PDA TR34（中文） 隔離罩系統(tǒng)驗證-Validation-Isolator System-2001

PDATECHNICALREPORTNO.34第34號PDA技DESIGNANDVALIDATIONOFISOLATORSYSTEMSFORMANUFACTURINGANDTESTINGOFHEALTHCAREPR衛(wèi)生保健產(chǎn)品生產(chǎn)和測試的隔離器系統(tǒng)的設(shè)計和驗證TableofContents內(nèi)容列表1.0INTRODUCTION概述1.1Preface緒言 11.2Scope范圍 11.3KeyDefinitions關(guān)鍵詞定義 1 22.0TYPESOFISOLATORS隔離器的類型2.1ClosedIsolators封閉式隔離器 22.1.1ClosedIsolatorsIntendedforAsepticApplications無菌應(yīng)用的封閉式隔離器 22.1.2ClosedIsolatorsIntendedforContainmentApplications抑制應(yīng)用的封閉式隔離器 22.1.3ClosedIsolatorsIntendedforAsepsisandContainment無菌和抑制應(yīng)用的封閉式隔離器 22.2OpenIsolators開放式隔離器 32.2.1OpenIsolatorsIntendedforAsepticApplications無菌應(yīng)用的開放式隔離器 32.2.2OpenIsolatorsIntendedforAsepsisandContainment無菌和抑制應(yīng)用的開放式隔離器 33.0ISOLATORDESIGNANDGENERALCONSTRUCTION隔離器設(shè)計和總體結(jié)構(gòu)3.1MaterialsofConstruction構(gòu)造材料 3.1.1PolyvinylChloride(PVC)聚氯乙烯（PVC） 33.1.2StainlessSteel不銹鋼 43.1.3GlazingMaterials玻璃質(zhì)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空氣處理系統(tǒng) 64.0FUNCTIONALSPECIFICATIONSFORISOLATORS隔離器的功能規(guī)格4.1AirSupplySpecifications進氣規(guī)格 4.1.1AirChangeRate換氣率 74.1.2AirVelocity氣流速度 74.1.3ParticulateAirSpecification塵埃粒子規(guī)格 74.1.4RecirculationRate再循環(huán)率 84.1.5TemperatureandHumidity溫度和濕度 84.1.6AerationoftheDecontaminatingAgent凈化劑的曝氣 84.2LeakTesting泄露測試 4.2.1PressureDecayTest降壓測試 94.2.2TracerGasDetectionTest探漏氣體檢測測試 94.3Ergonomics人體工程學(xué) 4.4RapidTransferPorts(RTPs)快速傳送接口 5.0FACILITYREQUIREMENTS設(shè)施要求5.1ClassificationoftheIsolatorRoom隔離器室的種類 5.2TemperatureandHumidityControl溫度和濕度控制 5.3ProcessUtilities公用工程 6.0USERREQUIREMENTSPECIFICATIONS(URS)用戶需求規(guī)格6.1GeneralUserRequirementSpecifications一般用戶需求規(guī)格 6.1.1SterilityAssurance無菌保證 6.1.2CleaningandCleaningValidation清潔和清潔驗證 6.1.3Containment抑制 6.1.4EnvironmentalControl環(huán)境控制 6.1.5LeakTesting泄露測試 6.1.6MonitoringSystems監(jiān)測系統(tǒng) 6.1.7MicrobiologicalMonitoringoftheEnvironment對環(huán)境的微生物監(jiān)測 6.1.8ProcessSimulation過程模擬 7.0RE-QUALIFICATIONTESTING再確認(rèn)測試 8.0CONCLUSION結(jié)論 APPENDIXA:Glossary附錄A詞匯表 20APPENDIXB:Ljungqvist/Reinmuller(L-R)Method附錄BLjungqvist/Reinmuller(L-R)方法 20APPENDIXC:TestMethods,PressureDropTest附錄C測試方法，降壓測試21APPENDIXD:IsolatorsandSterilityAssurance附錄D隔離器和無菌保證 22REFERENCESANDTEXTNOTES引用資料和文字附注231.0INTRODUCTION緒論1.1Preface前言Inrecentyears,isolationtechnologyhasrapidlyemergedasanalternativetohuman-scaleclassifiedenvironmentsfortheproductionandtestingofmanydifferenttypesofhealthcareproducts.Theoperationalcharacteristicsofisolatorsmakethemideallysuitedforuseinthepreparationofsterilematerials,aswellasinthecontainmentofpotentmaterials.Additionalapplicationscanbefoundinthepreparationofclinicalsupplies,sterilebulkdrugs/bio-pharmaceuticals,sterilecytotoxicmaterials,andinsterilitytesting.近幾年來，隔離器快速成為應(yīng)用于多種不同類型的衛(wèi)生保健產(chǎn)品的生產(chǎn)和測試的非傳統(tǒng)的人造級別環(huán)境。隔離器本身的操作性能參數(shù)使得它很好的適用于無菌材料的制備，也同樣適用于對藥效較強的原料的抑制，除此之外，它還附加有應(yīng)用于臨床補給的配制劑，無菌原料藥，生物制藥，無菌細(xì)胞毒素原料，和無菌測試的應(yīng)用。Theabsenceofauthoritativeimplementationandvalidationguidanceforthistechnologyandtheconsiderableconfusionthathasemergedbetween"isolators"and"barriers"wereprimemotivatorsforPDAtodevelopthisdocument.ItistheproductofaninternationalcommitteemadeupofrepresentativesofPDAU.S.,PDA'sJapanChapter,A3P,TheParenteralSociety,andR3-Nordic.由于缺少對這項技術(shù)的權(quán)威性貫徹和驗證指導(dǎo)，并且在很大程度上將“隔離器”和“屏蔽”兩者混淆的原因，鑒于以上原因，PDA在此基礎(chǔ)上提出了這份文件。它是由美國PDA的代表，PDA日本篇，A3P，注射藥物科學(xué)和R3-Nordic組成的國際委員會的提出并產(chǎn)生的。Thisdocumentshouldbeconsideredasguidance;itisnotintendedtoestablishanymandatoryorimpliedstandard.這份文件需要將其作為一種指導(dǎo)，并不是為了確定任何強制性的和隱含的標(biāo)準(zhǔn)。1.2Scope范圍Thistechnicalreportaddressesessentialuserrequirementsfortheapplicationofisolatortechnologytoabroadrangeofmanufacturing,development,andtestingapplicationsinthehealthcareproductmanufacturingindustry.Thistechnicalreportcoversnotonlyproductsterilityassurance,butalsotheuseofisolatorsforthecontainmentofhazardousmaterials.這篇報告明確說明了隔離器在衛(wèi)生保健產(chǎn)品的制造行業(yè)中所用到的一系列的制造，發(fā)展和測試的應(yīng)用方面的基本用戶要求。這篇技術(shù)報告不僅僅涵蓋了產(chǎn)品的無菌保證，同樣包含有隔離器對危險原料的抑制應(yīng)用。Animportantcomponentofthistechnicalreportistheglossary(AppendixA).Thehealthcareindustryhaslackedauniformsetofdefinitionswithrespecttoisolatortechnology.Thecommitteerecognizesthat,inordertosuggesttrulyusabletechnicalinformation,wemustensurethattherecanbenoconfusionamongreadersastotheapplicationofrecommendationsmadewithinthistechnicalreport.詞匯表（附錄A）是這篇技術(shù)報告中一個很重要的組成部分。在衛(wèi)生保健生產(chǎn)行業(yè)里，缺少一套對隔離器技術(shù)的統(tǒng)一的定義。委員會認(rèn)為，為了提出真實可行的技術(shù)資料，我們必須要保證使讀者不會混淆這篇技術(shù)報告中的應(yīng)用建議標(biāo)Thecommitteealsorecognizesthatinsomeregionsoftheworld,processingenvironmentscalled"isolators"arewidelyusedintheclinicalpharmacysetting.Thesedeviceshavesomegeneralfeaturesincommonwithisolatorsasdefinedinthisdocument,however,theyaredistinctlydifferentfromtheisolatorsystemscurrentlyinuseforsterileproductmanufacturingandtestinginthehealthcareproductindustry.Thistechnicalreportdoesnotpertaintodevicesthatdonotmeettheminimumperformancecriteriadefinedandexplainedinthisdocument.委員會同時認(rèn)為在世界上某些地區(qū)，被稱為“隔離器”的加工環(huán)境在很大范圍上應(yīng)用于臨床藥學(xué)的環(huán)境。這些設(shè)備在某種程度上與此文件中提到的隔離器具有相類似的特征。然而，它們無疑不同于目前衛(wèi)生保健產(chǎn)品工業(yè)中應(yīng)用于無菌制造和測試的隔離器系統(tǒng)。這篇技術(shù)報告并未附錄那些不符合此文件中定義的最低性能參數(shù)指標(biāo)的設(shè)備。1.3KeyDefinitions關(guān)鍵詞定義Theestablishmentofacleardistinctionbetweenwhatisandwhatisnotanisolatorisessentialtounderstandingthisdocument.PDAsuggeststhefollowingdefinitionofisolatorbeadoptedbytheworldwidehealthcareindustry:為了更好的了理解這份文件，必須要確定隔離器和非隔離器之間的區(qū)別。PDA提出了對以下在世界范圍的衛(wèi)生保健工業(yè)中應(yīng)用到的隔離器的定義：Anisolatorissealedorissuppliedwithairthroughamicrobiallyretentivefiltrationsystem(HEPAminimum)andmaybereproduciblydecontaminated(1).Whenclosed,itusesonlydecontaminated(wherenecessary)interfacesorRapidTransferPorts(RTPs)formaterialstransfer.Whenopen,itallowsfortheingressand/oregressofmaterialsthroughdefinedopeningsthathavebeendesignedandvalidatedtoprecludethetransferofcontamination.Itcanbeusedforasepticprocessingactivities,forcontainmentofpotentcompounds,orsimultaneouslyforbothasepsisandcontainment.隔離器是密閉的，或者是通過微生物截留過濾器系統(tǒng)(至少為HEPA)為其提供空氣并且可進行重復(fù)性凈化。當(dāng)關(guān)閉時，僅使用凈化排污接口或者專為物料傳送用的快速傳輸接口。當(dāng)其打開時，它可以允許通過被設(shè)計和經(jīng)過驗證的通道進行材料的進入和/或者輸出來防止污染的轉(zhuǎn)移。同樣它可以用于進行無菌操作的活動，用于對藥效較強的化合物的抑制或者同時用于無菌處理和抑制。Inmarkedcontrasttothe"isolator"definitionabove,PDAsuggeststhefollowingdefinitionfor"barriersystems:與上面定義的“隔離器”相比較，PDA對“障礙系統(tǒng)”做出了以下定義：barriersystemisanopensystemthatcanexchangecontaminantswiththesurroundingarea,andcannotbedecontaminatedtotheextentpossibleinanisolator.障礙系統(tǒng)是一個開放式的系統(tǒng)，它可以與周圍環(huán)境之間產(chǎn)生交叉污染，并且在凈化程度和范圍上都不能與隔離器相比。Isolators,whetheroperatedinaclosedoropenmanner,offersignificantadvantagesoverbarriersystems:isolatorscanbedecontaminatedusingreproducibleandvalidatedmethods,donotallowtheingressofairbornecontaminationfromthesurroundingenvironment,andpreventtheintroductionofpersonnelbornecontaminationintotheisolator.Incontrast,abarriersystemisanopensystemwhichcanexchangeunfilteredairwiththesurroundingenvironment,canonlybemanuallydisinfected,andisdirectlyaccessedbygownedpersonnel.當(dāng)隔離器處于密閉或者開放式的操作模式下時，與障礙系統(tǒng)向比它具有明顯的優(yōu)點：隔離器可以通過可再生的和驗證的方法進行凈化處理，并且不允許周圍環(huán)境中的空氣污染物進入，并且能防止由個人攜帶的污染物進入隔離器內(nèi)。相比之下，障礙系統(tǒng)只是一個能與周圍環(huán)境進行未過經(jīng)濾空的氣的交換的開放式系統(tǒng)，它只能利用手動消毒，并且允許穿著便裝的人員直接進入。1.4Purpose目的Theincreaseduseofisolatorsinthehealthcareproductindustryoverthelastdecadeandahalfhasbeenremarkable.Infact,isolatorsnowclearlyrepresentthemostrapidlygrowingtechnologyfortheproductionofhealthcareproducts.Inspiteoftherapidgrowththissegmentoftheindustryhasenjoyed,verylittletechnicalguidanceexistsforthosewhoworkinthisfield.過去十年里，隨著在衛(wèi)生保健產(chǎn)品工業(yè)當(dāng)中對隔離器的使用的增加其大多數(shù)備受關(guān)注。事實上，隔離器技術(shù)很明顯的成為在衛(wèi)生保健產(chǎn)品生產(chǎn)中發(fā)展最快的技術(shù)。盡管這種快速發(fā)展的技術(shù)在工業(yè)生產(chǎn)中得到應(yīng)用，但是在這方面的技術(shù)指導(dǎo)非常缺乏。Itwasoftensaidatthebeginningofthe"isolatorera"thatisolatorscouldbeconsiderednothingmorethansmallcleanrooms.Experiencehastaughtscientistsandengineersthatfunctionalrequirementsforisolatorsare,infact,distinctlydifferentfromthoseforhumanscaleor"conventional"cleanrooms.Althoughhumanscalecleanroomsandisolatorshavemuchincommon,theyhavemanyimportantdifferencesandthistechnicalreportendeavorstofocusonanddiscussthesedifferences.在開始經(jīng)常提到的“隔離器時代”中，隔離器被認(rèn)為僅僅是一個小型的潔凈室。實際上，經(jīng)驗提醒科學(xué)家和工程師，隔離器的功能要求明顯不同于人類尺度上的或者傳統(tǒng)意義上的潔凈室。盡管人類尺度意義上的潔凈室與隔離器有很多相似之處，但是它們之間依然有許多明顯區(qū)別，因此這篇技術(shù)報告嘗試著將重點關(guān)注和論述這些區(qū)別。2.0TYPESOFISOLATORS隔離器的類型2.1ClosedIsolators密閉式隔離器Isolatorsoperatedasclosedsystemsdonotexchangeunfilteredairorcontaminantswithadjacentenvironments.Theirabilitytooperatewithoutpersonnelaccesstothecriticalzonemakesisolatorscapableoflevelsofseparationbetweentheinternalandexternalenvironmentunattainablewithothertechnologies.Becauseoftheeffectivenessofthisseparation,closedisolatorsareideallysuitedforapplicationinthepreparationofsterileand/ortoxicmaterial.當(dāng)隔離器處于密閉式系統(tǒng)操作時，它和周圍相鄰環(huán)境中沒有與未過濾空氣或者污染物的交換。隔離器能夠在沒有人員進入其關(guān)鍵區(qū)域進行操作，表明了隔離器在其他技術(shù)不能達到的分離其內(nèi)部環(huán)境和外部環(huán)境的能力水平。鑒于這種高效的隔離效果，封閉式隔離器能很好的適用于無菌制備和/或者對有毒材料的處理。Therearetwotypesofclosedisolators:asepticandcontainment.Asepticisolatorsareintendedtoexcludeexternalcontaminationfromthecriticalzoneinsidetheisolator.Containmentisolatorsareintendedtopreventthereleaseoftoxicmaterialsprocessedinsidetheisolatortothesurroundingenvironmentinwhichpersonnelarelocated這里有兩種類型的封閉式的隔離器：無菌的和抑制的。無菌隔離器是用于從隔離器內(nèi)部的關(guān)鍵區(qū)域排除外部污染物。抑制作用的隔離器是用于在隔離器內(nèi)部進行有毒材料工藝時防止有毒材料被釋放到人員所處的周圍環(huán)境當(dāng)中。2.1.1ClosedIsolatorsIntendedforAsepticApplications無菌應(yīng)用的封閉式隔離器Theseunitsaretypicallyoperatedunderpositivepressureandaresubjecttovalidatabledecontaminationprocedurespriortouse.Isolatorsintendedfortheprocessingofsterilematerialsadheretothefollowinggeneralprinciples:此設(shè)備典型的是在正壓情況下進行操作的，并在使用前服從經(jīng)過驗證的凈化規(guī)程。用于無菌原料工藝的的隔離器遵循以下幾點總則：·Theymustnotexchangeairwiththesurroundingenvironmentexceptwhenthatairpassesthroughamicrobiallyretentivefilter.除非有高效微生物過濾器系統(tǒng)，它絕對不允許與周圍環(huán)境發(fā)生空氣交換。·Theymustbedecontaminatedinareproducibleandquantifiablemanner.必須利用可再生的和可量化的方式對其進行凈化處理?！llworkorhandlingofmaterialswithintheisolatorenclosuremustbeaccomplishedremotely;nohumanoperatororpartthereofcandirectlyentertheisolatorduringoperation.隔離器內(nèi)部所有對原料進行的加工或者處理都是在遠(yuǎn)程操作模式下完成的。操作期間操作人員或者其身體的任何部份不允許直接進入隔離器內(nèi)部進行操作?！llmaterialsthatentertheisolatormustbedecontaminatedorsterilizedandmustentereitherdirectlythroughadecontaminatingorsterilizingsystem,orviaarapidtransferport.所有進入隔離器的原料都是必須經(jīng)過凈化或者滅菌處理的，并且是通過凈化或者滅菌系統(tǒng)直接進入，又或者是通過快速傳輸接口進入的。2.1.2ClosedIsolatorsIntendedforContainmentApplications抑制應(yīng)用的封閉式隔離器Theseunitsgenerallyoperateundernegativepressureandareclearedofallpotentiallyhazardousmaterialspriortoopening.Isolatorsintendedforcontainmentapplicationsadheretothefollowinggeneralprinciples:這類設(shè)備通常是在負(fù)壓條件下進行操作的并且在將其打開之前已清除了所有潛在的有毒物質(zhì)的存在，用于抑制作用的隔離器遵循以下幾點總則：.Theymustnotexchangeairwiththesurroundingenvironmentexceptwhenthatairpassesthroughafiltercapableofretainingthematerialsbeingprocessed.除非通過有能保存加工處理的原料的高效過濾器，它們絕對不允許與周圍環(huán)境有空氣交換發(fā)生。.Allworkorhandlingofmaterialswithintheisolatorenclosuremustbeaccomplishedremotely.Nohumanoperatororpartthereofcandirectlyentertheisolatorduringoperation.隔離器內(nèi)部所有對原料進行的加工或者處理都是在遠(yuǎn)程操作模式下完成的。操作期間操作人員或者其身體的任何部份不允許直接進入隔離器內(nèi)部進行操作。?Allmaterialsexitingtheisolatormustbecleanedorcontainedinsuchawaythathazardousmaterialsarenotreleasedtothesurroundingenvironment.所有由隔離器排除的原料都必須經(jīng)過凈化或者對其進行包裝，以保證沒有危害物質(zhì)被釋放到周圍環(huán)境當(dāng)中。Theymustbecleanableinareproducibleandquantifiablemanner.必須利用可再生的和可量化的方式對其進行凈化處理。2.1.3ClosedIsolatorsIntendedforAsepsisandContainment同時用于無菌和抑制作用的封閉式隔離器Theseunitsaresubjecttotheconstraintsofsections2.1.1and2.1.2,above.Theyaretypicallyoperatedunderpositivepressure,withadditionalsafetymeasuressuchasnegativepressureairlocks.Theuseofsupplementarypersonalprotectiveequipmentbytheworkersmaybeconsidered.這些設(shè)備受上面第2.1.1和2.1.1章節(jié)的參數(shù)限制。通常情況下它們是在正壓情況下進行操作的，另外附加一些比如負(fù)壓氣塞的安全措施。工人所用到的輔助性的個人安全設(shè)施是需要考慮到的。2.2OpenIsolators開放式隔離器Openisolatorsdifferfromclosedisolatorsinthattheyaredesignedtoallowforthecontinuousorsemi-continuousingressand/oregressofmaterialsduringoperation,whilemaintainingalevelofprotectionovertheinternalenvironment.Openisolatorsdonotexchangeunfilteredairorcontaminantswithadjacentenvironments.Openisolatorsaredecontaminatedwhileclosed,andthenopenedduringmanufacturing.Openisolatorstypicallyareusedfortheasepticfillingoffinishedpharmaceuticals.與封閉式隔離器不同，它們在設(shè)計時考慮到了在保持對內(nèi)部環(huán)境的保護等級水平的基礎(chǔ)上，操作期間原料的連續(xù)或者半連續(xù)的進入和/或者送出。開放式隔離器不會與周圍相鄰環(huán)交換未過濾的空氣或者污染物。開放式隔離器在關(guān)閉時對其進行凈化，在生產(chǎn)中將其打開，開放式隔離器的典型應(yīng)用時用于成品藥的無菌灌裝。2.2.1OpenIsolatorsIntendedforAsepticApplications開放式隔離器的無菌應(yīng)用Withtheexceptionofthepresenceofopeningsduringmanufacturing,openisolatorssatisfythesamegeneralprinciplesasnotedaboveforclosedisolators.Therearenumerousdesignsthatcansuccessfullymanagetheingressandegressofcomponentsoffilledcontainers,whilepreventingtheingressofcontaminationfromthesurroundingenvironment除了工業(yè)生產(chǎn)中目前的開放式設(shè)備，開放式隔離器同樣的與上面提到的封閉式隔離器的要求總則一樣，目前很多種設(shè)計都能很成功在防止周圍環(huán)境中的污染進入的基礎(chǔ)上對灌裝容器的部件進行進/出處理。2.2.2OpenIsolatorsIntendedforAsepsisandContainment開放式隔離器的無菌和抑制應(yīng)用Theseisolatorssharesimilaritieswiththeordinaryopenisolator(see2.2.1)andthecontainmentisolator(see2.1.1).Forthesesystems,thedesignusuallyincorporatesacleaningprocesstoallowforremovalofanytoxiccontaminantfromtheexteriorofthesealedcontainerpriortoexitfromtheisolator.Thedesignmustalsopreventtheingressofairinordertopreservetheasepticnatureoftheinternalenvironment.這類隔離器與普通的開放式隔離器（見2.2.1）和抑制性隔離器（見2.2.1）有類似之處，對于這個系統(tǒng)而言，設(shè)計時通常包含一個潔凈工序，就是在密閉容器在移出隔離器之前清除其表面的所有有毒污染物。Thefollowingdiagramprovidesanoverviewofisolators,barriersystems,andcleanroomsdepictingsomeoftheiroperatingcharacteristicsandapplication.Itshouldbenotedthatthesystemsattheedgeofthedrawingareessentiallyequivalent,andaffordminimalprotectiontothematerialsandpersonnel.下面的示圖提供了隔離器，障礙系統(tǒng)和潔凈室的概觀，并描述了它們的一些操作參數(shù)和應(yīng)用。需要注意到的是圖紙邊上所畫的系統(tǒng)基本上是一樣的，并且要對原料和人員提供最基本的保護。3.0ISOLATORDESIGNANDGENERALCONSTRUCTION隔離器的設(shè)計和總體結(jié)構(gòu)Isolatorsmaybemanufacturedofanysuitablematerialprovidedtheisolatorsatisfiesthefunctionalrequirementsestablishedforit,andthematerialissufficientlyruggedtoresistpunctureordamagethatcouldaffectsystemintegrity.Ingeneral,isolatorsaretermedeither"flexiblewall"or"rigidwall"dependingupontheirgeneralconstruction.Isolatorsthatareusedincontainmentapplicationsareoftenofrigidwallconstructionbecausethesesystemsallowforamoreaggressivecleaningofsurfaces.隔離器可以是由任何能滿足隔離器本身功能要求的合適材料制成的，這類材料能很好的抵抗能對系統(tǒng)完整性造成影響的外部損傷。一般而言，鑒于其總體構(gòu)造可將隔離器稱為“柔性墻”或者“剛性墻”。由于允許對其表面進行腐蝕性清洗，因此用于抑制應(yīng)用的隔離器通常是剛性墻構(gòu)造。3.1MaterialsofConstruction構(gòu)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薄板是柔性墻隔離器構(gòu)造中最普遍的材料，柔性墻隔離器已經(jīng)成功的應(yīng)用于無菌測試和制造業(yè)隔離器。PVC隔離器表面的罩子是利用金屬材料(不銹鋼)框架將其支撐起來的。這里用到的PVC板需要有能足夠的厚度來抵抗外部的穿透力。UV（紫外）線，或者化學(xué)試劑比如溶劑等能對PVC材料的隔離器造成傷害。PVC最常見的用于0.5立方米到8立方米范圍內(nèi)的隔離器的表面材料，但是其他一些型號的也可能適用。通常來說可以承受反復(fù)暴露于滅菌/消毒劑的無電抗性的PVC材料廣泛地用于隔離器的和它內(nèi)部機構(gòu)。如果要考慮除塵度，那么的墻與地板的結(jié)合處和裂縫的光滑度是很重要的。如果要求要有較高的除塵度，則就需要考慮用到不銹鋼材料制成的具有光滑斜面的地板。3.1.2StainlessSteel不銹鋼Stainlesssteeliscommonlyusedasaflooringmaterialinbothrigidwallandflexiblewallisolators.Stainlesssteelisthemostcommonlyusedwallandceilingmaterialinrigidwallisolators.300seriesstainlesssteelsaregenerallyused,typicallyeither304or316grade.Whereweldingisaconsideration,orprolongedexposuretohalogensaltsorothercorrosivesubstancesisexpected,lowcarbon(304L,316L)shouldbeconsidered.Thesurfacefinishismostcriticalinthoseapplicationsforwhichcleanabilityisanimportantuserrequirement.Formanyasepticprocessapplications,onlyageneral"buff"finishisrequired;forcleanability,however,higherlevelsofpolishuptoandincludingelectropolish(RA5-7micrometers)canbeconsidered.不論是在剛性墻還是柔性墻的隔離器不銹鋼材料都是最普遍的用于制作其地板的材料。在剛性墻隔離器中不銹鋼最常見的應(yīng)用是用來制作其墻和頂板。300系列的不銹鋼是最常用的，通常用到是304不銹鋼或者是316不銹鋼。如果考慮到焊點，或者長期暴露于鹵素鹽或者其他一些預(yù)料到的腐蝕性的物質(zhì)中時，可以考慮用到低碳（304L，316L）不銹鋼。如果除塵度是很重要的使用要求，那么對其表面的拋光處理就是最重要的一個環(huán)節(jié)。對于一些無菌工藝的應(yīng)用，采用一般“拋光”處理即可，而對于有除塵度要求來說，要求將其提升到更好水平的拋光處理時可以考慮利用電解拋光法。3.1.3GlazingMaterials玻璃質(zhì)材料Manyisolatorshaverigidwindowstoalloweasyviewoftheprocessescontainedwithintheisolator.Themostcommonlyusedmaterialsforthesewindowsarepolycarbonate(i.e.,Lexan?),acrylicplastics,ortemperedglass.Themostimportantconsiderationintheuseofwindowsisthemountingofthewindowtotheisolatorframework.Thewindowmountingassemblyorframemayeitherbepermanentlyorsemi-permanentlyboltedinplace,oritmaybedesignedtobeeasilyopenedtoallowaccesstotheinterioroftheisolatorwhentheunitisundergoingmaintenanceorchangeover.Itisimportantthatthecleanabilityofthewindowmountandsealisconsideredandthatthegasketmaterialischosenwithfullconsiderationofitscompatibilitywithcleaningagentsandsanitizing/sterilizingchemicals.為了方便觀察隔離器內(nèi)部工藝，許多隔離器都安裝有固定的剛性窗口。最普遍的用于制作這種窗口的材料是聚碳酸酯（比如萊克桑），丙烯酸塑料，或者鋼化玻璃。這里首先要考慮的是窗口的安裝。這些窗口或者框架可以是被永久性鎖住或者是暫時性的鎖住，又或者是可以設(shè)計成可以很方便的打開用于專門人員進入隔離器內(nèi)部進行維護或者更換等。重要的是窗口的安裝要考慮到除塵度和密封性并且要考慮到所選擇的作為墊圈的材料與清潔劑和消毒/滅菌化學(xué)藥劑的相容性Windowsshouldprovideadistortionfreeviewoftheinterioroftheisolatorandadequatelightshouldbeprovidedforsafeandeffectiveworkingconditions.Itmaybepreferabletohavelightingfixtureslocatedoutsidetheisolatorinordertoavoidexposingthemtocleaningandsanitizingagents.窗口要保證對隔離器內(nèi)部操作無失真的觀察效果并且要為其內(nèi)部操作的安全和效率提供足夠的光線。為了避其暴露于清潔和消毒劑當(dāng)中更好的方法是在隔離器外部安裝有照明器材。Anumberofsuccessfulsmallrigidwallisolatordesignshaveutilizedaplasticenclosure,typicallyofacrylic,thatisbondedwithcement.Inthisdesign,theisolatorisbuiltcompletelywithoutaframe.Isolatorsofthisconstructionmaybeimpracticalforlargesystemswithcomplexair-handlingrequirements,however,theyareveryusefulforsmallportablesystemsandforcontainmentapplications.Framelessdesignshavetheadvantageofsuperiorvisibilityofinterioroperationsandrelativelylowercost.許多的成功性的小型剛性墻隔離器實例設(shè)計使用塑料作為其外殼的，代表性的材料是丙烯酸塑料，它是利用黏固劑進行黏合的。在這種情況下，這類隔離器的建造完全脫離的了框架結(jié)構(gòu)。對于有復(fù)合空氣處理要求的大型系統(tǒng)來說這類結(jié)構(gòu)的隔離器往往并不實用，然而，它們非常適用于便攜式系統(tǒng)和抑制應(yīng)用?？蚣芙Y(jié)構(gòu)的設(shè)計的優(yōu)點在與能夠很清晰的觀察隔離器內(nèi)部操作并且相對來說其成本較低。3.1.4OtherMaterials其他材料Anymaterialthatissuitablystrong,cleanable,andresistanttocleaningandsanitizingagentscouldbeusedtobuildisolatorsystems.Isolatorsareequippedwithgloves,half-suits,doorgaskets,filtergasketsandothermaterials,allofwhichmustbecompatiblewiththematerialsprocessedwithinand/orusedupontheisolatorforcleaninganddecontamination.Thereneedbenorestrictionontheuseofmaterialsprovidedthefunctionalrequirementsinclude:所有用于建造隔離器系統(tǒng)的材料都要符合牢固，可清洗性，并且對清潔劑和消毒劑有較好的抗性。隔離器裝備有手套，半身服，門墊圈，過濾器墊圈和其他一些材料，所有這些材料都要適合于上面說到的用于潔凈和凈化的隔離器中所提到的材料處理。需要指出的是對這些材料無使用限制并且對其功能要求如下：?Chemicalcompatibilitywithproductionmaterials,decontaminationandcleaningagents與生產(chǎn)原料，凈化機和清潔劑的化學(xué)相容性?Structuralintegrity構(gòu)造的整體性?Cleanability(tothedegreerequired)可清潔性3.2OperatorInterface操作界面Isolatorsaredesignedtopreventtheexchangeofcontaminationbetweentheenclosedworkenvironmentandthesurroundingenvironmentinwhichpersonnelarelocated.Therefore,manipulationsofmaterialswithintheisolatormustbemadeeitherviaglovesorbodysuits,orauto-manipulators.Thedesignexecutionofinterfacedevicesiscriticalbothtosuccessfulintegrationofequipmentintotheisolatorsystem,andtotheavoidanceofprocesshazardsthatcouldaffectproductqualityandoperatorsafety.Thefollowingguidelinesshouldbeconsideredindesignandrealizationofisolatorbasedsystems:隔離器的作用是用來防止在密閉的工作環(huán)境與人員所處的周圍環(huán)境之間發(fā)生污染的交換。因此，對隔離器內(nèi)部的原料的操作必須通過手套或者全身服，或者是自動機械臂實現(xiàn)。操作界面的設(shè)計操作對于成功地集成進入隔離器系統(tǒng)內(nèi)部的設(shè)備和避免可能影響產(chǎn)品質(zhì)量和操作人員安全的工藝風(fēng)險來說是至關(guān)重要的。在設(shè)計和實現(xiàn)隔離器的基礎(chǔ)系統(tǒng)時需要考慮到以下幾點指導(dǎo)方針：?Theuseofautomationtoreducetheneedforhumaninterfaceduringisolatoroperationsincludingcleaning.自動化技術(shù)的使用降低了在操作和清洗隔離器時對人工操做界面的需求。?Wherehumaninterfaceisunavoidable,ergonomicsshouldbesystematicallyevaluatedandcarefullyexecuted.如果人機操作接口是必不可少的，那么必須要對人機工程學(xué)進行系統(tǒng)的評估并謹(jǐn)慎的執(zhí)行。?Designororientationofequipmentsothattroubleshootingandroutinemaintenancecanbeaccomplishedwithoutdisruptiontotheisolatorenvironmentisbeneficialandshouldbeincorporatedwherepossible.對設(shè)備的設(shè)計或校準(zhǔn)以便故障診斷和日常維護可以在不破壞隔離器內(nèi)部環(huán)境的境況下實現(xiàn)，這是有益的并且要在合適的地方應(yīng)用到。3.2.1Gloves/Sleeves手套/套筒Oneofthemostcommonlyuseddevicesforconductingmanipulationswithintheisolatoristheglove/sleeveassembly.Theglove/sleeveassembliesusedwithinisolatorsfallintotwobroadcategories:一種最普遍用于控制隔離器內(nèi)部操作的設(shè)備就是手套/套筒的組合體。隔離器內(nèi)部用到的手套/套筒組合體分為兩種大致類型。?One-pieceassemblyinwhichthegloveandsleeveareofasingle,unbrokenpiece.Theseassembliescanbeofvariouslengthstoallowforeitherpartialorfullarmlengthmanipulations.單件組合體指手套和套筒都是單件連接的一整件。這種組合體可以提供不同長度，既允許手臂的部分進入進行操作也可以整只手臂都進去進行操作。?Two-pieceassembliesinwhichthegloveandsleeveareseparateandareconnectedatthegauntletbysometypeofsealsystem.Liketheone-pieceassemblies,thesetwo-piecearrangementscanbefoundinanumberoflengths.Mostimportantly,thetwo-pieceassemblyallowsfortherelativelysimplechange-outofgloves.Someisolatormanufacturerssuggestthatitispossibletochangethegloveinatwo-pieceglove/sleeveassemblywithoutcompromisingtheasepticenvironmentwithintheisolator.Thepracticeofchangingglovesduringasepticproductionoperationsmustbecautiouslyconsidered,however.雙件套組合體指手套和套筒是分開的并且利用某些類型的密封系統(tǒng)在長手套處有連接。與單件組合體一樣，雙件套組合同樣可以提供許多種不同長度。更重要的是，相對而言雙件套組合更容易更換手套。一些隔離器制造商建議在不破壞隔離器內(nèi)部環(huán)境時對雙件套組合進行手套更換。不管怎樣，在無菌生產(chǎn)操作中更換手套必須小心謹(jǐn)慎。Thematerialofconstructionofthegloveisgenerallyacompromisebetweentactilerequirementsandresistancetotearsandpinholes.Thedesignershouldconsiderthetypeofworkthatwillbeperformedusingthegloves,andthefrequencywithwhichtheywillbeusedduringoperations.CommonlyusedglovematerialsincludeNeoprene?andHypalon?.Someusershaveoptedtouseadoubleglovearrangementtominimizethepossibilityofatearorleakcompromisingtheenvironmentwithintheisolator.Intheseinstances,anordinarysetofsterilelatexglovesisplacedoverorundertheglovesinstalledontheisolator.Thelatexglovescanbechangedasoperationalconditionswarrant手套的構(gòu)造材料是介于有觸覺要求和能抗撕裂和刺穿之間的折中性材料。設(shè)計人員必須考慮到使用手套時的工作類型和在操作過程中對手套的使用頻率。通常用于制作手套的材料包括Neoprene?andHypalon?兩種。一些使用者往往在隔離器內(nèi)部環(huán)境中采用雙手套的方式將撕裂或者刺穿的可能性降到最小。在這個實例中，一個普通的無菌膠乳手套被置于安裝在隔離器上的手套的上面或者下面。如果操作條件許可，可以對膠乳手套進行更換。Anotherfactorthatmustbeconsideredintheselectionofglovematerialischemicalresistance.Itisimperativethattheglovesbesufficientlyresistanttodecontaminatingchemicals,cleaningagents,andprocessmaterials.在手套材料的選擇方面另一個必須考慮到的因素是化學(xué)抗性。極為重要的是手套對化學(xué)制劑，清潔劑和工藝原料有很好的抗性。Overand/orunderglovingduringcriticaltaskscanincreaseworkerprotectionbyaddinganextralayerofprotection.Overglovesmaybehardtofitoverthepermanentlyinstalledglovesontheisolatorandmayreducefeel,makingdelicatemanipulationsdifficult.However,overglovesprovidebetteroperatorprotection.Overglovescanbereplacedasrequiredbyextragloveskeptinsidetheisolator.Underglovesareeasiertofitontheoperator'shandsanddon'timpactmanipulations,buttheyarelesssafeastheupperarmisstillexposedundertheisolatorgloves.在關(guān)鍵性的任務(wù)中使用手套操作可通過增加額外防護層來提高對工人的保護。外層的手套在安裝上有困難并且能降低人的手指的感覺，在比較細(xì)膩的操作上有困難。盡管如此，外層的手套為操作者能提供更好的保護。在副手套保留在隔離器內(nèi)部時可以對外層手套進行更換。內(nèi)層的手套很容易的倍套在操作者手上并且不影響操作。但是由于手臂上半部分依然暴露于隔離器手套下，因此它能提供的安全防護有限。Theimpactofglovescanbereducedbycarefulselectionofmaterialsofconstruction.Theamountofusetheglovesreceiveandthetypesofmaterialsutilizedinproductionandcleaningoperationsaffectglovelife.Manysolventsandtheirvaporsareabletochemicallyattackgloves(thisincludesanydecontaminatingagents).Glovesshouldbechangedonaperiodicandpre-emptivebasisbeforelossofintegrity.Glovesshouldbeexaminedfrequentlypriortoandduringuse.Wherepossible,toolsshouldbeusedratherthanglovedhandstocontactcontaminatedparts,equipment,andsurfaces.Ingeneral,manualtasksshouldbeavoidedwhereverpossible.通過細(xì)心選擇手套的構(gòu)造材料可以降低手套帶來的負(fù)面影響。使用手套的數(shù)量和手套的構(gòu)造材料在生產(chǎn)和清潔操作中會影響手套的使用壽命。一些化學(xué)溶劑和它們的蒸汽會腐蝕手套（這里包含所有的去污劑）。在手套失去完整性之前應(yīng)對其進行定期的更換。在使