PDA TR48濕熱滅菌系統(tǒng)：設(shè)計(jì)、調(diào)試、運(yùn)行、確認(rèn)和維護(hù)-2010（中英文）

況況14-11234wangjin10235wj19146wangjin102378 4 5 8 19 19 20 22 22 23 24 264.0ComprehensiveSterilizerS 29 314.1.1EquipmentLocatConsiderations設(shè)備位置安裝、 31 35 37 39 405.0EquipmentVerificat 42 435.1.1FactoryAcceptanceTesti 435.1.2SiteAcceptanceTe 47 475.2.1StaticEquipmentQualificationorIQ靜態(tài)設(shè)備確認(rèn)或者 485.2.2DynamicEquipmentQu 50 51 516.2ThermalMeasure 526.3SterilizationCycleOptimiza 52 71 72 72 73 74 76 78AppendixADesignConsider 78 93 98MoistHeatSterilizationisaprocessthatusesmoistheatasthelethalagenttorenderliquidandporous/hardgoodsitemstreeofviablemicroorganisms.Therearetwomaintypesofprocessesusedinmoistheatsterilization:saturatedsteamsterilizationandairoverpressuresterilization.Saturatedsteamsterilizationisusedprimarilyforporous,hardgoodsloads,whileairoverpressureisusedforliquidloads.濕熱滅菌是一種采用濕熱作為滅菌手段來(lái)殺滅液體和多孔/堅(jiān)硬物品中活微生物的工藝。濕熱滅菌采用兩種主要的工藝：飽和蒸汽以及空氣超壓（用空氣加壓條件下）滅菌。飽和蒸汽滅菌主要用于多孔/堅(jiān)硬物品的滅菌，而空氣超壓滅菌則用于液體產(chǎn)品。Sterilizersareusedtosterilizemanytypesofarticles,including:滅菌柜可以用來(lái)給很多類(lèi)型的物品滅菌，包括：.Porous/hardgoods,e.g.,equipment,tools,laboratoryglassware,productcomponents,packaging,ordevices多孔/堅(jiān)硬物品，如設(shè)備、工器具、實(shí)驗(yàn)室玻璃器皿、產(chǎn)品組件、包裝材料或器具.Productcomponentsthatarenotpartofaporousorliquidload,e.g.,vialsandsyringes不屬于多孔或液體裝載的產(chǎn)品部件，如小瓶和針筒清潔材料和產(chǎn)品中間體在最終容器中的產(chǎn)品（最終滅菌產(chǎn)品）熱穩(wěn)定性差的培養(yǎng)基.Biologicalsolutionsandproducts,eq生物溶液及產(chǎn)品、設(shè)備、工器具Airover-pressureapplicationsareusedtominimizedestructionordistortionofplasticcontainersorsyringescontainingliquids.空氣超壓的濕熱滅菌用于減少裝有液體的針筒或塑料容器的損壞或變形。Theprimaryobjectiveofthetaskforcewastodevelopascience-basedtechnicalreportonmoistheatsterilizersthatmaybeusedinallregulatoryenvironmentsandcanbeusedbyorganizationstodeveloptheirownprogramforequipmentqualification.Tothisend,prescriptionhasbeenavoided,andregion-specificregulatoryexpectationsarenotalwaysaddressed.Thisreportshouldbeconsideredaguideandisnotintendedtoestablishstandardsforsterilizationsystems.Itisintendedtobeasingle-sourceoverviewthatcomplementsexistingdocumentslistedinthereferencesection.Referencestoappropriateandup-to-datescientificpublications,internationalregulatorydocuments,journalarticles,technicalpapersandbooksareusedwheremoredetailandsupportivedatacanbefound.特別工作組的主要目標(biāo)是編寫(xiě)一個(gè)有科學(xué)依據(jù)的關(guān)于濕熱滅菌柜的報(bào)告，這個(gè)報(bào)告適用于所有法規(guī)環(huán)境，也可供組織開(kāi)發(fā)自己的程序用于設(shè)備確認(rèn)。為此，已經(jīng)避免了法規(guī)，到地區(qū)性法規(guī)的期望也不是一直考慮。本報(bào)告無(wú)意去建立滅菌系統(tǒng)的標(biāo)準(zhǔn)，而應(yīng)將它看作一個(gè)指南。它作為一個(gè)專(zhuān)題性的綜述，對(duì)所列參考文獻(xiàn)進(jìn)行補(bǔ)充。本文參考了有關(guān)最新的科技出版物、國(guó)際法規(guī)、科技文章、技術(shù)論文及書(shū)籍，在這些參考文獻(xiàn)中，可查得更多細(xì)節(jié)和支持性數(shù)據(jù)。ThetaskforcewascomposedofEuropeanandNorthAmericanindustryprofessionalstoensurethemethods,terminologyandpracticesofsterilizationsciencepresentedreflectsoundscienceandcanbeusedglobally.Thistechnicalreportwasdisseminatedindraftforpublicreviewandcomment.特別工作組由歐洲及北美專(zhuān)業(yè)人員組成，以確保滅菌科學(xué)的方法，術(shù)語(yǔ)及做法能夠完整地體現(xiàn)其科學(xué)性并在全球范圍內(nèi)使用。本技術(shù)報(bào)告的草案曾公布征求公眾的審核及建議。ThisTechnicalReportaddressesmoistheatsterilizersintendedforuseinthepharmaceutical,medicaldeviceandbiotechnologyindustries.Thistechnicalreportfocusesonthedesignandoperationofmoistheatsterilizers,fromthedevelopmentofUserRequirementsSpecifications(URS)throughequipmentqualification(InstallationQualification(IQ)/OperationalQualification(OQ))andculminatingwithongoingmaintenancerequirements.ThefocusofthisreportdoesnotincludePerformanceQualification(PQ).ThereaderisdirectedtoPDATechnicalReportNo.1:ValidationofMoistHeatSterilizationProcessesCycleDesign,Development,QualificationandOngoingControlfordiscussionofloadcycledevelopmentandprocessPerformanceQualification.(1)本技術(shù)報(bào)告專(zhuān)注于制藥、醫(yī)療器械及生物技術(shù)行業(yè)所采用的濕熱滅菌柜。它將重點(diǎn)放在濕熱滅菌柜的設(shè)計(jì)和運(yùn)行上，從用戶需求說(shuō)明（URS）的編寫(xiě)開(kāi)始，經(jīng)設(shè)備確認(rèn)（安裝確認(rèn)、運(yùn)行確認(rèn)）并以日常的維修要求告終。本報(bào)告沒(méi)有包括性能確認(rèn)（PQ）。讀者可查閱注射劑協(xié)會(huì)第一號(hào)技術(shù)報(bào)告（濕熱滅菌工藝的驗(yàn)證：滅菌程序的設(shè)計(jì)、開(kāi)發(fā)、確認(rèn)以及日常監(jiān)控）中關(guān)于裝載程序的開(kāi)發(fā)和工藝性能確認(rèn)的討論。(1)Thistechnicalreportaddresses:本技術(shù)報(bào)告主要討論如下內(nèi)容：設(shè)定用戶需求及技術(shù)標(biāo)準(zhǔn)設(shè)計(jì)確認(rèn)（DQ）設(shè)備及控制系統(tǒng)的設(shè)計(jì).FunctionalRequirementsforthemoistheatsterilizerandexpectationsforutilitiessupportingthesterilizer濕熱滅菌柜的功能要求以及滅菌柜對(duì)公用系統(tǒng)的要求.EquipmentOperation,includingcalibrationandmaintenance設(shè)備運(yùn)行，包括校準(zhǔn)及維護(hù).EquipmentQualification,whichmayincludeFactoryAcceptanceTesting(FAT),SiteAcceptanceTesting(SAT),andcommissioning設(shè)備確認(rèn)，包括工廠驗(yàn)收測(cè)試（FAT現(xiàn)場(chǎng)用戶驗(yàn)收以及調(diào)試持續(xù)控制的需求程序的開(kāi)發(fā)ThisTechnicalReportwillnotaddress,andconsidersoutsidethescopeofitscontent,steam-in-place,whichwillbecoveredinasubsequentPDAtechnicalreport.Severalaspectsdescribedwithinthisdocumentmaybeusefulforconsiderationwhendevelopingthesetypesofsystems;howeverthecontentoftheTechnicalReporthasbeenpreparedspecificallyformoistheatsterilizers.Alife-cycleapproachisrecommendedforthespecification,design,testingandqualificationofmoistheatsterilizersystems,andthereadershouldconsultTechnicalReportNo.1inthisregard.(1)本技術(shù)報(bào)告不闡述并考慮此范圍以外的內(nèi)容，在線滅菌（SIP這將包含在注射劑協(xié)會(huì)后續(xù)的技術(shù)報(bào)告中。當(dāng)開(kāi)發(fā)這類(lèi)系統(tǒng)時(shí)，本報(bào)告所闡述的一些方面可能有助于考慮；然而，本技術(shù)報(bào)告的重心還是在濕熱滅菌柜上。建議濕熱滅菌系統(tǒng)的標(biāo)準(zhǔn)、設(shè)計(jì)、測(cè)試及確認(rèn)采用生命周期的方式，在這方面，請(qǐng)讀者參考第一號(hào)技術(shù)報(bào)告。（1）Thesterilizerlifecycleapproachtovalidationactivities(seeFigure1.1-1)shouldincludeaChangeControlProgramandaQualityRiskManagement(QRM)Program.AChangeControlProgramwouldencompasstherequirementsfordocumentingandverifyingallchangesmadetothesterilizerthatwouldaffectitsvalidatedstate.TheQRMprogramwouldprovidetheend-userwiththetoolsrequiredtomakeintelligentrisk-baseddecisionswithrespecttothedesignofthesterilizer,thesterilizationprocessitself,andtheoperationofthesterilizer.QRMmaybeusedduringqualificationandvalidationtoprioritizeanddeveloptestrequirementsandacceptancecriteria,andmayalsobeusedinconjunctionwithChangeControltodeterminetheappropriaterequalificationintervalforthesterilizer.PDATechnicalReportNo.44:QualityRiskManagementforAsepticProcessesoutlinesanapproachthatcanbeadopted(2)滅菌柜生命周期的驗(yàn)證活動(dòng)（見(jiàn)圖1.1-1）應(yīng)包括變更控制計(jì)劃以及質(zhì)量風(fēng)險(xiǎn)管理（QRM）計(jì)劃。變更控制計(jì)劃包括記錄并檢查對(duì)滅菌柜所作的所有變更，而這類(lèi)變更將影響滅菌柜已驗(yàn)證的狀態(tài)。質(zhì)量風(fēng)險(xiǎn)管理（QRM）計(jì)劃給最終用戶提供了一個(gè)必要的工具，以致用戶能夠就滅菌柜的設(shè)計(jì)，滅菌工藝本身以及滅菌柜的運(yùn)行做出明智的基于風(fēng)險(xiǎn)的各種決定。在確認(rèn)和驗(yàn)證過(guò)程中，質(zhì)量風(fēng)險(xiǎn)管理（QRM）可用于優(yōu)化和制訂測(cè)試要求及可接受標(biāo)準(zhǔn)，還可以結(jié)合變更控制用以決定滅菌柜的再確認(rèn)周期。注射劑協(xié)會(huì)第四十四號(hào)技術(shù)報(bào)告：無(wú)菌工藝的質(zhì)量風(fēng)險(xiǎn)管理概述了一種可供Pointstoconsiderforequipmentqualificationactivitiesareprovidedinthisreport.However,whentoconducttheseactivitiesandthepersonnelwhowillperformthemisdeterminedbytheuser.Activityoverlaporgapsshouldbeavoidedwherepossible.Personnelperformingtheseactivitiesshouldhavethesuitableskillsandqualificationscommensuratetotheirassignedresponsibilities.本報(bào)告中闡述了設(shè)備確認(rèn)活動(dòng)需考慮的問(wèn)題。然而，何時(shí)，由誰(shuí)來(lái)完成這些活動(dòng)，應(yīng)由用戶確定?？赡艿脑挘瑧?yīng)避免這類(lèi)活動(dòng)的重復(fù)或脫節(jié)。從事這些活動(dòng)的人員應(yīng)有適當(dāng)?shù)募寄芎唾Y質(zhì)，以履行他們的職責(zé)。PerformanceQualificationAndContinuingLifecycleManagement(Technical性能確認(rèn)和持續(xù)的生命周期管理（技術(shù)報(bào)告1）EquipmentQualification(IQ/OQPerformanceQualificationAndContinuingLifecycleManagement(Technical性能確認(rèn)和持續(xù)的生命周期管理（技術(shù)報(bào)告1）EquipmentQualification(IQ/OQ)(Section5.2)設(shè)備確認(rèn)（IQ/OQ）(5.2節(jié))CommissioningandQualification(Section5.0)調(diào)試和確認(rèn)（5.0節(jié)）CycleDevelopment(Section6.0)程序開(kāi)發(fā)（6.0節(jié)）SupplierControlSystemBenchTesting供應(yīng)商控制系統(tǒng)后備測(cè)試SiteAcceptanceTesting(Section5.1.2)現(xiàn)場(chǎng)驗(yàn)收測(cè)試（5.1.2節(jié)）FactoryAcceptanceTesting(Section5.1.1)工廠驗(yàn)收測(cè)試（5.1.1節(jié)）Figure1.1-1ValidationLife-CycleActivities圖1.1-1驗(yàn)證生命周期的活動(dòng)UserRequirementSpecification(Section4.1)用戶需求說(shuō)明（4.1節(jié)）RiskAnalysis風(fēng)險(xiǎn)分析FunctionalRequirementSpecification(Section4.3)功能需求(4.3節(jié))DetailedDesignSpecification(Section4.4)詳細(xì)設(shè)計(jì)說(shuō)明（4.4節(jié)）SterilizerConstructed,TestedandDocumentationProvided滅菌器建造，測(cè)試和提供文件CurrentFDA.ICH.ISOandotherregulatorydefinitionsareusedexceptwhenmoreclarityisaddedbytheTaskForce.Insomeinstancestwodefinitionsusedincurrentguidancesareprovidedwherebothareconsideredapplicable.Regulatoryguidelinesofferotherdefinitionsthatmaybeconsidered.除了那些需要特別工作組添加更多說(shuō)明的，本報(bào)告采用了當(dāng)前FDA、ICH、ISO和其它法規(guī)中的定義。有些情況下，提供當(dāng)前指南中使用的兩種定義，認(rèn)為這兩種均適用。也可考慮法規(guī)提供的其它定義。Variationsintheusageofsometermsmaydifferfromcompanytocompany,andsomemaybesubjecttochangeinthefuture.However,thetermsusedmustbeclearlydefinedandwellunderstoodwithinthecompanyandclearlydefinedininternalStandardOperatingProcedures(SOPs),standards,andinregulatoryfilings.Forthepurposesofthistechnicalreport,thefollowingdefinitionsareused.在術(shù)語(yǔ)的采用上，不同企業(yè)之間存在差異，有些定義在將來(lái)可能產(chǎn)生變化。然而，在企業(yè)內(nèi)部，必須對(duì)術(shù)語(yǔ)明確定義并有統(tǒng)一的理解，并在內(nèi)部的標(biāo)準(zhǔn)操作規(guī)程（SOP）、標(biāo)準(zhǔn)及提交給監(jiān)管機(jī)構(gòu)的文件中應(yīng)有明確的定義。本技術(shù)報(bào)告收載的術(shù)語(yǔ)如下：AcceptanceCriteria可接受標(biāo)準(zhǔn)Thepre-definedspecifications,standardsorrangesthatmustbemetunderstatedtestconditions.在規(guī)定的測(cè)試條件下必須滿足的預(yù)先設(shè)定的要求，標(biāo)準(zhǔn)或范圍。AirDetector空氣檢測(cè)器Aninstrumentthatmaybefittedtoasaturatedsteamsterilizerthatdetectsthepresenceofgasotherthansteaminthechamber.可安裝于飽和蒸汽滅菌器上用以檢測(cè)滅菌器腔室中空氣（不是蒸汽）的儀器。AirOverpressure(AOP)SterilizationProcess空氣超壓滅菌程序Amoistheatsterilizationprocessthatoperatesatacontrolledpressuregreaterthansaturatedsteampressureandtypicallyusescompressedairtobringthechambertothedesiredpressure.指在大于飽和蒸汽壓的控制壓力下運(yùn)行的濕熱滅菌程序，通常用壓縮空氣使滅菌腔室達(dá)到所需的壓力。AirRemovalTest空氣去除試驗(yàn)Atestusedtoevaluateairremovalandsteampenetrationinanemptysterilizerthatisusedforporous/hardgoodsloadsterilization(e.g.,Bowie-DickTest,DARTTM,LantorCube,Browns’Test).用于評(píng)估滅菌器空載條件下空氣去除和蒸汽穿透的一種試驗(yàn)（例如，Bowie-Dick測(cè)試法，DARTTM，LantorCube，Browns測(cè)試法此類(lèi)滅菌柜用于多孔/堅(jiān)硬物品類(lèi)裝載的滅菌。Calibration校準(zhǔn)Thedemonstrationthataninstrumentordeviceproducesresultswithinspecifiedlimitswhencomparedtothoseproducedbyareferencestandardorastandardthattraceabletonationalorinternationalstandards,overanappropriaterangeofmeasurements(calibrationrange).在適當(dāng)?shù)亩攘糠秶ㄐ?zhǔn)范圍）以內(nèi)，采用與相關(guān)標(biāo)準(zhǔn)或可溯源至國(guó)內(nèi)或國(guó)際的標(biāo)準(zhǔn)進(jìn)行比較，以證明一項(xiàng)儀器或設(shè)備所得結(jié)果符合規(guī)定限度標(biāo)準(zhǔn)的活動(dòng)。CalibrationTolerance校準(zhǔn)公差I(lǐng)nmetrology,themaximumpermissiblerangearoundaspecifiedvaluethatappliestoaproperlyfunctioningmeasuringinstrument.[Synonym:calibrationuncertainty,error]在計(jì)量學(xué)中，適當(dāng)?shù)墓δ苄詼y(cè)試儀表給定值周?chē)试S的最大范圍。[同義詞：校準(zhǔn)誤差，誤差]Chamber腔室Theprimarycomponentofasterilizer,containstheitemstobesterilized.Thechamberisapressureratedvessel.滅菌器用以放置被滅菌物品的主要組成部分。滅菌器腔室是一個(gè)有額定壓力的容器。ChamberLeakTest腔室檢漏測(cè)試Atestconductedtoevaluatepossibleairinfiltrationtothechamberundervacuum.[Synonym:VacuumLeaktest,AirLeakTest]一項(xiàng)評(píng)估在真空條件下空氣可能滲入腔室的測(cè)試。[同義詞：真空檢漏試驗(yàn)，空氣滲漏試驗(yàn)]Commissioning調(diào)試Aprescribednumberofactivitiesdesignedtotakeequipmentandsystemsfromastatic,substantiallycompletestatetoanoperablestate.(3)經(jīng)設(shè)計(jì)使設(shè)備和系統(tǒng)從一個(gè)基本完成的靜止?fàn)顟B(tài)成為一個(gè)可運(yùn)行狀態(tài)所需的一系列活動(dòng)。（3）ComputerizedSystem計(jì)算機(jī)化的系統(tǒng)Collectiveapplicationsoftware,dataandhardwareplatformthatprovidesfunctionality,controlanddatatoauserorothersystem.指向用戶或其它系統(tǒng)提供功能、控制和數(shù)據(jù)的應(yīng)用軟件、數(shù)據(jù)及硬件平臺(tái)的集成系統(tǒng)。ControlValve控制閥Adevicethatmodulatestheflowoffluid(e.g.gas,steam,water)inaconduitinresponsetoasignalfromaprocessmeasurementcontrolsystem.(4)DiscreteValve控制總閥Adevicedesignedforon/offoperation;fullyopenedorfullyclosed.一個(gè)設(shè)計(jì)用于運(yùn)行啟動(dòng)/關(guān)閉的裝置：有全開(kāi)或全關(guān)二種狀態(tài)。ProportionalControlValve比例控制閥Adevicethatisdesignedforprecisepositioningandcontinuousmovement,typicallyinresponsetoavaryinganalogsignal.[Synonym:ModulatingValve]一個(gè)設(shè)計(jì)通常用于響應(yīng)一個(gè)可變類(lèi)似信號(hào)，可精確定位并可連續(xù)調(diào)節(jié)的裝置。[同義詞：調(diào)幅閥]Cool-DownPhase冷卻階段Thephaseofasterilizationcyclethatoccursaftercompletionoftheexposurephase.[Synonym:post-conditioningphase,slowexhaustphase,dryingphase,equalizationphase]指滅菌周期中滅菌階段完成后的階段。[同義詞：滅菌后的階段，緩慢排放階段，干燥階段，平衡階段]CyclePhases程序階段Adiscreetseriesofsterilizerprocesssteps(suchas,heat-up,exposureandcooldown)performedsequentiallythatrepresentacompletesterilizationcycle.[Synonym:CycleSteps]滅菌柜滅菌過(guò)程中依次完成代表滅菌周期的各個(gè)步驟（如加熱、滅菌和冷卻）。[同義詞：程序步驟]Decommissioning退役Aplannedandorderlyremovalofafacility,operationorsystemfromuse.將一個(gè)設(shè)施/設(shè)備或系統(tǒng)按計(jì)劃和程序移除出使用的狀態(tài)。DesignQualification(DQ)設(shè)計(jì)確認(rèn)Documentedverificationthattheproposeddesignofthefacilities,equipment,orsystemissuitablefortheintendedpurpose.(5)確認(rèn)所建議的設(shè)施、設(shè)備或系統(tǒng)適用于預(yù)期目的并有文件和記錄的一系列活動(dòng)。DrynessFraction蒸汽干度Anabsolutemeasureofactuallatentheatofasampleofsteamrelativetothetheoreticallatentheatofsaturatedsteam.一個(gè)蒸汽樣品中，實(shí)際潛熱與飽和蒸汽理論潛熱之比（絕對(duì)度量）。DrynessValue干度值A(chǔ)dimensionlessquantity,derivedtoapproximatetheDrynessFractionthatisameasureoftheamountofliquid-phasewatercarriedbysteam.近似蒸汽干度且系無(wú)因次的量值，它是蒸汽所帶液相水量的測(cè)試值。Eductor噴射泵AdevicethatproducesvacuumbymeansoftheVenturieffect.[Syn.:Aspirator,ejectorpump]一種采用文丘里管效應(yīng)來(lái)獲得真空的裝置。[同義詞：抽氣泵，噴射器]ElectronicRecord電子記錄ArecordusedforGMPpurposesorforregulatorysubmissionthatisstoredelectronicallyforthepurposesofreproduction,retrievalorarchival.一種用于GMP目的或遞交法規(guī)監(jiān)管機(jī)構(gòu)以電子方式貯存可供復(fù)制、恢復(fù)或歸檔的記錄。EquilibrationTime平衡時(shí)間Theperiodthatelapsesbetweentheattainmentoftheminimumexposuretemperatureatthereferencemeasurementpoint(typicallythedrain)andtheattainmentofthesterilizationtemperatureatallpointswithintheload.指從滅菌柜參照測(cè)試點(diǎn)（通常是排水口）達(dá)到最低滅菌溫度開(kāi)始，至裝載所有測(cè)溫點(diǎn)均達(dá)到滅菌溫度之間所需的時(shí)間。ExposurePhase滅菌保溫階段Thephaseofthesterilizationcycleinwhichtheappropriateparametersaremaintainedwithindefinedrangesforthetime(exposuretimeordwellperiod)andtemperaturedeterminedtobenecessarytoachievethedesiredlethality.[Synonym:dwellperiod]系指滅菌周期中，為獲得設(shè)定殺滅效果，保持設(shè)定滅菌溫度的持續(xù)時(shí)間（保溫時(shí)間或保溫階段）。[同義詞：保溫期]F-Value(lethalityFactor)F值(殺滅因素)Ameasurementofsterilizationeffectiveness.F(Tref,Z)isthecalculatedequivalentlethality(usingaspecifiedzvalue),intermsofminutesatareferencetemperature(Tref)，deliveredbyasterilizationcycletoanitem.系滅菌效力的度量值。F(Tref，Z)是在規(guī)定的Z值下，一個(gè)滅菌程序賦予一被滅菌物品在參照溫度T℃下的等效滅菌時(shí)間。FphysicalAtermusedtodescribethedeliveredlethalitycalculatedbasedonthephysicalparametersofthecycle.TheFphysical-valueistheintegrationoftheintegrationoflethalrate(L)overtime.Thelethalrateiscalculatedforareferencetemperature(Tref)andz-valueusingtheequation:L=10(T-Tref)/z系按物理參數(shù)計(jì)算，用以描述滅菌周期賦于裝載殺滅力的術(shù)語(yǔ)。它是滅菌率L對(duì)時(shí)間的積分值。當(dāng)z值及參照溫度為T(mén)ref時(shí)，滅菌率L用公式：L=10(T-Tref)/z計(jì)算。AtermusedwhenthespecificreferenceconditionsofTref=121.1℃andz=10℃areusedtocalculatetheequivalentlethality.Forexample,whenthez-valueoftheBIis10℃acyclewithanForF(T=121℃,Z=10℃),equalto8minutesisequivalent(intermsofdeliveredlethality)toasquarewavecycleof8minutesat121.1℃.Asquarewavecyclethatprovidedanexposureof25.9minutesat116℃wouldalsoyieldanF0of8minutes.F0值（標(biāo)準(zhǔn)滅菌時(shí)間是指參照溫度Tref=121.1℃,Z取10℃時(shí)計(jì)算的等效滅菌時(shí)間。例如，當(dāng)生物指示劑的z取10℃,F（T=121.1℃,z=10℃)賦予產(chǎn)品8一個(gè)116℃滅菌25.9分鐘方形滅菌波是等效的，F(xiàn)0均為8分鐘。注意：參照溫度121.1℃在數(shù)學(xué)上近似250°F，為簡(jiǎn)化計(jì)算，本文此后將采用121℃。FactoryAcceptanceTest(FAT)工廠驗(yàn)收測(cè)試Atesttypicallyconductedbythesterilizermanufacturerafterthesystemhasbeenassembledandbeforethesystemisshippedtotheinstallationsite.在系統(tǒng)裝配并在發(fā)往安裝地點(diǎn)前通常由滅菌柜制造廠進(jìn)行的測(cè)試。GoodEngineeringPractices(GEP)良好工程管理規(guī)范Documentedprovenandacceptedengineeringmethodsandpracticesthatareappliedthroughouttheprojectlife-cycletodeliversolutionsthatarecosteffective,arecompliantwithregulationsandmeettherequirementsoftheuser.在整個(gè)項(xiàng)目生命周期的全過(guò)程中，為提供經(jīng)濟(jì)、符合法規(guī)要求和用戶需求的各種解決方案而采用的有文件證明的公認(rèn)的設(shè)計(jì)方法和實(shí)踐。GravityDisplacementProcess重力置換程序Asterilizationbasedontheprinciplethatairwithinthechamberiscoolerandheavierthansteam,andwillsinktothebottomofthechamber.以冷空氣比進(jìn)入腔室的蒸汽重而沉降在腔室底部的原理而運(yùn)行的滅菌工藝。HeatTransfer傳熱Energythatistransferredasaresultofatemperaturedifferencebetweenanobjectanditssurroundings.指因一個(gè)物體與其環(huán)境之間存在溫差所致的能量轉(zhuǎn)移。HeatPenetration熱穿透Heatpenetrationtestingusestemperaturemeasurementobtainedinsidealoaditemtoevaluatetheamountofenergyhasbeentransferredtothematerialsthataretobesterilized.為評(píng)價(jià)已傳給被滅菌品能量而進(jìn)行的裝載測(cè)溫試驗(yàn)。Heat-UpPhase加熱階段/升溫階段Thephaseofthesterilizationcyclethatoccurspriortotheexposurephase.系指滅菌程序達(dá)到滅菌溫度的前一個(gè)階段。InstallationQualification安裝確認(rèn)（IQ）Documentedverificationthattheequipmentorsystems,asinstalledormodified,complywiththeapproveddesign,themanufacturer’srecommendations.and/oruserrequirements.(5)指檢查、確認(rèn)已安裝或改造的系統(tǒng)或設(shè)備符合經(jīng)批準(zhǔn)的設(shè)計(jì)、供貨商的建議及/或用戶需求的有文件證明的相關(guān)活動(dòng)。LeakRate泄漏率Ameasuredquantityofairthatentersthesterilizerchamberduringaspecifiedlime.在一個(gè)規(guī)定的時(shí)間內(nèi)，測(cè)得進(jìn)入滅菌柜腔室空氣的量。LiquidLoad液體裝載Aloadconsistingofcontainersofaqueoussolutions.Thesterilizationofthecombinercontendisachievedthroughtransferofenergythroughthecontainerintotheaqueousliquid.指由裝藥液容器組成的裝載。能量透過(guò)容器傳給藥液，以實(shí)現(xiàn)產(chǎn)品的滅菌。LoadZone裝載區(qū)Areawithinthesterilizationchamberwherematerialstobesterilizedmaybeplaced.指滅菌柜腔室內(nèi)可放置被滅菌物品的區(qū)域。MaximumLoad最大裝載Themaximumquantityormassofitemspermittedinasterilizerload.一個(gè)滅菌柜內(nèi)允許的最大裝載量。MinimumLoad最小裝載Theminimumquantityormassofitemspermitteddinasterilizerload.Theminimumloadmayconsistofitem(s)thatarethegreatestheat-upand/orairremovalchallenge.一個(gè)滅菌柜內(nèi)允許的最小裝載量。最小裝載有可能面臨去除空氣（最長(zhǎng)升溫階段）的挑戰(zhàn)。MoistHeat濕熱Steam,steam-airmixtures,andsuperheatedwaterusedforsterilization.指用于滅菌的蒸汽、蒸汽-空氣混合物以及過(guò)熱水。MoistHeatSterilizer濕熱滅菌柜Equipment(e.g.,apressure-ratedvesselandassociatedcontrols)usedtoachievesterilizationthroughtime,temperatureandpressure.[Synonym:Autoclave,SteamSterilizer]通過(guò)溫度、壓力和時(shí)間來(lái)實(shí)現(xiàn)滅菌的設(shè)備（如帶相關(guān)控制的壓力容器）。[同義詞：高壓滅菌器，蒸汽滅菌柜]Non-condensableGases不凝性氣體Airandothergasthatwillnotcondensetoliquidstate,therebynotreleasinglatentheatundertheconditionsofsterilization.系指在滅菌條件下不會(huì)冷凝，因此不會(huì)釋放潛熱的空氣和其他氣體。OperatingParameters運(yùn)行參數(shù)Controlledand/ormeasuredvalues(e.g.,time,temperature,pressure)thatcollectivelydefineeachphaseofasterilizationcycle(e.g.heat-up.exposure,andcooldown).[Synonym:processparameter]用來(lái)定義每一個(gè)滅菌階段（如加熱、滅菌和冷卻）且需要加以收集和測(cè)試的參數(shù)（如時(shí)間、溫度CriticalParameters關(guān)鍵參數(shù)Valuesthatarccontrolledand/ormeasuredandarclinkedtosafetyandefficacyofaproduct.需要控制和/或測(cè)量且與產(chǎn)品的安全和功效相關(guān)的參數(shù)。關(guān)鍵參數(shù)不合格時(shí)，被滅菌產(chǎn)品不得放行。KeyParameters重要參數(shù)Valuesthatarecontrolledand/ormeasuredandareusedtoassuretheon-going"staleofcontrolofsterilizationruns.需控制/和測(cè)試以保證滅菌在“受控狀態(tài)”正常運(yùn)行的參數(shù)。OperationalQualification運(yùn)行確認(rèn)(OQ)Adocumenteddemonstrationthatequipment,facilitiesandoperationsfunctionasspecifiedinthedesignqualification.Documentedverificationthattheequipmentorsystems,asinstalledormodified,performasintendedthroughouttheanticipatedoperatingranges.(S)證明設(shè)備、設(shè)施及運(yùn)行符合設(shè)計(jì)確認(rèn)所規(guī)定的要求并有文件和記錄的活動(dòng)。證明所安裝或改造的設(shè)備、系統(tǒng)在整個(gè)運(yùn)行的范圍內(nèi)符合預(yù)期要求并有文件及記錄的活動(dòng)。(5)PerformanceQualification性能確認(rèn)(PQ)Documentedverificationthattheequipmentandancillarysystems,asconnectedtogether,canperformeffectivelyandreproduciblybasedontheapprovedprocessmethodandspecifications.(5)[Synonym：ProcessPerformanceQualification]證明一個(gè)已連接好的設(shè)備及輔助系統(tǒng)能根據(jù)批準(zhǔn)的工藝及技術(shù)要求有效并重現(xiàn)性運(yùn)行且有文件和記錄的相關(guān)活動(dòng)。(5)[同義詞：工藝性能確認(rèn)]PipingandInstrumentationDiagram(P&ID)管道儀表流程圖Aschematicdiagramthatshowstherelationalarrangementofpiping,components,instruments,andequipmentconnectionsofthesystem.Italsoillustratesthecontrolandfunctionalrelationship.指顯示系統(tǒng)設(shè)備連接、管道、部件、儀表相互關(guān)系并在圖中說(shuō)明控制和功能的相關(guān)性的示意圖。Porous/HardGoodsLoads（P/HG）多孔/堅(jiān)硬裝載Aporous/hardgoodsloadconsistsofitemsinwhichthebioburdenisinactivatedthroughdirectcontactwithsaturatedsteam.Porous/hardgoodsloaditemsinclude:itemslikelytocontainairlike:filters,stopper's,tubing(hoses),garments,cleaningequipment,ormachinechangepares.系指通過(guò)與飽和蒸汽直接接觸而殺滅其中微生物的被滅菌物品。多孔/堅(jiān)硬裝載包括：很可能包含空氣的裝載：過(guò)濾器、膠塞、軟管、拖把、工作服、清潔器具或設(shè)備的更換部件。Pre-vacuumProcess預(yù)真空程序Asterilizationprocessinwhichairisremovedfromthechamberusingavacuumpumporothermechanicalsystembeforetheexposurephasebegins.ThismethodisparticularlysuitedtoIoaditemsthatcantrapsuchtubing,filtersandfillingmachineassemblies.一個(gè)需要用真空泵或其它機(jī)械系統(tǒng)去除空氣后才開(kāi)始滅菌的滅菌程序。此方法尤其適用于夾帶空氣的物品，如軟管、過(guò)濾器和灌裝機(jī)的部件。ProgrammableLogicController(PLC)可編程序邏輯控制器Adigitalelectronicapparatuswithaprogrammablememorytorscoringinstructionstoimplementspecificfunctions,suchaslogic,sequencing,timing,countingandarithmetic,tocontrolmachinesandprocesses.指一個(gè)數(shù)字式帶可編程存儲(chǔ)器的電器裝置，此裝置儲(chǔ)存各種指令，以執(zhí)行如邏輯、程序、定時(shí)、計(jì)數(shù)和自動(dòng)化等操作。Proportional,Integral,Derivative(PID)比例-積分-微分控制，簡(jiǎn)稱(chēng)PID控制Controlactioninwhichtheoutputisproportionaltoalinearcombinationoftheinput,thetimeintegralofinput,andthetimerate-of-changeofinput.(6)輸出正比于時(shí)間，輸入積分時(shí)間以及輸入走時(shí)變化時(shí)間線性組合的控制行為。(6)QualitySystem質(zhì)量系統(tǒng)Formalizedbusinesspracticesthatdefinemanagementresponsibilitiesfororganizationalstructure,processes,procedures,andresourcesneededtofulfillproduce/servicerequirements,customersatisfaction,andcontinualimprovement(7)系指正式的經(jīng)營(yíng)方式，它確定滿足產(chǎn)品/服務(wù)要求、讓消費(fèi)者滿意及持續(xù)改進(jìn)所需組織機(jī)構(gòu)、過(guò)程、程序及資源的管理者責(zé)任。(7)ResistanceTemperatureDetector(s)(RTDs)電阻溫度檢測(cè)器Resistancetemperaturedetectoraretemperaturesensorsinwhichtheelectricalincreaseswiththeelementincreaseswithincreasesintemperature.Thiselectricalresistanceisthentranslatedintoatemperaturevalue(expressedasaresistanceversustemperaturecurve).電阻溫度檢測(cè)器系測(cè)溫探頭，其中的電阻值隨著溫度升高而增加，隨后按電阻-溫度曲線的方式轉(zhuǎn)化為溫度值。SiteAcceptanceTesting現(xiàn)場(chǎng)驗(yàn)收試驗(yàn)TheSATisaseriesofteststhatareperformedaspartofcommissioningaftertheunithasbeeninstalledinthefinallocation.在設(shè)備最終地點(diǎn)安裝后完成的作為試車(chē)組成部分一系列試驗(yàn)。SaturatedSteam飽和蒸汽Steamthatisatatemperatureandpressurechatcorrespondstothevaporizationcurveofwater.Itisinastateofequilibriumbetweenbeingaliquidandagaswithnoentrainedliquidwater.[Synonym:DrySaturatedSteam]指處于水蒸發(fā)曲線對(duì)應(yīng)點(diǎn)壓力及溫度的蒸汽。它是蒸汽中不夾帶液態(tài)水，處于汽液平衡狀態(tài)的蒸Steam蒸汽PlantSteam設(shè)備蒸汽Steamofundefinedchemicalorbiologicalqualityproducedfromaboiler，usuallycontainingboileradditives,withoutfurthertreatment.[Synonym:FactorySteam,HouseSteam.IndustrialSteam]由鍋爐生產(chǎn)通常含有鍋爐添加物不作進(jìn)一步處理且無(wú)化學(xué)及生物學(xué)質(zhì)量要求的蒸汽。[同義詞：工廠蒸汽，民用蒸汽，工業(yè)蒸汽]ProcessSteam工藝蒸汽Processsteamissimilartoplantsteam,exceptthesteamisgeneratedusingacontrolledfeedwatersourcetowhichnovolatileadditives(aminesorhydrazines)havebeenintroduced.Processsteammaybeappropriateformoistheatsterilizationofliquidloadswherethecontainersfilledandsealedpriortosterilization.工藝蒸汽與工業(yè)蒸汽相類(lèi)似，不同點(diǎn)在于工藝蒸汽采用受控的水源中無(wú)揮發(fā)性填加物（胺或肼）。工藝蒸汽可適用于容器灌封后液體產(chǎn)品的濕熱滅菌。PureSteam純蒸汽/清潔蒸汽CollectedcondensatethatcomplieswiththeCompendialrequirementstorWaterforInjection(WFI).(Synonym:CleanSteam)其冷凝水符合美國(guó)藥典“注射用水”（WFI）專(zhuān)論要求的蒸汽。[清潔蒸汽]Steam-AirMixtureprocess（SAM）蒸汽-空氣混合氣體的滅菌程序Asterilizationprocesstypicallyusedtorliquidloadsinwhichtheheatingmediumusedtoheattheloadisinamixtureofairandsteam.Thisadditionofairresultsinanairoverpressurecondition.一個(gè)以蒸汽和空氣混合物為加熱介質(zhì)的滅菌程序，它通常用于液體滅菌。引入空氣的結(jié)果是造成空氣加壓的條件。Sterilization滅菌Aprocessusedcoreaderanitemfreeofviableorganismswithaspecifiedprobability.指用以使一個(gè)產(chǎn)品達(dá)到規(guī)定微生物存活概率的工藝過(guò)程。SterilizationCycle滅菌周期Asequenceofdefinedoperatingparameters(e.g.,time,temperatureandpressure)andconditionsrequiredtorenderanitemsterile.指使物體成為無(wú)菌的一系列運(yùn)行參數(shù)（例如時(shí)間、溫度、壓力）和條件所組成的程序。SterilizationRun滅菌運(yùn)行Theexecutionofasterilizationcycle.指執(zhí)行滅菌周期Temperature溫度Temperatureisthemeasureofthermalenergy.溫度是熱能的度量。TemperatureDistribution熱分布Temperaturemeasurementoftheheatingmediumacrossthechamberloadzone.指對(duì)腔室中整個(gè)裝載區(qū)域加熱介質(zhì)溫度的測(cè)試。TemperatureProbe/Sensor溫度探頭/傳感器Agenerictermusedtodescribeanytypeoftemperaturemeasuringdevicethatworksthroughcontactwiththematerialoratmospheretobemeasured.[Synonym:LoadProbe,heatpenetrationprobe,temperaturedistributionprobe,drainprobe]一個(gè)描述任何一種通過(guò)與物料或大氣接觸測(cè)試溫度裝置的通俗術(shù)語(yǔ)。[同義詞：裝載探頭，熱穿透探頭，溫度分布探頭，排放口探頭]TerminalSterilization最終滅菌Aprocesswherebyproduceissterilizedwithinitssterilebarriersystem.(8)系指產(chǎn)品在其無(wú)菌密封系統(tǒng)中的滅菌。(8)Validation驗(yàn)證Adocumentedprogramthatprovidesahighdegreeofassurancethataspecificprocess,method,orsystemwillconsistentlyproducearesultmeetingpredeterminedacceptancecriteria.(5)Theproofofvalidationisobtainedthroughrationalexperimentaldesignandtheevaluationofdata,preferablybeginningfromtheprocessdevelopmentphaseandcontinuingthroughthecommercialproductionphase.一個(gè)能夠可靠地保證特殊的工藝、方法或系統(tǒng)能始終如一地獲得預(yù)期結(jié)果的有文件和記錄證明的程序。（5）驗(yàn)證的證據(jù)應(yīng)通過(guò)驗(yàn)證方案的合理設(shè)計(jì)并對(duì)數(shù)據(jù)資料進(jìn)行評(píng)估獲得，這些數(shù)據(jù)資料最好始于工藝的開(kāi)發(fā)階段，直至商業(yè)化生產(chǎn)。SterilizerSpecification滅菌柜規(guī)格說(shuō)明Documentsthatdefinesterilizersystemattributesandhowtheyshouldbemet.詳細(xì)闡述滅菌柜系統(tǒng)的屬性及如何實(shí)現(xiàn)這些屬性的文件。DesignSpecification(DS)設(shè)計(jì)說(shuō)明：Asetofspecificationsandinformationrelatedtotheinstallationfeatures(includingequipment,hardwareandsoftware)ofthesystemthatwillensuretherealizationoftheuserrequirements.(SynonymDetailedDesignSpecification(DD5))保證實(shí)現(xiàn)設(shè)施要求（包括設(shè)備、硬件及軟件）所需的一整套標(biāo)準(zhǔn)及信息。[同義詞：詳細(xì)設(shè)計(jì)標(biāo)準(zhǔn)/DDS]FunctionalSpecification(FRS)功能說(shuō)明：Adescriptionoffunctionalattributesandoperationalcharacteristicsofthesystemthatwillensurefulfillmentoftheuserrequirements.(Synonym;FunctionalRequirementSpecification,FunctionalDesignSpecification)為保證實(shí)現(xiàn)用戶需求而對(duì)系統(tǒng)功能及運(yùn)行特性的描述。[同義詞：功能要求標(biāo)準(zhǔn)，功能設(shè)計(jì)標(biāo)準(zhǔn)]用戶需求說(shuō)明UserRequirementSpecification(URS)：Adescriptionoffeaturesandperformancerequirementsofasystemthatwillfulfilltheneedsoftheenduser.為確保滿足最終用戶需求而對(duì)一個(gè)系統(tǒng)特點(diǎn)及功能要求的描述SuperheatedSteam過(guò)熱蒸汽Steamwhosetemperature,atagivenpressure,ishigherthanchatindicatedbytheequilibrationcurveforthevaporizationofwater.在一定壓力下，其溫度高于水蒸發(fā)曲線所指示溫度的蒸汽。SuperheatedWater過(guò)熱水Waterinaliquidphaseatatemperatureabove100°Crequiringoverpressuretomaintainthisstate.指在100℃以上并需一定壓力才能保持液態(tài)的水。SuperheatedWaterProcess過(guò)熱水程序Asterilizationprocessinwhichtheheatingmediumissuperheatedwaterthatiscontinuouslycirculatedwithairoverpressure.Thisprocessrequiresairoverpressuretokeepthewaterinaliquidstate.[Synonyms:watercascade,watersprayprocess,waterimmersionprocess,watersubmersionprocess,rainingwaterprocess,steam-air-waterprocess]在空氣加壓條件下，以不斷循環(huán)的過(guò)熱水為滅菌介質(zhì)的滅菌工藝。此工藝需要空氣超壓，以保持藝]Sterilizerdesignisprimarilybaseduponthetypesofcyclesthesterilizerisintendedtoperform.Mostmoistheatsterilizationcyclesrelyondirectcontactwithsaturatedsteam,whichiswatervaporinequilibriumwithliquidw