PDA TR40气体除菌过滤-2005（中英文）

PDAJournalofPharmaceuticalScienceandTechnologySterilizingFiltrationofGases气体过滤除菌TechnicalReportNo.40SupplementVol.58,No.S-1January/February2005 72.HISTORICALBACKGRO 73.HOWGASFILTERSWO 73.2RetentionofSmallerPart 7 8 93.2.4ElectrostaticAttr 93.3NetRetentionEfficiencyinFiltrationofDryGases 93.4FactorsthatAffecttheRetentionEfficienc 104.FILTERSELECTIONANDSYS 4.2IntegrityTesting 4.3FiltrationRateandThroughput过 114.4MaterialsofConstruction构造材料 4.4.4ParticleShedding 4.4.5Gas/FilterCompatibility气体/ 12 4.6DesignConsiderationsforCondensation 14 5.2FermentorInlet 5.4VentFiltersonCompendialWaterandProduct 5.5LyophilizerandAutocla 15 5.7Blow-Fill-SealEquipme 155.8EnvironmentalAirinIsola 166.STERILIZATIONOFHY 16 6.3OtherSterilizationMe 177.VALIDATIONOFFILTERRETENTIO 17 7.1.2ChallengeConcentrationandEffectiveCha 7.1.3Pre-ChallengeIntegrityTe 18 7.1.5Post-ChallengeIntegrityTe 19 7.2AerosolBacterialRetentionT 7.2.2PreparationoftheChallengeSuspension挑战悬浮液的制备 7.2.3AerosolBacterialChallengeConditi 7.2.3.2ChallengeCondi 207.2.3.3ChallengeConcentrationandL 207.2.4ChallengeTestMet 7.2.5InterpretationofResults结果解释 7.3Viral(Bacteriophage)AerosolCha 7.3.2ViralAerosolChallengeConditions 7.3.2.3ChallengeCondi 7.3.2.4ChallengeLevel/Infectivit 7.3.3ChallengeTestMet 237.3.4InterpretationofResults结果解释 8.PHYSICALINTEGRIT 248.1.2ManualDiffusive/ForwardFlo 8.1.2.1DownstreamMeasureme 8.1.2.2UpstreamMeasure 8.1.3ManualPressureHold/Pr 8.2WaterIntrusionIntegrityTestAppr 8.3AerosolIntegrit 8.5ConsiderationsforIntegrityTestP 8.6TroubleshootingIntegrityTestFail 9.USERRESPONSIBILITIESFORTHEV 33 AppendixA:TheoreticalAspectsofRetentionMechanismsinAir AppendixB:Maintenance,Preparation,andCharacterizationofBrevundimonas AppendixC:FilterValidationRecommend AppendixD:TheoreticalAspectsofIntegrityTesting SterilizingfiltrationofaprocesUndercertaincircumstances,othercontaminantssarmaceuticalindustry,particularlyintheproductionofparenterals,thereisawiderangfairorotherprocessgasesisa因此在医药企业中，尤其是注射用药物的生Earlyandcarefulscreeningofpotentialfiltertypesandconfigurationscamoreefficientprocessingandgreatersterilityassurance.Althoughothertypesoffilterscanbeemployedintheandremovalofliquiddropletsbycoalescence,thefocuobjectiveistoassistthereaderintheselection,qualification,andvalidmostgasapplicationsusehydrophobicfilters,thisdoesnotprecludetheuseofhinformationontheuseofhydrophilicfilters,refertoPDATechnicalReportNo.26.仔细筛选过滤类型和配置能减少技术和管理问题，减少延迟，增加效率并提高灭菌保证性。部分气体应用程序使用疏水过滤器，这并不妨碍在干燥气体系统中使用疏水过滤器。疏水过滤器使用的更多信息参见PDAThisreportisintendedtocomplementPDATechnicalReportNo.26:SterilizingFiltrationofLiquids,andlikeotherPDATechniFiltrationofairandothergaseshasalwaysbeenusedinawiderangeofapplicationswithinthepharmaceuticalandbiotechnologyindustry.Thefirstgenerationobottlestolargepackedtowers.Typically,suchdepthfilterswereusedinconjunctionwithelevatedtemoisturewithinthefiltermedi管道或瓶子里的小栓塞到大的填料塔。特别是，这样的深层过滤器用于连接Thesecondgenerationofgasfiltersconsistsofdepthcartridgesofborosilicateorpolypropylenecomposavailableinconfigurationsthatareeasiertouse,ansticsasaconsequenceofimprovednon-wovenmedia(fleece)technologiesandmoreappropriatemefconstruction.Theretentioncapabilityofsuchcartridgescphthalate)test(discussedlaterinSectsomelimitations,particularlywithregardtothepotentialforbacterialbreakthrough.Thisledtothedevelopmentofhydrophobmembranefilterelemen第二代气体过滤器由硼硅酸盐或聚丙烯合成物深层支架组成。这些支架可用于更易于使用的们作为改进的非织物（羊毛）介质技术的结果，具有更好的持续滞留特性和更适合的实施方法滴气溶胶挑战试验如DOP测试。然而这些第二代支架的深层介质持续体现出限制性，尤其与细Comparedtotheearlierdepthmedia,hydrophobicmembranematerialshavetheadvantagblockage.Whilesomeoftheearlymembraneshadtoberenderedhydrophobicbysiliconecoatingorsimilarsurmadeofinherentlyhydrophobicpolymershavebeenavailableforovertwodecades.Themostcommonpolymersusedofhydrophobicmembranesarepolytetrafluoroethylene(PTFE),polyviny(PE).Hydrophobicmembranescanbeproducedinmoredefinedrangesofretentionratingsthandepthmedia,andtheirretentioncapabelementsareavailableinvaadvantageoverdepthmediaisthattheretentionintegritytests,asdiscussedlaterinthisrepo与早期深层介质对比，疏水膜材料本身就有更耐水阻塞的优点。而一些早期的膜通由固有疏水性聚合物制成的膜已经使用超过20年乙烯。疏水膜与深层介质相比，能产生更清晰范5的不同压力。过滤器滤芯可用于各种结构，包括Ingasfiltration,asinliquidfiltration,sizeexclusion(alsoreferredtoretentionfromadrygasstream.Asthenameimplipaththroughthefiltermaterial.fretentionisindependentofthevelocityoftheairstreamthroughthefilter.Retention气体过滤和液体过滤一样，尺寸排阻（也指过滤筛或机械滞留）是微粒从干燥气体蒸汽中思，这个机制应用于因为太大而不能渗透过给定的小孔的微粒，它们沿着弯曲的途过程中不变形，滞留的类型不依赖于穿过过滤器的空气蒸汽速度。尺寸3.2RetentionofSmallinterception,inertialimpaction,andelectrostaticattraction.Thesemechanismscontributiontotheoverallretentionefficiencydependsstronglyonthesizeofthe气体中小于实际孔尺寸的微粒滞留率还能通过一些额外的机制发生，例如扩散拦截、惯性接触或足够接近过滤材料的微粒，具有相对强的粘着力。这些额外的机制总是出现，但是他们3.2.1DiffusionalIntercInthediffusionalintercausedbyconstantandrandombombardmentoftheparticlesbyairmolecules.Brownianmotionbetweentheparticleandthefiltermedium;hence,itincreasestheprobabilityofparticlesizedecrea在扩散拦截机制中，图2说明，由于微粒任意撞击引起的布朗运动使微粒偏离气流流线，布朗运动增加了微粒和过滤介质接触的可能性。因此，增加了微粒滞留的可能性。然而，对更小的颗粒布朗运动变得更显著，3.2.2InertialImFigure3illustratesthemechanismofinertialimpaction.Theinertiaoftheparticlekeepsitfromfollowingthestreamlinesasthegascircumventsthefiltermaterial,causingittocollidewiththefiltermedium.This图3说明惯性阻塞的机制。当气体包围过滤材料时hence,theretentionefficiencybythismechanismincreaseswithparticlesize.Inthecaseofsub-micretentionoflargeparticlesbythismecdepthfilters,however,inertialimpactionplaysagreaterrolebyretainingparticlesthatarelesslikelytobeexclusion.因此，这个机制下的滞留效率随微粒尺寸增加。次留。然而，在粗糙深层过滤器中，惯性阻塞起了更3.2.3GravitationalSedimeParticlescanalsodeviatefromtheflowpathandcollidewiththefiltermediabygravitationalsedimentation.Muchlikeinertialimpthismechanismismorepronouncedforlargerparticles,particularlythoseofhighmembranes,thismechanismisnotveryimpocaseindepthfilters)aremorelikelyret对于次微米疏水膜，这个机制不是很重要，因为通过重力沉降保留下的微粒更可能因为尺3.2.4ElectrostaticADependingonthenatureoftheparticleandthefiltermaterial,intermolecularforcesmayretainpartincontactwiththefiltermaterial.Theywillbefirmlyretained,evenduringpressurepstrongerthanthedragexertedbythegasstreamflowupontheparticleandULPA(UltraLowPenetrationAir)filters,whicharenotwithinthescopeofthisdocument,electrostaticcaptureofparticloppositechargeisaneffectivemechanism.Theeffectivenessofsuchfiltersdependsontwthevelocity.Humiditymustbelowbecauseelectrostaticchar基于微粒的性质和过滤器材料，分子间作用力使很接近的微粒与过滤器材料接触。甚至在压因为结合力比气流对粒子的拖拽力强很多倍。特别电荷的粒子的静电俘获是有效的机制。这种过滤器Dryairalsoreducesthedangeroftimethatissufficientlylongtogenerateenoughsepa3.3NetRetentionEfficiencyinFiltrationofDryGases干燥空气过滤的净保留效率smallparticlesareretainedpredominantlybyinertialimpaction,gravitationalsedimentation,andsizeexclusionbecomemorepronounced.Thesizediffusionalinterceptiontoinertialimpactiontypicallyoccursincludesparticlesofasizethatarenotcapturedbyeitheroftheseretentionmechanisms,asillustratedinFigure4.ThesizeoftheparticleleastlikelytoberetPenetratingParticleSize(微粒的净保留效率是各个机制观察效果的总和。以给定的气流速度，非常小的微粒主要被扩制不很显著，而惯性阻塞、重力沉降、尺寸排阻更为明显。从扩散拦截到惯性阻塞，尺寸范被这些机制中的任何一种所虏获。在图4中说明。被滞留可能性最小的粒子TheMPPSwillnotonlydependonthetypeoffiltermaterial,butalsoonthegasvelocitpronouncedathighervelocitiesandpressures;thinterceptiondiminishes.Theeffectofairvelocityontheinertialimpactionmechanismislesspronounced,particularlyinthecaseoftightereffectisashiftoftheMPPSasafunctionofairvelocretentioncharacteristicsfromadrygasstream.Additionalinformationonthetheo以较高气流速度，通过扩散拦截机制俘获给定大小的粒子的可能性减小。在惯性阻塞这样的信息已经考虑在内。关于滞留机制理3.4FactorsthatAffecttheRetentionEffi7Asdiscussedabove,themostreliablemechanismofparticleretentionfromagasstrearetentionefficiencyremainsrelativelyunaffectedbyonthesizeofthecontaminanttoberetainedinrelationtotheactualporesizeofthemembraneinquesti如上讨论，微粒从膜过滤器干燥气流中滞留的最可靠机制是尺寸排usedwiththenominalmicrffiltersoffered.Suchnomenclatureisintendedmainlyforlabelingpurposes.Howevfilterforagivenapplicationbasedsolelyonthenumeriretentivehydrophobicgasfiltersas0.2micronasar准确的孔尺寸不能与生产商对各种不同类型的过滤器指定的微米等级混淆。这样的术语级上缺少一致性或者使用不同的过滤器材料，甚至对于同一家生产商，选择过滤器同的滞留机制涉及无菌气体过滤，孔径率比在液体过滤中的意义又更少。大部分厂Therefore,gasfiltersarebestdescribedbythpresenceofmoistureintheformofcondensateaffectsthefiltrdiscussedforvariousapplicationslaterinthisrep因此，气体过滤器通过它们在挑战实验中的性能进行描述，这部分在章节7中。最多的应用，湿气以冷凝物的形式出现，对过滤工艺产生不利影响，但是保持过滤元件干燥的方法在这4.FILTERSELECTIONANDSYSTEMDESISelectionofasterilizinggasfilterrequiresconsiderationofmanyimportantissdurability,compatibilitywithprocessingconditions,andultimatelytheoverallecono气体灭菌过滤器的挑选要求考虑许多重要问题，滞留效率的范围通过物理耐受力，与工艺条件的兼容挑选标准的重要性主要取决于应用，但是对于许多应用，以berequiredforsomeofthemretentionefficiencyrequirementscanbeclassifiedinthefollowingth在医药企业中，疏水膜过滤应用于许多方面。一些更关键的应用要求非常严格的滞留期望值，criticalsurfacesoftheassociatedequipment.Examplesincludethefiltrationofcompressedgasesassociateblanketgasandventingofsterilebulkproductholdingtanks,andvacuumbreakapplicationsselectedforsuchcriticalapplicationsshouldbequalifianappropriatephysicalintegritytestthatiscorrelatedtothebacterialretentioncapabilit最严格的预期值出现在气体灭菌应用中，过滤的气体直接接触灭菌终产品或者相关设关的压缩气体的过滤、填充气、无菌散装产品储存器的排气、冷冻干燥器中真空辅助刹车应用程序挑选过滤器应符合适当的液态细菌滞留挑战测试，并且必须有合适的与液体过滤器中细菌滞留能力相关的物理完整性测Examplesincludemanyintermedwithaerosol-basedbacterialchallengetestsandwithphysicalintegrityteststh相对紧要的程序是那些过滤气体不能直接接触无菌产品或其表面的。实例包括许多中间处理于这些应用，过滤器符合气溶胶细菌挑战测试以及与气溶胶的Applicationsthatonlyrecapabilityoffiltersusedinthistypeofapplication.仅要求减少生物负荷的应用程序没有这么严格的要求。因为滞留期望值与高效空气过滤器的期望Classificationofagivconsideration.Otherapplicationtations,orvirusretentionincriticalapplications.Anumberofafcontaminants,includingbacteriaandphage,undervariouscontechnicalliterature.However,theapplicabilityofsuchdatatoagivensituationmustbecarefullyevonacase-by-casebaAsdictatedbytheapplication,itmaybeimportanttobeabletoverifyphysicaltesttoassurethedesiredretentioncapability.Mor通过非破坏性物理测试方法验证过滤器元件的完整性是重要的，这些物理测试可以保证达到4.3FiltrationRateanmaterials,thethickness,porosityandpore-sizedistributionofthemedia,amongothers,aswellastheretentionchar在给定压力下，过滤器的流速取决于许多因素，包括膜类型和载体材料，厚度，孔隙率，媒介Foragiventypeoffilter,theflowrateincreaseswiththeeffectivefiltratiofilterareaornumberofindividuversusdifferentialpressuredata,typicallypresentedbythefiltermantheextentofpluggingtobetoleratedhastobeconsideredinthecalculationoftnecessarytoconsiderthepressuredropoftheentiresystthesterilizingfilterholder.Considerationshouldaorsteam-in-placerequirem对于给定类型的过滤器，流速随有效过滤面积增加，但不是线性比例。对特别的无菌过滤应用件的数量可以从洁净气体流量与压差的数据比进行评估，以图形或者表格的形式由生产厂商给积时，在堵塞可忍受的范围内考虑添加合适的修正值。有必要考虑整个系统的压力下降，包括以及无菌滤纸夹。对于应用的任何特殊特性都应该考虑到，例如高泵出率或者steam-Thethroughputofthesterilizingfiltercanbeincreasedconotbelimitedbyplugging,butratherbythenumberofsterilizationcycles,theelementcanwithstandbeforelosingphysicalinte无菌过滤器的生产能力能通过使用预过滤增加。此外，过滤器使用寿命不会被阻塞限制4.4MaterialsofCon9Sterilizingmembranestypicallyaremanufacturedfrompolymerssuchmembrane,assembledfilterelements,particularlypleatedfilmaterials.Typically,theselayersconsistofahydrophobicpolypropylenenon-wovenmedium(fleece),andthepinpolypropylenebyathermalbondingprocess.Polypropylenestainlesssteelorothermaterialstoenhancethedurabilityofthecartridgegivenapplication.Themaresistance,chemicalcompatibilityandresistancetooxidation,anparticularapplicatio无菌膜用聚合物制成，例如聚四氟乙烯聚合物、聚偏二氟乙烯,聚丙烯或聚乙烯。除了膜，组装过滤元件，特别是滤芯包括上/下游支撑物和排水材料。通常，这些薄层有疏水聚丙烯非织物媒介组成，并且通过热结合法包埋件常用的材料，包括外部的保持架，内部的支撑核心，和密封盖。有些滤芯元件和环形适配器便增强支架的耐用性。各种环形材料可用于满足给定应用的需要。构造的材料对组装过滤器元热阻、化学相容性和抗氧化性和力学性能。用户应Inordertoreducethepotentialforblockagebymoistureaccumulatingwithinthefilterelement,particularlywithintheporestrumembrane,thematerialsofconstructionshouldbehydrophobic.Hydrophobicityisarecomparedtothecohesiveenergyoftheliquid.Water,withasurfacetensionof72dynescohesiveforceexceedstheadhesiveforce,通过在过滤器元件中增加湿度，减少堵塞的可能性。特别是在薄膜的孔隙结构，构造的材料表面能量与液体的内聚能相比较。水，表面张力Thedegreeofhydrophobicityofamaterialcanbeexpressoccurs,namely,thecriticalsurfacetension.Ofthepopularmaterialsmentioned,PTFEisthemosthydrophobicandpolyethascanbeseenfromthecritiThefilterelementhastobeabletowithstandtherigorsoftheintendedapplicathematerialsofconstructionpressurelimitsacrosstheelementafiltersinaccordancewiththeneedsoftheirparticularpoffilterintegrityandtheassociatedreductioninretentioncapability.Lossofintegritycanalsobetheconsefmaterialsofconstructionmustbeselectedorthefilterchange-outfrequencyshould滤芯必须能经受住特定应用的要求。过滤器厂商口和不同的压力限制指定为温度的根据和水流方向。用户依照特殊过程的需要选择过滤器，并且必须对于这样的应用，必须挑选合适的结构材料或者应该调整过滤器Durabilityisparticularlyimportanumberofsteamsterilizationcyclesagivenfilterelementcanwithsdiscussedinmoredetailb耐用性在过滤器元件的蒸汽灭菌中尤其重要。事实上，一些应用的经济性视蒸汽灭菌However,mostelementssThesetestsinvolveastatimembraneandsupportmaterialsdonotadverselyaffectthesafetyoftheproduct.FiltersupplitothestandardUnitedStatesPharmacop件的评估。进行这些测试以保证滤膜和支撑材料不影响产品的安全性。过滤器供应商提供毒性数据，依据标准Particlesheddingneedslinesandbreakingthevacuumattheendoffreeze-drparticles,thepossibilityofmediamigrationshouldbeconsideredatheliquidisconsideredtoprovideamorestringenttest虑媒介移动的可能性并评估那些被认为是重要的应用。用液体评估颗粒脱落，液体的高粘度被认为是提4.4.5Gas/FilterIncompatibilitiesbetweenthefilterandthExcessivetemperaturescanresult(underflowconditions),cancaususceptiblesupportcomponentslongbeforethereisanyloss或者可能导致完整性损失。有任何完整性损失之前，取决于温度、浓度、和时间的氧化气体Duetoflammabilityissuall-fluoropolymermaterialsofconstructiverifythatthefiltefwatervaporcanoccurwithinthefiltrationsystem.Accinterferingwithfilterperformance.Theaccumulaabove,reducestheseadverseef在许多的应用中，气体过滤器与水或含水产品直接接触。甚至，水汽凝结会在过滤系统中发生体的流动，因此干扰过滤器性能。积聚的水会促进细菌和真菌的生长，并且在所有无菌气体Eventhemosthydrophobicoffilterscanendupliquid-loggedundersomecircumstances,particularlyduringsteamingandintegritblow-downtime,providerecommendsthatflushingwithaminimumof75cubicfeetofairuleofthumbfordryinghydrophobicf器providedthatthefilterassemblyisproperlyoriented,withtheoutletendpointeddownward。4.6DesignConsiderationsforCondensatioAccumulationofwaterwithinthefilterelementorthehminimizedbytheuseofcoalescingpre-filters.Theaccumulationofmoisturewithinthefilterhousingcanbereducedbyopeningthelowerhousingvent.Accumulationofmoisturewithinthefiltermembrane(typically3-5°Cabove)relativetotheprocesstemperhousing中水滴的量能通过使用聚结预过滤达到最小。Housing中湿气的积累通过打开下箱体出气孔而减小。处理滤膜上积累的湿气可以通过保持过滤系统在相对工艺温度更高的温Potentialsolutionstotheproblemincludeselectingafiltelementitself.解决问题的方法包括：挑选备有蒸汽夹套的过滤器壳或者装有电热示踪剂或外壳和相关管道是Whenusingsteam-jacketedorheat-tracedhousings,itshouldbenotedthatmanymaterialsofconstruction(especificationsfrommanymanufacturerswillstatealomaterials(suchasspeciallyformulatedpolypropylene同高气流会加速对氧化过滤元件的破坏。避免温度超过过滤5.EXAMPLESOFSPECIMostapplicationsforh•Thefiltermustretainmicroorganisms,evenun过滤器应该具有耐高温和机械抗力，足以承受•Thefiltershouldwithstandmul•Thefiltershould•Themembraneshouldbehydrophobictoresis•Thefiltermustbeintegritytestablewitha•Thefilter'smaterialsofconstructionshouldbecompatiblewithtTherelativeimportanceorneedforsuThebroadest,mostcriticaluseofsterilizinggradehydrophobicmembranefiltefilledproducts.Thisincludesprocessgasesusedintanksorheadspacegasesus无菌等级疏水膜过滤器的最广泛、最关键的应用是对于那些直接接触医减少降解。接触溶液的任何气体应该是无菌的，以保持灭菌产品的低生物负Duetothecriticalnatureoftheseapplberoutinelyintegrity-testedinusetoassuretheirefficacy.Membranematerialsshouldbfuse,especiallyiffilterunitsaresteamed-orsterilized-in-place.13Thevolumeofairrequiredtomaintainthefermentalargefilterassemblies.Theairsupplyneedstoberelicontaminationproblemsintheprocess.Filtersusedinfermentationprocessesshouldmeethhighflowratesatarelativelylowprevolume,yetshowreliablemicrobialretentioncsterilizationcyclesatelevatedtemperatu要求保持发酵过程的空气体积取决于工艺和培养物体积，并且过滤系统应该按大小分类。数百万立方米，并且要求大型过滤装配。为了避免过程中的污染问题，空气供给应该能够为过程的过滤器应该满足高微生物滞留标准，以及在相对低压条件下提供高流速。对于这种应积，表明可靠的微生物滞留能力。优化过滤器滤芯的构造以避免水封阻。元件也要求耐高温inturn,canresultinanundesirableincreaseoftheheadpressurewicanbeavoidedbychoosingthreachingthefilter.Thisisoftenaccomplishedbyhavingtheof膜过滤器应用于发酵尾气。这个应用中的挑战是高湿度和发酵尾气中高水平微生物污染。当气水封。应该设计尾气系统防止冷凝和气溶胶达到过滤Also,thereisapotentialforfoamtobecarriedodesignedandoperatedtoavoidfoaming.Foamingistypicallyreducedwithadditionofantifoamagentsormodificmedia.Indifficultprocesses,itmaybenecessarytoinstallame还有一种可能性是尾气中带有泡沫，能导致过滤器封阻。因此，系统应该设计并防止泡沫产生减少泡沫。在复杂的工艺中，可能需要安装分离器以消除泡沫5.4VentFiltersonCompendialWaterandProducontaminationofthecontentsincriticalapplications,tadditiontotherigorofthesteamcycle,anotherchallengepresentedbythisapplicationisblockageofflowduetoentrapmentofmois储存罐或传输罐也要蒸汽灭菌，因为灭菌循环末期进入罐中的空气必须是无菌的。另外蒸汽循bulkofthecondensationwilltakeplacerapidly,theventfiltershouldbeproperlysizedtodelivertheequivalentofthetankvolumeofairinasmallperiodoftime.Ifnoappropriatemeasuresaretakentopreventthedisruptionofairflowthroughthevenconsiderablymoreexpensive.避免气流通过排气过滤器时被封阻，在蒸汽循环末期尤其重要。当容器冷却后，蒸汽凝结产生真定律或者蒸汽表测定。例如，100°C，每升蒸汽凝结后为0.6毫升，体积减小几乎1700倍。因为大量冷凝发生迅速短时间内传递与容器体积等量的空气。如果没有适当的措施来防止气流通过过滤器的干扰，那pressurehighenoughtodisplacethemoistureloasheat-tracedhousings,shouldbeseriouslyconsidered.Specialcareneedstobeassociatedwithblockageinthisapplication.Itisalsopruden器配套。然而，依赖这些特性的风险是产品损失，存在明显的故障停机时间以取代阀瓣，以5.5LyophilizerandAutoclav冷冻干燥器和高压灭菌锅真空辅助刹车autoclavewillcomeincontactwithsterilecommoditiesorequipmenlyophilization/autoclavecyclemustbesteaminginplace.Thefiltermanufacturer'srecommendationsforsteamingorsterilizatioconsiderationsforintegritytestpract空气进入冷冻干燥器腔室内，将直接与无菌产品接触。同样的，进入高压灭的措施。过滤器元件需要灭菌，大部分采用蒸汽灭菌。过滤器生产商对蒸汽或灭菌的建议应该上要求蒸汽。由于过滤器会经历重复蒸汽灭菌循环，过滤器应该耐用且通过完整性测试5.6GasUsedforDry用于干燥和输送管线/灌装线的气体usedtoacceleratethedryingprocaccomplishedbypressurizingtheheadspaceintheholdingtank此外，在许多过程中，无菌散装产品必须从灭菌腔内转移到灌装生产线。通过在储存器的shouldberoutinelysterilizedandintegrity-testedtoassuretheexpectedmi这种关键应用中的气体必须是无菌的，并且无粒子，以及选择合适的过滤Largeamountsofsterilecompressedairareneededtorunblportionsofthemachinetopreventtheingressofenvironmentalaircontainicriticalsurfacesaswelladurableandreliable.Thefiltersmustberoutinelysterilizedandintegrity-testedtoassur大量的无菌压缩空气需要进行吹风-填充-密封操作。通常，设备与一些不同的空气过滤系统配套，为了提供无菌气体到各个过程步骤，例如铸造主要容器或保护设备的关键部位以防止带有细菌和微粒的环境空气进入。耐用并可靠。过滤器必须无菌且通过完整性测试以5.8EnvironmentalAirin15Isolatortechnologyhandweighingandhandlingofsterileandevennon-sterilepotentcompounds.Dependingonthornegativepressurerelativetothesurroundingenvironment.Whicheverthemodeofoperation,filtrationofmake-upandexhaustairaccomplishtheairexchangretentionoftoxicpowdersfromtheexhaustortheadmissiprogramthatshouldbeimplement在过去的几十年中，分离技术在关键应用中已经普及了，例如无菌测试，无菌灌装，和灭菌的称重和处理，甚至非无菌化合物。依赖于这些应用，分离器可以在与周围环境呈正压或负压下运行。无论何种运行模式，过滤器无论是有毒粉末滞留或无菌空气进入，就越应该进行无菌6.STERILIZATIONOFHYDROPHOsterilizationmethodforhydrophopoorheattransfercharacteristicsoftheplasticcomponents,thelargsteampenetration,andthelimitedstabilityofsomeofthematerialsofconstructionatelevatedtemperatures.Therefore,filterusersshouvalidatethesterilizationofthefiltertodocumentthatanappropriatelevelo用于无菌过滤操作的过滤器元件必须是无菌的。对疏水膜过滤器灭菌的最普通方法是一传导特性、滤孔内大量空气、蒸汽渗透、和构造材料在高温下的限制稳定性，可能阻碍蒸汽灭菌Thefilterelementmustwithstfollowthefiltermanufacturers'sterilizationguidelinestoavoidexcessiveexposurebesusceptibletodamageifnotsterilizedproperly.Usersshouldcontactthefiltermanufacturer过滤器元件必须承受与灭菌过程相关的压力，这个灭菌过程要求无菌并不存在物理完整性损失。在许多的应用中，“无菌等级”疏水膜过滤器重复使用或长期使用。因此，应该承受多重灭菌循环。通常，使用者应该按过多暴露，因为如果灭菌不恰当，过滤器膜或者其他元件可能被破坏。使用者应该联系adverselyaffectthephysicalintegrityofthefilter.However,highertemperature大多数无菌膜过滤器由生产商通过高压灭菌器灭菌温度最少121°C最高140°C，证明其合格。温度高于140°C可能使许多塑料部件不稳定，并对物理完整性测试带来不利影响。然而，如果能够证明过滤器不会受suitablemicrobialbarrierthatpreventscontaminationofthesterilefiltercomponentspost-sterilization.Thebarriermustallowpenetration.Thefiltercartridgeshouldbeproperlysupportedduringsterilizaticycleinitiationbyaseriesofvacuumcyclesorflushingthechamberwithpulsesofsteafiltershouldbeorientedhorizontally,orwiththeoutletpointeddownward,tosterilizationparameters.Forallapplications,theautoclavecycleshouldbevalidatedtoyieldthed使用高压灭菌法，过滤器的准备是非常关键的。重要的是要保护使用合适的微生物屏障的过滤元件。微生物屏障必须允许蒸汽进入灭菌器，以充分灭菌。至关重要的是，过滤器进，汽渗透。该滤芯在消毒期间应有适当支持物支撑，以防止变形。为确保正确蒸汽渗透，必须或与出口向下，以方便去除冷空气和从核心凝结。通常，使用缓慢的排气或液体循环。用户制造商的规格。更大的过滤器或连接管或附属设备的过滤器可能需要调整杀菌参数。对于所Dryingofthesterilizedfilterisgenerallyaccomplishedbyapplyingapperformedoff-linepriortoinstallationofthefilter.Ifthesecases,theintegritytestsh消毒过滤器的干燥通常是通过应用完成后循环真空和空的位置。在这类应用中，过滤器安装前，完整性测试也可进行。这些情况下，完整性测试应在适当的环境进行，如工作的HEPAe