上市后临床跟踪管理程序.doc

上市后临床跟踪控制程序上市后临床跟踪控制程序文件编号：QP-29版本：A0生效日期：页码：17编制：审核：批准：1.PURPOSEThepurposeofthisworkinstructionistodefinetheprocesstodetermineanddocumentwhetherapost-marketclinicalfollow-upstudyisrequiredforTDIFootAnkleArray8chmedicaldevicesbearingtheCEmark.Theprocesswillleadtoadeterminationofwhetherapost-marketclinicalfollow-upstudyisrequiredandprovideguidanceforpost-marketclinicalmonitoringrequirementsifastudyisnotrequired.2.SCOPETheworkinstructionappliestoallmedicaldevicebusinessesandsitesoperatingundertheTDIFootAnkleArray8chHealthcareQualityManagementSystem.OnlymedicaldevicesbearingtheCEMarkwillberequiredtofollowthisworkinstruction.3.REFERENCES3.1.ExternalReferences3.1.1.LawsCouncilDirective9342EECof14June1993concerningmedicaldevicesincludingamendmentsthrough05September20073.1.2.GuidanceDocumentsEuropeanCommissionEnterprise-Directorate-GeneralMEDDEV2.12-2GuidelinesonPostMarketClinicalFollow-UpdatedMay2004MEDDEV2.7.1Rev.3guidelinesonmedicaldevice-clinicaluation-aguideanufacturersandnotifiedbodiesdatedApril2009GHTFPost-MarketClinicalFollow-UpStudiesSG5(PD)N4R7(Proposeddocument23July2008)GHTFClinicalInvestigationsSG5(PD)N3R7(20January2008)4.ROLESANDRESPONSIBILITIESImportant:Whenatitleofapositionislistedinthisworkinstructionitrelatestothatpositionoritsequivalent.Belowaretherolesandresponsibilitiesdiscussedwithinthisdocument.Table4-1:RolesandResponsibilitiesRoleResponsibilityDesignEngineeringandorEngineeringRepresentativeProvideconsultationtotheProductRegulatoryAffairsRepresentativeindeterminingforagivenprojectproductwhetherapost-marketclinicalfollow-upstudyisrequiredProvideconsultationtotheProductRegulatoryAffairsRepresentativetodetermineifanequivalentdeviceexistsProvideconsultationtotheProductRegulatoryAffairsRepresentativeinidentifyingemergingrisksforthemedicaldeviceProvideconsultationtotheResearchManagerordesigneetodeterminethetypeofpost-marketclinicalfollow-upstudytobeimplementedifapplicableProductRegulatoryAffairsRepresentativeDetermineforagiveprojectproductwhetherapost-marketclinicalfollow-upstudyisrequiredDetermineifanequivalentdeviceexistsIdentifypotentialemergingrisksReviewriskassessmentCompletethePost-MarketClinicalFollow-UpJustificationregardingdecisiontoperastudyCompletethePost-MarketClinicalFollow-UpPlanthatdetailsthepost-marketclinicalfollow-upplanDeterminehowoftenclinicaldatamustbereviewedReviewandapprovetheclinicaluationperedbytheResearchManagerordesigneeRegulatoryAffairsRepresentativeProvideconsultationtotheResearchManagertodeterminethetypeofpost-marketclinicalfollow-upstudytobeimplementedifapplicableTable4-1:RolesandResponsibilitiesRoleResponsibilityResearchManagerordesigneeProvideconsultationtotheProductRegulatoryAffairsRepresentativeindeterminingforagivenprojectproductwhetherapost-marketclinicalfollow-upstudyisrequiredProvideconsultationtotheProductRegulatoryAffairsRepresentativetodetermineifanequivalentdeviceexistsProvideconsultationtotheProductRegulatoryAffairsRepresentativetoidentifypotentialemergingrisksReviewthePost-MarketClinicalFollow-UpJustificationandPost-MarketClinicalFollow-UpPlantoconfirmthedecisionsregardingtheneedforapost-marketclinicalfollow-upstudyandclinicalfollow-upDeterminehowoftenclinicaldatamustbereviewedDeterminethetypeofpost-marketclinicalfollow-upstudytobeimplementedifapplicableReviewnewdata(i.e.literatureadverseeventscomplaintsetc)anddetermineifapost-marketclinicalfollow-upstudyisnecessarybasedonnewination(clinicaluation)MedicalAffairsRepresentativeReviewthePost-MarketClinicalFollow-UpJustificationandPost-MarketClinicalFollow-UpPlantoconfirmthedecisionsregardingtheneedforapost-marketclinicalfollow-upstudyandclinicalfollow-upReviewandapprovetheclinicaluationperedbytheResearchManagerordesignee5.WORKINSTRUCTIONPost-marketclinicalmonitoringisanessentialelementinestablishinglongtermsafetyfollow-updataandpossibleemergentrisksedicaldevices.Theserisksanddatacannotadequatelybedetectedandcharacterizedbyrelyingsolelyonpre-marketclinicalinvestigations.Postmarketclinicalmonitoringmayincludeacombinationofseveralstrategies:ProductcomplaintreviewPost-marketeventreportingreviewofusersandpatientsLiteraturereviewPost-marketclinicalfollow-upstudies(PMCFS)ThisworkinstructionwascreatedtodeterminewhenaPMCFSisnecessarytomaintainanadequatepost-marketsurveillancesystemasrequiredbytheMedicalDeviceDirective9342ECC(MDD)asamendedbyMDD200747EC.Itwillalsoprovideguidanceonthepost-marketclinicalmonitoringrequirementsifaPMCFSisnotrequired.Figure5-1:High-LevelProcessOverviewforPost-MarketClinicalFollow-UpDeterminewhetheranequivalentdeviceexistsIdentifyresidualrisksemergingrisksReviewRiskAssessmentdocumentuateneedforPMCFSPMCFSRequiredPMCFSDeterminationPerPMCFSinaccordancewithGEHC_GQP_10.03andGEHC_GQP_10.03.002YESAtaminimumreviewclinicaldataincludingAEscomplaintsandliteratureNOReviewnewdataanddeterminetheneedtoaPMCFSbasedonnewination5.1.GeneralRequirements5.1.1.PriortoM3sign-offtheProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandtheDesignEngineeringandorEngineeringRepresentativeshalldetermineforagivenprojectprogramwhetheraPMCFSisrequired.Theyshallalsodeterminethepost-marketclinicalfollow-upplan.5.1.2.APMCFSmaynotberequiredforproductsforwhichmediumlong-termclinicalperanceandsafetyisalreadyknownfromprevioususeofthedeviceorwhereotherappropriatepost-marketsurveillanceactivitieswouldprovidesufficientdatatoaddresstherisks.5.2.DeterminingtheTypeofPost-MarketClinicalFollow-UpRequiredPost-marketclinicalmonitoringshallhaveoneoftwooutcomes(1)PMCFSrequiredor(2)noPMCFSrequired.TheneedforaPMCFSshallbebasedonacombinationofseveralfactorsdetailedinthissection.5.2.1.TheProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandDesignEngineeringandorEngineeringRepresentativeshalldeterminewhetheranequivalentdeviceexists.Equivalenceshallbedemonstratedinalltheessentialcharacteristicspreciselydefinedbelow.Equivalencemeans:ClinicalUsedforthesameclinicalconditionorpurposeUsedatthesamesiteinthebodyUsedinsimilarpopulation(includingageanatomyphysiology)HavesimilarrelevantcriticalperanceaccordingtoexpectedclinicaleffectforspecificintendeduseTechnicalUsedundersimilarconditionsofuseHavesimilarspecificationsandpropertiesBeofsimilardesignUsesimilardeploymentsHavesimilarprinciplesofoperationBiologicalSameorsimilaruseofmaterialsincontactwithhumantissuesorbodyfluids5.2.2.ProductsforwhichthemediumlongtermclinicalperanceandsafetyisalreadyknownfromprevioususeofthedeviceorfromfullytransferableexperiencewithequivalentdevicesshallnotrequireaPMCFS.NOTE:Ifthedevicequotedasthe“equivalent”requiresaPMCFSthenthenewproductshallbesubjecttothesamerequirement.5.2.3.TheneedforaPMCFSshallbedeterminedbasedontheidentificationofresidualrisksthatmayimpacttheriskbenefitratio.Astudyshouldalwaysbeconsideredfordeviceswheretheidentificationofpossibleemergingrisksandtheuationoflongtermsafetyandperanceareessential.TheProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandDesignEngineeringandorEngineeringRepresentativeshallidentifysuchemergingriskthefollowingcriteriashouldbetakenintoaccount:innovatione.g.wherethedesignofthedevicethematerialstheprinciplesofoperationthetechnologyorthemedicalindicationsarenovelhighriskanatomicallocations(i.e.heartcentralnervoussystemetc.)severityofdiseasetreatmentchallengessensitivityoftargetpopulation(i.e.infantschildrenpregnantwomenetc.)identificationofanacceptableriskduringthepre-CEclinicaluationwhichshouldbemonitoredinalongertermandorthroughalargerpopulationwellknownrisksidentifiedfromtheliteratureorsimilarmarketeddevicesdiscrepancybetweenthepre-marketfollow-uptimescalesandtheexpectedlifeoftheproduct5.2.4.Aproperlyconductedriskanalysisisessentialindeterminingwhatclinicalevidencemaybeneededforaparticulardevice.Anyrisksidentifiedasan“unacceptable”riskattheconclusionofthedevelopmentprocessshallrequireaPMCFS.Astudyshouldalsobeconsideredforrisksidentifiedas“acceptable”or“riskmitigationrequired”ifthedevicemeetsanyoftheothercharacteristicsidentifiedin5.2.1and5.2.2.TheriskassessmentshallbeperedaccordingtotheRiskManagementProcedure.TheProductRegulatoryAffairsRepresentativeshallreviewtheriskassessment.5.2.5.TheProductRegulatoryAffairsRepresentativeshallcompletethePostMarketClinicalFollow-UpStudyDetermination(AppendixA)oncethedecisionregardingtheneedforastudyhasbeendetermined.NOTE:ThismayalsobeusedasaguideinmakingthedeterminationabouttheneedtoperaPMCFS.5.2.6.TheProductRegulatoryAffairsRepresentativeshallcompletethePost-MarketClinicalFollow-UpPlan(AppendixB)thatdetailstheplanforpost-marketclinicalfollow-up.5.2.7.TheResearchManagerordesigneeandMedicalAffairsRepresentativeshallreviewthePost-MarketClinicalFollow-UpJustificationandThePost-MarketClinicalFollow-UpPlantoconfirmthedecisionsregardingpost-marketclinicalmonitoring.5.3.NoPostMarketClinicalFollow-UpStudyRequired5.3.1.IfitwasdeterminedthatnoPMCFSisrequired(basedonsection5.2)post-marketclinicalmonitoringisstillrequiredforthemedicaldevice.5.3.2.JustificationregardingthedecisionnottoperaPMCFSmustbeclearlydocumentedandmaintainedinthedesignhistorytechnicalfile(see5.2.5).5.3.3.Post-MarketClinicalMonitoringRequirements(minimum).Ataminimumthefollowingpost-marketclinicalmonitoringactivitiesshallbecompletedaccordingtoTDIFootAnkleArray8chestablishedproceduresworkinstructions.TheseelementswillbesintothePost-MarketLiteratureuationandMarketAnalysisReport.ReviewofproductcomplaintsaccordingtoComplaintHandlingProcedureReviewofpostmarketadverseeventsaccordingtoPostMarketEventReportingProcedureLiteraturereviewaccordingtoTDIFootAnkleArray8chuationofClinicalDatatoSupportCEMarkingWorkInstruction..ReviewofproductcomplaintspostmarketadverseeventsandtheliteraturereviewshallbecompletedattheintervalsspecifiedinTable5-1.Thetimingoutlinedprovidestheminimumrequirements.TheProductRegulatoryAffairsRepresentativeandortheResearchManagerordesigneecandeterminethatclinicaldatashallbereviewedmoreoften.Table5-1:TimingforReviewofClinicalDatabasedonMedicalDeviceClassDeviceClassificationTimingforreviewofclinicaldata(minimum)ClassIAnnuallyClassIIaIIbAtaminimumannuallyshouldconsidermoreoftenClassIIISemi-annually(i.e.twiceayear)shouldconsidermoreoften.AttheintervaloutlinedinTable5-1theResearchManagerordesigneeshallcompletealiteraturereviewandanalysisofpost-marketexperiences(plaintsandadverseevents)andre-uateifaPMCFSneedstobeconductedbasedonthisdata.ThePostMarketLiteratureuationandMarketAnalysisConclusion(AppendixD)shallbecompletedandmaintainedaspartofthedevicesdesignhistorytechnicalfile.TheProductRegulatoryAffairsRepresentativeandMedicalAffairsRepresentativeshallreviewandapprovethisdocument.NOTE:TheliteraturereviewshallbecutedaccordingtotheuationofClinicalDatatoSupportCEMarkingWorkInstructionsection5.5.Howeverthefollowingstemplatesshallbeusedinplaceofthosespecifiedinthisworkinstruction:a.InsteadofusingTheLiteratureuationPlantemplatereferencedusethePostMarketLiteratureuationandMarketExperiencePlan(AppendixC)b.InsteadofusingTheLiteratureuationReportandConclusiontemplateusethePost-MarketLiteratureuationandMarketAnalysisReportandConclusion(AppendixD)5.4.PostMarketClinicalFollow-UpStudyRequired5.4.1.IfitwasdeterminedthataPMCFSisrequiredinadditiontotherequirementslistedunder5.3.3studiessuchasextendedfollow-upofpatientsenrolledinthepre-markettrialsprospectivestudyofarepresentativesubsetofpatientsafterthedeviceisplacedonthemarketoranopenregistrymaybepered.5.4.2.ThePMCFSshallbecarriedoutinaccordancewithTDIFootAnkleArray8chsResearchInvolvingHumanSubjectsProcedure5.4.3.TheResearchManagerordesigneeinconsultationwiththeRegulatoryAffairsRepresentativeandtheDesignEngineeringandorEngineeringRepresentativewilldeterminethetypeofPMCFSthatwillbeimplemented.5.4.4.Thestudyshouldtakeintoaccountthefollowing:ResultsoftheclinicalinvestigationincludingadverseeventsidentifiedAveragelifeexpectancyofthedeviceTheclaimsmadebythemanufacturerforthedevicePerancesforwhichequivalenceisclaimedNewinationbecomingavailable.AttheintervaloutlinedinTable5-1theResearchManagerordesigneeshallcompletealiteraturereviewandanalysisofpost-marketexperiences(plaintsandadverseevents)andreviewtheongoingresultsdataofthePMCFS.ThePostMarketLiteratureuationandMarketAnalysisConclusion(AppendixD)shallbemaintainedaspartofthedevicesdesignhistorytechnicalfile.TheProductRegulatoryAffairsRepresentativeandMedicalAffairsRepresentativeshallreviewandapprovethisdocument.NOTE:TheliteraturereviewshallbecutedaccordingtotheuationofClinicalDatatoSupportCEMarkingWorkInstructionsection5.5.Howeverthefollowingstemplatesshallbeusedinplaceofthosespecifiedinthisworkinstruction:a.InsteadofusingTheLiteratureuationPlantemplatereferencedusethePostMarketLiteratureuationandMarketExperiencePlan(AppendixC)b.InsteadofusingTheLiteratureuationReportandConclusiontemplateusethePost-MarketLiteratureuationandMarketAnalysisReportandConclusion(AppendixD)5.5.Elementsofapost-marketclinicalfollow-upstudy5.5.1.Post-marketclinicalfollow-upstudiesareperedonadevicewithinitsintendedusepurpose(s)accordingtotheinstructionsforuse.5.5.2.APMCFSshallincludetheelementsdefinedintheWritingClinicalInvestigationalPlansandProtocolsWorkInstruction.5.5.3.Theobjective(s)ofaPMCFSshouldbestatedclearlyandshouldaddresstheresidualrisk(s)identified.Itshouldbeulatedtoaddressoneormorespecificquestionsrelatingtotheclinicalsafetyorperanceofthedevice.5.5.4.Post-marketclinicalfollow-upstudiesshouldbedesignedtoaddresstheobjective(s)ofthestudy.Thedesignmayvarybasedontheobjective(s)andshouldbescientificallysoundtoallowforvalidconclusionstobedrawn.5.5.5.Thestudydesigncantakeseveralsforexample:theextendedfollow-upofpatientsenrolledinpre-marketinvestigationsanewclinicalinvestigationareviewofdataderivedfromadeviceregistryareviewofrelevantretrospectivedatafrompatientspreviouslyexposedtothedevice.theanalysisplanincludinganyinterimreportingandproceduresforearlystudytermination.5.5.6.ThedataandconclusionsderivedfromthePMCFSareusedtoprovideclinicalevidencetosupportthepost-marketsurveillanceprogram.ThisprocessmayresultintheneedtoreassesswhetherthedevicecontinuestocomplywiththeEssentialPrinciples.Suchassessmentsmayresultincorrectiveorpreventiveactions.6.APPENDIX6.1.AppendixA:Post-MarketClinicalFollow-UpStudyDeterminationXXXXXXXHealthcareXXXXXXXDevice:Thisisusedtodocumenttherationalefordeterminingtheneedforapost-marketclinicalfollow-upstudy.Oncecompletethisshallbesavedaspartofthedevicestechnicalfile.Section1:DetermineiftheproposedequivalentdevicemeetstherequirementsofequivalenceasoutlinedinMEDDEV.2.7.1.Thereisnoproposedequivalentdevice(proceedtoSection2)Proposedequivalentdevicemanufacturerdevicename:Proposedequivalentdevicemodelnumber:Questions1-10mustbeansweredyesornainorderfortheproposedequivalentdevicetomeetthedefinitionofequivalent.ClinicalEquivalence:1.IstheproposedequivalentdeviceusedforthesameclinicalconditionorpurposeasthedeviceExplain:YesNo2.IstheproposedequivalentdeviceusedatthesamesiteinthebodyasthedeviceExplain:YesNo3.Istheproposedequivalentdeviceusedinasimilarpopulation(includingageanatomyphysiology)astheXXXXXXXdeviceExplain:YesNo4.DoestheproposedequivalentdevicehavesimilarrelevantcriticalperanceaccordingtoexpectedclinicaleffectforaspecificintendeduseastheXXXXXXXdeviceExplain:YesNoTechnicalEquivalence:5.IstheproposedequivalentdeviceusedundersimilarconditionsofuseastheXXXXXXXproductExplain:YesNo6.Doestheproposedequivalentdevicehavesimilarspecificationsandproperties(i.e.tensilestrengthviscositysurfacecharacteristics)astheXXXXXXXdeviceExplain:YesNo7.IstheproposedequivalentdeviceofsimilardesignastheXXXXXXXdeviceExplain:YesNo8.DoestheproposedequivalentdevicehavesimilarprinciplesofoperationastheXXXXXXXdeviceExplain:YesNo9.IfapplicabledoestheproposedequivalentdeviceusesimilardeploymentsastheXXXXXXXdeviceExplain:YesNoNABiologicalEquivalence:10.IfapplicabledoestheproposedequivalentdeviceusethesamematerialsincontactwiththesamehumantissueorbodyfluidsastheXXXXXXXdeviceExplain:YesNoNAAdditional:11.Doestheproposedequivalentdevicerequireapost-marketclinicalfollow-upstudyaspartofitsregulatoryapprovalExplain:YesNoSection2:uatetheresidualrisksAllthequestionsbelowrefertheXXXXXXXdevice.12.Isthedeviceinnovative(i.e.wherethedesignofthedevicethematerialstheprinciplesofoperationthetechnologyorthemedicalindicationarenovel)Ifapplicabledescribe:Description:YesNo13.Doesthedevicetargetahigh-riskanatomicalsite(i.e.heartcentralnervoussystem)Ifapplicableidentifysite:Anatomicalsite:YesNo14.DoesthedevicetargetaseverediseaseoradiseasethatposestreatmentchallengesDescription:YesNo15.Doesthedevicetargetasensitivetargetpopulation(i.e.infantschildrenpregnantwomenetc.)Ifapplicableidentifytargetpopulation:Targetpopulation:YesNo16.Wasanacceptableriskidentifiedduringthepre-CEclinicaluationthatshouldbemonitoredinalongertermandorinalargerpopulationIfapplicableidentifyrisk:Risks:YesNo17.Havewell-knownrisksbeenidentifiedinliteratureorsimilarmarketdevicesIfapplicableidentifyrisks:Risks:YesNo18.Wasthereadiscrepancybetweenthepre-marketfollow-uptimescalesandtheexpectedlifeoftheproductIfapplicabledescribe:Description:YesNo19.DidtheXXXXXXXpost-developmentriskassessmentidentifyanyrisksthatfellintotheunacceptablecategoryontheriskacceptabilitymatrixIfapplicableidentifyrisks:Unacceptablerisks:YesNoSection3:DeterminewhetheraPost-MarketClinicalFollow-UpStudyneedstobepered.APost-MarketClinicalFollow-UpStudy(PMCFS)shouldalwaysbeconsideredfordeviceswheretheidentificationofpossibleemergingrisksandtheuationoflong-termsafetyperancearecritical.Productsforwhichthemediumlong-termclinicalperanceandsafetyisalreadyknowfromprevioususeofthedeviceorfromfullytransferableexperiencewithanequivalentdevicemaynotrequireaPMCFS.HoweveriftheequivalentdeviceisrequiredtoperaPMCFSaspartofitsregulatoryapprovaltheXXXXXXXdeviceissubjecttothesamerequirement.PMCFSwillbeperedPMCFSwillnotbeperedRationalefordecision:Approvals:ResearchManagerordesigneeMedicalAffairsRepresentative6.2.AppendixB:Post-MarketClinicalFollow-UpPlanXXXXXXXHealthcareXXXXXXXDevice:MDDClassification:ClassIClassIIaClassIIbClassIIIThisisusedtodocumenttheplanforpost-m