1、BRITISH STANDARD BS EN 13975:2003 Sampling procedures used for acceptance testing of in vitro diagnostic medical devices Statistical aspects The European Standard EN 13975:2003 has the status of a British Standard ICS 11.100 BS EN 13975:2003 This British Standard was published under the authority of
2、 the Standards Policy and Strategy Committee on 28 March 2003 BSI 28 March 2003 ISBN 0 580 41510 4 National foreword This British Standard is the official English language version of EN 13975:2003. The UK participation in its preparation was entrusted to Technical Committee CH/212, IVDs, which has t
3、he responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which implement international or European publications referred to in this document may be found in the BSI Catalogue under the section enti
4、tled “International Standards Correspondence Index”, or by using the “Search” facility of the BSI Electronic Catalogue or of British Standards Online. This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. Complianc
5、e with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to understand the text; present to the responsible international/European committee any enquiries on the interpretation, or proposals for change, and keep the UK interests informed; monitor related int
6、ernational and European developments and promulgate them in the UK. Summary of pages This document comprises a front cover, an inside front cover, the EN title page, pages 2 to 12, an inside back cover and a back cover. The BSI copyright date displayed in this document indicates when the document wa
7、s last issued. Amendments issued since publication Amd. No. Date CommentsEUROPEANSTANDARD NORMEEUROPENNE EUROPISCHENORM EN13975 March2003 ICS11.100 Englishversion Samplingproceduresusedforacceptancetestingofinvitro diagnosticmedicaldevicesStatisticalaspects Procduresdchantillonnageutilisespourlaccep
8、tation desessaisdesdispositifsmdicauxdediagnosticinvitro Aspectsstatistiques ProbenahmeverfahrenfrdieAnnahmeprfungvonInvitro DiagnostikaStatistischeAspekte ThisEuropeanStandardwasapprovedbyCENon14November2002. CENmembersareboundtocomplywiththeCEN/CENELECInternalRegulationswhichstipulatetheconditions
9、forgivingthisEurope an Standardthestatusofanationalstandardwithoutanyalteration.Uptodatelistsandbibliographicalreferencesconcernings uchnational standardsmaybeobtainedonapplicationtotheManagementCentreortoanyCENmember. ThisEuropeanStandardexistsinthreeofficialversions(English,French,German).Aversion
10、inanyotherlanguagemadebytra nslation undertheresponsibilityofaCENmemberintoitsownlanguageandnotifiedtotheManagementCentrehasthesamestatusasthe official versions. CENmembersarethenationalstandardsbodiesofAustria,Belgium,CzechRepublic,Denmark,Finland,France,Germany,Greece, Hungary,Iceland,Ireland,Ital
11、y,Luxembourg,Malta,Netherlands,Norway,Portugal,Slovakia,Spain,Sweden,SwitzerlandandUn ited Kingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMALISATION EUROPISCHESKOMITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2003CEN Allrightsofexploitationinanyformandbyanymeansreserved
12、 worldwideforCENnationalMembers. Ref.No.EN13975:2003EEN13975:2003(E) 2 Foreword Thisdocument(EN13975:2003)hasbeenpreparedbyTechnicalCommitteeCEN/TC140,“Invitrodiagnostic medicaldevices“thesecretariatofwhichisheldbyDIN. ThisEuropeanStandardshallbegiventhestatusofanationalstandard,eitherbypublicationo
13、fanidenticaltextor byendorsement,atthelatestbySeptember2003,andconflictingnationalstandardsshallbewithdrawnatthe latestbySeptember2003. ThisdocumenthasbeenpreparedunderamandategiventoCENbytheEuropeanCommissionandtheEuropean FreeTradeAssociation,andsupportsrequirementsofEUDirective(s). Forrelationshi
14、pwithEUDirective(s),seeinformativeannexZA,whichisanintegralpartofthisdocument. AnnexAisinformative. AccordingtotheCEN/CENELECInternalRegulations,thenationalstandardsorganizationsofthefollowing countriesareboundtoimplementthisEuropeanStandard:Austria,Belgium,CzechRepublic,Denmark,Finland, France,Germ
15、any,Greece,Hungary,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal, Slovakia,Spain,Sweden,SwitzerlandandtheUnitedKingdom.EN13975:2003(E) 3 Introduction ThisEuropeanStandardrelatestoAnnexVI“ECVERIFICATION“oftheDirective98/79/ECoftheEuropean ParliamentandoftheCouncilof27October1998o
16、ninvitrodiagnosticmedicaldevices,settingoutrequirements forsamplingproceduresusedforacceptancetestingofinvitrodiagnosticmedicaldevicesbyanotifiedbody. InAnnexVIthreeprovisionsforverificationaredescribed: Section5providesforverificationbyexaminationandtestingofeveryfinisheddevice; Section6.3providesf
17、orverificationbasedonstatisticalcontrolbyattributesand/orvariables; Section2.2providesforalternativeconformityassessmentproceduresforthosesituationswherestatistical verificationasspecifiedinSection6.3isconsideredtobenotappropriate. Thefirstprovisionisnotconsideredinthepresentstandardsincetheassociat
18、edsamplingplanrequiresno statisticalconsiderations. Thesecondprovisionisappliedwhensufficientcertaintyontheresultofsuchverificationonfinisheddevicescan begainedbyasamplingplanestablishedonastatisticalbasis.Forthispurposeexistingstandardsonacceptance testingcanbeapplied. Thethirdprovisionisaddressedi
19、nSection2.2ofAnnexVIwhichstatesthat: “TotheextentthatforcertainaspectsthefinaltestingaccordingtoSection6.3isnotappropriate,adequate inprocesstesting,monitoringandcontrolmethodsshallbeestablishedbythemanufacturerwiththeapprovalof thenotifiedbody.TheprovisionofAnnexIV,Section5,shallapplyaccordinglyinr
20、elationtotheabovementioned approvedprocedures.“ AnnexIV,Section5,prescribessurveillanceandapprovalofamanufacturersqualitysystem. Itiscurrentstateoftheartthatinspectionandverificationofthefinisheddevicesiscomplementarytoprocess controlandfinaltestingperformedbythemanufacturer.Performanceverificationi
21、sgenerallyperformedby measurementsondefinedcontrolmaterialsoradefinedpanelofreferencespecimens(e.g.sera). Validconclusionscanonlybedrawnfromalimitednumberofunitsofthefinalproduct,ifadequateinprocess testing,monitoringandcontrolproceduresensurethehomogeneityofthefinalproductbatchanditscomponentsat th
22、eintermediatestage(s)ofmanufactureaswellasthesuitabilityoftheprocessapplied.Anysamplingplanused forfinaltestingofinvitrodiagnosticmedicaldevicesisbasedonstatisticalconsiderations.Thisdoesnot necessarilymeanthatalargenumberofunitsissampledandtested.Inmanycasesusingverysmallsamplesizes (sometimesequal
23、tooneunit)canbeanacceptableapproach,providedthatanadequatelevelofconformityhas beendemonstratedbyotherappropriatemeans. Followingthislastapproach,thisstandardcanalsobeusedforestablishingsamplingprocedureswhenannexIIIor IVorVIIisapplied.EN13975:2003(E) 4 1Scope ThisEuropeanStandardspecifiessamplingpr
24、ocedurerequirementsforacceptancetestingoffinishedinvitro diagnosticmedicaldevices,whichrequireECverificationbyanotifiedbody. Twodifferentprovisionsareaddressed: a) verificationbytestingattributesand/orvariablesonastatisticalbasis; b) verificationbytestingahomogeneousbatchwhichhasbeendefinedbyappropr
25、iatemeansofprocess validationandinprocesscontrol. Thisstandardspecifiesrequirementsandcriteriafortestingprocedurestoestablishandverifythehomogeneityof processesandproducts.Thisstandardisalsoapplicablefordrawingupsamplingplansforfinishedproducts accordingtotherequirementslaiddownformanufacturersprodu
26、ctcertificationandproductionqualitysystems. 2 Normativereferences ThisEuropeanStandardincorporatesbydatedorundatedreferenceprovisionsfromotherpublications.These normativereferencesarecitedattheappropriateplacesinthetextandthepublicationsarelistedhereafter.For datedreferences,subsequentamendmentsto,o
27、rrevisionsof,anyofthesepublicationsapplytothisEuropean Standardonlywhenincorporatedinitbyamendmentorrevision.Forundatedreferencesthelatesteditionofthe publicationreferredtoapplies(includingamendments). ISO28591, Samplingproceduresforinspectionbyattributes Part1:Samplingplansindexedbyacceptable quali
28、tylevel(AQL)forlotbylotinspection. ISO28592, Samplingproceduresforinspectionbyattributes Part2:Samplingplansindexedbylimitingquality (LQ)forisolatedlotinspection. ISO28593, Samplingproceduresforinspectionbyattributes Part3:Skiplotsamplingprocedures. ISO3951, Samplingproceduresandchartsforinspectionb
29、yvariablesforpercentnonconforming. 3 Termsanddefinitions ForthepurposesofthisEuropeanStandard,thefollowingtermsanddefinitionsapply. 3.1 acceptablequalitylevel AQL qualitylevelthatforthepurposeofsamplinginspectionofacontinuousseriesofbatchesisthelimitofa satisfactoryprocessaverage 3.2 acceptancetesti
30、ng samplinginspection processofinspectingasampleoftheunitsofproductthatmakeupabatchforthepurposeofacceptingor rejectingtheentirebatch,asprescribedintheassociatedpreestablishedsamplingplanEN13975:2003(E) 5 3.3 batch lot definedamountofmaterial,eitherstartingmaterial,intermediateorfinishedproductwhich
31、isuniforminits propertiesandhasbeenproducedinoneprocessorseriesofprocesses EN375:2001 3.4 batchacceptance procedureofestablishingconformityofabatchwiththedevicespecifications 3.5 invitrodiagnosticmedicaldevice IVDMD anymedicaldevicewhichisareagent,reagentproduct,calibrator,controlmaterial,kit,instru
32、ment,apparatus, equipmentorsystem,whetherusedaloneorincombination,intendedbythemanufacturertobeusedinvitrofor theexaminationofspecimens,includingbloodandtissuedonations,derivedfromthehumanbody,solelyor principallyforthepurposeofprovidinginformationconcerningaphysiologicalorpathologicalstate,orconcer
33、ning congenitalabnormality,ortodeterminethesafetyandcompatibilitywithpotentialrecipients,ortomonitor therapeuticmeasures Directive98/79/EC NOTE1 Aspecimenreceptacle,whethervacuumtypeornot,isconsideredtobeaninvitrodiagnosticmedicaldevicewhen itisspecificallyintendedbyitsmanufacturerfortheprimaryconta
34、inmentandpreservationofspecimensderivedfromthehuma n bodyforthepurposeofinvitrodiagnosticexamination. NOTE2 Productsforgenerallaboratoryusearenotinvitrodiagnosticmedicaldevicesunlesssuchproducts,inviewoftheir properties,arespecificallyintendedbytheirmanufacturertobeusedforinvitrodiagnosticexaminatio
35、n. 3.6 inspectionbyattributes inspectionmethodwherebytheunitofproductisclassifiedsimplyasconformingornonconformingwithrespectto agivenrequirementorsetofrequirements 3.7 inspectionbyvariables inspectionmethodwherebyaspecifiedquantitativepropertyismeasuredinasampleofunitsofproduct,either componentsorf
36、inisheddevices,toestablishstatisticallytheacceptabilityofabatch 3.8 limitingquality LQ whenabatchisconsideredinisolation,aqualitylevelwhichforthepurposesofsamplinginspectionislimitedtoa lowprobabilityofacceptance ISO28591:1999 3.9 sample oneormoreunitsofproduct,eithercomponentsorfinisheddevices,draw
37、nfromabatchwithoutregardtothe qualityoftheunits 3.10 samplesize numberofunitsofproductinthesample 3.11 samplingplan planthatindicatesthenumberofunitsofproduct,eithercomponentsorfinisheddevices,fromeachbatchwhichis tobedrawnforinspectionandtheassociatedcriteriafordeterminingtheacceptabilityofthebatch
38、EN13975:2003(E) 6 NOTE Asamplingplaneithercontainsorreferstoinstructionsforthesamplingstrategy. 3.12 samplingstrategy establishedmethodforobtaininganadequatesample EXAMPLE Randomselection,stratified,withstatedfrequency,rationalsubgrouping. 3.13 validation confirmation,throughtheprovisionofobjectivee
39、vidence,thattherequirementsforaspecificintendeduseor applicationhavebeenfulfilled ENISO9000:2000 NOTE1 Processvalidationmeansestablishingbyobjectiveevidencethataprocessconsistentlyproducesaresultor productmeetingitspredeterminedspecifications. NOTE2 Designvalidationmeansestablishingbyobjectiveeviden
40、cethatdevicespecificationsconformwithuserneedsand intendeduse(s). 3.14 verification confirmation,throughtheprovisionofobjectiveevidence,thatspecifiedrequirementshavebeenfulfilled ENISO9000:2000 4Procedures 4.1General Samplingproceduresusedforbatchacceptancetestingshallbeanintegralpartoftheoperationa
41、lqualitycontrol strategyforanyparticularinvitrodiagnosticmedicaldeviceandshalltakethenatureofthatproductandpossible consequencesofnonconformityintoaccount,i.e.ensureahighlevelofsafetyandperformanceaccordingtothe stateoftheart. Batchacceptanceshallbebasedon,either: verificationbyexaminationandtesting
42、ofeveryunitofproduct(finisheddevices); statisticalverificationofabatchoffinisheddevices; processcontrol,complemented,whereappropriate,byfinaltestingoffinisheddevices; anappropriatecombinationofsuchqualitycontrolmeasures. NOTE Thesamplingprocedureforverificationandtestingofeveryunitofproductrequiresn
43、ostatisticalconsiderationsand isthereforenotelaboratedinthisstandard. Samplingproceduresforbatchacceptance,asapartoftheoperationalqualitycontrolstrategy,shallbeproperly validated. Validationshalldemonstrateamongstothersthat: thesuitabilityofstartingandmanufacturingmaterialsisdefinedbyrelevantcharacteristics; thevariationofingredientsintermsofe.g.amount,concentrationoractivitylieswithinspecifiedtolerance limitsasshownbyappropriatecontrolofprocesses;EN13975:2003(E) 7 producthomogeneitywithinspecifiedlimitsisensured; themanuf
