PDA TR40氣體除菌過濾-2005（中英文）

PDAJournalofPharmaceuticalScienceandTechnologySterilizingFiltrationofGases氣體過濾除菌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過 114.4MaterialsofConstruction構造材料 4.4.4ParticleShedding 4.4.5Gas/FilterCompatibility氣體/ 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挑戰(zhàn)懸浮液的制備 7.2.3AerosolBacterialChallengeConditi 7.2.3.2ChallengeCondi 207.2.3.3ChallengeConcentrationandL 207.2.4ChallengeTestMet 7.2.5InterpretationofResults結果解釋 7.3Viral(Bacteriophage)AerosolCha 7.3.2ViralAerosolChallengeConditions 7.3.2.3ChallengeCondi 7.3.2.4ChallengeLevel/Infectivit 7.3.3ChallengeTestMet 237.3.4InterpretationofResults結果解釋 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因此在醫(yī)藥企業(yè)中，尤其是注射用藥物的生Earlyandcarefulscreeningofpotentialfiltertypesandconfigurationscamoreefficientprocessingandgreatersterilityassurance.Althoughothertypesoffilterscanbeemployedintheandremovalofliquiddropletsbycoalescence,thefocuobjectiveistoassistthereaderintheselection,qualification,andvalidmostgasapplicationsusehydrophobicfilters,thisdoesnotprecludetheuseofhinformationontheuseofhydrophilicfilters,refertoPDATechnicalReportNo.26.仔細篩選過濾類型和配置能減少技術和管理問題，減少延遲，增加效率并提高滅菌保證性。部分氣體應用程序使用疏水過濾器，這并不妨礙在干燥氣體系統(tǒng)中使用疏水過濾器。疏水過濾器使用的更多信息參見PDAThisreportisintendedtocomplementPDATechnicalReportNo.26:SterilizingFiltrationofLiquids,andlikeotherPDATechniFiltrationofairandothergaseshasalwaysbeenusedinawiderangeofapplicationswithinthepharmaceuticalandbiotechnologyindustry.Thefirstgenerationobottlestolargepackedtowers.Typically,suchdepthfilterswereusedinconjunctionwithelevatedtemoisturewithinthefiltermedi管道或瓶子里的小栓塞到大的填料塔。特別是，這樣的深層過濾器用于連接Thesecondgenerationofgasfiltersconsistsofdepthcartridgesofborosilicateorpolypropylenecomposavailableinconfigurationsthatareeasiertouse,ansticsasaconsequenceofimprovednon-wovenmedia(fleece)technologiesandmoreappropriatemefconstruction.Theretentioncapabilityofsuchcartridgescphthalate)test(discussedlaterinSectsomelimitations,particularlywithregardtothepotentialforbacterialbreakthrough.Thisledtothedevelopmentofhydrophobmembranefilterelemen第二代氣體過濾器由硼硅酸鹽或聚丙烯合成物深層支架組成。這些支架可用于更易于使用的們作為改進的非織物（羊毛）介質(zhì)技術的結果，具有更好的持續(xù)滯留特性和更適合的實施方法滴氣溶膠挑戰(zhàn)試驗如DOP測試。然而這些第二代支架的深層介質(zhì)持續(xù)體現(xiàn)出限制性，尤其與細Comparedtotheearlierdepthmedia,hydrophobicmembranematerialshavetheadvantagblockage.Whilesomeoftheearlymembraneshadtoberenderedhydrophobicbysiliconecoatingorsimilarsurmadeofinherentlyhydrophobicpolymershavebeenavailableforovertwodecades.Themostcommonpolymersusedofhydrophobicmembranesarepolytetrafluoroethylene(PTFE),polyviny(PE).Hydrophobicmembranescanbeproducedinmoredefinedrangesofretentionratingsthandepthmedia,andtheirretentioncapabelementsareavailableinvaadvantageoverdepthmediaisthattheretentionintegritytests,asdiscussedlaterinthisrepo與早期深層介質(zhì)對比，疏水膜材料本身就有更耐水阻塞的優(yōu)點。而一些早期的膜通由固有疏水性聚合物制成的膜已經(jīng)使用超過20年乙烯。疏水膜與深層介質(zhì)相比，能產(chǎn)生更清晰范5的不同壓力。過濾器濾芯可用于各種結構，包括Ingasfiltration,asinliquidfiltration,sizeexclusion(alsoreferredtoretentionfromadrygasstream.Asthenameimplipaththroughthefiltermaterial.fretentionisindependentofthevelocityoftheairstreamthroughthefilter.Retention氣體過濾和液體過濾一樣，尺寸排阻（也指過濾篩或機械滯留）是微粒從干燥氣體蒸汽中思，這個機制應用于因為太大而不能滲透過給定的小孔的微粒，它們沿著彎曲的途過程中不變形，滯留的類型不依賴于穿過過濾器的空氣蒸汽速度。尺寸3.2RetentionofSmallinterception,inertialimpaction,andelectrostaticattraction.Thesemechanismscontributiontotheoverallretentionefficiencydependsstronglyonthesizeofthe氣體中小于實際孔尺寸的微粒滯留率還能通過一些額外的機制發(fā)生，例如擴散攔截、慣性接觸或足夠接近過濾材料的微粒，具有相對強的粘著力。這些額外的機制總是出現(xiàn)，但是他們3.2.1DiffusionalIntercInthediffusionalintercausedbyconstantandrandombombardmentoftheparticlesbyairmolecules.Brownianmotionbetweentheparticleandthefiltermedium;hence,itincreasestheprobabilityofparticlesizedecrea在擴散攔截機制中，圖2說明，由于微粒任意撞擊引起的布朗運動使微粒偏離氣流流線，布朗運動增加了微粒和過濾介質(zhì)接觸的可能性。因此，增加了微粒滯留的可能性。然而，對更小的顆粒布朗運動變得更顯著，3.2.2InertialImFigure3illustratesthemechanismofinertialimpaction.Theinertiaoftheparticlekeepsitfromfollowingthestreamlinesasthegascircumventsthefiltermaterial,causingittocollidewiththefiltermedium.This圖3說明慣性阻塞的機制。當氣體包圍過濾材料時hence,theretentionefficiencybythismechanismincreaseswithparticlesize.Inthecaseofsub-micretentionoflargeparticlesbythismecdepthfilters,however,inertialimpactionplaysagreaterrolebyretainingparticlesthatarelesslikelytobeexclusion.因此，這個機制下的滯留效率隨微粒尺寸增加。次留。然而，在粗糙深層過濾器中，慣性阻塞起了更3.2.3GravitationalSedimeParticlescanalsodeviatefromtheflowpathandcollidewiththefiltermediabygravitationalsedimentation.Muchlikeinertialimpthismechanismismorepronouncedforlargerparticles,particularlythoseofhighmembranes,thismechanismisnotveryimpocaseindepthfilters)aremorelikelyret對于次微米疏水膜，這個機制不是很重要，因為通過重力沉降保留下的微粒更可能因為尺3.2.4ElectrostaticADependingonthenatureoftheparticleandthefiltermaterial,intermolecularforcesmayretainpartincontactwiththefiltermaterial.Theywillbefirmlyretained,evenduringpressurepstrongerthanthedragexertedbythegasstreamflowupontheparticleandULPA(UltraLowPenetrationAir)filters,whicharenotwithinthescopeofthisdocument,electrostaticcaptureofparticloppositechargeisaneffectivemechanism.Theeffectivenessofsuchfiltersdependsontwthevelocity.Humiditymustbelowbecauseelectrostaticchar基于微粒的性質(zhì)和過濾器材料，分子間作用力使很接近的微粒與過濾器材料接觸。甚至在壓因為結合力比氣流對粒子的拖拽力強很多倍。特別電荷的粒子的靜電俘獲是有效的機制。這種過濾器Dryairalsoreducesthedangeroftimethatissufficientlylongtogenerateenoughsepa3.3NetRetentionEfficiencyinFiltrationofDryGases干燥空氣過濾的凈保留效率smallparticlesareretainedpredominantlybyinertialimpaction,gravitationalsedimentation,andsizeexclusionbecomemorepronounced.Thesizediffusionalinterceptiontoinertialimpactiontypicallyoccursincludesparticlesofasizethatarenotcapturedbyeitheroftheseretentionmechanisms,asillustratedinFigure4.ThesizeoftheparticleleastlikelytoberetPenetratingParticleSize(微粒的凈保留效率是各個機制觀察效果的總和。以給定的氣流速度，非常小的微粒主要被擴制不很顯著，而慣性阻塞、重力沉降、尺寸排阻更為明顯。從擴散攔截到慣性阻塞，尺寸范被這些機制中的任何一種所虜獲。在圖4中說明。被滯留可能性最小的粒子TheMPPSwillnotonlydependonthetypeoffiltermaterial,butalsoonthegasvelocitpronouncedathighervelocitiesandpressures;thinterceptiondiminishes.Theeffectofairvelocityontheinertialimpactionmechanismislesspronounced,particularlyinthecaseoftightereffectisashiftoftheMPPSasafunctionofairvelocretentioncharacteristicsfromadrygasstream.Additionalinformationonthetheo以較高氣流速度，通過擴散攔截機制俘獲給定大小的粒子的可能性減小。在慣性阻塞這樣的信息已經(jīng)考慮在內(nèi)。關于滯留機制理3.4FactorsthatAffecttheRetentionEffi7Asdiscussedabove,themostreliablemechanismofparticleretentionfromagasstrearetentionefficiencyremainsrelativelyunaffectedbyonthesizeofthecontaminanttoberetainedinrelationtotheactualporesizeofthemembraneinquesti如上討論，微粒從膜過濾器干燥氣流中滯留的最可靠機制是尺寸排usedwiththenominalmicrffiltersoffered.Suchnomenclatureisintendedmainlyforlabelingpurposes.Howevfilterforagivenapplicationbasedsolelyonthenumeriretentivehydrophobicgasfiltersas0.2micronasar準確的孔尺寸不能與生產(chǎn)商對各種不同類型的過濾器指定的微米等級混淆。這樣的術語級上缺少一致性或者使用不同的過濾器材料，甚至對于同一家生產(chǎn)商，選擇過濾器同的滯留機制涉及無菌氣體過濾，孔徑率比在液體過濾中的意義又更少。大部分廠Therefore,gasfiltersarebestdescribedbythpresenceofmoistureintheformofcondensateaffectsthefiltrdiscussedforvariousapplicationslaterinthisrep因此，氣體過濾器通過它們在挑戰(zhàn)實驗中的性能進行描述，這部分在章節(jié)7中。最多的應用，濕氣以冷凝物的形式出現(xiàn)，對過濾工藝產(chǎn)生不利影響，但是保持過濾元件干燥的方法在這4.FILTERSELECTIONANDSYSTEMDESISelectionofasterilizinggasfilterrequiresconsiderationofmanyimportantissdurability,compatibilitywithprocessingconditions,andultimatelytheoverallecono氣體滅菌過濾器的挑選要求考慮許多重要問題，滯留效率的范圍通過物理耐受力，與工藝條件的兼容挑選標準的重要性主要取決于應用，但是對于許多應用，以berequiredforsomeofthemretentionefficiencyrequirementscanbeclassifiedinthefollowingth在醫(yī)藥企業(yè)中，疏水膜過濾應用于許多方面。一些更關鍵的應用要求非常嚴格的滯留期望值，criticalsurfacesoftheassociatedequipment.Examplesincludethefiltrationofcompressedgasesassociateblanketgasandventingofsterilebulkproductholdingtanks,andvacuumbreakapplicationsselectedforsuchcriticalapplicationsshouldbequalifianappropriatephysicalintegritytestthatiscorrelatedtothebacterialretentioncapabilit最嚴格的預期值出現(xiàn)在氣體滅菌應用中，過濾的氣體直接接觸滅菌終產(chǎn)品或者相關設關的壓縮氣體的過濾、填充氣、無菌散裝產(chǎn)品儲存器的排氣、冷凍干燥器中真空輔助剎車應用程序挑選過濾器應符合適當?shù)囊簯B(tài)細菌滯留挑戰(zhàn)測試，并且必須有合適的與液體過濾器中細菌滯留能力相關的物理完整性測Examplesincludemanyintermedwithaerosol-basedbacterialchallengetestsandwithphysicalintegrityteststh相對緊要的程序是那些過濾氣體不能直接接觸無菌產(chǎn)品或其表面的。實例包括許多中間處理于這些應用，過濾器符合氣溶膠細菌挑戰(zhàn)測試以及與氣溶膠的Applicationsthatonlyrecapabilityoffiltersusedinthistypeofapplication.僅要求減少生物負荷的應用程序沒有這么嚴格的要求。因為滯留期望值與高效空氣過濾器的期望Classificationofagivconsideration.Otherapplicationtations,orvirusretentionincriticalapplications.Anumberofafcontaminants,includingbacteriaandphage,undervariouscontechnicalliterature.However,theapplicabilityofsuchdatatoagivensituationmustbecarefullyevonacase-by-casebaAsdictatedbytheapplication,itmaybeimportanttobeabletoverifyphysicaltesttoassurethedesiredretentioncapability.Mor通過非破壞性物理測試方法驗證過濾器元件的完整性是重要的，這些物理測試可以保證達到4.3FiltrationRateanmaterials,thethickness,porosityandpore-sizedistributionofthemedia,amongothers,aswellastheretentionchar在給定壓力下，過濾器的流速取決于許多因素，包括膜類型和載體材料，厚度，孔隙率，媒介Foragiventypeoffilter,theflowrateincreaseswiththeeffectivefiltratiofilterareaornumberofindividuversusdifferentialpressuredata,typicallypresentedbythefiltermantheextentofpluggingtobetoleratedhastobeconsideredinthecalculationoftnecessarytoconsiderthepressuredropoftheentiresystthesterilizingfilterholder.Considerationshouldaorsteam-in-placerequirem對于給定類型的過濾器，流速隨有效過濾面積增加，但不是線性比例。對特別的無菌過濾應用件的數(shù)量可以從潔凈氣體流量與壓差的數(shù)據(jù)比進行評估，以圖形或者表格的形式由生產(chǎn)廠商給積時，在堵塞可忍受的范圍內(nèi)考慮添加合適的修正值。有必要考慮整個系統(tǒng)的壓力下降，包括以及無菌濾紙夾。對于應用的任何特殊特性都應該考慮到，例如高泵出率或者steam-Thethroughputofthesterilizingfiltercanbeincreasedconotbelimitedbyplugging,butratherbythenumberofsterilizationcycles,theelementcanwithstandbeforelosingphysicalinte無菌過濾器的生產(chǎn)能力能通過使用預過濾增加。此外，過濾器使用壽命不會被阻塞限制4.4MaterialsofCon9Sterilizingmembranestypicallyaremanufacturedfrompolymerssuchmembrane,assembledfilterelements,particularlypleatedfilmaterials.Typically,theselayersconsistofahydrophobicpolypropylenenon-wovenmedium(fleece),andthepinpolypropylenebyathermalbondingprocess.Polypropylenestainlesssteelorothermaterialstoenhancethedurabilityofthecartridgegivenapplication.Themaresistance,chemicalcompatibilityandresistancetooxidation,anparticularapplicatio無菌膜用聚合物制成，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，組裝過濾元件，特別是濾芯包括上/下游支撐物和排水材料。通常，這些薄層有疏水聚丙烯非織物媒介組成，并且通過熱結合法包埋件常用的材料，包括外部的保持架，內(nèi)部的支撐核心，和密封蓋。有些濾芯元件和環(huán)形適配器便增強支架的耐用性。各種環(huán)形材料可用于滿足給定應用的需要。構造的材料對組裝過濾器元熱阻、化學相容性和抗氧化性和力學性能。用戶應Inordertoreducethepotentialforblockagebymoistureaccumulatingwithinthefilterelement,particularlywithintheporestrumembrane,thematerialsofconstructionshouldbehydrophobic.Hydrophobicityisarecomparedtothecohesiveenergyoftheliquid.Water,withasurfacetensionof72dynescohesiveforceexceedstheadhesiveforce,通過在過濾器元件中增加濕度，減少堵塞的可能性。特別是在薄膜的孔隙結構，構造的材料表面能量與液體的內(nèi)聚能相比較。水，表面張力Thedegreeofhydrophobicityofamaterialcanbeexpressoccurs,namely,thecriticalsurfacetension.Ofthepopularmaterialsmentioned,PTFEisthemosthydrophobicandpolyethascanbeseenfromthecritiThefilterelementhastobeabletowithstandtherigorsoftheintendedapplicathematerialsofconstructionpressurelimitsacrosstheelementafiltersinaccordancewiththeneedsoftheirparticularpoffilterintegrityandtheassociatedreductioninretentioncapability.Lossofintegritycanalsobetheconsefmaterialsofconstructionmustbeselectedorthefilterchange-outfrequencyshould濾芯必須能經(jīng)受住特定應用的要求。過濾器廠商口和不同的壓力限制指定為溫度的根據(jù)和水流方向。用戶依照特殊過程的需要選擇過濾器，并且必須對于這樣的應用，必須挑選合適的結構材料或者應該調(diào)整過濾器Durabilityisparticularlyimportanumberofsteamsterilizationcyclesagivenfilterelementcanwithsdiscussedinmoredetailb耐用性在過濾器元件的蒸汽滅菌中尤其重要。事實上，一些應用的經(jīng)濟性視蒸汽滅菌However,mostelementssThesetestsinvolveastatimembraneandsupportmaterialsdonotadverselyaffectthesafetyoftheproduct.FiltersupplitothestandardUnitedStatesPharmacop件的評估。進行這些測試以保證濾膜和支撐材料不影響產(chǎn)品的安全性。過濾器供應商提供毒性數(shù)據(jù)，依據(jù)標準Particlesheddingneedslinesandbreakingthevacuumattheendoffreeze-drparticles,thepossibilityofmediamigrationshouldbeconsideredatheliquidisconsideredtoprovideamorestringenttest慮媒介移動的可能性并評估那些被認為是重要的應用。用液體評估顆粒脫落，液體的高粘度被認為是提4.4.5Gas/FilterIncompatibilitiesbetweenthefilterandthExcessivetemperaturescanresult(underflowconditions),cancaususceptiblesupportcomponentslongbeforethereisanyloss或者可能導致完整性損失。有任何完整性損失之前，取決于溫度、濃度、和時間的氧化氣體Duetoflammabilityissuall-fluoropolymermaterialsofconstructiverifythatthefiltefwatervaporcanoccurwithinthefiltrationsystem.Accinterferingwithfilterperformance.Theaccumulaabove,reducestheseadverseef在許多的應用中，氣體過濾器與水或含水產(chǎn)品直接接觸。甚至，水汽凝結會在過濾系統(tǒng)中發(fā)生體的流動，因此干擾過濾器性能。積聚的水會促進細菌和真菌的生長，并且在所有無菌氣體Eventhemosthydrophobicoffilterscanendupliquid-loggedundersomecircumstances,particularlyduringsteamingandintegritblow-downtime,providerecommendsthatflushingwithaminimumof75cubicfeetofairuleofthumbfordryinghydrophobicf器providedthatthefilterassemblyisproperlyoriented,withtheoutletendpointeddownward。4.6DesignConsiderationsforCondensatioAccumulationofwaterwithinthefilterelementorthehminimizedbytheuseofcoalescingpre-filters.Theaccumulationofmoisturewithinthefilterhousingcanbereducedbyopeningthelowerhousingvent.Accumulationofmoisturewithinthefiltermembrane(typically3-5°Cabove)relativetotheprocesstemperhousing中水滴的量能通過使用聚結預過濾達到最小。Housing中濕氣的積累通過打開下箱體出氣孔而減小。處理濾膜上積累的濕氣可以通過保持過濾系統(tǒng)在相對工藝溫度更高的溫Potentialsolutionstotheproblemincludeselectingafiltelementitself.解決問題的方法包括：挑選備有蒸汽夾套的過濾器殼或者裝有電熱示蹤劑或外殼和相關管道是Whenusingsteam-jacketedorheat-tracedhousings,itshouldbenotedthatmanymaterialsofconstruction(especificationsfrommanymanufacturerswillstatealomaterials(suchasspeciallyformulatedpolypropylene同高氣流會加速對氧化過濾元件的破壞。避免溫度超過過濾5.EXAMPLESOFSPECIMostapplicationsforh?Thefiltermustretainmicroorganisms,evenun過濾器應該具有耐高溫和機械抗力，足以承受?Thefiltershouldwithstandmul?Thefiltershould?Themembraneshouldbehydrophobictoresis?Thefiltermustbeintegritytestablewitha?Thefilter'smaterialsofconstructionshouldbecompatiblewithtTherelativeimportanceorneedforsuThebroadest,mostcriticaluseofsterilizinggradehydrophobicmembranefiltefilledproducts.Thisincludesprocessgasesusedintanksorheadspacegasesus無菌等級疏水膜過濾器的最廣泛、最關鍵的應用是對于那些直接接觸醫(yī)減少降解。接觸溶液的任何氣體應該是無菌的，以保持滅菌產(chǎn)品的低生物負Duetothecriticalnatureoftheseapplberoutinelyintegrity-testedinusetoassuretheirefficacy.Membranematerialsshouldbfuse,especiallyiffilterunitsaresteamed-orsterilized-in-place.13Thevolumeofairrequiredtomaintainthefermentalargefilterassemblies.Theairsupplyneedstoberelicontaminationproblemsintheprocess.Filtersusedinfermentationprocessesshouldmeethhighflowratesatarelativelylowprevolume,yetshowreliablemicrobialretentioncsterilizationcyclesatelevatedtemperatu要求保持發(fā)酵過程的空氣體積取決于工藝和培養(yǎng)物體積，并且過濾系統(tǒng)應該按大小分類。數(shù)百萬立方米，并且要求大型過濾裝配。為了避免過程中的污染問題，空氣供給應該能夠為過程的過濾器應該滿足高微生物滯留標準，以及在相對低壓條件下提供高流速。對于這種應積，表明可靠的微生物滯留能力。優(yōu)化過濾器濾芯的構造以避免水封阻。元件也要求耐高溫inturn,canresultinanundesirableincreaseoftheheadpressurewicanbeavoidedbychoosingthreachingthefilter.Thisisoftenaccomplishedbyhavingtheof膜過濾器應用于發(fā)酵尾氣。這個應用中的挑戰(zhàn)是高濕度和發(fā)酵尾氣中高水平微生物污染。當氣水封。應該設計尾氣系統(tǒng)防止冷凝和氣溶膠達到過濾Also,thereisapotentialforfoamtobecarriedodesignedandoperatedtoavoidfoaming.Foamingistypicallyreducedwithadditionofantifoamagentsormodificmedia.Indifficultprocesses,itmaybenecessarytoinstallame還有一種可能性是尾氣中帶有泡沫，能導致過濾器封阻。因此，系統(tǒng)應該設計并防止泡沫產(chǎn)生減少泡沫。在復雜的工藝中，可能需要安裝分離器以消除泡沫5.4VentFiltersonCompendialWaterandProducontaminationofthecontentsincriticalapplications,tadditiontotherigorofthesteamcycle,anotherchallengepresentedbythisapplicationisblockageofflowduetoentrapmentofmois儲存罐或傳輸罐也要蒸汽滅菌，因為滅菌循環(huán)末期進入罐中的空氣必須是無菌的。另外蒸汽循bulkofthecondensationwilltakeplacerapidly,theventfiltershouldbeproperlysizedtodelivertheequivalentofthetankvolumeofairinasmallperiodoftime.Ifnoappropriatemeasuresaretakentopreventthedisruptionofairflowthroughthevenconsiderablymoreexpensive.避免氣流通過排氣過濾器時被封阻，在蒸汽循環(huán)末期尤其重要。當容器冷卻后，蒸汽凝結產(chǎn)生真定律或者蒸汽表測定。例如，100°C，每升蒸汽凝結后為0.6毫升，體積減小幾乎1700倍。因為大量冷凝發(fā)生迅速短時間內(nèi)傳遞與容器體積等量的空氣。如果沒有適當?shù)拇胧﹣矸乐箽饬魍ㄟ^過濾器的干擾，那pressurehighenoughtodisplacethemoistureloasheat-tracedhousings,shouldbeseriouslyconsidered.Specialcareneedstobeassociatedwithblockageinthisapplication.Itisalsopruden器配套。然而，依賴這些特性的風險是產(chǎn)品損失，存在明顯的故障停機時間以取代閥瓣，以5.5LyophilizerandAutoclav冷凍干燥器和高壓滅菌鍋真空輔助剎車autoclavewillcomeincontactwithsterilecommoditiesorequipmenlyophilization/autoclavecyclemustbesteaminginplace.Thefiltermanufacturer'srecommendationsforsteamingorsterilizatioconsiderationsforintegritytestpract空氣進入冷凍干燥器腔室內(nèi)，將直接與無菌產(chǎn)品接觸。同樣的，進入高壓滅的措施。過濾器元件需要滅菌，大部分采用蒸汽滅菌。過濾器生產(chǎn)商對蒸汽或滅菌的建議應該上要求蒸汽。由于過濾器會經(jīng)歷重復蒸汽滅菌循環(huán)，過濾器應該耐用且通過完整性測試5.6GasUsedforDry用于干燥和輸送管線/灌裝線的氣體usedtoacceleratethedryingprocaccomplishedbypressurizingtheheadspaceintheholdingtank此外，在許多過程中，無菌散裝產(chǎn)品必須從滅菌腔內(nèi)轉移到灌裝生產(chǎn)線。通過在儲存器的shouldberoutinelysterilizedandintegrity-testedtoassuretheexpectedmi這種關鍵應用中的氣體必須是無菌的，并且無粒子，以及選擇合適的過濾Largeamountsofsterilecompressedairareneededtorunblportionsofthemachinetopreventtheingressofenvironmentalaircontainicriticalsurfacesaswelladurableandreliable.Thefiltersmustberoutinelysterilizedandintegrity-testedtoassur大量的無菌壓縮空氣需要進行吹風-填充-密封操作。通常，設備與一些不同的空氣過濾系統(tǒng)配套，為了提供無菌氣體到各個過程步驟，例如鑄造主要容器或保護設備的關鍵部位以防止帶有細菌和微粒的環(huán)境空氣進入。耐用并可靠。過濾器必須無菌且通過完整性測試以5.8EnvironmentalAirin15Isolatortechnologyhandweighingandhandlingofsterileandevennon-sterilepotentcompounds.Dependingonthornegativepressurerelativetothesurroundingenvironment.Whicheverthemodeofoperation,filtrationofmake-upandexhaustairaccomplishtheairexchangretentionoftoxicpowdersfromtheexhaustortheadmissiprogramthatshouldbeimplement在過去的幾十年中，分離技術在關鍵應用中已經(jīng)普及了，例如無菌測試，無菌灌裝，和滅菌的稱重和處理，甚至非無菌化合物。依賴于這些應用，分離器可以在與周圍環(huán)境呈正壓或負壓下運行。無論何種運行模式，過濾器無論是有毒粉末滯留或無菌空氣進入，就越應該進行無菌6.STERILIZATIONOFHYDROPHOsterilizationmethodforhydrophopoorheattransfercharacteristicsoftheplasticcomponents,thelargsteampenetration,andthelimitedstabilityofsomeofthematerialsofconstructionatelevatedtemperatures.Therefore,filterusersshouvalidatethesterilizationofthefiltertodocumentthatanappropriatelevelo用于無菌過濾操作的過濾器元件必須是無菌的。對疏水膜過濾器滅菌的最普通方法是一傳導特性、濾孔內(nèi)大量空氣、蒸汽滲透、和構造材料在高溫下的限制穩(wěn)定性，可能阻礙蒸汽滅菌Thefilterelementmustwithstfollowthefiltermanufacturers'sterilizationguidelinestoavoidexcessiveexposurebesusceptibletodamageifnotsterilizedproperly.Usersshouldcontactthefiltermanufacturer過濾器元件必須承受與滅菌過程相關的壓力，這個滅菌過程要求無菌并不存在物理完整性損失。在許多的應用中，“無菌等級”疏水膜過濾器重復使用或長期使用。因此，應該承受多重滅菌循環(huán)。通常，使用者應該按過多暴露，因為如果滅菌不恰當，過濾器膜或者其他元件可能被破壞。使用者應該聯(lián)系adverselyaffectthephysicalintegrityofthefilter.However,highertemperature大多數(shù)無菌膜過濾器由生產(chǎn)商通過高壓滅菌器滅菌溫度最少121°C最高140°C，證明其合格。溫度高于140°C可能使許多塑料部件不穩(wěn)定，并對物理完整性測試帶來不利影響。然而，如果能夠證明過濾器不會受suitablemicrobialbarrierthatpreventscontaminationofthesterilefiltercomponentspost-sterilization.Thebarriermustallowpenetration.Thefiltercartridgeshouldbeproperlysupportedduringsterilizaticycleinitiationbyaseriesofvacuumcyclesorflushingthechamberwithpulsesofsteafiltershouldbeorientedhorizontally,orwiththeoutletpointeddownward,tosterilizationparameters.Forallapplications,theautoclavecycleshouldbevalidatedtoyieldthed使用高壓滅菌法，過濾器的準備是非常關鍵的。重要的是要保護使用合適的微生物屏障的過濾元件。微生物屏障必須允許蒸汽進入滅菌器，以充分滅菌。至關重要的是，過濾器進，汽滲透。該濾芯在消毒期間應有適當支持物支撐，以防止變形。為確保正確蒸汽滲透，必須或與出口向下，以方便去除冷空氣和從核心凝結。通常，使用緩慢的排氣或液體循環(huán)。用戶制造商的規(guī)格。更大的過濾器或連接管或附屬設備的過濾器可能需要調(diào)整殺菌參數(shù)。對于所Dryingofthesterilizedfilterisgenerallyaccomplishedbyapplyingapperformedoff-linepriortoinstallationofthefilter.Ifthesecases,theintegritytestsh消毒過濾器的干燥通常是通過應用完成后循環(huán)真空和空的位置。在這類應用中，過濾器安裝前，完整性測試也可進行。這些情況下，完整性測試應在適當?shù)沫h(huán)境進行，如工作的HEPAe