上市后临床跟踪管理程序

精心整理精心整理精心整理 上市后临床跟踪控制程序 文件编号：QP-29 版本：A/0 生效日期： 页码：3 编制： 审核： 批准：1.PurposeThepurposeofthisworkinstructionistodefinetheprocesstodetermineanddocumentwhetherapost-marketclinicalfollow-upstudyisrequiredforTDIFoot/AnkleArray8chmedicaldevicesbearingtheCEmark.Theprocesswillleadtoadeterminationofwhetherapost-marketclinicalfollow-upstudyisrequiredandprovideguidanceforpost-marketclinicalmonitoringrequirementsifastudyisnotrequired.2.ScopeTheworkinstructionappliestoallmedicaldevicebusinessesandsitesoperatingundertheTDIFoot/AnkleArray8chHealthcareQualityManagementSystem.OnlymedicaldevicesbearingtheCEMarkwillberequiredtofollowthisworkinstruction.3.References3.1.ExternalReferencesLaws·CouncilDirective93/42/EECof14June1993concerningmedicaldevicesincludingamendmentsthrough05September2007GuidanceDocuments·EuropeanCommissionEnterprise-Directorate-GeneralMEDDEV2.12-2GuidelinesonPostMarketClinicalFollow-UpdatedMay2004·MEDDEV2.7.1Rev.3guidelinesonmedicaldevice-clinicalevaluation-aguideformanufacturersandnotifiedbodiesdatedApril2009·GHTFPost-MarketClinicalFollow-UpStudies;SG5(PD)N4R7(Proposeddocument23July2008)·GHTFClinicalInvestigations;SG5(PD)N3R7(20January2008)4.RolesandResponsibilitiesImportant:Whenatitleofapositionislistedinthisworkinstruction,itrelatestothatpositionoritsequivalent.Belowaretherolesandresponsibilitiesdiscussedwithinthisdocument. Table4‑1:RolesandResponsibilities Role Responsibility DesignEngineeringand/orEngineeringRepresentative ·ProvideconsultationtotheProductRegulatoryAffairsRepresentativeindeterminingforagivenproject/productwhetherapost-marketclinicalfollow-upstudyisrequired·ProvideconsultationtotheProductRegulatoryAffairsRepresentativetodetermineifanequivalentdeviceexists·ProvideconsultationtotheProductRegulatoryAffairsRepresentativeinidentifyingemergingrisksforthemedicaldevice·ProvideconsultationtotheResearchManagerordesigneetodeterminethetypeofpost-marketclinicalfollow-upstudytobeimplemented,ifapplicable ProductRegulatoryAffairsRepresentative ·Determineforagiveproject/productwhetherapost-marketclinicalfollow-upstudyisrequired·Determineifanequivalentdeviceexists·Identifypotentialemergingrisks·Reviewriskassessment·CompletethePost-MarketClinicalFollow-UpJustificationFormregardingdecisiontoperformastudy·CompletethePost-MarketClinicalFollow-UpPlanformthatdetailsthepost-marketclinicalfollow-upplan·Determinehowoftenclinicaldatamustbereviewed·ReviewandapprovetheclinicalevaluationperformedbytheResearchManagerordesignee RegulatoryAffairsRepresentative ·ProvideconsultationtotheResearchManagertodeterminethetypeofpost-marketclinicalfollow-upstudytobeimplemented,ifapplicable ResearchManagerordesignee ·ProvideconsultationtotheProductRegulatoryAffairsRepresentativeindeterminingforagivenproject/productwhetherapost-marketclinicalfollow-upstudyisrequired·ProvideconsultationtotheProductRegulatoryAffairsRepresentativetodetermineifanequivalentdeviceexists·ProvideconsultationtotheProductRegulatoryAffairsRepresentativetoidentifypotentialemergingrisks·ReviewthePost-MarketClinicalFollow-UpJustificationformandPost-MarketClinicalFollow-UpPlanformtoconfirmthedecisionsregardingtheneedforapost-marketclinicalfollow-upstudyandclinicalfollow-up·Determinehowoftenclinicaldatamustbereviewed·Determinethetypeofpost-marketclinicalfollow-upstudytobeimplemented,ifapplicable·Reviewnewdata(i.e.literature,adverseevents,complaints,etc,)anddetermineifapost-marketclinicalfollow-upstudyisnecessarybasedonnewinformation(clinicalevaluation) MedicalAffairsRepresentative ·ReviewthePost-MarketClinicalFollow-UpJustificationformandPost-MarketClinicalFollow-UpPlanformtoconfirmthedecisionsregardingtheneedforapost-marketclinicalfollow-upstudyandclinicalfollow-up·ReviewandapprovetheclinicalevaluationperformedbytheResearchManagerordesignee5.WorkInstructionPost-marketclinicalmonitoringisanessentialelementinestablishinglongtermsafetyfollow-updataandpossibleemergentrisksformedicaldevices.Theserisksanddatacannotadequatelybedetectedandcharacterizedbyrelyingsolelyonpre-marketclinicalinvestigations.Postmarketclinicalmonitoringmayincludeacombinationofseveralstrategies:·Productcomplaintreview·Post-marketeventreportingreviewofusersandpatients·Literaturereview·Post-marketclinicalfollow-upstudies(PMCFS)ThisworkinstructionwascreatedtodeterminewhenaPMCFSisnecessarytomaintainanadequatepost-marketsurveillancesystem,asrequiredbytheMedicalDeviceDirective93/42/ECC(MDD)asamendedbyMDD2007/47/EC.Itwillalsoprovideguidanceonthepost-marketclinicalmonitoringrequirementsifaPMCFSisnotrequired.Figure5-1:High-LevelProcessOverviewforPost-MarketClinicalFollow-Up5.1.GeneralRequirementsPriortoM3sign-off,theProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandtheDesignEngineeringand/orEngineeringRepresentativeshalldetermineforagivenproject/programwhetheraPMCFSisrequired.Theyshallalsodeterminethepost-marketclinicalfollow-upplan.APMCFSmaynotberequiredforproductsforwhichmedium/long-termclinicalperformanceandsafetyisalreadyknownfromprevioususeofthedeviceorwhereotherappropriatepost-marketsurveillanceactivitieswouldprovidesufficientdatatoaddresstherisks.5.2.DeterminingtheTypeofPost-MarketClinicalFollow-UpRequiredPost-marketclinicalmonitoringshallhaveoneoftwooutcomes,(1)PMCFSrequiredor(2)noPMCFSrequired.TheneedforaPMCFSshallbebasedonacombinationofseveralfactorsdetailedinthissection.TheProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandDesignEngineeringand/orEngineeringRepresentativeshalldeterminewhetheranequivalentdeviceexists.Equivalenceshallbedemonstratedinalltheessentialcharacteristicspreciselydefinedbelow.Equivalencemeans:·Clinical·Usedforthesameclinicalconditionorpurpose;·Usedatthesamesiteinthebody;·Usedinsimilarpopulation(includingage,anatomy,physiology);·Havesimilarrelevantcriticalperformanceaccordingtoexpectedclinicaleffectforspecificintendeduse·Technical·Usedundersimilarconditionsofuse;·Havesimilarspecificationsandproperties;·Beofsimilardesign;·Usesimilardeploymentmethods·Havesimilarprinciplesofoperation·Biological·SameorsimilaruseofmaterialsincontactwithhumantissuesorbodyfluidsProductsforwhichthemedium/longtermclinicalperformanceandsafetyisalreadyknownfromprevioususeofthedevice,orfromfullytransferableexperiencewithequivalentdevicesshallnotrequireaPMCFS.NOTE:Ifthedevicequotedasthe“equivalent”requiresaPMCFS,thenthenewproductshallbesubjecttothesamerequirement.TheneedforaPMCFSshallbedeterminedbasedontheidentificationofresidualrisksthatmayimpacttherisk/benefitratio.Astudyshouldalwaysbeconsideredfordeviceswheretheidentificationofpossibleemergingrisksandtheevaluationoflongtermsafetyandperformanceareessential.TheProductRegulatoryAffairsRepresentativeinconsultationwiththeResearchManagerordesigneeandDesignEngineeringand/orEngineeringRepresentativeshallidentifysuchemergingrisk,thefollowingcriteriashouldbetakenintoaccount:·innovation,e.g.,wherethedesignofthedevice,thematerials,theprinciplesofoperation,thetechnologyorthemedicalindicationsarenovel;·highriskanatomicallocations(i.e.,heart,centralnervoussystem,etc.);·severityofdisease/treatmentchallenges;·sensitivityoftargetpopulation(i.e.,infants,children,pregnantwomen,etc.);·identificationofanacceptableriskduringthepre-CEclinicalevaluation,whichshouldbemonitoredinalongertermand/orthroughalargerpopulation;·wellknownrisksidentifiedfromtheliteratureorsimilarmarketeddevices;·discrepancybetweenthepre-marketfollow-uptimescalesandtheexpectedlifeoftheproduct;Aproperlyconductedriskanalysisisessentialindeterminingwhatclinicalevidencemaybeneededforaparticulardevice.Anyrisksidentifiedasan“unacceptable”riskattheconclusionofthedevelopmentprocessshallrequireaPMCFS.Astudyshouldalsobeconsideredforrisksidentifiedas“acceptable”or“riskmitigationrequired”ifthedevicemeetsanyoftheothercharacteristicsidentifiedin5.2.1aTheProductRegulatoryAffairsRepresentativeshallcompletethePostMarketClinicalFollow-UpStudyDeterminationForm(AppendixA)oncethedecisionregardingtheneedforastudyhasbeendetermined.NOTE:ThisformmayalsobeusedasaguideinmakingthedeterminationabouttheneedtoperformaPMCFS.TheProductRegulatoryAffairsRepresentativeshallcompletethePost-MarketClinicalFollow-UpPlan(AppendixB)thatdetailstheplanforpost-marketclinicalfollow-up.TheResearchManagerordesigneeandMedicalAffairsRepresentativeshallreviewthePost-MarketClinicalFollow-UpJustificationFormandThePost-MarketClinicalFollow-UpPlantoconfirmthedecisionsregardingpost-marketclinicalmonitoring.5.3.NoPostMarketClinicalFollow-UpStudyRequiredIfitwasdeterminedthatnoPMCFSisrequired(basedonsection5.2),post-marketclinicalmonitoringisstillrequiredforthemedicaldevice.JustificationregardingthedecisionnottoperformaPMCFSmustbeclearlydocumentedandmaintainedinthedesignhistory/technicalfile(see5.2.5).Post-MarketClinicalMonitoringRequirements(minimum)5.3.1.1.Ataminimum,thefollowingpost-marketclinicalmonitoringactivitiesshallbecompletedaccordingtoTDIFoot/AnkleArray8chestablishedprocedures/workinstructions.TheseelementswillbeinputsintothePost-MarketLiteratureEvaluationandMarketAnalysisReport.·ReviewofproductcomplaintsaccordingtoComplaintHandlingProcedure·ReviewofpostmarketadverseeventsaccordingtoPostMarketEventReportingProcedure·LiteraturereviewaccordingtoTDIFoot/AnkleArray8chEvaluationofClinicalDatatoSupportCEMarkingWorkInstruction.5.3.1.2.Reviewofproductcomplaints,postmarketadverseeventsandtheliteraturereviewshallbecompletedattheintervalsspecifiedinTable5-1.Thetimingoutlinedprovidestheminimumrequirements.TheProductRegulatoryAffairsRepresentativeand/ortheResearchManagerordesigneecandeterminethatclinicaldatashallbereviewedmoreoften.Table5-1:TimingforReviewofClinicalDatabasedonMedicalDeviceClass DeviceClassification Timingforreviewofclinicaldata(minimum) ClassI Annually ClassIIa,IIb Ataminimumannually,shouldconsidermoreoften ClassIII Semi-annually(i.e.twiceayear),shouldconsidermoreoften5.3.1.3.AttheintervaloutlinedinTable5-1,theResearchManagerordesigneeshallcompletealiteraturereviewandanalysisofpost-marketexperiences(i.e.complaintsandadverseevents)andre-evaluateifaPMCFSneedstobeconductedbasedonthisdata.ThePostMarketLiteratureEvaluationandMarketAnalysisConclusionform(AppendixD)shallbecompletedandmaintainedaspartofthedevice’sdesignhistory/technicalfile.TheProductRegulatoryAffairsRepresentativeandMedicalAffairsRepresentativeshallreviewandapprovethisdocument.NOTE:TheliteraturereviewshallbeexecutedaccordingtotheEvaluationofClinicalDatatoSupportCEMarkingWorkInstruction,section5.5.However,thefollowingforms/templatesshallbeusedinplaceofthosespecifiedinthisworkinstruction:a.InsteadofusingTheLiteratureEvaluationPlantemplatereferenced,usethePostMarketLiteratureEvaluationandMarketExperiencePlanform(AppendixC)b.InsteadofusingTheLiteratureEvaluationReportandConclusiontemplate,usethePost-MarketLiteratureEvaluationandMarketAnalysisReportandConclusionform(AppendixD)5.4.PostMarketClinicalFollow-UpStudyRequiredIfitwasdeterminedthataPMCFSisrequired,inadditiontotherequirementslistedunder5.3.3,studiessuchasextendedfollow-upofpatientsenrolledinthepre-markettrials,prospectivestudyofarepresentativesubsetofpatientsafterthedeviceisplacedonthemarket,oranopenregistrymaybeperformed.ThePMCFSshallbecarriedoutinaccordancewithTDIFoot/AnkleArray8ch’sResearchInvolvingHumanSubjectsProcedureTheResearchManagerordesigneeinconsultationwiththeRegulatoryAffairsRepresentativeandtheDesignEngineeringand/orEngineeringRepresentativewilldeterminethetypeofPMCFSthatwillbeimplemented.Thestudyshouldtakeintoaccountthefollowing:·Resultsoftheclinicalinvestigationincludingadverseeventsidentified·Averagelifeexpectancyofthedevice·Theclaimsmadebythemanufacturerforthedevice·Performancesforwhichequivalenceisclaimed·Newinformationbecomingavailable5.4.1.1.AttheintervaloutlinedinTable5-1,theResearchManagerordesigneeshallcompletealiteraturereviewandanalysisofpost-marketexperiences(i.e.complaintsandadverseevents)andreviewtheongoingresults/dataofthePMCFS.ThePostMarketLiteratureEvaluationandMarketAnalysisConclusionform(AppendixD)shallbemaintainedaspartofthedevice’sdesignhistory/technicalfile.TheProductRegulatoryAffairsRepresentativeandMedicalAffairsRepresentativeshallreviewandapprovethisdocument.NOTE:TheliteraturereviewshallbeexecutedaccordingtotheEvaluationofClinicalDatatoSupportCEMarkingWorkInstruction,section5.5.However,thefollowingforms/templatesshallbeusedinplaceofthosespecifiedinthisworkinstruction:a.InsteadofusingTheLiteratureEvaluationPlantemplatereferenced,usethePostMarketLiteratureEvaluationandMarketExperiencePlanform(AppendixC)b.InsteadofusingTheLiteratureEvaluationReportandConclusiontemplate,usethePost-MarketLiteratureEvaluationandMarketAnalysisReportandConclusionform(AppendixD)5.5.Elementsofapost-marketclinicalfollow-upstudyPost-marketclinicalfollow-upstudiesareperformedonadevicewithinitsintendeduse/purpose(s)accordingtotheinstructionsforuse.APMCFSshallincludetheelementsdefinedintheWritingClinicalInvestigationalPlansandProtocolsWorkInstruction.Theobjective(s)ofaPMCFSshouldbestatedclearlyandshouldaddresstheresidualrisk(s)identified.Itshouldbeformulatedtoaddressoneormorespecificquestionsrelatingtotheclinicalsafetyorperformanceofthedevice.Post-marketclinicalfollow-upstudiesshouldbedesignedtoaddresstheobjective(s)ofthestudy.Thedesignmayvarybasedontheobjective(s)andshouldbescientificallysoundtoallowforvalidconclusionstobedrawn.Thestudydesigncantakeseveralforms,forexample:·theextendedfollow-upofpatientsenrolledinpre-marketinvestigations;·anewclinicalinvestigation;·areviewofdataderivedfromadeviceregistry;·areviewofrelevantretrospectivedatafrompatientspreviouslyexposedtothedevice.·theanalysisplanincludinganyinterimreporting;and·proceduresforearlystudytermination.ThedataandconclusionsderivedfromthePMCFSareusedtoprovideclinicalevidencetosupportthepost-marketsurveillanceprogram.ThisprocessmayresultintheneedtoreassesswhetherthedevicecontinuestocomplywiththeEssentialPrinciples.Suchassessmentsmayresultincorrectiveorpreventiveactions.6.Appendix6.1.AppendixA:Post-MarketClinicalFollow-UpStudyDetermination XXXXXXXHealthcare<NameofRegulatoryAffairsRepresentative><Location/ContactInformation>XXXXXXXDevice:      Thisformisusedtodocumenttherationalefordeterminingtheneedforapost-marketclinicalfollow-upstudy.Oncecomplete,thisformshallbesavedaspartofthedevice’stechnicalfile. Section1:DetermineiftheproposedequivalentdevicemeetstherequirementsofequivalenceasoutlinedinMEDDEV.2.7.1. FORMCHECKBOXThereisnoproposedequivalentdevice(proceedtoSection2) Proposedequivalentdevicemanufacturer/devicename:Proposedequivalentdevicemodelnumber:      Questions1-10mustbeansweredyesorn/ainorderfortheproposedequivalentdevicetomeetthedefinitionofequivalent. ClinicalEquivalence: 1.Istheproposedequivalentdeviceusedforthesameclinicalconditionorpurposeasthedevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 2.Istheproposedequivalentdeviceusedatthesamesiteinthebodyasthedevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 3.Istheproposedequivalentdeviceusedinasimilarpopulation(includingage,anatomy,physiology)astheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 4.DoestheproposedequivalentdevicehavesimilarrelevantcriticalperformanceaccordingtoexpectedclinicaleffectforaspecificintendeduseastheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX TechnicalEquivalence: 5.IstheproposedequivalentdeviceusedundersimilarconditionsofuseastheXXXXXXXproduct?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 6.Doestheproposedequivalentdevicehavesimilarspecificationsandproperties(i.e.tensilestrength,viscosity,surfacecharacteristics)astheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 7.IstheproposedequivalentdeviceofsimilardesignastheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 8.DoestheproposedequivalentdevicehavesimilarprinciplesofoperationastheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX 9.Ifapplicable,doestheproposedequivalentdeviceusesimilardeploymentmethodsastheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOXN/AFORMCHECKBOX BiologicalEquivalence: 10.Ifapplicable,doestheproposedequivalentdeviceusethesamematerialsincontactwiththesamehumantissueorbodyfluidsastheXXXXXXXdevice?Explain:      YesFORMCHECKBOXNoFORMCHECKBOXN/AFORMCHECKBOX Additional: 11.Doestheproposedequivalentdevicerequireapost-marketclinicalfollow-upstudyaspartofitsregulatoryapproval?Explain:      YesFORMCHECKBOXNoFORMCHECKBOX Section2:Evaluatetheresidualrisks AllthequestionsbelowrefertheXXXXXXXdevice. 12.Isthedeviceinnovative(i.e.wherethedesignofthedevice,thematerials,theprinciplesofoperation,thetechnologyorthemedicalindicationarenovel)?Ifapplicable,describe:Description:      YesFORMCHECKBOXNoFORMCHECKBOX 13.Doesthedevicetargetahigh-riskanatomicalsite(i.e.,heart,centralnervoussystem)?Ifapplicable,identifysite:Anatomicalsite:      YesFORMCHECKBOXNoFORMCHECKBOX 14.Doesthedevicetargetaseverediseaseoradiseasethatposestreatmentchallenges?Description:      YesFORMCHECKBOXNoFORMCHECKBOX 15.Doesthedevicetargetasensitivetargetpopulation(i.e.,infants,children,pregnantwomen,etc.)?Ifapplicable,identifytargetpopulation:Targetpopulation:      YesFORMCHECKBOXNoFORMCHECKBOX 16.Wasanacceptableriskidentifiedduringthepre-CEclinicalevaluationthatshouldbemonitoredinalongertermand/orinalargerpopulation?Ifapplicable,identifyrisk:Risks:      YesFORMCHECKBOXNoFORMCHECKBOX 17.Havewell-knownrisksbeenidentifiedinliteratureorsimilarmarketdevices?Ifapplicable,identifyrisks:Risks:      YesFORMCHECKBOXNoFORMCHECKBOX 18.Wasthereadiscrepancybetweenthepre-marketfollow-uptimescalesandtheexpectedlifeoftheproduct?Ifapplicable,describe:Description:      YesFORMCHECKBOXNoFORMCHECKBOX 19.DidtheXXXXXXXpost-developmentriskassessmentidentifyanyrisksthatfellintotheunacceptablecategoryontheriskacceptabilitymatrix?Ifapplicable,identifyrisks:Unacceptablerisks:      YesFORMCHECKBOXNoFORMCHECKBOX Section3:DeterminewhetheraPost-MarketClinicalFollow-UpStudyneedstobeperformed. APost-MarketClinicalFollow-UpStudy(PMCFS)shouldalwaysbeconsideredfordeviceswheretheidentificationofpossibleemergingrisksandtheevaluationoflong-termsafetyperformancearecritical.Productsforwhichthemedium/long-termclinicalperformanceandsafetyisalreadyknowfromprevioususeofthedeviceorfromfullytransferableexperiencewithanequivalentdevicemaynotrequireaPMCFS.However,iftheequivalentdeviceisrequiredtoperformaPMCFSaspartofitsregulatoryapproval,theXXXXXXXdeviceissubjecttothesamerequirement. FORMCHECKBOXPMCFSwillbeperformed FORMCHECKBOXPMCFSwillnotbeperformed Rationalefordecision:Approvals:ResearchManagerordesignee<InsertTitleHere>MedicalAffairsRepresentative<InsertTitleHere>6.2.AppendixB:Post-MarketClinicalFollow-UpPlan XXXXXXXHealthcare<NameofRegulatoryAffairsRepresentative><Location/ContactInformation>XXXXXXXDevice:     MDDClassification:FORMCHECKBOXClassIFORMCHECKBOXClassIIaFORMCHECKBOXClassIIbFORMCHECKBOXClassIII Thisformisusedtodocumenttheplanforpost-marketclinicalfollow-up.Oncecomplete,thisformshallbesavedaspartofthedevice’stechnicalfile. I.Literaturereviewandanalysisofpost-marketexperience(i.e.