Supplement-11-冷冻卡车确认 中英文 完

QualificationofrefrigeratedroadWHOTechnicalReportSeries,No.96Annex9:Modelguidanceforthestorageandtransportoftimeandtemperature-sensitivepharmaceuticalproductsAugust2014©WorldHealthOrganization2014WHOPress,WorldHealthOrgani3264;fax:+41227914857;rtranslateWHOpublications–whetherforsaleorfornoncommercialdistribution–shouldbtoWHOPress,attheaboveaddress(fax:+41227914806;e-maexpressionofanyopinionwhatsoeveronthepartoftheWostatusofanycountry,territory,cityorareaorofitsauthoritifrontiersorboundaries.DoThementionofspecificcompaniesorofendorsedorrecommendedbytthatarenotmentionAllreasonableprecautionshavebecontainedinthispublication.Howeveranykind,eitherexpresseduse.ThenamedauthorsaloneareTheauthorofthisdocumentisRic±KDifferenceinabsolutATPAgreementontheInternationalStandardOperatingTimeandTemperature-Sensitemperatureatpre-determinedtimeprogrammablealarmcapermanentlystored,sharedandanalysedviaproprietaryhardwarethroughhosteddatabasCoefficientofheattransfW,perdegreetemperaturedifference,T,betweentheintInstallationqualification(IQ):TheprocessofoequipmentandsupportingsystemsOperationalqualification(OQ):Theprocessofobtainiconditions,thatthepremises,equipmentandsupportingsystemsoperatPerformancequalification(PQ):Theprocessofobtaipremises,equipmentandsupportingsystems,asconnectedtoaccordancewiththeapprovedprocessmethodandspecificatiPharmaceuticalproduct:Anyproductintadministrationtofoodproducinganimals,bypharmaceuticallegislatibiologicalsandvaccinesQualification:Documentedtestingthatdemonstrateswithaprocesswillmeetitspre-determRefrigeratedvehicle:Roadtransportvehiclesuchasavan,truckothermostaticallycontrolledcargocompartmentismaintainedatathantheexternalambientconditions.Theenvironmtemperature-controlledortemperature-modified.StandardOperatingProcedure(SOP):AsecoveringthosefeaturesofoperadriveperformanceimprovementandimproveorganizatiTemperature-controlled:IncludesanyenvironmentinwhichthetecontrolledataleveldifferentfromthatofthealeveldifferentfromthatofthesurroundTimeandtemperaturesensitivepharmaceuticalproduct(TTSPP)productwhich,whennotstoredortransportedwithinpre-definedenvironmentalValidation:Documentedtestingperformedunderhighlycontrolledcondit1DefinitionfromWHO/QAS/08.252Rev1Sept2009.ProposalforrevisionofWHOgooddistributionpracticesforpharmaceuticalproducts-Draftforcomments.2DefinitionfromPDATech3PDATechnicalReportNo.39:GuidanceforTemperatureControlledMedicinalProducts:MaintainingtheQualityofTemperature-SensitiveMedicinalProductsthroughtheTransportationEnvironment,2007.ThistechnicalsupplementhasbeenwrittentoamplifReportSeriesNo.961,2011,Annex9:Modelguidanceforthestorageandtranspotemperature-sensitivepharmaceuticalproducts4.Itoutlinestheactionsthatneedtrefrigeratedvehiclesequippedwithactivetemperature-controlsystemswhichareusedTTSPPs.RelatedtopicsarecoveredinthefollowingTechni本补充技术文件是为了细化在WHO第961号技术报告附录9“时间温度敏感药品的贮运”中给lCheckingtheaccuracyoftemperaturecontrolandmInthecontextofthisseriusedtoestablishtha在本技术补充文件系列中，确认是指检查和测试用运行环境中适合其目的。此过程一般分为三个阶段，每个阶段必须在前一阶段全部完成后才能开始。Stage1(forequipment):Establishbylaspecificitemofequipmentperformsinaccisdesignqualification.WhilstdesignqualificationdeenvironmentbecausetheUR第一阶段（对设备而言在严格控制的条件下，采用实Stage1(forinstallatiohasbeenassembledinaandinstallationdrawings.Thisisinstal第1阶段（对安装的物体而言）：通过记录检查和测试情况，证明所安装的物体根据用户Stage2:Establishbyfurtherdocumentedtestingundercontr4/medicinedocs/documents/s18683en/s18683en.pdf5TheinstallationwilltypicallyincorporatecomponentsthathavStage3:Carryoutafinalstageofdocumentetheequipmentorinstallation,togetherwithallunderroutineoperatingconditions.Thisisperformancequali第3阶段：进行最后阶段的记录测试情况，以高度的保证来证明该设备或安装的物体，与其所有辅Whererefrigeratedvehiclesaredirectlyownedand/oropetheshipperhasadutytoensurethatthecarrier’svehiclesareapprop运输服务，则承运人有责任确保运货卡车经过适当的确认。确认程序应：Demonstratethatthetemperaturedistributionwithinthepayloadareaofthetemperatucompartmentismaintainedwithinth+8.0°C).Thequalificationproceduremustbeabletoasusedloadlayouts.Qualificationshouldbeduringnormaloperation,oDefinezoneswithintheveareasincloseproximitytocoolingcoilso定义卡车载货区域内的不能用来装载TTSPP的Demonstratethetimetakenfortemperaturestoeeventthatthetemperature-controllingunitfails.Similartestsshoudooropeningtimesthatwilloccurduringdeli证明温控单元失效时，温度超出指定最高或最低值DocumentthequalificationexerciseforinternalqualThisprocedureconstitutesatemperature-mappingexercisesimilartothatemployedfortemperature-controlledstoragefaciliti本程序包括一个温度分布研究，类似于对固定的温控存贮设施所使用Analternativeapproachistoperformaninitialfullqualitype,combinedwithaninstallationqualificatioCarryoutadditionalqualificationexerciseswheneversignificantmodificationsConsidertheneedforre-qualificationwhenevertemperaturemonitoringshowsunexplainedv如果对卡车进行了任何重大改装，则需要进行TheserequirementsaretoensurethatTTSPP’scanbesafelytranstemperatureprofiledefinedforeachproductauthoritiesandothTheobjectiveoftheTechnicalSuppleusedfortransportingTTSPP’sinawaywhichmeWhenarefrigeratedvehicleisrequiredperformanceanddetailedcharacteristicsareclearlprovideequipmentthatmatchestheneedsoftheoperdonecorrectlythereisahighprobability在采购冷冻卡车后，购买方必须尽其责任来确保提供符合运行环境所需的设备。只能使用根据行业usedtodemonstratethatthespecifiedperenvironment.Thisprocessshouldtakeplacebeforethe卡车一旦移交，则需要对其实际性能进行确QualificationproceduresManufacturingPractice).Thequalificatidocumentedevidencethattheequipment确认程序越来越被认为是CGMP的一种要求（现行InstallationQualifica安装确认（IQ）确认设备安装正确，符合其原始要求，确认具备其使用所需OperationalQualification(OQ)-verifiesthatproductqualityoperatecorrectlyoverallexpectedambient运行确认（OQ）确认相关设备在预期的环境中正PerformanceQualification(PQ)-verifiesthat性能确认（PQ）确认相关设备的部件在有效的及一段时间内重复运行状态下给维持和确保产品providesufficientinformationtoenableTheimportanceandregulatorysignificanceofverificatiabove.Thissectiondescribesthe上面已经列出了查核、验证和确认的重要性和2.1AssociatedmateriThefollowingarerequiredlAsufficientquantityofelectronicdatatogetherwiththenecessarydownlWherepossible,anATP-approvedtemperature-controllerecommendedguidelil可能时，应使用一个ATP批准的温控箱。药品的Thefollowingchecksshouldbecarriedouttoisaninspectionproceduredesignedtoensrequirementsshouldhavebeenstatedclear6See:/immunization_standards/vaccine_quality/pqs_catalogue/categorypage.aspx?id_cat=357PracticalGuidelines-ColdChainforMedicinesTheATPagreementstipulatesthatrefrigeratithepredictedambienttethetemperature-controlledcompartmentneedstobemainATP协议说明了冷冻设备应具备在+30.0°C环境下运行时，总体至少1.75倍的侵入隔热体热量的致冷能ATPregulationsstatethatforfrozentransportthethermalinsulationoftherefrigeratedshouldhaveaK-coefficientofheattransferof≤0.4W/m2K,ATP法规说对于冷冻运输，冷冻车厢的隔热能力热传导K系数应≤0.4W/m2K，对于低温≤0.7W/m2K。建议所选择的新卡车均具备热传导系数<0.4WcheckedaccordingtothRefrigerationequipmentmainte在确认开始之前，应根据维保程序对温控和隔热能力进行检Thefieldshipmenttestisdesignedtosatis运输现场测试是为了满足运行确认和性能确认阶段的要求。Thepurposeofthistestistodemonstratewhethertheproducttemperaturedistrtemperature-controlledcompartment,ismaintainedwithinthespecifiedlidesignedtocovercommonlyusedloadlayoutsatthe本测试的目的是证明温控车厢内产品温度分布能Ideallyatemperature-controlledchamberwouldbemonitoredenvironment.Adownsideofthisapproachisthedifficultaccuratelytopredicttherealworldcond最理想的是采用温控箱来进行测试，因为这样可在大部情况下其实没有大型的测试箱来使用。但是，在环境温度下的静态测试对于OQ可能仍是适当Whenconductingafieldshipmenttestunderrealoperatingcon在进行真实运营条件下运输现场测试时，有以下两种lUserealproducts:InthlUseexpiredordummyproducuserealproductsthahavingsimilarthermalp使用具有与要运输的实际产品相似热学性质、质量和包装的customsandsecurityrestricl海关清关：如果在不同国家之间运输超过了效期的产品Thevehicleshouldbepackedaccolayoutcommonlyused.Althoughthepreciseproductstransported,geoperatingrefrigeratedve卡车要根据生产商的指示进行覆盖，应能反Temperatureprobesshouldbefixedwithinthepatemperatureprobesshouldtemperaturemappingoftherefrigeratedcompartmentshouldbeexercise.Thishelpsensurethatvulner温度探头应固定在运输产品的包装内。最理想的是将温为了找出这些“最差情形”位置，在开始确认Iftherearemultipledrop-offpocompartmentmustremainattachedtothepa如果在运输路线中会有多个卸货点，则在定位温度探头时要考虑这个因素。至少有2个覆盖载AstatictemperaturemappingexerciseisrecommendedThiswillestablish"wo建议在实施动态确认测试前进行静态温度分布里的最热点和最冷点）这些位置可以在动态测试中作为EDLM定位点Asaminimum,aseriesoffourtestssha.Testperformancewithmaximumpayloadduringtb.Testperformancewithminimumpayloadduringc.Testperformancewithmaximumpayloaddurd.TestperformancewithminimumpayloadTheoperatormaywishtorepeatthesetestsforstatisticalconfirmation.See操作者可能会希望重复这些测试，以获得统计学确认。参见补充技术文件“运输路线概况确认”。typicalworst-casescenario.Preferablythetestsshouldscenariowouldusuallyincludemultipledrop-offswithassociateddooropenings,timebetweendrop-offsandovernightstopso在测试过程中，卡车要按照既定的操作方法运行常包括多点卸货，此时门会反复开关，在卸货点之间行程保持最短，在夜间停车时停止供电。Followingthecompletionofeachtest,Note:Warmseasonandcoldseasontestingavehiclecanonlybeprovisionallyqualifiedaftercompletionofthefirsttwotests.Thmustbecompletedsatisfactorilybeforethevchamberisavailable,thetwoseasontestscanexercise,ascantheeffectofmultipledrop-offsan注：上述热季与冷季测试是说卡车只有在季节到来时才能全面确认，这可能会需要6个月之久。这表有测试用箱，则2个季节测试可以在静态温度分布情形下进行模拟测试，但会对多点卸货情形和requiredtemperaturerange-0.5°Candthemaximumshou果要求温度为+2.0°C到+8.0°C，则所记录的最低温度不应低于+2.0°C-0.5°C，最高温度则不应超过2.4Temperature-contrAtemperature-controlfailuretestisrequiredto完整的OQ和PQ需要进行温控失效测试。该测试确定正常运行中断时导致关键失败的时Thepurposeofthetestistodemonstratethetimetakenfortemperaturmaximumorminimumintheeventthatthetemperabecarriedoutusingreal用模拟运输过程中真实产品来实施，因为产品可能会被损坏。因此，建议使用模拟装载。thatexpiredproductspoint.Alternatively,useasubstitutewithsimilarthermproducts.Thechoseinvolved,theproductemptyboxeswhichrepresenttypicalpackagingtype(s);th并进行完整的风险评估很重要的一点是过效期的产品不会在运输终点因为管理不当或盗窃而被上售。也可以使用与实际产品具有类似热学性质、质线。例如，如果涉及到穿越国界，所选产品型的空盒子。这种选择模拟了最差情形（最低）热学质量情形。在所有情形下，应使用如附录1，图AAgainthevehicleshouldbepackedaccordiextremesofheatandcoldlikel这时卡车还是要根据生产商的指示进行覆盖，反Temperatureprobesshouldbefixedwithinthethatthetemperatureoftheproductitselfisrecordedandnotthesurroundingair;airtemperaturewithintheloadcompartmentmayfluctuateoutsideofthedesi8WHOPQSspecificationsrequireEDLMdevicestohavetemperaturesremainunchan温度探头应固定在运输的产品包装内，以确保产品本身informativetoinclu理想的情况是温度探头应分布在整个装载货可能超出温度范围的点布置温度探头也可以提供有用信息。参Thetemperature-controlsystemshouldbesettocontroltheproducttempreconditionedtothedesignatedtempepointtemperature.Generally,themid-pointoftheproductswhilstallowingforsomevariationinthtostabilize.Thistimewillvaryfordifferenttypesofinsulatedshouldbesufficient.Anearestthedoorstoallowfortemperaturereadingstobetakenmonitoringtheprogre温控系统应进行设定，以控制产品温度在标准运行温度冷至指定温度，并经过检查确认系统已到达指定的温度在接近门的产品上附着一个手持式监测温度探头，这样Oncestabilizationisachieved,thetemperature-controlsystemwhenasingleproducttemperatureexceedsthedesignatedmaximumoperatingtemperatureclassification.Followingthedeterminetheoverallperf最高或最低要求运行温度时，则测试完成。在测试结束后，从数据记录仪上下载数据，确认总体性能。Thetimetakenfortheproducttemperatcontingencyproceduresandrequiredresponsetimesduringatrans在所测试单元的OQ上应记录超出最高或最低产品要求温度限度的时间长度。这些数据可以用于帮Comprehensivedocumentatio9See:EVM-SOP-E7-06:Respondingtoemergenciesduringvaccinetransportoperationslong-termperformanceofthevehbodiestodemonstratecompliancewith全面的文件记录是确认过程必不可少的部分，因Theinsulatedbodyandtheasshowatleastthefolqualificationforaparticularinsulatedbody.Alllistofanysubsequentmodifications.Recordstheserecordsshouldbemadeavailableforfuturequalifica行记录，同时还应保存所有后续的改造情况。要记Intheeventthatavhighlightingthereasons如果卡车无法满足确认要求，则要给出一份建Qualificationrecordsshouldbe确认记录应按常规要求保存，与建议和改造记录放在TheEDLMsusedforqualification,asw