MEDDEV 2.12-2 rev2 2012 PMS

EUROPEANCOMMISSIONDIRECTORATEGENERALforHEALTHandCONSUMERSConsumerAffairsHealthtechnologyandCosmeticsMEDDEV2.12/2rev2January2012GUIDELINESONMEDICALDEVICESPOSTMARKETCLINICALFOLLOW-UPSTUDIESAGUIDEFORMANUFACTURERSANDNOTIFIEDBODIESNoteThepresentGuidelinesarepartofasetofGuidelinesrelatingtoquestionsofapplicationofEC-DirectivesonmedicalDevices.Theyarelegallynotbinding.TheGuidelineshavebeencarefullydraftedthroughaprocessofintensiveconsultationofthevariousinterestparties(competentauthorities,Commissionservices,industries,otherinterestedparties)duringwhichintermediatedraftswherecirculatedandcommentsweretakenupinthedocument.Therefore,thisdocumentreflectspositionstakenbyrepresentativesofinterestpartiesinthemedicaldevicessector.CONTENTS12341.Introduction................................................................................................................................352.Scope..........................................................................................................................................463.References..................................................................................................................................474.Definitions..................................................................................................................................685.Circumstanceswhereapostmarketclinicalfollowupstudyinindicated.................................896.Elementsofapost-marketclinicalfollowupstudy.................................................................10107.Theuseofstudydata................................................................................................................12118Theroleofthenotifiedbodyinpost-marketclinicalfollowup..............................................12121314.Preface15ThisdocumentisintendedtobeaguideformanufacturersandNotifiedBodieson16howtocarryoutPost-MarketClinicalFollow-up(PMCF)studiesinordertofulfil17Post-MarketSurveillance(PMS)obligationsaccordingtoSection3.1ofAnnexII,18Section3ofAnnexIV,Section3ofAnnexV,Section3.1ofAnnexVIorSection419ofAnnexVIIoftheMedicalDevicesDirective(93/42/EEC)andSection3.1of20Annex2,Section3ofAnnex4,Section3.1ofAnnex5oftheActiveImplantable21MedicalDevicesDirective(90/385/EEC).TheseSectionsrefertorequirementsof22AnnexXofDirective93/42/EECandAnnex7ofDirective90/385/EEC,respectively.2324Attentionisdrawntoparagraph8ofArticle15ofDirective93/42/EECwhichspells25outtheprovisionsofArticle15thatarenotapplicabletoclinicalinvestigations26conductedusingCE-markeddeviceswithintheirintendeduse.27SimilarlywhenPMCFstudiesareconductedusingCEmarkeddeviceswithintheir28intendeduse,theprovisionsofsection2.3.5ofAnnexXofDirective93/42/EECdo29notapply.However,theprovisionsofDirective93/42/EECconcerninginformation30andnotificationofincidentsoccurringfollowingplacingdevicesonthemarketare31fullyapplicable.321.Introduction3334Whileclinicalevidenceisanessentialelementofthepremarketconformity35assessmentprocesstodemonstrateconformitytoEssentialRequirements,itis36importanttorecognisethattheremaybelimitationstotheclinicaldataavailablein37thepre-marketphase.Suchlimitationsmaybeduetothedurationofpre-market38clinicalinvestigations,thenumberofsubjectsandinvestigatorsinvolvedinan39investigation,therelativeheterogeneityofsubjectsandinvestigatorsand/orthe40controlledsettingofaclinicalinvestigationversusthefullrangeofclinicalconditions41encounteredingeneralmedicalpractice.4243Apreconditionforplacingaproductonthemarketisthatconformitytotherelevant44EssentialRequirements,includingafavourablebenefit/riskratio,hasbeen45demonstrated.Theextentofthedatathatcanbegatheredinthepre-marketphase46doesnotnecessarilyenablethemanufacturertodetectrarecomplicationsorproblems47thatonlybecomeapparentafterwide-spreadorlongtermuseofthedevice.Aspartof48themanufacturer’squalitysystem,anappropriatepost-marketsurveillanceplaniskey49toidentifyingandinvestigatingresidualrisksassociatedwiththeuseofmedical50devicesplacedonthemarket.Theseresidualrisksshouldbeinvestigatedandassessed51inthepost-marketphasethroughsystematicPost-MarketClinicalFollow-up(PMCF)52study(ies).5354Clinicaldataobtainedfrompost-marketsurveillanceandduringPMCFstudiesbythe55manufacturerarenotintendedtoreplacethepre-marketdatanecessarytodemonstrate56conformitywiththeprovisionsofthelegislation.However,theyarecriticaltoupdate57theclinicalevaluationthroughoutthelife-cycleofthemedicaldeviceandtoensure58thelongtermsafetyandperformanceofdevicesaftertheirplacingonthemarket.5960PMCFstudiesareoneofseveraloptionsavailableinpost-marketsurveillanceand61contributetotheriskmanagementprocess.62636465662.Scope6768Theobjectiveofthisdocumentistoprovideguidanceontheappropriateuseand69conductofPMCFstudiestoaddressissueslinkedtoresidualrisks.Theintentionis70nottoimposenewregulatoryrequirements.7172PMCFstudiesareanimportantelementtobeconsideredinPMCForPMSplans.The73principlesforPMCFstudiessetoutinthisguidancearenotintendedtoreplacePMCF74orPMSplans.TheyareormaybeapplicabletoPMCFstudiesconductedforother75purposes.7677This