesaretheinitialassessmentsofsafety,tolerability,orfeasibilityofadministrationofinvestigationalproducts.SuchtrialsincludemostPhase1trials,includingtheinitialintroductionofaninvestigationalnewdrugintohumans,andsomePhase2trialsofCGTproducts.ThescopeofthisguidanceislimitedtoproductsforwhichOCTGThasregulatoryauthority.CGTproductswithinthescopeofthisguidancemeetthedefinitionof“biologicalproduct”insection351(i)ofthePublicHealthService(PHS)Act(42U.S.C.262(i)).Thisguidancedoesnotapplytothosehumancells,tissues,andcellular-andtissue-basedproducts(HCT/Ps)regulatedsolelyundersection361ofthePHSAct(42U.S.C.264),asdescribedinTitle21CodeofFederalRegulations(CFR)Part1271(21CFRPart1271),toproductsregulatedasmedicaldevicesundertheFederalFood,Drug,andCos