PDA TR34（中文） 隔离罩系统验证-Validation-Isolator System-2001

PDATECHNICALREPORTNO.34第34号PDA技DESIGNANDVALIDATIONOFISOLATORSYSTEMSFORMANUFACTURINGANDTESTINGOFHEALTHCAREPR卫生保健产品生产和测试的隔离器系统的设计和验证TableofContents内容列表1.0INTRODUCTION概述1.1Preface绪言 11.2Scope范围 11.3KeyDefinitions关键词定义 1 22.0TYPESOFISOLATORS隔离器的类型2.1ClosedIsolators封闭式隔离器 22.1.1ClosedIsolatorsIntendedforAsepticApplications无菌应用的封闭式隔离器 22.1.2ClosedIsolatorsIntendedforContainmentApplications抑制应用的封闭式隔离器 22.1.3ClosedIsolatorsIntendedforAsepsisandContainment无菌和抑制应用的封闭式隔离器 22.2OpenIsolators开放式隔离器 32.2.1OpenIsolatorsIntendedforAsepticApplications无菌应用的开放式隔离器 32.2.2OpenIsolatorsIntendedforAsepsisandContainment无菌和抑制应用的开放式隔离器 33.0ISOLATORDESIGNANDGENERALCONSTRUCTION隔离器设计和总体结构3.1MaterialsofConstruction构造材料 3.1.1PolyvinylChloride(PVC)聚氯乙烯（PVC） 33.1.2StainlessSteel不锈钢 43.1.3GlazingMaterials玻璃质材料 43.1.4OtherMaterials其他材料 43.2OperatorInterface操作界面 43.2.1Gloves/Sleeves手套/套筒 53.2.2SuitsorHalf-Suits全身服或者半身服 53.2.3AirHandlingSystem空气处理系统 64.0FUNCTIONALSPECIFICATIONSFORISOLATORS隔离器的功能规格4.1AirSupplySpecifications进气规格 4.1.1AirChangeRate换气率 74.1.2AirVelocity气流速度 74.1.3ParticulateAirSpecification尘埃粒子规格 74.1.4RecirculationRate再循环率 84.1.5TemperatureandHumidity温度和湿度 84.1.6AerationoftheDecontaminatingAgent净化剂的曝气 84.2LeakTesting泄露测试 4.2.1PressureDecayTest降压测试 94.2.2TracerGasDetectionTest探漏气体检测测试 94.3Ergonomics人体工程学 4.4RapidTransferPorts(RTPs)快速传送接口 5.0FACILITYREQUIREMENTS设施要求5.1ClassificationoftheIsolatorRoom隔离器室的种类 5.2TemperatureandHumidityControl温度和湿度控制 5.3ProcessUtilities公用工程 6.0USERREQUIREMENTSPECIFICATIONS(URS)用户需求规格6.1GeneralUserRequirementSpecifications一般用户需求规格 6.1.1SterilityAssurance无菌保证 6.1.2CleaningandCleaningValidation清洁和清洁验证 6.1.3Containment抑制 6.1.4EnvironmentalControl环境控制 6.1.5LeakTesting泄露测试 6.1.6MonitoringSystems监测系统 6.1.7MicrobiologicalMonitoringoftheEnvironment对环境的微生物监测 6.1.8ProcessSimulation过程模拟 7.0RE-QUALIFICATIONTESTING再确认测试 8.0CONCLUSION结论 APPENDIXA:Glossary附录A词汇表 20APPENDIXB:Ljungqvist/Reinmuller(L-R)Method附录BLjungqvist/Reinmuller(L-R)方法 20APPENDIXC:TestMethods,PressureDropTest附录C测试方法，降压测试21APPENDIXD:IsolatorsandSterilityAssurance附录D隔离器和无菌保证 22REFERENCESANDTEXTNOTES引用资料和文字附注231.0INTRODUCTION绪论1.1Preface前言Inrecentyears,isolationtechnologyhasrapidlyemergedasanalternativetohuman-scaleclassifiedenvironmentsfortheproductionandtestingofmanydifferenttypesofhealthcareproducts.Theoperationalcharacteristicsofisolatorsmakethemideallysuitedforuseinthepreparationofsterilematerials,aswellasinthecontainmentofpotentmaterials.Additionalapplicationscanbefoundinthepreparationofclinicalsupplies,sterilebulkdrugs/bio-pharmaceuticals,sterilecytotoxicmaterials,andinsterilitytesting.近几年来，隔离器快速成为应用于多种不同类型的卫生保健产品的生产和测试的非传统的人造级别环境。隔离器本身的操作性能参数使得它很好的适用于无菌材料的制备，也同样适用于对药效较强的原料的抑制，除此之外，它还附加有应用于临床补给的配制剂，无菌原料药，生物制药，无菌细胞毒素原料，和无菌测试的应用。Theabsenceofauthoritativeimplementationandvalidationguidanceforthistechnologyandtheconsiderableconfusionthathasemergedbetween"isolators"and"barriers"wereprimemotivatorsforPDAtodevelopthisdocument.ItistheproductofaninternationalcommitteemadeupofrepresentativesofPDAU.S.,PDA'sJapanChapter,A3P,TheParenteralSociety,andR3-Nordic.由于缺少对这项技术的权威性贯彻和验证指导，并且在很大程度上将“隔离器”和“屏蔽”两者混淆的原因，鉴于以上原因，PDA在此基础上提出了这份文件。它是由美国PDA的代表，PDA日本篇，A3P，注射药物科学和R3-Nordic组成的国际委员会的提出并产生的。Thisdocumentshouldbeconsideredasguidance;itisnotintendedtoestablishanymandatoryorimpliedstandard.这份文件需要将其作为一种指导，并不是为了确定任何强制性的和隐含的标准。1.2Scope范围Thistechnicalreportaddressesessentialuserrequirementsfortheapplicationofisolatortechnologytoabroadrangeofmanufacturing,development,andtestingapplicationsinthehealthcareproductmanufacturingindustry.Thistechnicalreportcoversnotonlyproductsterilityassurance,butalsotheuseofisolatorsforthecontainmentofhazardousmaterials.这篇报告明确说明了隔离器在卫生保健产品的制造行业中所用到的一系列的制造，发展和测试的应用方面的基本用户要求。这篇技术报告不仅仅涵盖了产品的无菌保证，同样包含有隔离器对危险原料的抑制应用。Animportantcomponentofthistechnicalreportistheglossary(AppendixA).Thehealthcareindustryhaslackedauniformsetofdefinitionswithrespecttoisolatortechnology.Thecommitteerecognizesthat,inordertosuggesttrulyusabletechnicalinformation,wemustensurethattherecanbenoconfusionamongreadersastotheapplicationofrecommendationsmadewithinthistechnicalreport.词汇表（附录A）是这篇技术报告中一个很重要的组成部分。在卫生保健生产行业里，缺少一套对隔离器技术的统一的定义。委员会认为，为了提出真实可行的技术资料，我们必须要保证使读者不会混淆这篇技术报告中的应用建议标Thecommitteealsorecognizesthatinsomeregionsoftheworld,processingenvironmentscalled"isolators"arewidelyusedintheclinicalpharmacysetting.Thesedeviceshavesomegeneralfeaturesincommonwithisolatorsasdefinedinthisdocument,however,theyaredistinctlydifferentfromtheisolatorsystemscurrentlyinuseforsterileproductmanufacturingandtestinginthehealthcareproductindustry.Thistechnicalreportdoesnotpertaintodevicesthatdonotmeettheminimumperformancecriteriadefinedandexplainedinthisdocument.委员会同时认为在世界上某些地区，被称为“隔离器”的加工环境在很大范围上应用于临床药学的环境。这些设备在某种程度上与此文件中提到的隔离器具有相类似的特征。然而，它们无疑不同于目前卫生保健产品工业中应用于无菌制造和测试的隔离器系统。这篇技术报告并未附录那些不符合此文件中定义的最低性能参数指标的设备。1.3KeyDefinitions关键词定义Theestablishmentofacleardistinctionbetweenwhatisandwhatisnotanisolatorisessentialtounderstandingthisdocument.PDAsuggeststhefollowingdefinitionofisolatorbeadoptedbytheworldwidehealthcareindustry:为了更好的了理解这份文件，必须要确定隔离器和非隔离器之间的区别。PDA提出了对以下在世界范围的卫生保健工业中应用到的隔离器的定义：Anisolatorissealedorissuppliedwithairthroughamicrobiallyretentivefiltrationsystem(HEPAminimum)andmaybereproduciblydecontaminated(1).Whenclosed,itusesonlydecontaminated(wherenecessary)interfacesorRapidTransferPorts(RTPs)formaterialstransfer.Whenopen,itallowsfortheingressand/oregressofmaterialsthroughdefinedopeningsthathavebeendesignedandvalidatedtoprecludethetransferofcontamination.Itcanbeusedforasepticprocessingactivities,forcontainmentofpotentcompounds,orsimultaneouslyforbothasepsisandcontainment.隔离器是密闭的，或者是通过微生物截留过滤器系统(至少为HEPA)为其提供空气并且可进行重复性净化。当关闭时，仅使用净化排污接口或者专为物料传送用的快速传输接口。当其打开时，它可以允许通过被设计和经过验证的通道进行材料的进入和/或者输出来防止污染的转移。同样它可以用于进行无菌操作的活动，用于对药效较强的化合物的抑制或者同时用于无菌处理和抑制。Inmarkedcontrasttothe"isolator"definitionabove,PDAsuggeststhefollowingdefinitionfor"barriersystems:与上面定义的“隔离器”相比较，PDA对“障碍系统”做出了以下定义：barriersystemisanopensystemthatcanexchangecontaminantswiththesurroundingarea,andcannotbedecontaminatedtotheextentpossibleinanisolator.障碍系统是一个开放式的系统，它可以与周围环境之间产生交叉污染，并且在净化程度和范围上都不能与隔离器相比。Isolators,whetheroperatedinaclosedoropenmanner,offersignificantadvantagesoverbarriersystems:isolatorscanbedecontaminatedusingreproducibleandvalidatedmethods,donotallowtheingressofairbornecontaminationfromthesurroundingenvironment,andpreventtheintroductionofpersonnelbornecontaminationintotheisolator.Incontrast,abarriersystemisanopensystemwhichcanexchangeunfilteredairwiththesurroundingenvironment,canonlybemanuallydisinfected,andisdirectlyaccessedbygownedpersonnel.当隔离器处于密闭或者开放式的操作模式下时，与障碍系统向比它具有明显的优点：隔离器可以通过可再生的和验证的方法进行净化处理，并且不允许周围环境中的空气污染物进入，并且能防止由个人携带的污染物进入隔离器内。相比之下，障碍系统只是一个能与周围环境进行未过经滤空的气的交换的开放式系统，它只能利用手动消毒，并且允许穿着便装的人员直接进入。1.4Purpose目的Theincreaseduseofisolatorsinthehealthcareproductindustryoverthelastdecadeandahalfhasbeenremarkable.Infact,isolatorsnowclearlyrepresentthemostrapidlygrowingtechnologyfortheproductionofhealthcareproducts.Inspiteoftherapidgrowththissegmentoftheindustryhasenjoyed,verylittletechnicalguidanceexistsforthosewhoworkinthisfield.过去十年里，随着在卫生保健产品工业当中对隔离器的使用的增加其大多数备受关注。事实上，隔离器技术很明显的成为在卫生保健产品生产中发展最快的技术。尽管这种快速发展的技术在工业生产中得到应用，但是在这方面的技术指导非常缺乏。Itwasoftensaidatthebeginningofthe"isolatorera"thatisolatorscouldbeconsiderednothingmorethansmallcleanrooms.Experiencehastaughtscientistsandengineersthatfunctionalrequirementsforisolatorsare,infact,distinctlydifferentfromthoseforhumanscaleor"conventional"cleanrooms.Althoughhumanscalecleanroomsandisolatorshavemuchincommon,theyhavemanyimportantdifferencesandthistechnicalreportendeavorstofocusonanddiscussthesedifferences.在开始经常提到的“隔离器时代”中，隔离器被认为仅仅是一个小型的洁净室。实际上，经验提醒科学家和工程师，隔离器的功能要求明显不同于人类尺度上的或者传统意义上的洁净室。尽管人类尺度意义上的洁净室与隔离器有很多相似之处，但是它们之间依然有许多明显区别，因此这篇技术报告尝试着将重点关注和论述这些区别。2.0TYPESOFISOLATORS隔离器的类型2.1ClosedIsolators密闭式隔离器Isolatorsoperatedasclosedsystemsdonotexchangeunfilteredairorcontaminantswithadjacentenvironments.Theirabilitytooperatewithoutpersonnelaccesstothecriticalzonemakesisolatorscapableoflevelsofseparationbetweentheinternalandexternalenvironmentunattainablewithothertechnologies.Becauseoftheeffectivenessofthisseparation,closedisolatorsareideallysuitedforapplicationinthepreparationofsterileand/ortoxicmaterial.当隔离器处于密闭式系统操作时，它和周围相邻环境中没有与未过滤空气或者污染物的交换。隔离器能够在没有人员进入其关键区域进行操作，表明了隔离器在其他技术不能达到的分离其内部环境和外部环境的能力水平。鉴于这种高效的隔离效果，封闭式隔离器能很好的适用于无菌制备和/或者对有毒材料的处理。Therearetwotypesofclosedisolators:asepticandcontainment.Asepticisolatorsareintendedtoexcludeexternalcontaminationfromthecriticalzoneinsidetheisolator.Containmentisolatorsareintendedtopreventthereleaseoftoxicmaterialsprocessedinsidetheisolatortothesurroundingenvironmentinwhichpersonnelarelocated这里有两种类型的封闭式的隔离器：无菌的和抑制的。无菌隔离器是用于从隔离器内部的关键区域排除外部污染物。抑制作用的隔离器是用于在隔离器内部进行有毒材料工艺时防止有毒材料被释放到人员所处的周围环境当中。2.1.1ClosedIsolatorsIntendedforAsepticApplications无菌应用的封闭式隔离器Theseunitsaretypicallyoperatedunderpositivepressureandaresubjecttovalidatabledecontaminationprocedurespriortouse.Isolatorsintendedfortheprocessingofsterilematerialsadheretothefollowinggeneralprinciples:此设备典型的是在正压情况下进行操作的，并在使用前服从经过验证的净化规程。用于无菌原料工艺的的隔离器遵循以下几点总则：·Theymustnotexchangeairwiththesurroundingenvironmentexceptwhenthatairpassesthroughamicrobiallyretentivefilter.除非有高效微生物过滤器系统，它绝对不允许与周围环境发生空气交换。·Theymustbedecontaminatedinareproducibleandquantifiablemanner.必须利用可再生的和可量化的方式对其进行净化处理。·Allworkorhandlingofmaterialswithintheisolatorenclosuremustbeaccomplishedremotely;nohumanoperatororpartthereofcandirectlyentertheisolatorduringoperation.隔离器内部所有对原料进行的加工或者处理都是在远程操作模式下完成的。操作期间操作人员或者其身体的任何部份不允许直接进入隔离器内部进行操作。·Allmaterialsthatentertheisolatormustbedecontaminatedorsterilizedandmustentereitherdirectlythroughadecontaminatingorsterilizingsystem,orviaarapidtransferport.所有进入隔离器的原料都是必须经过净化或者灭菌处理的，并且是通过净化或者灭菌系统直接进入，又或者是通过快速传输接口进入的。2.1.2ClosedIsolatorsIntendedforContainmentApplications抑制应用的封闭式隔离器Theseunitsgenerallyoperateundernegativepressureandareclearedofallpotentiallyhazardousmaterialspriortoopening.Isolatorsintendedforcontainmentapplicationsadheretothefollowinggeneralprinciples:这类设备通常是在负压条件下进行操作的并且在将其打开之前已清除了所有潜在的有毒物质的存在，用于抑制作用的隔离器遵循以下几点总则：.Theymustnotexchangeairwiththesurroundingenvironmentexceptwhenthatairpassesthroughafiltercapableofretainingthematerialsbeingprocessed.除非通过有能保存加工处理的原料的高效过滤器，它们绝对不允许与周围环境有空气交换发生。.Allworkorhandlingofmaterialswithintheisolatorenclosuremustbeaccomplishedremotely.Nohumanoperatororpartthereofcandirectlyentertheisolatorduringoperation.隔离器内部所有对原料进行的加工或者处理都是在远程操作模式下完成的。操作期间操作人员或者其身体的任何部份不允许直接进入隔离器内部进行操作。•Allmaterialsexitingtheisolatormustbecleanedorcontainedinsuchawaythathazardousmaterialsarenotreleasedtothesurroundingenvironment.所有由隔离器排除的原料都必须经过净化或者对其进行包装，以保证没有危害物质被释放到周围环境当中。Theymustbecleanableinareproducibleandquantifiablemanner.必须利用可再生的和可量化的方式对其进行净化处理。2.1.3ClosedIsolatorsIntendedforAsepsisandContainment同时用于无菌和抑制作用的封闭式隔离器Theseunitsaresubjecttotheconstraintsofsections2.1.1and2.1.2,above.Theyaretypicallyoperatedunderpositivepressure,withadditionalsafetymeasuressuchasnegativepressureairlocks.Theuseofsupplementarypersonalprotectiveequipmentbytheworkersmaybeconsidered.这些设备受上面第2.1.1和2.1.1章节的参数限制。通常情况下它们是在正压情况下进行操作的，另外附加一些比如负压气塞的安全措施。工人所用到的辅助性的个人安全设施是需要考虑到的。2.2OpenIsolators开放式隔离器Openisolatorsdifferfromclosedisolatorsinthattheyaredesignedtoallowforthecontinuousorsemi-continuousingressand/oregressofmaterialsduringoperation,whilemaintainingalevelofprotectionovertheinternalenvironment.Openisolatorsdonotexchangeunfilteredairorcontaminantswithadjacentenvironments.Openisolatorsaredecontaminatedwhileclosed,andthenopenedduringmanufacturing.Openisolatorstypicallyareusedfortheasepticfillingoffinishedpharmaceuticals.与封闭式隔离器不同，它们在设计时考虑到了在保持对内部环境的保护等级水平的基础上，操作期间原料的连续或者半连续的进入和/或者送出。开放式隔离器不会与周围相邻环交换未过滤的空气或者污染物。开放式隔离器在关闭时对其进行净化，在生产中将其打开，开放式隔离器的典型应用时用于成品药的无菌灌装。2.2.1OpenIsolatorsIntendedforAsepticApplications开放式隔离器的无菌应用Withtheexceptionofthepresenceofopeningsduringmanufacturing,openisolatorssatisfythesamegeneralprinciplesasnotedaboveforclosedisolators.Therearenumerousdesignsthatcansuccessfullymanagetheingressandegressofcomponentsoffilledcontainers,whilepreventingtheingressofcontaminationfromthesurroundingenvironment除了工业生产中目前的开放式设备，开放式隔离器同样的与上面提到的封闭式隔离器的要求总则一样，目前很多种设计都能很成功在防止周围环境中的污染进入的基础上对灌装容器的部件进行进/出处理。2.2.2OpenIsolatorsIntendedforAsepsisandContainment开放式隔离器的无菌和抑制应用Theseisolatorssharesimilaritieswiththeordinaryopenisolator(see2.2.1)andthecontainmentisolator(see2.1.1).Forthesesystems,thedesignusuallyincorporatesacleaningprocesstoallowforremovalofanytoxiccontaminantfromtheexteriorofthesealedcontainerpriortoexitfromtheisolator.Thedesignmustalsopreventtheingressofairinordertopreservetheasepticnatureoftheinternalenvironment.这类隔离器与普通的开放式隔离器（见2.2.1）和抑制性隔离器（见2.2.1）有类似之处，对于这个系统而言，设计时通常包含一个洁净工序，就是在密闭容器在移出隔离器之前清除其表面的所有有毒污染物。Thefollowingdiagramprovidesanoverviewofisolators,barriersystems,andcleanroomsdepictingsomeoftheiroperatingcharacteristicsandapplication.Itshouldbenotedthatthesystemsattheedgeofthedrawingareessentiallyequivalent,andaffordminimalprotectiontothematerialsandpersonnel.下面的示图提供了隔离器，障碍系统和洁净室的概观，并描述了它们的一些操作参数和应用。需要注意到的是图纸边上所画的系统基本上是一样的，并且要对原料和人员提供最基本的保护。3.0ISOLATORDESIGNANDGENERALCONSTRUCTION隔离器的设计和总体结构Isolatorsmaybemanufacturedofanysuitablematerialprovidedtheisolatorsatisfiesthefunctionalrequirementsestablishedforit,andthematerialissufficientlyruggedtoresistpunctureordamagethatcouldaffectsystemintegrity.Ingeneral,isolatorsaretermedeither"flexiblewall"or"rigidwall"dependingupontheirgeneralconstruction.Isolatorsthatareusedincontainmentapplicationsareoftenofrigidwallconstructionbecausethesesystemsallowforamoreaggressivecleaningofsurfaces.隔离器可以是由任何能满足隔离器本身功能要求的合适材料制成的，这类材料能很好的抵抗能对系统完整性造成影响的外部损伤。一般而言，鉴于其总体构造可将隔离器称为“柔性墙”或者“刚性墙”。由于允许对其表面进行腐蚀性清洗，因此用于抑制应用的隔离器通常是刚性墙构造。3.1MaterialsofConstruction构造材料3.1.1PolyvinylChloride(PVC)聚氯乙烯（PVC）PVCsheetingis,byfar,themostcommonmaterialofconstructionforflexiblewallisolators.Flexiblewallisolatorshavebeensuccessfullyusedforbothsterilitytestingandmanufacturingisolators.ThePVCisolatorcanopyisgenerallyexternallysupportedbyametal(typicallystainlesssteel)frame.ThePVCmaterialshouldbethickenoughtoresistpuncture.PVCisolatorsmaybedamagedbyexposuretoUVlight,orchemicalssuchassolvents.PVCismostcommonlyusedinisolatorswhichcoverageneralsizerangeofabout0.5percubicmetertoabout8percubicmeter,althoughothersizesarepossible.Thegenerallynon-reactivenatureofPVCenablesthematerialtowithstandrepeatedexposuretosterilizing/sanitizingagentscommonlyusedwithisolatorsandtheircontents.Ifcleanabilityisanissue,smoothwallfloorjunctionsandseamsareessential.Theuseofaproperlyslopedsmoothstainlesssteelfloorshouldbeconsideredwheresuperiorcleanabilityisrequired.PVC薄板是柔性墙隔离器构造中最普遍的材料，柔性墙隔离器已经成功的应用于无菌测试和制造业隔离器。PVC隔离器表面的罩子是利用金属材料(不锈钢)框架将其支撑起来的。这里用到的PVC板需要有能足够的厚度来抵抗外部的穿透力。UV（紫外）线，或者化学试剂比如溶剂等能对PVC材料的隔离器造成伤害。PVC最常见的用于0.5立方米到8立方米范围内的隔离器的表面材料，但是其他一些型号的也可能适用。通常来说可以承受反复暴露于灭菌/消毒剂的无电抗性的PVC材料广泛地用于隔离器的和它内部机构。如果要考虑除尘度，那么的墙与地板的结合处和裂缝的光滑度是很重要的。如果要求要有较高的除尘度，则就需要考虑用到不锈钢材料制成的具有光滑斜面的地板。3.1.2StainlessSteel不锈钢Stainlesssteeliscommonlyusedasaflooringmaterialinbothrigidwallandflexiblewallisolators.Stainlesssteelisthemostcommonlyusedwallandceilingmaterialinrigidwallisolators.300seriesstainlesssteelsaregenerallyused,typicallyeither304or316grade.Whereweldingisaconsideration,orprolongedexposuretohalogensaltsorothercorrosivesubstancesisexpected,lowcarbon(304L,316L)shouldbeconsidered.Thesurfacefinishismostcriticalinthoseapplicationsforwhichcleanabilityisanimportantuserrequirement.Formanyasepticprocessapplications,onlyageneral"buff"finishisrequired;forcleanability,however,higherlevelsofpolishuptoandincludingelectropolish(RA5-7micrometers)canbeconsidered.不论是在刚性墙还是柔性墙的隔离器不锈钢材料都是最普遍的用于制作其地板的材料。在刚性墙隔离器中不锈钢最常见的应用是用来制作其墙和顶板。300系列的不锈钢是最常用的，通常用到是304不锈钢或者是316不锈钢。如果考虑到焊点，或者长期暴露于卤素盐或者其他一些预料到的腐蚀性的物质中时，可以考虑用到低碳（304L，316L）不锈钢。如果除尘度是很重要的使用要求，那么对其表面的抛光处理就是最重要的一个环节。对于一些无菌工艺的应用，采用一般“抛光”处理即可，而对于有除尘度要求来说，要求将其提升到更好水平的抛光处理时可以考虑利用电解抛光法。3.1.3GlazingMaterials玻璃质材料Manyisolatorshaverigidwindowstoalloweasyviewoftheprocessescontainedwithintheisolator.Themostcommonlyusedmaterialsforthesewindowsarepolycarbonate(i.e.,Lexan®),acrylicplastics,ortemperedglass.Themostimportantconsiderationintheuseofwindowsisthemountingofthewindowtotheisolatorframework.Thewindowmountingassemblyorframemayeitherbepermanentlyorsemi-permanentlyboltedinplace,oritmaybedesignedtobeeasilyopenedtoallowaccesstotheinterioroftheisolatorwhentheunitisundergoingmaintenanceorchangeover.Itisimportantthatthecleanabilityofthewindowmountandsealisconsideredandthatthegasketmaterialischosenwithfullconsiderationofitscompatibilitywithcleaningagentsandsanitizing/sterilizingchemicals.为了方便观察隔离器内部工艺，许多隔离器都安装有固定的刚性窗口。最普遍的用于制作这种窗口的材料是聚碳酸酯（比如莱克桑），丙烯酸塑料，或者钢化玻璃。这里首先要考虑的是窗口的安装。这些窗口或者框架可以是被永久性锁住或者是暂时性的锁住，又或者是可以设计成可以很方便的打开用于专门人员进入隔离器内部进行维护或者更换等。重要的是窗口的安装要考虑到除尘度和密封性并且要考虑到所选择的作为垫圈的材料与清洁剂和消毒/灭菌化学药剂的相容性Windowsshouldprovideadistortionfreeviewoftheinterioroftheisolatorandadequatelightshouldbeprovidedforsafeandeffectiveworkingconditions.Itmaybepreferabletohavelightingfixtureslocatedoutsidetheisolatorinordertoavoidexposingthemtocleaningandsanitizingagents.窗口要保证对隔离器内部操作无失真的观察效果并且要为其内部操作的安全和效率提供足够的光线。为了避其暴露于清洁和消毒剂当中更好的方法是在隔离器外部安装有照明器材。Anumberofsuccessfulsmallrigidwallisolatordesignshaveutilizedaplasticenclosure,typicallyofacrylic,thatisbondedwithcement.Inthisdesign,theisolatorisbuiltcompletelywithoutaframe.Isolatorsofthisconstructionmaybeimpracticalforlargesystemswithcomplexair-handlingrequirements,however,theyareveryusefulforsmallportablesystemsandforcontainmentapplications.Framelessdesignshavetheadvantageofsuperiorvisibilityofinterioroperationsandrelativelylowercost.许多的成功性的小型刚性墙隔离器实例设计使用塑料作为其外壳的，代表性的材料是丙烯酸塑料，它是利用黏固剂进行黏合的。在这种情况下，这类隔离器的建造完全脱离的了框架结构。对于有复合空气处理要求的大型系统来说这类结构的隔离器往往并不实用，然而，它们非常适用于便携式系统和抑制应用。框架结构的设计的优点在与能够很清晰的观察隔离器内部操作并且相对来说其成本较低。3.1.4OtherMaterials其他材料Anymaterialthatissuitablystrong,cleanable,andresistanttocleaningandsanitizingagentscouldbeusedtobuildisolatorsystems.Isolatorsareequippedwithgloves,half-suits,doorgaskets,filtergasketsandothermaterials,allofwhichmustbecompatiblewiththematerialsprocessedwithinand/orusedupontheisolatorforcleaninganddecontamination.Thereneedbenorestrictionontheuseofmaterialsprovidedthefunctionalrequirementsinclude:所有用于建造隔离器系统的材料都要符合牢固，可清洗性，并且对清洁剂和消毒剂有较好的抗性。隔离器装备有手套，半身服，门垫圈，过滤器垫圈和其他一些材料，所有这些材料都要适合于上面说到的用于洁净和净化的隔离器中所提到的材料处理。需要指出的是对这些材料无使用限制并且对其功能要求如下：•Chemicalcompatibilitywithproductionmaterials,decontaminationandcleaningagents与生产原料，净化机和清洁剂的化学相容性•Structuralintegrity构造的整体性•Cleanability(tothedegreerequired)可清洁性3.2OperatorInterface操作界面Isolatorsaredesignedtopreventtheexchangeofcontaminationbetweentheenclosedworkenvironmentandthesurroundingenvironmentinwhichpersonnelarelocated.Therefore,manipulationsofmaterialswithintheisolatormustbemadeeitherviaglovesorbodysuits,orauto-manipulators.Thedesignexecutionofinterfacedevicesiscriticalbothtosuccessfulintegrationofequipmentintotheisolatorsystem,andtotheavoidanceofprocesshazardsthatcouldaffectproductqualityandoperatorsafety.Thefollowingguidelinesshouldbeconsideredindesignandrealizationofisolatorbasedsystems:隔离器的作用是用来防止在密闭的工作环境与人员所处的周围环境之间发生污染的交换。因此，对隔离器内部的原料的操作必须通过手套或者全身服，或者是自动机械臂实现。操作界面的设计操作对于成功地集成进入隔离器系统内部的设备和避免可能影响产品质量和操作人员安全的工艺风险来说是至关重要的。在设计和实现隔离器的基础系统时需要考虑到以下几点指导方针：•Theuseofautomationtoreducetheneedforhumaninterfaceduringisolatoroperationsincludingcleaning.自动化技术的使用降低了在操作和清洗隔离器时对人工操做界面的需求。•Wherehumaninterfaceisunavoidable,ergonomicsshouldbesystematicallyevaluatedandcarefullyexecuted.如果人机操作接口是必不可少的，那么必须要对人机工程学进行系统的评估并谨慎的执行。•Designororientationofequipmentsothattroubleshootingandroutinemaintenancecanbeaccomplishedwithoutdisruptiontotheisolatorenvironmentisbeneficialandshouldbeincorporatedwherepossible.对设备的设计或校准以便故障诊断和日常维护可以在不破坏隔离器内部环境的境况下实现，这是有益的并且要在合适的地方应用到。3.2.1Gloves/Sleeves手套/套筒Oneofthemostcommonlyuseddevicesforconductingmanipulationswithintheisolatoristheglove/sleeveassembly.Theglove/sleeveassembliesusedwithinisolatorsfallintotwobroadcategories:一种最普遍用于控制隔离器内部操作的设备就是手套/套筒的组合体。隔离器内部用到的手套/套筒组合体分为两种大致类型。•One-pieceassemblyinwhichthegloveandsleeveareofasingle,unbrokenpiece.Theseassembliescanbeofvariouslengthstoallowforeitherpartialorfullarmlengthmanipulations.单件组合体指手套和套筒都是单件连接的一整件。这种组合体可以提供不同长度，既允许手臂的部分进入进行操作也可以整只手臂都进去进行操作。•Two-pieceassembliesinwhichthegloveandsleeveareseparateandareconnectedatthegauntletbysometypeofsealsystem.Liketheone-pieceassemblies,thesetwo-piecearrangementscanbefoundinanumberoflengths.Mostimportantly,thetwo-pieceassemblyallowsfortherelativelysimplechange-outofgloves.Someisolatormanufacturerssuggestthatitispossibletochangethegloveinatwo-pieceglove/sleeveassemblywithoutcompromisingtheasepticenvironmentwithintheisolator.Thepracticeofchangingglovesduringasepticproductionoperationsmustbecautiouslyconsidered,however.双件套组合体指手套和套筒是分开的并且利用某些类型的密封系统在长手套处有连接。与单件组合体一样，双件套组合同样可以提供许多种不同长度。更重要的是，相对而言双件套组合更容易更换手套。一些隔离器制造商建议在不破坏隔离器内部环境时对双件套组合进行手套更换。不管怎样，在无菌生产操作中更换手套必须小心谨慎。Thematerialofconstructionofthegloveisgenerallyacompromisebetweentactilerequirementsandresistancetotearsandpinholes.Thedesignershouldconsiderthetypeofworkthatwillbeperformedusingthegloves,andthefrequencywithwhichtheywillbeusedduringoperations.CommonlyusedglovematerialsincludeNeoprene®andHypalon®.Someusershaveoptedtouseadoubleglovearrangementtominimizethepossibilityofatearorleakcompromisingtheenvironmentwithintheisolator.Intheseinstances,anordinarysetofsterilelatexglovesisplacedoverorundertheglovesinstalledontheisolator.Thelatexglovescanbechangedasoperationalconditionswarrant手套的构造材料是介于有触觉要求和能抗撕裂和刺穿之间的折中性材料。设计人员必须考虑到使用手套时的工作类型和在操作过程中对手套的使用频率。通常用于制作手套的材料包括Neoprene®andHypalon®两种。一些使用者往往在隔离器内部环境中采用双手套的方式将撕裂或者刺穿的可能性降到最小。在这个实例中，一个普通的无菌胶乳手套被置于安装在隔离器上的手套的上面或者下面。如果操作条件许可，可以对胶乳手套进行更换。Anotherfactorthatmustbeconsideredintheselectionofglovematerialischemicalresistance.Itisimperativethattheglovesbesufficientlyresistanttodecontaminatingchemicals,cleaningagents,andprocessmaterials.在手套材料的选择方面另一个必须考虑到的因素是化学抗性。极为重要的是手套对化学制剂，清洁剂和工艺原料有很好的抗性。Overand/orunderglovingduringcriticaltaskscanincreaseworkerprotectionbyaddinganextralayerofprotection.Overglovesmaybehardtofitoverthepermanentlyinstalledglovesontheisolatorandmayreducefeel,makingdelicatemanipulationsdifficult.However,overglovesprovidebetteroperatorprotection.Overglovescanbereplacedasrequiredbyextragloveskeptinsidetheisolator.Underglovesareeasiertofitontheoperator'shandsanddon'timpactmanipulations,buttheyarelesssafeastheupperarmisstillexposedundertheisolatorgloves.在关键性的任务中使用手套操作可通过增加额外防护层来提高对工人的保护。外层的手套在安装上有困难并且能降低人的手指的感觉，在比较细腻的操作上有困难。尽管如此，外层的手套为操作者能提供更好的保护。在副手套保留在隔离器内部时可以对外层手套进行更换。内层的手套很容易的倍套在操作者手上并且不影响操作。但是由于手臂上半部分依然暴露于隔离器手套下，因此它能提供的安全防护有限。Theimpactofglovescanbereducedbycarefulselectionofmaterialsofconstruction.Theamountofusetheglovesreceiveandthetypesofmaterialsutilizedinproductionandcleaningoperationsaffectglovelife.Manysolventsandtheirvaporsareabletochemicallyattackgloves(thisincludesanydecontaminatingagents).Glovesshouldbechangedonaperiodicandpre-emptivebasisbeforelossofintegrity.Glovesshouldbeexaminedfrequentlypriortoandduringuse.Wherepossible,toolsshouldbeusedratherthanglovedhandstocontactcontaminatedparts,equipment,andsurfaces.Ingeneral,manualtasksshouldbeavoidedwhereverpossible.通过细心选择手套的构造材料可以降低手套带来的负面影响。使用手套的数量和手套的构造材料在生产和清洁操作中会影响手套的使用寿命。一些化学溶剂和它们的蒸汽会腐蚀手套（这里包含所有的去污剂）。在手套失去完整性之前应对其进行定期的更换。在使