1、BRITISH STANDARD BS EN 13641:2002 Elimination or reduction of risk of infection related to in vitro diagnostic reagents The European Standard EN 13641:2002 has the status of a British Standard ICS 11.100 NO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBS EN 13641:2002 This Brit
2、ish Standard, having been prepared under the direction of the Health and Environment Sector Policy and Strategy Committee, was published under the authority of the Standards Policy and Strategy Committee on 27 May 2002 BSI 27 May 2002 ISBN 0 580 39780 7 National foreword This British Standard is the
3、 official English language version of EN 13641:2002. The UK participation in its preparation was entrusted to Technical Committee CH/69, In vitro diagnostic systems, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cr
4、oss-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 entitled “International Standards Correspondence Index”, or by using the “Search” facility of the BSI Electronic Catalogue or o
5、f British Standards Online. This publication does not purport to include all the necessary provisions of a contract. Users of this publication are responsible for their correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to
6、 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 international and European developments and promulgate them in the UK. Summary of pages This document co
7、mprises a front cover, an inside front cover, the EN title page, pages 2 to 8, an inside back cover and a back cover. The BSI copyright date displayed in this document indicates when the document was last issued. Amendments issued since publication Amd. No. Date CommentsEUROPEANSTANDARD NORMEEUROPEN
8、NE EUROPISCHENORM EN13641 May2002 ICS11.100 Englishversion Eliminationorreductionofriskofinfectionrelatedtoinvitro diagnosticreagents Eliminationourductiondurisquedinfectionrelatifaux ractifsdediagnosticinvitro EliminierungoderHerabsetzungdesvonReagenzienfrin vitrodiagnostischeUntersuchungenausgehen
9、den Infektionsrisikos ThisEuropeanStandardwasapprovedbyCENon5January2002. CENmembersareboundtocomplywiththeCEN/CENELECInternalRegulationswhichstipulatetheconditionsforgivingthisEurope an Standardthestatusofanationalstandardwithoutanyalteration.Uptodatelistsandbibliographicalreferencesconcernings uch
10、national standardsmaybeobtainedonapplicationtotheManagementCentreortoanyCENmember. ThisEuropeanStandardexistsinthreeofficialversions(English,French,German).Aversioninanyotherlanguagemadebytra nslation undertheresponsibilityofaCENmemberintoitsownlanguageandnotifiedtotheManagementCentrehasthesamestatu
11、sasthe official versions. CENmembersarethenationalstandardsbodiesofAustria,Belgium,CzechRepublic,Denmark,Finland,France,Germany,Greece, Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal,Spain,Sweden,SwitzerlandandUnitedKingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMA
12、LISATION EUROPISCHESKOMITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2002CEN Allrightsofexploitationinanyformandbyanymeansreserved worldwideforCENnationalMembers. Ref.No.EN13641:2002EEN13641:2002(E) 2 Foreword ThisdocumentEN13641:2002hasbeenpreparedbyTechnicalCommitteeCEN/TC140“Invitr
13、odiagnostic medicaldevices“,thesecretariatofwhichisheldbyDIN . ThisEuropeanStandardshallbegiventhestatusofanationalstandard,eitherbypublicationofanidenticaltextor byendorsement,atthelatestbyNovember2002,andconflictingnationalstandardsshallbewithdrawnatthelatest byNovember2002. Thisdocumenthasbeenpre
14、paredunderamandategiventoCENbytheEuropeanCommissionandtheEuropean FreeTradeAssociation,andsupportsessentialrequirementsofEUDirective(s). ForrelationshipwithEUDirective(s),seeinformativeannexZA,whichisanintegralpartofthisdocument. ThisstandardincludesaBibliography. AccordingtotheCEN/CENELECInternalRe
15、gulations,thenationalstandardsorganizationsofthefollowing countriesareboundtoimplementthisEuropeanStandard:Austria,Belgium,CzechRepublic,Denmark,Finland, France,Germany,Greece,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal,Spain, Sweden,SwitzerlandandtheUnitedKingdom.EN13641:2002
16、(E) 3 Introduction Althoughmedicallaboratorystaffroutinelyhandlespecimensthatarepotentiallyinfectiousandappropriate protectivemeasuresandsafetyprocedureshavetobefollowed,accordingtotheprovisionsofthe Directive98/79/EConinvitrodiagnosticmedicaldevices(IVDMDs)(seeBibliography,1)theadditionalriskof acc
17、identalinfectioncausedbyIVDMDscontaininginfectiousorpotentiallyinfectiousmaterialistobereducedtoa minimum.ThisrequirementoftheEUDirectiveisanessentialrequirementrelatingtothedesignandmanufacture ofIVDMDs.Manufacturersareobligedtoensurebyappropriatedesignfeaturesandmanufacturingprocedures thattherisk
18、ofinfectionpresentedbytheproductitselfisminimal.TheEUDirectivedoesnotspecificallyaddress thefollowingaspectswhicharecoveredbyspecificinternational,Europeanand/ornationallegislation: generalaspectsofworkersprotectionandthemeasuresthathavetobeimplementedwheninfectiousor potentiallyinfectiousmaterialsa
19、rehandledinlaboratoriesormanufacturingsites, transportationofinfectiousgoods, disposalroutesandprocesses.EN13641:2002(E) 4 1 Scope ThisEuropeanStandardspecifiesrequirementsrelatedtodesignandmanufactureinordertoeffectivelycontrol theriskofinfectioncausedbyinvitrodiagnosticreagentsincludingreagentprod
20、ucts,calibrators,controlmaterials andkits,hereinaftercalledIVDreagents.Thestandardisapplicabletoinvitrodiagnosticreagentscontaining materialofhumanorigin.Thestandardisalsoapplicabletoinvitrodiagnosticreagentscontainingmaterials obtainedbybiotechnologyprocessesormaterialsofanimalorigin,inparticularin
21、viewofrelevantzoonoses,when theresultsofariskanalysisrevealthatthereisariskofhumaninfection. Thestandarddoesnotapplytothefollowing: instrumentsandspecimenreceptacles; NOTE 1 Thepreventionofinfectionduetohandlingofbiologicalmaterialsthroughoutsuchequipmentis addressedinotherrelevantInternationaland/o
22、rEuropeanStandards. generalaspectsofworkersprotection; transportationofinfectiousgoods; disposalmeasures. NOTE2Someofthemostrelevantdocumentsrelatingtoaspectsnotcoveredbythisstandardarelistedin Bibliographyforinformation. 2 Normativereferences ThisEuropeanStandardincorporatesbydatedorundatedreferenc
23、e,provisionsfromotherpublications.These normativereferencesarecitedattheappropriateplacesinthetext,andthepublicationsarelistedhereafter.For datedreferences,subsequentamendmentstoorrevisionsofanyofthesepublicationsapplytothisEuropean Standardonlywhenincorporatedinitbyamendmentorrevision.Forundatedref
24、erencesthelatesteditionofthe publicationreferredtoapplies(includingamendments). EN375, Informationsuppliedbythemanufacturerwithinvitrodiagnosticreagentsforprofessionaluse. EN376, Informationsuppliedbythemanufacturerwithinvitrodiagnosticreagentsforselftesting. 3 Termsanddefinitions Forthepurposesofth
25、isEuropeanStandard,thefollowingtermsanddefinitionsapply. 3.1 potentiallyinfectiousbiologicalmaterial materialwhichmightcontaininfectiousviabletransmissibleagentsalbeitwithalowprobability NOTEPotentiallyinfectiousbiologicalmaterialincludesallhumanandallanimalsourcedmaterials,includingthespecimens for
26、 routinediagnosticexaminationandbiologicalmaterialsofunknownorigin. 3.2 infectiousbiologicalmaterial materialwhichisknownorhighlylikelytocontainviablemicroorganismsorothertransmissibleagentswhichare knownorsuspectedtocausediseaseinhumans NOTEOthertransmissibleagentsaree.g.prions.EN13641:2002(E) 5 3.
27、3 invitrodiagnosticreagent IVDreagent invitrodiagnosticmedicaldevicewhichisareagent,reagentproduct,calibrator,controlmaterialorkit NOTE1Forthedefinitionofaninvitrodiagnosticmedicaldevicesee1. NOTE2InsomecasesaparticularIVDreagent,asdefinedforuseinhumanmedicine,mayservealsoinveterinarymedicine. EN375
28、:2001 4 Requirementsrelatedtodesignandmanufacture 4.1 General InordertoeliminateorreducetoaminimumtheriskofinfectionrelatedtoIVDreagentsthefollowingaspectsshall beconsidered: rationaleforusinginfectiousorpotentiallyinfectiousbiologicalmaterial; sourcingandtestingrequirements(stipulatedinmaterialspec
29、ifications); inactivationorotherappropriatemeasurestoreducetheriskofinfection; warningstobegivenintheinformationsuppliedbythemanufacturer. 4.2 Useofinfectiousbiologicalmaterialsorpotentiallyinfectiousbiologicalmaterials TheuseofinfectiousbiologicalmaterialsinIVDreagentsshallbeavoidedasfaraspossible.
30、IfIVDreagents containsuchmaterialasaningredientorcomponent,itsuseshallbebasedonasoundscientificortechnical rationale.Infectiousmaterialmaybeusedonlyifitisindispensableforthediagnosticpurposeoftheproduct (e.g.positivecontrols,materialsneededtoutiliserelevantantigensorantibodiesinthefinalkitconfigurat
31、ion.) Theuseofpotentiallyinfectiousbiologicalmaterialsshallbecriticallyquestionedinanycase(weighingrisks againstbenefit). Ifeithertypeofmaterialisused,additionalmeasuresasspecifiedin4.3,4.4andclause5shallbeconsideredto reducetheriskofinfectiontoaminimum.Thejustificationforuseofsuchmaterialsshallbedo
32、cumented. 4.3 Rawmaterialspecifications 4.3.1 General Forallinfectiousandpotentiallyinfectiousbiologicalmaterialsusedinthemanufactureofreagents,appropriate specificationsshallbedefined(includingsourcingandtestingrequirements)inordertocontroladequatelytherisk ofinfection. 4.3.2 Sourcingrequirements A
33、ppropriateproceduresforsourcinginfectiousorpotentiallyinfectiousbiologicalmaterialsshallbeestablishedand documentedbytheIVDreagentsmanufacturer. Informationshallbeavailableon supplieroftherawmaterial;EN13641:2002(E) 6 typeofmaterial(e.g.blood,plasma,serum,tissue,urine,cells); natureofthesource(e.g.h
34、uman,animal,microbial); origin(e.g.geographicalsite,humandonorsgroup); purificationproceduresandchemicaltreatments,ifperformed. 4.3.3 Testingrequirements Testingofmarkersforthemostrelevantinfections,suchasHIV1andHIV2antibodies,HCVantibodiesand HB s Agshallbeperformed. Asarule,testsbasedonCEMarkedIVD
35、reagentsshallbeused,whereavailable.Othertechniquesmaybeused onlyiftheirrelevantperformancecharacteristicsareatleastequivalentanddocumented. Inthecaseofhumanblood,includingplasmaandserum,eachindividualdonationshallbetested.Ifinjustified casestestingisperformedonpooledmaterial,anappropriatelysensitive
36、testingtechnologyshallbeused(e.g. PCRorotheramplificationtechniques). Traceabilityoftestresultsshallbeensured.Acertificateofanalysisforthesourcematerialmaybeconsidered. Onlymaterialsfoundtobenonreactiveintheabovementionedtestsshallbeused,exceptwhenreactivematerial isindispensableforthediagnosticpurp
37、ose.Anyexceptionshallbejustifiedanddocumented. 4.4 Manufacturingprocess Ifinfectiousbiologicalmaterialsareused,inactivationorotherappropriatemeasurestoreducetoaminimumthe riskofinfectionshallbeperformedunlesstheperformanceoftheIVDreagentisadverselyaffected.Adequate evidenceoneffectivenessandlimitati
38、onsofsuchmeasuresshallbeavailable(e.g.useofliteratureevidence, “stateoftheart“procedures,validationdata). Duringtheproductionprocessappropriateorganisationalandhygienicmeasuresshallbetakentoprevent secondarycontamination(inparticularcrosscontamination).InfectiousmaterialsandIVDreagentscontaining inf
39、ectiousmaterialsshallbestoredandfilledinappropriatecontainersthateffectivelyavoiddisseminationof infectiousagents. 5 Informationsuppliedbythemanufacturer InadditiontotherequirementsspecifiedinEN375andEN376appropriatestatementsabouttherelevantinfection markerstestedandtheoutcomeobtainedshallbeinclude
40、dintheinstructionsforuse. Anywarninggivenshallbeappropriatetotheparticularriskofinfection(potentialorknown)presentedbythe reagent.Differentwordingshallbeconsideredfordifferentlevelsofrisk. Forexample,incasealltheperformedtestsshownoreactivityfortherelevantinfectionmarkersoraneffective treatmenthasbe
41、enperformed,averygeneralwarningabouttheresidualriskmaybesufficient.Bycontrast,an explicitandveryclearwarningshallbemadeifinfectiousmaterialispresentforjustifiedreasonsandadditional measuresshallbesuggestedtotheusertoreducetheriskofinfection.EN13641:2002(E) 7 AnnexZA (informative) ClausesofthisEurope
42、anStandardaddressingessentialrequirementsorotherprovisionsof EUDirectives ThisEuropeanStandardhasbeenpreparedunderamandategiventoCENbytheEuropeanCommissionandthe EuropeanFreeTradeAssociation,andsupportsessentialrequirementsoftheEUDirective98/79/EC. WARNING OtherrequirementsandotherEUDirectivesmaybea
43、pplicabletotheproduct(s)fallingwithinthe scopeofthisstandard. Thefollowingclausesofthisstandard,asdetailedinTableZA.1,arelikelytosupportrequirementsoftheEU Directive98/79/EC. Compliancewiththeseclausesofthisstandardprovidesonemeansofconformingtothespecificessential requirementsoftheDirectiveconcerne
44、dandassociatedEFTAregulations. TableZA.1CorrespondencebetweenthisEuropeanStandardandDirective98/79/EC Clauses/subclausesof thisEuropeanStandard Correspondingessentialrequirementsof Directive98/79/EC Qualifyingremarks/Notes 4.1 A.1,A.2,B.2.1 4.2 B.2.1,B.2.2 4.3.1 B.2.2 4.3.2 B.2.2,B.2.5 4.3.3 B.2.1,B.2.2 4.4 B.2.1,B.2.2 5 B.8.4(j),B.8.7(q),B.8.
