1、BRITISH STANDARD BS EN ISO 18153:2003 In vitro diagnostic medical devices Measurement of quantities in biological samples Metrological traceability of values for catalytic concentration of enzymes assigned to calibrators and control materials The European Standard EN ISO 18153:2003 has the status of
2、 a British Standard ICS 07.100.10 BS EN ISO 18153:2003 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 42141 4 National foreword This British Standard is the official English language version of EN
3、 ISO 18153:2003. It is identical with ISO 18153:2003. 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-r
4、eferences 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 of Bri
5、tish Standards Online. This publication 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; prese
6、nt 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 comprises a front cover, an i
7、nside front cover, the EN title page, pages 2 to 16, an inside back cover 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 ENISO1
8、8153 August2003 ICS07.100.10 Englishversion InvitrodiagnosticmedicaldevicesMeasurementofquantities inbiologicalsamplesMetrologicaltraceabilityofvaluesfor catalyticconcentrationofenzymesassignedtocalibratorsand controlmaterials(ISO18153:2003) DispositifsmdicauxdediagnosticinvitroMesuragedes grandeurs
9、dansdeschantillonsdoriginebiologique Traabilitmtrologiquedesvaleursdeconcentration catalytiquedesenzymesattribuesauxagents dtalonnageetauxmatriauxdecontrle(ISO 18153:2003) InvitroDiagnostikaMessungvonGreninProben biologischenUrsprungsMetrologischeRckfhrbarkeit vonWertenderkatalytischenKonzentrationv
10、onEnzymen, dieKalibratorenundKontrollmaterialienzugeordnetsind (ISO18153:2003) ThisEuropeanStandardwasapprovedbyCENon11March2003. CENmembersareboundtocomplywiththeCEN/CENELECInternalRegulationswhichstipulatetheconditionsforgivingthisEurope an Standardthestatusofanationalstandardwithoutanyalteration.
11、Uptodatelistsandbibliographicalreferencesconcernings uchnational standardsmaybeobtainedonapplicationtotheManagementCentreortoanyCENmember. ThisEuropeanStandardexistsinthreeofficialversions(English,French,German).Aversioninanyotherlanguagemadebytra nslation undertheresponsibilityofaCENmemberintoitsow
12、nlanguageandnotifiedtotheManagementCentrehasthesamestatusasthe official versions. CENmembersarethenationalstandardsbodiesofAustria,Belgium,CzechRepublic,Denmark,Finland,France,Germany,Greece, Hungary,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal,Slovakia,Spain,Sweden,Switzerland
13、andUn ited Kingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMALISATION EUROPISCHESKOMITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2003CEN Allrightsofexploitationinanyformandbyanymeansreserved worldwideforCENnationalMembers. Ref.No.ENISO18153:2003EENISO18153:2003(E) 2 Con
14、tents page Foreword3 Introduction .4 1 Scope 6 2 Normativereferences 6 3 Termsanddefinitions. .6 4 Metrologicaltraceabilitychainandcalibrationhierarchy . 8 4.1 Principles8 4.2 Structure .9 5 Validationofmetrologicallytraceablecalibration 11 5.1 Principles11 5.2 Analyticalspecificityofmeasurementproc
15、edures 11 5.3 Commutabilityofcalibrators 12 5.4 Commutabilityofcontrolmaterials 12 AnnexA (informative) ListofIFCCprimaryreferencemeasurementprocedures .13 AnnexB (informative) Listofcertifiedreferencematerials(CRM).14 AnnexZA (informative)ClausesofthisEuropeanStandardaddressingessentialrequirements
16、orother provisionsofEUDirectives 15 Bibliography 16ENISO18153:2003(E) 3 Foreword Thisdocument(ENISO18153:2003)hasbeenpreparedbyTechnicalCommitteeCEN/TC140“Invitrodiagnostic medicaldevices“,thesecretariatofwhichisheldbyDIN,incollaborationwithTechnicalCommitteeISO/TC212 “Clinicallaboratorytestingandin
17、vitrodiagnostictestsystems“. ThisEuropeanStandardENISO18153:2003includingtheAmendmentshallbegiventhestatusofanational standard,eitherbypublicationofanidenticaltextorbyendorsement,atthelatestbyFebruary2004,and conflictingnationalstandardsshallbewithdrawnatthelatestbyFebruary2004. Thisdocumenthasbeenp
18、reparedunderamandategiventoCENbytheEuropeanCommissionandtheEuropean FreeTradeAssociation,andsupportsessentialrequirementsofEUDirective(s). ForrelationshipwithEUDirective(s),seeinformativeannexZA,whichisanintegralpartofthisdocument. TheInternationalFederationofClinicalChemistryandLaboratoryMedicine(I
19、FCC),theEuropeanConfederationof LaboratoryMedicine(ECLM),andtheEuropeanDiagnosticManufacturersAssociation(EDMA)havecontributedto itspreparation. ThisstandardincludesaBibliography. AnnexesAandBareinformative. AccordingtotheCEN/CENELECInternalRegulations,thenationalstandardsorganizationsofthefollowing
20、 countriesareboundtoimplementthisEuropeanStandard:Austria,Belgium,CzechRepublic,Denmark,Finland, France,Germany,Greece,Hungary,Iceland,Ireland,Italy,Luxembourg,Malta,Netherlands,Norway,Portugal, Slovakia,Spain,Sweden,SwitzerlandandtheUnitedKingdom.ENISO18153:2003(E) 4 Introduction TheDirective98/79/
21、EConinvitrodiagnosticmedicaldevicesrequiresthatthemetrologicallytraceabilityofvalues assignedtocalibratorsandcontrolmaterialsbeassuredthroughavailablereferencemeasurementmaterialsand referencemeasurementproceduresofhigherorder.Followingthisconcept,theEuropeanStandard prEN ISO 17511on“traceability“ha
22、sbeenelaboratedwhichdescribesahierarchicalorderofmeasurement proceduresandcalibrationmaterials.Thegeneralrulesexpressedinthatstandardalsoapplytoquantities involvingcatalyticactivity.Wheneverpossible,metrologicaltraceabilityshouldbedemonstratedtotheSIunitwhich formsthetopofthecalibrationhierarchy. Fo
23、rthemeasurementofthecatalyticactivityconcentrationofenzymes(hereaftercalledcatalyticconcentration),a hierarchyofcalibratorsandmeasurementproceduresisdescribedinthepresentstandard.Forenzyme measurements,thedefinitionofthederivedcoherentSIunit“molepersecondcubicmetre“,giventhespecial name“katalpercubi
24、cmetre“bytheGeneralConferenceonWeightsandMeasures,isthetopofthehierarchy followedbyaprimaryreferencemeasurementproceduretowhichlowerlevelmeasurementprocedures, calibrators,andcontrolmaterialsshouldbetracedwheneverpossible. Enzymesinbloodorotherbiologicalfluidscanbemeasuredfordiagnosticpurposesinterm
25、softheircatalytic concentrations.Theanalyticalprincipleofthemeasurementofthecatalyticrateofconversionofsubstratehas considerableadvantagesofspeed,lowlimitofdetection,analyticalspecificity,andlowcost.Resultsofcatalytic concentrationmeasurementsareonlycomparableiftheenzymeactivitiesaremeasuredunderthe
26、same conditions.Therefore,anenzymemeasurandcannotbedescribedonlybykindofquantity(e.g.catalytic concentration),nameofenzymeandofsystem,butrequiresalsothespecifiedmeasurementprocedureand especiallytheindicatorcomponentofthemeasuredreaction.Atthetopofthecalibrationhierarchy,the measurementprocedureshou
27、ldbeinternationallyagreed,e.g.creatinekinasemeasuredbytheconversionrateof NADHintheIFCCreferencemeasurementprocedure. Thus,theprimaryreferencemeasurementprocedureisanintegralpartofthedefinitionofthemeasurandandhas tobefollowedinalldetail,e.g.asconcerns: kindofsubstrate(wherethespecificityoftheenzyme
28、allowsthistobevaried)anditsconcentration, activatorsandtheirconcentrations, directionofcatalysedreaction, indicator component, buffersystemandpH, temperature, preincubationtime, materialusedforstartingthereaction, lag time, reactiontime.ENISO18153:2003(E) 5 Thedisadvantageoftheproceduredependenceoft
29、hedefinitionoftheenzymemeasurandandthereforeofthe resultsofthemeasurementsarewellknown:problemsarecausedinexternalqualityassessment(EQA)andin assessingthetransferabilityofmethods;amultiplicityofbiologicalreferenceintervalsexistswiththeconsequent riskofclinicalmisinterpretationofenzymeresults.Thestan
30、dardizationofroutineenzymemeasurementsis importanttolaboratorymedicine,toimprovetheclinicalutilityandcomparabilityofresultsthroughtheeliminationof existingdifferencesinbiologicalreferenceintervals. Twoapproachescanbeconsidered: a) theexclusiveroutineuseofarecommendedorstandardizedprocedureforeachenz
31、yme; b) calibrationofoneormoreroutineproceduresbycommutableenzymecalibrationmaterialswithvalues assignedbyachosenreferencemeasurementprocedure. The“recommendedprocedure“approach(a)hasbeenpursuedvigorouslyformorethantwentyyears.Ithashad considerablesuccessinimprovingthequalityandcomparabilityofenzyme
32、measurementsandindiscouragingthe useofanalyticallyunsatisfactoryprocedures.However,therecommendedprocedureapproachtostandardization appearstohavereachedthelimitsofitsusefulness.Itsdisadvantagesinclude:absenceofaconsensusofchoice amonganumberofdifferingrecommendations;intentionalorunintentionalmodifi
33、cationofrecommended proceduresinroutineuse;unresponsivenessofrecommendedprocedurestoanalyticalandtechnical improvement;andpartlynonadaptabilityofrecommendedprocedurestopreferredautomation.Asachangein routineenzymeprocedures,whetherrecommendedornot,inevitablyentailsachangeofbiologicalreference values
34、,itisunderstandablyunwelcometoclinicians. Improvementofthedesignandanalyticalperformanceofenzymemeasurementswill,andshould,continue. However,thisshouldfollowthenormalpracticeofdevelopmentanddisseminationofscientificadvances.Attempts todevelopandpromotefurtherstandardizedproceduresforuniversalusearen
35、eitherpracticablenordesirable. The“referencemeasurementprocedureandcalibrationmaterial“approach(b)has,incontrast,receivedrelatively littleattention.Amongtheobjectionsthathavebeenraisedare: 1. lackofstableenzymereferencematerialsinappropriatematricestoserveascalibrators; 2. dissimilaritybetweencandid
36、ateenzymecalibratorsandtheanalyteenzymesinhumansamples,including differencesinisoforms; 3. absenceofaconstantinterprocedureratiobetweenacalibrating(reference)procedureandcalibrated (routine)procedure(s),forboththeenzymecalibratorandpatientssamplescontainingtheanalyteenzyme (alsodescribedasalackofcom
37、mutability). Theconverseoftheseobjectionsconstitutesalistofspecifications,bothforhigherorderenzymereference materialsandforfamiliesofmeasurementproceduresbetweenwhichcalibrationisproposed.Thecalibratorshould bestableandhaveananalyteenzymethatiscloseinitscatalyticpropertieswithinitsmatrixtothoseofthe
38、analyte enzymeintheroutinesamples.Theproceduresthemselvesshouldhavethesamespecificityforthecatalytic activityofthetargetenzyme. Harmonizationoftheresultsofroutineenzymemeasurementscanthusbeachievedbyselectingareference measurementprocedureandidentifyingafamilyofrelatedproceduresforeachclinicallyimpo
39、rtantenzyme. Resultsobtainedbyanyprocedureincludedwithinsuchafamilywillbemetrologicallytraceabletothechosen referencemeasurementprocedure.ENISO18153:2003(E) 6 1Scope ThisEuropeanStandardspecifieshowtoassurethemetrologicaltraceabilityofvaluesassignedtocalibratorsand controlmaterialsintendedtoestablis
40、horverifytruenessofmeasurementofthecatalyticconcentrationofenzymes. Thecalibratorsandcontrolmaterialsarethoseprovidedbythemanufacturersaspartof,ortobeusedtogether with,invitrodiagnosticmedicaldevices. Thefollowingsubjectsareoutsidethescopeofthisstandard: a) requirementsforthedesignorselectionofarefe
41、rencemeasurementprocedure; b) quantitiesinvolvingmassofenzymeorimmunoreactivityofenzymes; c) controlmaterialsthatdonothaveanassignedvalueandareusedonlyforassessingtheprecisionofa measurementprocedure,eitheritsrepeatabilityorreproducibility(precisioncontrolmaterials); d) controlmaterialsintendedforin
42、tralaboratoryqualitycontrolpurposesandsuppliedwithintervalsofsuggested acceptablevalues,eachintervalobtainedbyinterlaboratoryconsensuswithrespecttoonespecified measurementprocedure,andwithlimitingvaluesthatarenotmetrologicallytraceable; e)metrologicaltraceabilityofroutineresultstotheproductcalibrato
43、randtheirrelationstoanymedical discriminationlimit; f) propertiesinvolvingnominalandordinalscales. 2 Normativereferences ThisEuropeanStandardincorporatesbydatedorundatedreference,provisionsfromotherpublications.These normativereferencesarecitedattheappropriateplacesinthetext,andthepublicationsarelis
44、tedhereafter.For datedreferences,subsequentamendmentstoorrevisionsofanyofthesepublicationsapplytothisEuropean Standardonlywhenincorporatedinitbyamendmentorrevision.Forundatedreferencesthelatesteditionofthe publicationreferredtoapplies(includingamendments). prENISO17511, InvitrodiagnosticmedicaldevicesMeasurementofquantitiesinbi
