洁净区空气和污染控制翻译课件

Airandcontaminationcontrol

空气和污染控制Airandcontaminationcontrol

1Airandcontaminationcontrol

空气和污染控制Withoutairwecannotbreathe,soaslongaswerequirepersonneltooperateourprocessesweneedanairsupply.没有空气我们无法呼吸，所以只要我们需要人员操作我们的工艺，我们就需要空气供应。Evenincleanruralareasairiscontaminatedwithabout108particlesof0.5µmandgreaterperm3,manyofthesewillbemicroorganismsdependingonthenatureoftheareaandtheseasonoftheyear–soairisa

contaminationproblem即使在干净的农村地区，空气也被大约108颗每平方米0.5微米甚至更大的颗粒污染，其中许多是微生物，这取决于该地区的性质和一年中的季节-因此空气是一个污染问题Howeverinthepharmaceuticalindustryairflowistheanswertomanycontaminationproblems然而，在制药工业中，空气流动是许多污染问题的答案Sowearegoingtodiscussthisdualrelationshipofthepharmaceuticalindustrywithair因此，我们将讨论制药业与空气的这种双重关系Airandcontaminationcontrol

2Airasacontaminationsource

空气作为污染源Microorganismsdonotgrowandincreaseinnumbersinair微生物不会在空气中生长和增加MostmicroorganismsfindithardtosurviveinairbecausetheenvironmentissodesiccatingandbecauseoftheexposuretoUVradiation.大多数微生物发现它难以在空气中存活，因为环境是如此干燥并且因为暴露于紫外线辐射Survivaloftendependsonbeingcarriedon“rafts”ofphysicalmatter,suchasskinflakes.生存通常取决于携带物理物质的“筏”，例如皮屑。TypicalairbornemicroorganismsaresporesofthegenusBacillusandrelatedgenera,andMicrococcusorStaphylococcus.典型的空气传播微生物是芽孢杆菌属和相关属的孢子，以及微球菌或葡萄球菌。Airasacontaminationsource

3Controllingairbornecontaminationincleanrooms控制洁净室中的空气污染Therearefourprincipleapplyingtocontrolofair-bornemicroorganismsincleanrooms.

控制洁净室中的空气传播微生物有四个原则。Filtration过滤Dilution稀释DirectionalAirFlow定向气流AirMovement空气运动IwilladdresseachoneseparatelyControllingairbornecontamina4FiltrationFiltrationremovesmicroorganisms:过滤去除微生物：HEPA(highefficiencyparticulateair)filtersremoveuptoabout99.997%ofparticlesfromairHEPA（高效微粒空气）过滤器可从空气中去除高达约99.997％的颗粒HEPAFiltersareprotectedfromblockagebypre-filterswhichremoveuptoabout90%ofparticlesfromairHEPA过滤器通过预过滤器防止堵塞，预过滤器可从空气中去除多达约90％的颗粒Thereforeifaircontainsabout3x108particlesperm3,andyouhaveonepre-filterandoneHEPAFilter:因此，如果空气中每立方米包含约3x108个颗粒，并且您有一个预过滤器和一个HEPA过滤器：Pre-filterleavesabout3x107perm3asachallengetotheHEPAfilter预过滤器每立方米约3x107，作为对HEPA过滤器的挑战TheterminalHEPAFilterleavesabout103perm3.终端HEPA过滤器每立方米留下约103个。InEUGMPthisiswithinthelimitsforGradeAandB“atrest”(Annex1.4)在欧盟GMP中，这是A级和B级“静态”的限制（附件1.4）FiltrationFiltrationremovesm5Filtration过滤Infactmostpharmaceuticalairhandlingsystemrecirculateupto80%oftheairsuppliedtocleanrooms.实际上，大多数制药空气处理系统再循环高达80％的空气供应给洁净室。ThereforetheinitialchallengetotheHEPAFiltersisprobablyonlyabout106particlesperm3.因此，对HEPA过滤器的最初挑战可能是每立方米仅约106个颗粒。Soweprobablygetnomorethan3x102particlesperm3suppliedtopharmaceuticalcleanrooms因此，我们可能每立方米提供不超过3x102颗粒供应给制药洁净室ThisisevenfurtherwithinthelimitsofGradeAandGradeB“atrest”inEUGMP(Annex1.4)这进一步在欧盟GMP中的A级和B级“静态”范围内（附件1.4）Filtration过滤Infactmostpharm6Filtration过滤AirmustbepassedthroughHEPAfilters空气必须通过HEPA过滤器Thesewillhaveacertified“efficiencyrating”whichappliestothemedium这些将具有适用于介质的经认证的“效率等级”BPLusesH14filtersBPL使用H14过滤器Oninstallationandatintervalitisnecessarytotesttheintegrityofthewholeassemblyoffilterandductwork在安装和间隔时，有必要测试整个过滤器和管道系统组件的完整性Filtration过滤Airmustbepassed7Filtration过滤StructuralSlab结构板（建筑）HEPAFilter高效过滤器Inletduct入口管道Falseceiling天花板Integritytestprobe完整性测试探针Gaskets垫圈Seals密封件TypicalHEPAfilterinstallation典型的HEPA过滤器安装Filtration过滤StructuralSlab结构板8Filtration过滤BecausepotentialleakageisnotconfinedtothefiltermediathereisarequirementtoperformanInSituFilterINTEGRITYTest由于潜在泄漏不仅限于过滤介质，因此需要执行原位过滤器完整性测试ThisiscommonlycalledtheDOPtestafterDi-octylphthallateoneofthefirstsubstancesusedasanaerosolchallengeforthistest这通常被称为DOP测试之后的二辛基邻苯二甲酸酯作为该测试的气溶胶挑战的第一种物质之一Thestandardisthatthetolerableleakageofanaerosolchallengeshallbenotmorethan0.01%-thisisNOTthereciprocaloftheefficiency标准是气溶胶挑战的可容忍泄漏不应超过0.01％-这不是效率的倒数Filtration过滤Becausepotential9Dilution稀释Particlesbuildupinenclosedspaceswherethereisnoventilation–thatiswhyinthepasttherewassomuchtuberculosisinwinterintheslumsofnorthernEurope颗粒在没有通风的封闭空间中积聚-这就是为什么过去在欧洲北部贫民窟冬季有如此多的结核病Ventilationistheprocessbywhichanyparticlesgeneratedincleanrooms(inadditiontothosewhichpassthefilters)arecarriedawayforanyremainingintheroomtobedilutedwithnew“clean”air通风是将洁净室中产生的任何颗粒（除了通过过滤器的颗粒）带走的过程，以便用新的“清洁”空气稀释房间内剩余的任何颗粒。Theminimumventilationrateexpectedinpharmaceuticalcleanroomsis20airchangesperhour(themodernrequirementuptotwiceasmanyasthis,andupto75forachangingroom)–theairinacleanroomisreplacedatleastevery3minutes.Anofficemighthave2-3air-changesperhour.制药洁净室预计的最低通风率为每小时20次换气（现代要求高达此数量的两倍，更换房间高达75次）-洁净室内的空气至少每隔3分钟更换一次。办公室每小时可能有2-3次换气。Dilution稀释Particlesbuildupi10Dilution稀释Ventilationismeasuredasairchangesperhour通气量以每小时换气量来衡量Thisisnota“real”measure,itisacalculatedmeasurebasedonairvelocitymeasurement这不是“真实”测量，它是基于空气速度测量的计算测量Theairvelocityismeasuredclosetoitspointofentryintotheclean-roomusingananemometerorabalometer使用风速计或压力计测量空气速度接近其进入洁净室的点Thevelocityismeasuredasunitsoflengthdividedbyunitsoftime(ftperminute,metresperhouretc)速度以长度单位除以时间单位（英尺/分钟，米/小时等）来衡量Thevelocityismultipliedbytheareaoftheentryductsmeasuredinunitsofarea(squarefeetorm2etc)givingafigurewhichnowinunitsofvolumedividedbyunitsoftimeisanexpressionofhowmuchairissuppliedperunittime速度乘以以面积（平方英尺或平方英尺等）为单位测量的进入管道的面积，给出一个数字，现在以体积单位除以时间单位表示每单位时间供应多少空气Ifthisfigureisthendividedbythevolumeofthecleanroommeasuredin(say)m3orft3yougetthenumberofairchangesperhour如果这个数字除以洁净室的体积（例如）m3或ft3，你会得到每小时的换气次数Dilution稀释Ventilationismeasu11Dilution稀释Cleanroomshavea‘clean-up’time.洁净室有一个“清理”时间Thisthetimetakenforaroomtoreturntoasetlevelofparticlesintheairafterithasbeenusedforanactivity.Thisisrequiredtotakeplacewithin20minutesoftheroomlastbeingused.这是房间用于活动后返回空气中颗粒水平所需的时间。这需要在最后一次使用房间的20分钟内进行Thisisan‘optional’testforcleanrooms,althoughoneoftenundertakenfornewfacilities(inISO14644).这是洁净室的“可选”测试，尽管通常用于新设施（ISO14644）。Dilution稀释Cleanroomshavea‘c12Directionalairflow定向气流Firstofallimagineyouhavearoomfullof“clean”air首先想象你有一个充满“干净”空气的房间Thenimaginethatyouhavefreeaccesstothisroomfromasurroundingareacontainingnormalenvironmentalair然后想象您可以从包含正常环境空气的周边区域自由进入这个房间Whathappensnext?接下来发生什么？Wemakesurethatthe“dirty”airdoesnotenterthecleanroombyensuringthatthereisalwaysaflowofairinanoutwarddirection我们确保“脏”空气不会进入洁净室，确保始终有向外流动的空气流Directionalairflow定向气流Firsto13Directionalairflow定向气流Thewayinwhichthe“dirty”airispreventedfromenteringthecleanroomisbyensuringaveryhighrateofairsupplytothecleanroomthuskeepingitatahigherpressurethanitssurroundings防止“脏”空气进入洁净室的方式是确保洁净室的空气供应速度非常快，从而使其保持在比周围环境更高的压力下Ifthereiscontactwith“outside”air,anymixingofthetwotypesofairtakesplaceoutsidethecleanroombecausethedirectionofairflowisfromthecleantothedirtyarea如果与“外部”空气接触，则两种类型空气的混合发生在洁净室外，因为气流的方向是从清洁区域到脏区域Thisdirectionalairflowismeasuredandmonitoredthroughpressuredifferentials–airwillalwaysmovefromanareawhereitisatahighpressuretoonewherethereisalowpressure–it’saLawofPhysics通过压差测量和监测这种定向气流-空气总是从高压区域移动到低压区域-这是一个物理定律Particlesandmicroorganismscannot“swimupstream”againstadirectionalairflow颗粒和微生物不能对着定向气流“游向上游”Directionalairflow定向气流Theway14Directionalairflow定向气流Airlocksareplacedovertheaccessandexitdoorsofcleanroomstomakesurethatthehighpressurewithinthecleanroomisnotlosttooeasily空气锁放置在洁净室的入口和出口门上方，以确保洁净室内的高压不会太容易丢失EUGMPAnnex1statesthatairlocks:欧盟GMP附件1规定空气锁：Bothair-lockdoorsshouldnotopensimultaneously(Annex1.52)两个气闸门不应同时打开（附件1.52）Aninterlockingsystemoravisualand/oraudiblewarningsystemshouldbeoperatedtopreventtheopeningofmorethanonedooratatime(Annex1.52)应操作联锁系统或视觉和/或声音警告系统，以防止一次打开多个门（附件1.52）Changingroomsshouldbedesignedasairlocks(Annex1.51)更衣室应设计为气闸（附件1.51）Directionalairflow定向气流Airloc15Directionalairflow定向气流ΔPΔPΔPThisiscalledapressuredifferential“cascade”这被称为压差“级联”Outwardairflowsfromareaswhichrequireseriouslevelsofprotectionfromcontaminationtolesscriticalareashelpstomaintaintheintegrityoftheareasofthecleanerenvironments从需要严重保护的区域向外流动的空气不受污染到不太关键的区域有助于保持清洁环境区域的完整性Directionalairflow定向气流ΔPΔPΔPT16DirectionalairflowFillingRoomPersonnelEntry(Filling)MaterialsEntryPersonnelAccess(Support)FilledProduct“Hatch”TunnelPersonnelExit(Filling)ΔPΔPΔPΔPΔPΔPΔPΔPAirpressurecascade:Annex1.31:…Indicatorsofpressuredifferenceshouldbefittedbetweenareaswherethesedifferencesareimportant.ThesepressuredifferencesshouldberecordedregularlyorotherwisedocumentedDirectionalairflowFillingRoo17Airmovement空气运动Inasepticmanufacture,wearetryingtoavoidcontamination–particularlycontaminationofproductandequipment.在无菌生产中，我们正在努力避免污染-特别是产品和设备的污染。Forproductorequipmenttobecontaminatedfromair-bornemicroorganisms,theyhavetosettleoutoftheairontowhateveryouaretryingtoprotect.对于被空气传播的微生物污染的产品或设备，它们必须从空气中沉淀到您想要保护的任何物质上。Itisanimportantprincipletounderstandthataslongasparticlesandmicroorganismsstaysuspendedintheairtheyarenotreallyaproblem–itisonlywhentheysettleoutthattheybecomeanactualcauseofcontamination了解一个重要的原则是，只要颗粒和微生物悬浮在空气中，它们就不是真正的问题-只有当他们落下安家时，他们才会成为污染的真正原因Airmovement空气运动Inasepticman18Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果：Activeairsamples:活动空气样本Mediancount0cfu/m3计数0

cfu/m3Settleplates沉降碟Mediancount0cfu/4hours计数0

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese19Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果Activeairsamples:活动空气样本Mediancount3cfu/m3计数3

cfu/m3Settleplates沉降碟Mediancount0cfu/4hours计数0

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese20Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果Activeairsamples:活动空气样本Mediancount3cfu/m3计数3

cfu/m3Settleplates沉降碟Mediancount3cfu/4hours计数3

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese21Airmovement空气运动Inasepticmanufacture,wearetryingtoavoidcontamination–particularlycontaminationofproductandequipment.在无菌生产中，我们正在努力避免污染-特别是产品和设备的污染Forproductorequipmenttobecontaminatedfromair-bornemicroorganisms,theyhavetosettleoutoftheairontowhateveryouaretryingtoprotect.对于被空气传播的微生物污染的产品或设备，它们必须从空气中沉淀到您想要保护的任何物质上。Airmovement空气运动Inasepticman22Airmovement空气运动Weusetheprincipleofairmovementintwobeneficialwaysincleanrooms:我们在洁净室中以两种有益的方式使用空气流动原理：Turbulentairflow湍流气流Unidirectionalairflow(UDAF)单向气流（UDAF）Airmovement空气运动Weusethepri23Turbulentflowcleanrooms湍流洁净室MostEuropeancleanroomsareoftheturbulentairflowtype大多数欧洲洁净室属于湍流气流类型Airisdriveninthroughgrillesandductsatceilingheightandremovedthroughlowlevelducts,andwhileitisintheroomitsinitialsupplyvelocityissufficienttokeepitinconstantturbulence–thereforeparticlesandmicroorganismsdonotsettleout空气通过格栅和管道在天花板高度驱动，并通过低水平管道移除，当它在室内时，其初始供应速度足以使其保持恒定的湍流-因此颗粒和微生物不会沉淀出来Ofcoursethisisan“ideal”andyoumaygetdeadairbeneathtablesetc,当然这是一个“理想”，你可能会在桌子下面等空气，Weneedtoknowaboutthesedeadareas,andifwecan’tengineerthemout,wehavetobecarefularoundthembecausethat’swherecontaminationmayoccur(andconsidertargetingmonitoringattheselocations)我们需要了解这些死区，如果我们无法解决这些问题，我们必须小心谨慎，因为这可能会发生污染（并考虑在这些位置进行监控）Turbulentflowcleanrooms湍流洁净室24Unidirectionalairflow单向气流IntheUSAtherearesomeUnidirectionalAirFlowCleanRoomsbutinEuropeweusuallyonlyseeUnidirectionalAirFlowprovidinglocalisedprotectionoverbenchesandinB-F-Sintheairshoweratpointoffill.在美国有一些单向气流洁净室，但在欧洲，我们通常只能看到单向气流在长凳上提供局部保护，在填充点的空气淋浴中提供B-F-S。Theideaofunidirectionalairflowisthatifairissuppliedataveryhighvelocitythroughspeciallydesignedgrillesitwillflowforquiteadistanceinstraightlines单向气流的想法是，如果通过特殊设计的格栅以非常高的速度供应空气，它将以直线流动相当远的距离Unidirectionalairflowblowsawayallthecontaminationandparticlesthatcomeintoitspath单向气流吹走了进入其路径的所有污染物和颗粒Unidirectionalairflowiscapableofsweepingupmicroorganismsthataresittingonsurfacesandtherebycleaningthesurfacesup单向气流能够清扫坐在表面上的微生物，从而清洁表面Unidirectionalairflow单向气流Int25Airstudies气流流形Whenthepressurecascadeisbalancedinafacilitytheoutwardairflow(althoughindicatedbypositiveΔP’s)shouldbeconfirmedbysmoketestsandrecordedonvideo.ItisimportantthatthesmokeisvisibleandcanberecordedonVCRorDVD.当压力级联在设施中平衡时，外部气流（尽管由正ΔP表示）应通过烟雾测试确认并记录在视频中。重要的是烟雾是可见的并且可以记录在VCR或DVD上。Thesmoketestistheonlyeffectivewayofdeterminingifairflowisturbulentorunidirectionalandalsoitsdirectioninrelationtoprotectingtheproductwhilepersonnelareoperationalintheareas烟雾测试是确定气流是湍流还是单向的唯一有效方法，也是确保人员在该区域运行时保护产品的方向These‘airflowvisualisations’areexpectedforasepticfilling.这些“气流可视化”预计用于无菌灌装。Airstudies气流流形Whenthepress26Puttingthistogether...Re-circulatingairTerminalHEPAFilter高效Extractduct回风管道UDAF单向流Puttingthistogether...Re-cir27Puttingittogether...ΔPΔPΔPΔPLAFCleanroomMaybeaChangeRoomMaybeaMaterialsEntryMaybeaCorridorwithViewingWindowsintotheCleanRoom也许一个带有观察窗进入洁净室的走廊TerminalHEPAfilterinceilingExtractductatlowlevelPressuredifferentialsThesearetypically10-15Pascals(EUGMPstates12.5astherecommendedtarget)压差这些通常为10-15帕斯卡（欧盟GMP规定12.5为推荐目标）Puttingittogether...ΔPΔPΔPΔP28Summary概要Airisasourceofmicrobiologicalcontaminationinasepticmanufacturingfacilities空气是无菌生产设施中微生物污染的来源Itisalsoameansofcontrollingcontamination它也是控制污染的一种手段Butitsvelocityisimportanttoensureitmovesinthecorrectdirectionandthemeansoffiltrationmustensurethatthemainsupplyofairtopharmaceuticalcleanroomshasaverylowparticlecountandbioburden但其速度对于确保其向正确方向移动非常重要，过滤方式必须确保制药洁净室的主要空气供应具有非常低的颗粒数和生物负载Summary概要Airisasourceofmi29Airandcontaminationcontrol

空气和污染控制Airandcontaminationcontrol

30Airandcontaminationcontrol

空气和污染控制Withoutairwecannotbreathe,soaslongaswerequirepersonneltooperateourprocessesweneedanairsupply.没有空气我们无法呼吸，所以只要我们需要人员操作我们的工艺，我们就需要空气供应。Evenincleanruralareasairiscontaminatedwithabout108particlesof0.5µmandgreaterperm3,manyofthesewillbemicroorganismsdependingonthenatureoftheareaandtheseasonoftheyear–soairisa

contaminationproblem即使在干净的农村地区，空气也被大约108颗每平方米0.5微米甚至更大的颗粒污染，其中许多是微生物，这取决于该地区的性质和一年中的季节-因此空气是一个污染问题Howeverinthepharmaceuticalindustryairflowistheanswertomanycontaminationproblems然而，在制药工业中，空气流动是许多污染问题的答案Sowearegoingtodiscussthisdualrelationshipofthepharmaceuticalindustrywithair因此，我们将讨论制药业与空气的这种双重关系Airandcontaminationcontrol

31Airasacontaminationsource

空气作为污染源Microorganismsdonotgrowandincreaseinnumbersinair微生物不会在空气中生长和增加MostmicroorganismsfindithardtosurviveinairbecausetheenvironmentissodesiccatingandbecauseoftheexposuretoUVradiation.大多数微生物发现它难以在空气中存活，因为环境是如此干燥并且因为暴露于紫外线辐射Survivaloftendependsonbeingcarriedon“rafts”ofphysicalmatter,suchasskinflakes.生存通常取决于携带物理物质的“筏”，例如皮屑。TypicalairbornemicroorganismsaresporesofthegenusBacillusandrelatedgenera,andMicrococcusorStaphylococcus.典型的空气传播微生物是芽孢杆菌属和相关属的孢子，以及微球菌或葡萄球菌。Airasacontaminationsource

32Controllingairbornecontaminationincleanrooms控制洁净室中的空气污染Therearefourprincipleapplyingtocontrolofair-bornemicroorganismsincleanrooms.

控制洁净室中的空气传播微生物有四个原则。Filtration过滤Dilution稀释DirectionalAirFlow定向气流AirMovement空气运动IwilladdresseachoneseparatelyControllingairbornecontamina33FiltrationFiltrationremovesmicroorganisms:过滤去除微生物：HEPA(highefficiencyparticulateair)filtersremoveuptoabout99.997%ofparticlesfromairHEPA（高效微粒空气）过滤器可从空气中去除高达约99.997％的颗粒HEPAFiltersareprotectedfromblockagebypre-filterswhichremoveuptoabout90%ofparticlesfromairHEPA过滤器通过预过滤器防止堵塞，预过滤器可从空气中去除多达约90％的颗粒Thereforeifaircontainsabout3x108particlesperm3,andyouhaveonepre-filterandoneHEPAFilter:因此，如果空气中每立方米包含约3x108个颗粒，并且您有一个预过滤器和一个HEPA过滤器：Pre-filterleavesabout3x107perm3asachallengetotheHEPAfilter预过滤器每立方米约3x107，作为对HEPA过滤器的挑战TheterminalHEPAFilterleavesabout103perm3.终端HEPA过滤器每立方米留下约103个。InEUGMPthisiswithinthelimitsforGradeAandB“atrest”(Annex1.4)在欧盟GMP中，这是A级和B级“静态”的限制（附件1.4）FiltrationFiltrationremovesm34Filtration过滤Infactmostpharmaceuticalairhandlingsystemrecirculateupto80%oftheairsuppliedtocleanrooms.实际上，大多数制药空气处理系统再循环高达80％的空气供应给洁净室。ThereforetheinitialchallengetotheHEPAFiltersisprobablyonlyabout106particlesperm3.因此，对HEPA过滤器的最初挑战可能是每立方米仅约106个颗粒。Soweprobablygetnomorethan3x102particlesperm3suppliedtopharmaceuticalcleanrooms因此，我们可能每立方米提供不超过3x102颗粒供应给制药洁净室ThisisevenfurtherwithinthelimitsofGradeAandGradeB“atrest”inEUGMP(Annex1.4)这进一步在欧盟GMP中的A级和B级“静态”范围内（附件1.4）Filtration过滤Infactmostpharm35Filtration过滤AirmustbepassedthroughHEPAfilters空气必须通过HEPA过滤器Thesewillhaveacertified“efficiencyrating”whichappliestothemedium这些将具有适用于介质的经认证的“效率等级”BPLusesH14filtersBPL使用H14过滤器Oninstallationandatintervalitisnecessarytotesttheintegrityofthewholeassemblyoffilterandductwork在安装和间隔时，有必要测试整个过滤器和管道系统组件的完整性Filtration过滤Airmustbepassed36Filtration过滤StructuralSlab结构板（建筑）HEPAFilter高效过滤器Inletduct入口管道Falseceiling天花板Integritytestprobe完整性测试探针Gaskets垫圈Seals密封件TypicalHEPAfilterinstallation典型的HEPA过滤器安装Filtration过滤StructuralSlab结构板37Filtration过滤BecausepotentialleakageisnotconfinedtothefiltermediathereisarequirementtoperformanInSituFilterINTEGRITYTest由于潜在泄漏不仅限于过滤介质，因此需要执行原位过滤器完整性测试ThisiscommonlycalledtheDOPtestafterDi-octylphthallateoneofthefirstsubstancesusedasanaerosolchallengeforthistest这通常被称为DOP测试之后的二辛基邻苯二甲酸酯作为该测试的气溶胶挑战的第一种物质之一Thestandardisthatthetolerableleakageofanaerosolchallengeshallbenotmorethan0.01%-thisisNOTthereciprocaloftheefficiency标准是气溶胶挑战的可容忍泄漏不应超过0.01％-这不是效率的倒数Filtration过滤Becausepotential38Dilution稀释Particlesbuildupinenclosedspaceswherethereisnoventilation–thatiswhyinthepasttherewassomuchtuberculosisinwinterintheslumsofnorthernEurope颗粒在没有通风的封闭空间中积聚-这就是为什么过去在欧洲北部贫民窟冬季有如此多的结核病Ventilationistheprocessbywhichanyparticlesgeneratedincleanrooms(inadditiontothosewhichpassthefilters)arecarriedawayforanyremainingintheroomtobedilutedwithnew“clean”air通风是将洁净室中产生的任何颗粒（除了通过过滤器的颗粒）带走的过程，以便用新的“清洁”空气稀释房间内剩余的任何颗粒。Theminimumventilationrateexpectedinpharmaceuticalcleanroomsis20airchangesperhour(themodernrequirementuptotwiceasmanyasthis,andupto75forachangingroom)–theairinacleanroomisreplacedatleastevery3minutes.Anofficemighthave2-3air-changesperhour.制药洁净室预计的最低通风率为每小时20次换气（现代要求高达此数量的两倍，更换房间高达75次）-洁净室内的空气至少每隔3分钟更换一次。办公室每小时可能有2-3次换气。Dilution稀释Particlesbuildupi39Dilution稀释Ventilationismeasuredasairchangesperhour通气量以每小时换气量来衡量Thisisnota“real”measure,itisacalculatedmeasurebasedonairvelocitymeasurement这不是“真实”测量，它是基于空气速度测量的计算测量Theairvelocityismeasuredclosetoitspointofentryintotheclean-roomusingananemometerorabalometer使用风速计或压力计测量空气速度接近其进入洁净室的点Thevelocityismeasuredasunitsoflengthdividedbyunitsoftime(ftperminute,metresperhouretc)速度以长度单位除以时间单位（英尺/分钟，米/小时等）来衡量Thevelocityismultipliedbytheareaoftheentryductsmeasuredinunitsofarea(squarefeetorm2etc)givingafigurewhichnowinunitsofvolumedividedbyunitsoftimeisanexpressionofhowmuchairissuppliedperunittime速度乘以以面积（平方英尺或平方英尺等）为单位测量的进入管道的面积，给出一个数字，现在以体积单位除以时间单位表示每单位时间供应多少空气Ifthisfigureisthendividedbythevolumeofthecleanroommeasuredin(say)m3orft3yougetthenumberofairchangesperhour如果这个数字除以洁净室的体积（例如）m3或ft3，你会得到每小时的换气次数Dilution稀释Ventilationismeasu40Dilution稀释Cleanroomshavea‘clean-up’time.洁净室有一个“清理”时间Thisthetimetakenforaroomtoreturntoasetlevelofparticlesintheairafterithasbeenusedforanactivity.Thisisrequiredtotakeplacewithin20minutesoftheroomlastbeingused.这是房间用于活动后返回空气中颗粒水平所需的时间。这需要在最后一次使用房间的20分钟内进行Thisisan‘optional’testforcleanrooms,althoughoneoftenundertakenfornewfacilities(inISO14644).这是洁净室的“可选”测试，尽管通常用于新设施（ISO14644）。Dilution稀释Cleanroomshavea‘c41Directionalairflow定向气流Firstofallimagineyouhavearoomfullof“clean”air首先想象你有一个充满“干净”空气的房间Thenimaginethatyouhavefreeaccesstothisroomfromasurroundingareacontainingnormalenvironmentalair然后想象您可以从包含正常环境空气的周边区域自由进入这个房间Whathappensnext?接下来发生什么？Wemakesurethatthe“dirty”airdoesnotenterthecleanroombyensuringthatthereisalwaysaflowofairinanoutwarddirection我们确保“脏”空气不会进入洁净室，确保始终有向外流动的空气流Directionalairflow定向气流Firsto42Directionalairflow定向气流Thewayinwhichthe“dirty”airispreventedfromenteringthecleanroomisbyensuringaveryhighrateofairsupplytothecleanroomthuskeepingitatahigherpressurethanitssurroundings防止“脏”空气进入洁净室的方式是确保洁净室的空气供应速度非常快，从而使其保持在比周围环境更高的压力下Ifthereiscontactwith“outside”air,anymixingofthetwotypesofairtakesplaceoutsidethecleanroombecausethedirectionofairflowisfromthecleantothedirtyarea如果与“外部”空气接触，则两种类型空气的混合发生在洁净室外，因为气流的方向是从清洁区域到脏区域Thisdirectionalairflowismeasuredandmonitoredthroughpressuredifferentials–airwillalwaysmovefromanareawhereitisatahighpressuretoonewherethereisalowpressure–it’saLawofPhysics通过压差测量和监测这种定向气流-空气总是从高压区域移动到低压区域-这是一个物理定律Particlesandmicroorganismscannot“swimupstream”againstadirectionalairflow颗粒和微生物不能对着定向气流“游向上游”Directionalairflow定向气流Theway43Directionalairflow定向气流Airlocksareplacedovertheaccessandexitdoorsofcleanroomstomakesurethatthehighpressurewithinthecleanroomisnotlosttooeasily空气锁放置在洁净室的入口和出口门上方，以确保洁净室内的高压不会太容易丢失EUGMPAnnex1statesthatairlocks:欧盟GMP附件1规定空气锁：Bothair-lockdoorsshouldnotopensimultaneously(Annex1.52)两个气闸门不应同时打开（附件1.52）Aninterlockingsystemoravisualand/oraudiblewarningsystemshouldbeoperatedtopreventtheopeningofmorethanonedooratatime(Annex1.52)应操作联锁系统或视觉和/或声音警告系统，以防止一次打开多个门（附件1.52）Changingroomsshouldbedesignedasairlocks(Annex1.51)更衣室应设计为气闸（附件1.51）Directionalairflow定向气流Airloc44Directionalairflow定向气流ΔPΔPΔPThisiscalledapressuredifferential“cascade”这被称为压差“级联”Outwardairflowsfromareaswhichrequireseriouslevelsofprotectionfromcontaminationtolesscriticalareashelpstomaintaintheintegrityoftheareasofthecleanerenvironments从需要严重保护的区域向外流动的空气不受污染到不太关键的区域有助于保持清洁环境区域的完整性Directionalairflow定向气流ΔPΔPΔPT45DirectionalairflowFillingRoomPersonnelEntry(Filling)MaterialsEntryPersonnelAccess(Support)FilledProduct“Hatch”TunnelPersonnelExit(Filling)ΔPΔPΔPΔPΔPΔPΔPΔPAirpressurecascade:Annex1.31:…Indicatorsofpressuredifferenceshouldbefittedbetweenareaswherethesedifferencesareimportant.ThesepressuredifferencesshouldberecordedregularlyorotherwisedocumentedDirectionalairflowFillingRoo46Airmovement空气运动Inasepticmanufacture,wearetryingtoavoidcontamination–particularlycontaminationofproductandequipment.在无菌生产中，我们正在努力避免污染-特别是产品和设备的污染。Forproductorequipmenttobecontaminatedfromair-bornemicroorganisms,theyhavetosettleoutoftheairontowhateveryouaretryingtoprotect.对于被空气传播的微生物污染的产品或设备，它们必须从空气中沉淀到您想要保护的任何物质上。Itisanimportantprincipletounderstandthataslongasparticlesandmicroorganismsstaysuspendedintheairtheyarenotreallyaproblem–itisonlywhentheysettleoutthattheybecomeanactualcauseofcontamination了解一个重要的原则是，只要颗粒和微生物悬浮在空气中，它们就不是真正的问题-只有当他们落下安家时，他们才会成为污染的真正原因Airmovement空气运动Inasepticman47Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果：Activeairsamples:活动空气样本Mediancount0cfu/m3计数0

cfu/m3Settleplates沉降碟Mediancount0cfu/4hours计数0

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese48Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果Activeairsamples:活动空气样本Mediancount3cfu/m3计数3

cfu/m3Settleplates沉降碟Mediancount0cfu/4hours计数0

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese49Airmovement空气运动ConsidertheseGradeBresults:考虑这些B级结果Activeairsamples:活动空气样本Mediancount3cfu/m3计数3

cfu/m3Settleplates沉降碟Mediancount3cfu/4hours计数3

cfu/4小时IsthedataOK?数据好吗？Airmovement空气运动Considerthese50Airmovement空气运动Inasepticmanufacture,wearetryingtoavoidcontamination–particularlycontaminationofproductandequipment.在无菌生产中，我们正在努力避免污染-特别是产品和设备的污染Forproductorequipmenttobecontaminatedfromair-bornemicroorganisms,theyhavetosettleoutoftheairontowhateveryouaretryingtoprotect.对于被空气传播的微生物污染的产品或设备，它们必须从空气中沉淀到您想要保护的任何物质上。Airmovement空气运动Inasepticman51Airmovement空气运动Weusetheprincipleofairmovementintwobeneficialwaysincleanrooms:我们在洁净室中以两种有益的方式使用空气流动原理：Turbulentairflow湍流气流Unidirectionalairflow(UDAF)单向气流（UDAF）Airmovement空气运动Weusethepri52Turbulentflowcleanrooms湍流洁净室MostEuropeancleanroomsareoftheturbulentairflowtype大多数欧洲洁净室属于湍流气流类型Airisdriven