ISO17665.2-2009蒸汽灭菌验证实施指南

ReferencenumberISO/TS17665-2:2009(E)©ISO2009TECHNICALSPECIFICATIONISO/TS17665-2Firstedition2009-01-15Sterilizationofhealthcareproducts—Moistheat—Part2:GuidanceontheapplicationofISO17665-1Stérilisationdesproduitsdesanté—Chaleurhumide—Partie2:Directivesrelativesàl'applicationdel'ISO17665-1ISO/TS17665-2:2009(E)PDFdisclaimerThisPDFfilemaycontainembeddedtypefaces.InaccordancewithAdobe'slicensingpolicy,thisfilemaybeprintedorviewedbutshallnotbeeditedunlessthetypefaceswhichareembeddedarelicensedtoandinstalledonthecomputerperformingtheediting.Indownloadingthisfile,partiesacceptthereintheresponsibilityofnotinfringingAdobe'slicensingpolicy.TheISOCentralSecretariatacceptsnoliabilityinthisarea.AdobeisatrademarkofAdobeSystemsIncorporated.DetailsofthesoftwareproductsusedtocreatethisPDFfilecanbefoundintheGeneralInforelativetothefile;thePDF-creationparameterswereoptimizedforprinting.EverycarehasbeentakentoensurethatthefileissuitableforusebyISOmemberbodies.Intheunlikelyeventthataproblemrelatingtoitisfound,pleaseinformtheCentralSecretariatattheaddressgivenbelow.COPYRIGHTPROTECTEDDOCUMENT©ISO2009Allrightsreserved.Unlessotherwisespecified,nopartofthispublicationmaybereproducedorutilizedinanyformorbyanymeans,electronicormechanical,includingphotocopyingandmicrofilm,withoutpermissioninwritingfromeitherISOattheaddressbeloworISO'smemberbodyinthecountryoftherequester.ISOcopyrightofficeCasepostale56•CH-1211Geneva20Tel.+41227490111Fax+41227490947E-mailcopyright@iso.orgWebwww.iso.orgPublishedinSwitzerlandii©ISO2009–AllrightsreservedISO/TS17665-2:2009(E)©ISO2009–AllrightsreservediiiContentsPageForeword............................................................................................................................................................ivIntroduction........................................................................................................................................................v1Scope.....................................................................................................................................................12Normativereferences...........................................................................................................................13Termsanddefinitions...........................................................................................................................24Qualitymanagementsystemelements..............................................................................................25Sterilizingagentcharacterization.......................................................................................................25.1Sterilizingagent....................................................................................................................................25.2Microbicidaleffectiveness...................................................................................................................25.3Materialeffects......................................................................................................................................35.4Environmentalconsiderations............................................................................................................36Processandequipmentcharacterization..........................................................................................36.1Process..................................................................................................................................................36.2Equipment.............................................................................................................................................67Productdefinition.................................................................................................................................78Processdefinition.................................................................................................................................89Validation.............................................................................................................................................109.1General.................................................................................................................................................109.2Installationqualification(IQ).............................................................................................................119.3Operationalqualification(OQ)...........................................................................................................119.4Performancequalification(PQ).........................................................................................................139.5Reviewandapprovalofthevalidation.............................................................................................1410Routinemonitoringandcontrol........................................................................................................1511Productreleasefromsterilization.....................................................................................................1612Maintainingprocesseffectiveness...................................................................................................1712.1Demonstrationofcontinuedeffectiveness......................................................................................1712.2Recalibration.......................................................................................................................................1712.3Maintenanceofequipment................................................................................................................1712.4Requalification....................................................................................................................................1712.5Assessmentofchange.......................................................................................................................18AnnexA(informative)Evaluationofasterilizationprocessprimarilybasedonthemeasurementofphysicalparameters.......................................................................................................................19AnnexB(informative)Evaluationofasterilizationprocessprimarilybasedonbiologicalinactivationandanaccompanyingmechanicalairremovalprocedure.......................................27AnnexC(informative)Temperatureandpressureofsaturatedsteamforuseinmoistheatsterilization..........................................................................................................................................30AnnexD(informative)Specialconsiderationsforhealthcaresettings.....................................................32AnnexE(informative)Indexofnormativeclauses/subclausesofISO17665-1andcitedreferencesorrelatedguidancegiveninISO17665-1andISO/TS17665-2......................................................41Bibliography.....................................................................................................................................................44ISO/TS17665-2:2009(E)iv©ISO2009–AllrightsreservedForewordISO(theInternationalOrganizationforStandardization)isaworldwidefederationofnationalstandardsbodies(ISOmemberbodies).TheworkofpreparingInternationalStandardsisnormallycarriedoutthroughISOtechnicalcommittees.Eachmemberbodyinterestedinasubjectforwhichatechnicalcommitteehasbeenestablishedhastherighttoberepresentedonthatcommittee.Internationalorganizations,governmentalandnon-governmental,inliaisonwithISO,alsotakepartinthework.ISOcollaboratescloselywiththeInternationalElectrotechnicalCommission(IEC)onallmattersofelectrotechnicalstandardization.InternationalStandardsaredraftedinaccordancewiththerulesgivenintheISO/IECDirectives,Part2.ThemaintaskoftechnicalcommitteesistoprepareInternationalStandards.DraftInternationalStandardsadoptedbythetechnicalcommitteesarecirculatedtothememberbodiesforvoting.PublicationasanInternationalStandardrequiresapprovalbyatleast75%ofthememberbodiescastingavote.Inothercircumstances,particularlywhenthereisanurgentmarketrequirementforsuchdocuments,atechnicalcommitteemaydecidetopublishothertypesofdocument:⎯anISOPubliclyAvailableSpecification(ISO/PAS)representsanagreementbetweentechnicalexpertsinanISOworkinggroupandisacceptedforpublicationifitisapprovedbymorethan50%ofthemembersoftheparentcommitteecastingavote;⎯anISOTechnicalSpecification(ISO/TS)representsanagreementbetweenthemembersofatechnicalcommitteeandisacceptedforpublicationifitisapprovedby2/3ofthemembersofthecommitteecastingavote.AnISO/PASorISO/TSisreviewedafterthreeyearsinordertodecidewhetheritwillbeconfirmedforafurtherthreeyears,revisedtobecomeanInternationalStandard,orwithdrawn.IftheISO/PASorISO/TSisconfirmed,itisreviewedagainafterafurtherthreeyears,atwhichtimeitmusteitherbetransformedintoanInternationalStandardorbewithdrawn.Attentionisdrawntothepossibilitythatsomeoftheelementsofthisdocumentmaybethesubjectofpatentrights.ISOshallnotbeheldresponsibleforidentifyinganyorallsuchpatentrights.ISO/TS17665-2waspreparedbyTechnicalCommitteeISO/TC198,Sterilizationofhealthcareproducts.ISO17665consistsofthefollowingparts,underthegeneraltitleSterilizationofhealthcareproducts—Moistheat:⎯Part1:Requirementsforthedevelopment,validationandroutinecontrolofasterilizationprocessformedicaldevices⎯Part2:GuidanceontheapplicationofISO17665-1[TechnicalSpecification]ISO/TS17665-2:2009(E)©ISO2009–AllrightsreservedvIntroductionTheguidancegiveninthisTechnicalSpecificationisnotintendedasachecklistforassessingcompliancewithISO17665-1.ThisguidanceisintendedtoassistinobtainingauniformunderstandingandimplementationofISO17665-1byprovidingexplanationsandacceptablemethodsforachievingcompliancewithspecifiedrequirements.Ithighlightsimportantaspectsandprovidesexamples.Methodsotherthanthosegiveninthisguidancemaybeused.However,theuseofalternativemethodshastobedemonstratedtobeeffectiveinachievingcompliancewithISO17665-1.Themainbodyofthisdocumentisapplicabletoallsettingswheremoistheatsterilizationiscarriedout.TheannexestothisguidancedocumentalsospecifydetailedmeansofimplementingtherequirementsofISO17665-1andrepresentcurrentbestpractices.ThenumberingoftheclausesinthemainbodyofthisTechnicalSpecificationcorrespondstothatinISO17665-1.Medicaldevicesreprocessedinhealthcarefacilitiesincludeawidevarietyofproductwithvaryinglevelsofbioburden.Appropriateandthoroughcleaningand,wherenecessaryforsafehandling,decontaminationprocessesareessentialpriortopresentingproductforsterilization.Mixedproductloadsarecommoninhealthcarefacilitieswiththroughputvolumesdictatedbyhistoricalandpredicteddemandforsterileproduct.Healthcarefacilitiesdonotnormallyspecifysterilizationprocessesforanyindividualmedicaldevice.Also,itisimpracticalforhealthcarefacilitiestodeterminebioburdenonamedicaldevice.Itisimportantthatspecifiedinstrumentsbedisassembledbeforedecontaminationandthoroughlyinspectedaftercompletionofthesterilizationprocess.Reassemblyandassessmentoffunctionalityarealsoneeded.Therefore,themedicaldevicemanufacturer'sinstructions(seeISO17664[23])shouldbefollowedforallaspectsofcleaning,disinfection,packagingandsterilization.Manydevicescanbefullyimmersedandcanbewashedanddisinfectedinautomatedequipment(seeISO15883[19-22]).Fordevicesthatcannotbefullyimmersedandthatcannottoleratethermaldecontamination,alternativemethodsofdisinfectionshouldbeusedtoensuresafehandling.Suchproceduresandpoliciesshouldbeinplacetoensurethatmedicaldevicesundergoappropriatereprocessing.Particularattentionneedstobepaidtothedryingandstorageofsterilemedicaldevices.RequirementsforpackagingofmedicaldevicesarecoveredinISO11607-1[8]andISO11607-2[9].Ifmultiplesterilizationcyclescanleadtodegradationandlimittheusefullifeofamedicaldevice,themanufacturerwillspecifythenumberofreprocessingcyclesthatcannormallybetolerated.Whenselectingamedicaldevice,priorityshouldbegiventopropertiessuchaseaseofcleaninganddisassembly.AdditionalguidancespecifictohealthcareisofferedinAnnexDofthisTechnicalSpecification.TECHNICALSPECIFICATIONISO/TS17665-2:2009(E)©ISO2009–Allrightsreserved1Sterilizationofhealthcareproducts—Moistheat—Part2:GuidanceontheapplicationofISO17665-11ScopeThisTechnicalSpecificationprovidesgeneralguidanceonthedevelopment,validationandroutinecontrolofmoistheatsterilizationprocessesandisintendedtoexplaintherequirementssetforthinISO17665-1.TheguidancegiveninthisTechnicalSpecificationisprovidedtopromotegoodpracticerelatedtomoistheatsterilizationprocessesandtoassistthosedevelopingandvalidatingamoistheatsterilizationprocessaccordingtoISO17665-1.NOTE1ThestructureofthemainbodyofthisISOTechnicalSpecification(Clauses1to12)correspondstothestructureofISO17665-1,sothattheguidancegivenunderaparticularclauseorsubclauseofthispartofISO17665appliestotherequirementsgiveninthecorrespondingclauseorsubclauseofISO17665-1.Forexample,guidanceforsubclause5.2ofISO17665-1:2006isgivenin5.2.ThisguidanceisprovidedinadditiontotheguidancegiveninISO17665-1:2006,AnnexA.SeealsoAnnexeE.NOTE2SpecialconsiderationsspecifictosterilizationprocessesperformedinhealthcarefacilitiesaregiveninAnnexD.2NormativereferencesThefollowingreferenceddocumentsareindispensablefortheapplicationofthisdocument.Fordatedreferences,onlytheeditioncitedapplies.Forundatedreferences,thelatesteditionofthereferenceddocument(includinganyamendments)applies.ISO17665-1:2006,Sterilizationofhealthcareproducts—Moistheat—Part1:Requirementsforthedevelopment,validationandroutinecontrolofasterilizationprocessformedicaldevicesNOTEThenormativereferencesinISO17665-1refertopublishedstandards,thecontentofwhichshouldbeusedtoassistindemonstratingcompliancetotheclauseinwhichtheyarecited.Somearerequiredmainlyformoistheatsterilizationinindustryorformanufacturersofmoistheatsterilizersandcouldgobeyondtypicalpracticeforthoseperformingsterilizationinhealthcarefacilities.ISO17665-1specifiesanumberofmethodsandproceduresthatcanbeusedtomonitorsterilizationprocesses.Theequipmentrequiredwillnormallybecommerciallyavailable.Anumberofthenormativereferencesciteddescribethespecificationandtestmethodsusedbycommercialsupplierstoqualifytheirproducts.Theuserofsuchproductsshouldensurethatpurchasedproductscomplywiththesestandards,butwillnotnormallyneedtorefertothestandards.ISO17665-1specifiestheuseofpackagingcomplyingwithISO11607-1andISO11607-2.HealthcarefacilitiesshouldpurchasepackagingcomplyingwiththeseInternationalStandards.OnemethodofprocessvalidationspecifiedinISO17665-1isbasedonthedeterminationofbioburden.TheISO11737[6],[7]seriesspecifiesanumberofmicrobiologicalmethodsusedduringthisprocess.Healthcarefacilitieswouldnotnormallyutilizethisapproachforprocessvalidation.ISO/TS17665-2:2009(E)2©ISO2009–Allrightsreserved3TermsanddefinitionsForthepurposesofthisTechnicalSpecification,thetermsanddefinitionsgiveninISO17665-1andthefollowingapply.3.1testsforsterilitytechnicaloperationdefinedinpharmacopoeiaperformedonproductfollowingexposuretoasterilizationprocess4QualitymanagementsystemelementsTheguidanceofferedinAnnexAofISO17665-1:2006applies.NOTEForadditionalconsiderationsspecifictohealthcarefacilities,seeClauseD.2.5Sterilizingagentcharacterization5.1Sterilizingagent5.1.1Moistheatiswateratelevatedtemperatures.Moistheatmaybeprovidedassaturatedsteamorcanbegeneratedinsitubyapplyingthermalenergytowateralreadypresentintheproduct.Moistureactsasthemediumfortransferringthermalenergytomicroorganisms.5.1.2Contaminantssuspendedinthesterilizingagentcanbebothtoxicandcorrosiveandmaygenerateabarrierbetweenthemicroorganismandthesterilizingagent.Theyoriginatefromwater,thatisheatedorevaporatedintosteamorfromcontactbetweenmaterialsandthesterilizingagentduringgenerationandtransporttothesterilizer(seeClause6,Clause7andAnnexA).Ifthelevelofcontaminantsinthesterilizingagentcanbeaffectedbythequalityofthefeedwatertothesteamgenerationsystem,thefeedwaterqualityshouldbespecified.5.2MicrobicidaleffectivenessThemicrobicidalactivityofmoistheatisbasedonthetemperatureandthedurationofcontactbetweenwatermoleculesandmicroorganisms.Forthepurposeofmoistheatsterilizationthereareanumberofacceptabletimeandtemperaturecombinationsrecognisedbysomepharmacopoeias.ThesecombinationsincludebutarenotlimitedtothoselistedinTable1.Allcombinationslistedarebasedontheconceptofoverkillwithasafetyfactorthathasbeenestablishedforsaturatedsteamorwaterincontactwiththemicroorganism.Superheatedsteambehavesmorelikeadrygasandhasalowmicrobicidaleffectivenesscomparedwithsaturatedsteam.Superheatedsteamcanresultfrompressurereductionand/orthermodynamiccompressionofsaturatedsteam.Itcanalsooccurfromtherehydrationofpartsofthesterilizationload,particularlythosepartscontainingnaturalfibres.Superheatedsteamconditionscanbeminimizedbyengineeringofthesteamsupplysystem,forexampleby:a)havingaseriesofpressurereductionstagesfromthesupplypipetothesterilizerchamberandensuringthepressurereductionratioforeachstagedoesnotexceed2:1;b)ensuringsteamvelocitydoesnotexceed25m/s;c)ensuringmaterialsmadefromnaturalfibresarepre-conditionedtoahumiditygreaterthan40%RHpriortosterilization.ISO/TS17665-2:2009(E)©ISO2009–Allrightsreserved3Table1—ExamplesofminimumtemperaturesandtimesestablishedforadequatelevelsofmicrobiallethalityinsterilizationprocessesTemperatureTime°Cmin121151261013435.3MaterialeffectsMaterialeffectsaregenerallylimitedtodeformationandfracturecausedbythetemperaturesandpressuresofthesterilizingagent.5.4EnvironmentalconsiderationsPrinciplesofanenvironmentalmanagementsystemcanbeappliedtoamoistheatsterilizationprocess.ISO14001[11]providesaspecificationforanenvironmentalmanagementsystem.ISO14040[12]providesguidanceondesigningalifecycleassessmentstudy.Thepresenceofnoxioussubstancesintheexhaustsfromthesterilizershouldbeconsidered.FurtherguidanceonthisclauseisgiveninE.3ofISO14937:—[15].6ProcessandequipmentcharacterizationNOTEThepurposeofthisactivityistocharacterizetheentiresterilizationprocessandtheequipmentnecessarytodeliverthesterilizationprocesssafelyandreproducibly.6.1Process6.1.1GeneralAsterilizationprocessshouldbespecifiedforeachproductfamilyand/orloadconfigurationpresentedforsterilization.Processparametersshouldapplytotheequipmentused.Theyshouldbeoptimisedtoensurethatfordefinedproductfamiliesspecifiedexposureconditionswillberoutinelyobtainedthroughoutthesterilizerchamber,andthemaximumtemperaturesandratesofchangeofprocessvariable(e.g.temperatureandpressure)willnotcausedamageordegradationtotheproduct.Thesterilizationprocessspecificationshouldincludealltheprocessparametersthatdefinetheexposureprofilethroughouttheoperatingcycle.Itshouldalsoincludetheonesusedtoverifyreproducibility.Theportionoftheoperatingcycleoverwhichlethalityisestablishedshouldbeidentified,andtheupperandlowerlimitsofeachprocessparameterthatcanaffectboththislethalityandtheperformanceofthemedicaldeviceshouldbedefined.Provisionshouldbemadetorecorddataforjudgingtheeffectivenessandsuitabilityofaroutinesterilizationprocess.Theaccuracyofmeasurementshouldberelatedtothetolerancesoftheprocessparameters.Ifitisproposedtouseanexistingsterilizationprocesstotreatanewmedicaldevice,theexistingsterilizationprocessshouldbedetailedandcontaininformationanddatasufficienttoenableprocessdefinition(seeClause8)tobecarriedoutfortheproposednewmedicaldevice(s)orloadingconfiguration.Thechallengeidentifiedforthenewmedicaldeviceorloadingconditionshouldbelessthanorequaltothechallengefromtheexistingsterilizationload(s).Forsomeproductfamilies,assurancethatdefinedexposureconditionswillbereproducedmightonlybepossibleifthesizeofthesterilizationloadandtheloadconfigurationhavebeenclearlydefined.ISO/TS17665-2:2009(E)4©ISO2009–AllrightsreservedIfbiologicalindicatorsandchemicalindicatorsaretobeused,theyshouldnotreplaceroutinemonitoring,measurementofprocessvariablesandanyperiodictests.Compatibilityofanewmedicaldevicetotheleastfavourablesterilizationprocessconditionsshouldbeassessed.Suchassessmentshouldincludeprocessparametertolerances,uncertaintiesofmeasurementassociatedwithprocessparametersandthequalityoftheservices(seeAnnexA).Anyrestrictionsonthesizeandmassofthesterilizationloadanditsconfigurationshouldbeidentifiedandincludedintheoperatinginstructions.Therelationshipbetweenthetemperaturemeasure