EN ISO 17511-2003 en In vitro diagnostic medical devices - Measurement of quantities in biological samples - Metrological traceability of values assigned to calibrators and control.pdf

1、BRITISH STANDARD BS EN ISO 17511:2003 In vitro diagnostic medical devices Measurement of quantities in biological samples Metrological traceability of values assigned to calibrators and control materials The European Standard EN ISO 17511:2003 has the status of a British Standard ICS 07.100.10 BS EN

2、 ISO 17511:2003 This British Standard was published under the authority of the Standards Policy and Strategy Committee on 19 August 2003 BSI 19 August 2003 ISBN 0 580 42473 1 National foreword This British Standard is the official English language version of EN ISO 17511:2003. It is identical with I

3、SO 17511:2003. The UK participation in its preparation was entrusted to Technical Committee CH/212, In vitro diagnostics, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its secretary. Cross-references The British Standards which i

4、mplement 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 of British Standards Online. This publication

5、 does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to understand the text; present to the responsible international/Eur

6、opean 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 comprises a front cover, an inside front cover, the EN title page, p

7、ages 2 to 29 and a back cover. The BSI copyright notice displayed in this document indicates when the document was last issued. Amendments issued since publication Amd. No. Date CommentsEUROPEANSTANDARD NORMEEUROPENNE EUROPISCHENORM ENISO17511 August2003 ICS07.100.10 Englishversion Invitrodiagnostic

8、medicaldevicesMeasurementofquantities inbiologicalsamplesMetrologicaltraceabilityofvalues assignedtocalibratorsandcontrolmaterials(ISO17511:2003) DispositifsmdicauxdediagnosticinvitroMesuragedes grandeursdansdeschantillonsdoriginebiologique Traabilitmtrologiquedesvaleursattribuesauxagents dtalonnage

9、etauxmatriauxdecontrle(ISO 17511:2003) InvitroDiagnostikaMessungvonGreninProben biologischenUrsprungsMetrologischeRckfhrbarkeit vonWerten,dieKalibriermaterialienundKontrollmaterialien zugeordnetsind(ISO17511:2003) ThisEuropeanStandardwasapprovedbyCENon11March2003. CENmembersareboundtocomplywiththeCE

10、N/CENELECInternalRegulationswhichstipulatetheconditionsforgivingthisEurope an Standardthestatusofanationalstandardwithoutanyalteration.Uptodatelistsandbibliographicalreferencesconcernings uchnational standardsmaybeobtainedonapplicationtotheManagementCentreortoanyCENmember. ThisEuropeanStandardexists

11、inthreeofficialversions(English,French,German).Aversioninanyotherlanguagemadebytra nslation undertheresponsibilityofaCENmemberintoitsownlanguageandnotifiedtotheManagementCentrehasthesamestatusasthe official versions. CENmembersarethenationalstandardsbodiesofAustria,Belgium,CzechRepublic,Denmark,Finl

12、and,France,Germany,Greece, Hungary,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal,Slovakia,Spain,Sweden,SwitzerlandandUn ited Kingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMALISATION EUROPISCHESKOMITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2003CE

13、N Allrightsofexploitationinanyformandbyanymeansreserved worldwideforCENnationalMembers. Ref.No.ENISO17511:2003EENISO17511:2003(E) 2 Contents page Foreword3 Introduction .4 1 Scope 6 2 Normativereferences 6 3 Termsanddefinitions. .6 4 Metrologicaltraceabilitychainandcalibrationhierarchy . 12 4.1 Prin

14、ciples12 4.2 Structureandnomenclature .13 4.3 Considerationsinestablishingmetrologicaltraceability 17 4.4 Functionsofreferencematerials .18 5 Calibrationtransferprotocols 18 5.1 Availabilityandstructure 18 5.2 Caseswithprimaryreferencemeasurementprocedureandprimarycalibrator(s)giving metrologicaltra

15、ceabilitytoSI .19 5.3 Caseswithinternationalconventionalreferencemeasurementprocedure(whichisnot primary)andinternationalconventionalcalibrator(s)withoutmetrologicaltraceabilitytoSI20 5.4 Caseswithinternationalconventionalreferencemeasurementprocedure(whichisnot primary)butnointernationalconventiona

16、lcalibratorandwithoutmetrologicaltraceabilityto SI21 5.5 Caseswithinternationalconventionalcalibrator(whichisnotprimary)butnointernational conventionalreferencemeasurementprocedureandwithoutmetrologicaltraceabilitytoSI .22 5.6 Caseswithmanufacturersselectedmeasurementprocedurebutneitherinternational

17、 conventionalreferencemeasurementprocedurenorinternationalconventionalcalibratorand withoutmetrologicaltraceabilitytoSI .23 5.7 Truenesscontrolmaterials .24 6 Expressionofuncertaintyofmeasurement 24 7 Validationofmetrologicallytraceablecalibration 25 8 Informationonmetrologicaltraceabilitytobegiveni

18、ntheinstructionsforuseofaninvitro diagnosticmedicaldevice 26 AnnexZA (informative)ClausesofthisEuropeanStandardaddressingessentialrequirementsorother provisionsofEUDirectives 27 Bibliography 28ENISO17511:2003(E) 3 Foreword Thisdocument(ENISO17511:2003)hasbeenpreparedbyTechnicalCommitteeCEN/TC140“Inv

19、itrodiagnostic medicaldevices“,thesecretariatofwhichisheldbyDIN,incollaborationwithTechnicalCommitteeISO/TC212 “Clinicallaboratorytestingandinvitrodiagnostictestsystems“. ThisEuropeanStandardENISO17511:2003includingtheAmendmentshallbegiventhestatusofanational standard,eitherbypublicationofanidentica

20、ltextorbyendorsement,atthelatestbyFebruary2004,and conflictingnationalstandardsshallbewithdrawnatthelatestbyFebruary2004. ThisdocumenthasbeenpreparedunderamandategiventoCENbytheEuropeanCommissionandtheEuropean FreeTradeAssociation,andsupportsessentialrequirementsofEUDirective(s). Forrelationshipwith

21、EUDirective(s),seeinformativeannexZA,whichisanintegralpartofthisdocument. TheInternationalFederationofClinicalChemistryandLaboratoryMedicine(IFCC),theEuropeanConfederationof LaboratoryMedicine(ECLM),andtheEuropeanDiagnosticManufacturersAssociation(EDMA)havecontributedto itspreparation. Thisstandardi

22、ncludesaBibliography. AccordingtotheCEN/CENELECInternalRegulations,thenationalstandardsorganizationsofthefollowing countriesareboundtoimplementthisEuropeanStandard:Austria,Belgium,CzechRepublic,Denmark,Finland, France,Germany,Greece,Hungary,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,P

23、ortugal, Slovakia,Spain,Sweden,SwitzerlandandtheUnitedKingdom.ENISO17511:2003(E) 4 Introduction Formeasurementsofquantitiesinlaboratorymedicine,itisessentialthatthequantityisadequatelydefinedand thattheresultsreportedtothephysiciansorotherhealthcarepersonelandpatientsareadequatelyaccurate(true andpr

24、ecise)toallowcorrectmedicalinterpretationandcomparabilityovertimeandspace. NOTEInthisEuropeanStandardtheconcept“accuracyofmeasurement“(see3.1)isrelatedtoboth“truenessof measurement“(see3.33)and“precisionofmeasurement“(see3.23)whereastheDirective98/79/EConinvitrodiagnostic medicaldevicesusesthetermac

25、curacyinsteadoftrueness. Toallowcorrectmedicalinterpretationinvolvesmorethanthemetrological(analytical)aspectsofthetraceability chain.Asthemeasurementresultsareeventuallyusedbythephysicianforthebenefitofthepatients,the physicianshouldgatherinformationonanumberofotheraspects,suchasknowledgeaboutthepr

26、eandpost analyticalphase,thediagnosticsensitivityandspecificity,andrelevantreferenceinterval(s).ThepresentEuropean StandarddealsonlywiththeanalyticalaspectsofmeasurementsinLaboratoryMedicine(seealso1e). Themeasurementofquantitiesinbiologicalsamplesrequiresreferencemeasurementsystemsincluding: thedef

27、initionoftheanalyteinthebiologicalsamplewithregardtotheintendedclinicaluseofthemeasurement results; areferencemeasurementprocedurefortheselectedquantityinhumansamples; suitablereferencematerialsfortheselectedquantity,e.g.primarycalibratorsandsecondarymatrixbased calibratorsthatarecommutable. Thetrue

28、nessofmeasurementofavalueassignedtoadefinedquantityofacalibratorortruenesscontrolmaterial, dependsonthemetrologicaltraceabilityofthevaluethroughanunbrokenchainofalternatingmeasurement proceduresandmeasurementstandards(calibrators),usuallyhavingsuccessivelydecreasinguncertaintiesof measurement(seeFig

29、ure1).Theuncertaintyofthevalueassignedtoagivencalibratorortruenesscontrol materialdependsonthestatedmetrologicaltraceabilitychainandthecombineduncertaintiesofitslinks. TheidealendpointofametrologicaltraceabilitychainisthedefinitionoftherelevantunitoftheInternational SystemofUnits(SI),buttheselection

30、ofstepsandthelevelatwhichmetrologicaltraceabilityforagivenvalue stops,dependontheavailabilityofhigherordermeasurementproceduresandcalibrators.Inmanycases,at present,thereisnometrologicaltraceabilityabovethemanufacturersselectedmeasurementprocedureorthe manufacturersworkingcalibrator.Insuchcases,true

31、nessisreferredtothatlevelofthecalibrationhierarchyuntil aninternationallyagreedreferencemeasurementprocedureand/orcalibratorbecomesavailable. Theobjectiveofachosenmetrologicallytraceablecalibrationistotransferthedegreeoftruenessofareference material,and/orreferencemeasurementprocedure,toaprocedureth

32、atisofalowermetrologicalorder,e.g.a routineprocedure.Metrologicaltraceabilityofcalibrationrequiresthatthereferenceandroutinemeasurement proceduresmeasurethesamemeasurablequantitywithananalyteofthesamepertinentcharacteristics. Inthiscontext,itisimportanttorecognizethatdifferentprocedurespurportingtom

33、easurethesamequantitymayin factgivedifferentresultswhenappliedtoaparticularsampleorreferencematerial.Thismayarise,forexample, whentwoormoreimmunoprocedurespurportingtomeasuretheconcentrationofahormonesuchasthyrotropin (thyroidstimulatinghormone,TSH)areappliedtoareferencematerialofthehormone,becauset

34、herespective reagentsrecognizeandreacttodifferentextentswithvariousepitopesinthematerial,thusleadingtoresultsfor differentalthoughrelatedquantities. Laboratorymedicineroutinelyprovidesresultsfor400to700typesofquantity.Formostofthese,themetrological traceabilityoftheassignedvalueforaproductcalibrator

35、stopsafteronlyonemetrologicallyhigherstepconsisting ofa(reference)measurementprocedure,oraftertwostepsconsistingofameasurementprocedureanda (reference)calibrator.Thereasonisthatmanyofsuchquantitiesarerelatedtomixturesofmolecularspecieswith clinicallyrelevantpropertiesincommon,butwithdifferentstructu

36、resandmolecularmassesinvaryingproportions, e.g.glycoproteins.ENISO17511:2003(E) 5 DependingonthepossibilityofmetrologicaltraceabilitytoSIandontheavailabilityofvariousmetrologicallevelsof measurementproceduresandcalibrators,thefollowingfivetypicalupperendsofthemetrologicaltraceabilitychain canbeident

37、ified. a) QuantitiesforwhichresultsofmeasurementsaremetrologicallytraceabletoSI. Aprimaryreferencemeasurementprocedureandoneormore(certified)primaryreferencematerials(usedas calibrators)areavailable.Theselevelsexistforapproximately25to30typesofquantityhavingwelldefined components,e.g.someelectrolyte

38、s,metabolites,steroidhormones,andsomethyroidhormones.Thesetypes ofquantitycoveralargeproportionoftheroutineresultsprovidedbymedicallaboratories(see4.2.2,5.2, Figures1and2). b) QuantitiesforwhichresultsofmeasurementsarenotmetrologicallytraceabletoSI. 1) Aninternationalconventionalreferencemeasurement

39、procedure(see3.12)(whichcannotbecalleda primaryreferencemeasurementprocedure)andoneormoreinternationalconventionalcalibrationmaterials (see3.11)withvaluesassignedbythatprocedureareavailable.Theseconditionsapplyforquantitieswith componentssuchasHbA 1c (see5.3andFigure3). 2) Aninternationalconventiona

40、lreferencemeasurementprocedureisavailablebutnointernational conventionalcalibrationmaterials.Theseconditionsapplyforabout30typesofquantitywithcomponentssuch ashaemostaticfactors(see5.4andFigure4). 3) Oneormoreinternationalconventionalcalibrationmaterials(usedascalibrators)withaprotocolforvalue assig

41、nmentareavailable,butnointernationalconventionalreferencemeasurementprocedure.These conditionsapplyforover300typesofquantity,e.g.,forquantitiesreferredtoWorldHealthOrganizations InternationalStandards,suchasproteinhormones,someantibodies,andtumourmarkers(see5.5and Figure5). 4) Neitherreferencemeasur

42、ementprocedurenorreferencematerialsforcalibrationareavailable.The manufacturercanestablishinhousemeasurementprocedure(s)andcalibrator(s)tosupportvalue assignmenttohisproductcalibrator.Theseconditionsapplyforabout300typesofquantitywithcomponents suchastumourmarkersandantibodies(see5.6andFigure6). The

43、principlesoftherespectivetransferprotocols(calibrationhierarchies)arepresented,giventheprovisionsof theEuropeanStandardsEN12286onpresentationofreferencemeasurementproceduresandEN12287onthe descriptionofreferencematerials. Itistheaimofmetrologyinlaboratorymedicinetoimprovemetrologicaltraceabilityforr

44、esultsofatypeofquantity fromtheconditionsdescribedunderb2),b3),andb4)tothoseofb1)byprovidingthemissingreference measurementproceduresandreferencematerials,basedoninternationalconsensus. Thespecialproblemsofmetrologicaltraceabilityforvaluesofcatalyticconcentrationofenzymesareconsideredin prENISO18153.ENISO17511:2003(E) 6 1Scope ThisEuropeanStand