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(gòu)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(jié)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(jié)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(xì)篩選過濾類型和配置能減少技術(shù)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(yīng)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(jìn)的非織物（羊毛）介質(zhì)技術(shù)的結(jié)果，具有更好的持續(xù)滯留特性和更適合的實(shí)施方法滴氣溶膠挑戰(zhàn)試驗(yàn)如DOP測(cè)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(xì)Comparedtotheearlierdepthmedia,hydrophobicmembranematerialshavetheadvantagblockage.Whilesomeoftheearlymembraneshadtoberenderedhydrophobicbysiliconecoatingorsimilarsurmadeofinherentlyhydrophobicpolymershavebeenavailableforovertwodecades.Themostcommonpolymersusedofhydrophobicmembranesarepolytetrafluoroethylene(PTFE),polyviny(PE).Hydrophobicmembranescanbeproducedinmoredefinedrangesofretentionratingsthandepthmedia,andtheirretentioncapabelementsareavailableinvaadvantageoverdepthmediaisthattheretentionintegritytests,asdiscussedlaterinthisrepo與早期深層介質(zhì)對(duì)比，疏水膜材料本身就有更耐水阻塞的優(yōu)點(diǎn)。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(jié)構(gòu)，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(jī)械滯留）是微粒從干燥氣體蒸汽中思，這個(gè)機(jī)制應(yīng)用于因?yàn)樘蠖荒軡B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(shí)際孔尺寸的微粒滯留率還能通過一些額外的機(jī)制發(fā)生，例如擴(kuò)散攔截、慣性接觸或足夠接近過濾材料的微粒，具有相對(duì)強(qiáng)的粘著力。這些額外的機(jī)制總是出現(xiàn)，但是他們3.2.1DiffusionalIntercInthediffusionalintercausedbyconstantandrandombombardmentoftheparticlesbyairmolecules.Brownianmotionbetweentheparticleandthefiltermedium;hence,itincreasestheprobabilityofparticlesizedecrea在擴(kuò)散攔截機(jī)制中，圖2說明，由于微粒任意撞擊引起的布朗運(yùn)動(dòng)使微粒偏離氣流流線，布朗運(yùn)動(dòng)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(duì)更小的顆粒布朗運(yùn)動(dòng)變得更顯著，3.2.2InertialImFigure3illustratesthemechanismofinertialimpaction.Theinertiaoftheparticlekeepsitfromfollowingthestreamlinesasthegascircumventsthefiltermaterial,causingittocollidewiththefiltermedium.This圖3說明慣性阻塞的機(jī)制。當(dāng)氣體包圍過濾材料時(shí)hence,theretentionefficiencybythismechanismincreaseswithparticlesize.Inthecaseofsub-micretentionoflargeparticlesbythismecdepthfilters,however,inertialimpactionplaysagreaterrolebyretainingparticlesthatarelesslikelytobeexclusion.因此，這個(gè)機(jī)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(duì)于次微米疏水膜，這個(gè)機(jī)制不是很重要，因?yàn)橥ㄟ^重力沉降保留下的微粒更可能因?yàn)槌?.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?yàn)榻Y(jié)合力比氣流對(duì)粒子的拖拽力強(qiáng)很多倍。特別電荷的粒子的靜電俘獲是有效的機(jī)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(gè)機(jī)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(kuò)制不很顯著，而慣性阻塞、重力沉降、尺寸排阻更為明顯。從擴(kuò)散攔截到慣性阻塞，尺寸范被這些機(jī)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(kuò)散攔截機(jī)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(guān)于滯留機(jī)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(jī)制是尺寸排usedwiththenominalmicrffiltersoffered.Suchnomenclatureisintendedmainlyforlabelingpurposes.Howevfilterforagivenapplicationbasedsolelyonthenumeriretentivehydrophobicgasfiltersas0.2micronasar準(zhǔn)確的孔尺寸不能與生產(chǎn)商對(duì)各種不同類型的過濾器指定的微米等級(jí)混淆。這樣的術(shù)語級(jí)上缺少一致性或者使用不同的過濾器材料，甚至對(duì)于同一家生產(chǎn)商，選擇過濾器同的滯留機(jī)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?cè)谔魬?zhàn)實(shí)驗(yàn)中的性能進(jìn)行描述，這部分在章節(jié)7中。最多的應(yīng)用，濕氣以冷凝物的形式出現(xiàn)，對(duì)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(biāo)準(zhǔn)的重要性主要取決于應(yīng)用，但是對(duì)于許多應(yīng)用，以berequiredforsomeofthemretentionefficiencyrequirementscanbeclassifiedinthefollowingth在醫(yī)藥企業(yè)中，疏水膜過濾應(yīng)用于許多方面。一些更關(guān)鍵的應(yīng)用要求非常嚴(yán)格的滯留期望值，criticalsurfacesoftheassociatedequipment.Examplesincludethefiltrationofcompressedgasesassociateblanketgasandventingofsterilebulkproductholdingtanks,andvacuumbreakapplicationsselectedforsuchcriticalapplicationsshouldbequalifianappropriatephysicalintegritytestthatiscorrelatedtothebacterialretentioncapabilit最嚴(yán)格的預(yù)期值出現(xiàn)在氣體滅菌應(yīng)用中，過濾的氣體直接接觸滅菌終產(chǎn)品或者相關(guān)設(shè)關(guān)的壓縮氣體的過濾、填充氣、無菌散裝產(chǎn)品儲(chǔ)存器的排氣、冷凍干燥器中真空輔助剎車應(yīng)用程序挑選過濾器應(yīng)符合適當(dāng)?shù)囊簯B(tài)細(xì)菌滯留挑戰(zhàn)測(cè)試，并且必須有合適的與液體過濾器中細(xì)菌滯留能力相關(guān)的物理完整性測(cè)Examplesincludemanyintermedwithaerosol-basedbacterialchallengetestsandwithphysicalintegrityteststh相對(duì)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(shí)例包括許多中間處理于這些應(yīng)用，過濾器符合氣溶膠細(xì)菌挑戰(zhàn)測(cè)試以及與氣溶膠的Applicationsthatonlyrecapabilityoffiltersusedinthistypeofapplication.僅要求減少生物負(fù)荷的應(yīng)用程序沒有這么嚴(yán)格的要求。因?yàn)闇羝谕蹬c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(cè)試方法驗(yàn)證過濾器元件的完整性是重要的，這些物理測(cè)試可以保證達(dá)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(duì)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(duì)特別的無菌過濾應(yīng)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(jìn)行評(píng)估，以圖形或者表格的形式由生產(chǎn)廠商給積時(shí)，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(gè)系統(tǒng)的壓力下降，包括以及無菌濾紙夾。對(duì)于應(yīng)用的任何特殊特性都應(yīng)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(yù)過濾增加。此外，過濾器使用壽命不會(huì)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(jié)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(qiáng)支架的耐用性。各種環(huán)形材料可用于滿足給定應(yīng)用的需要。構(gòu)造的材料對(duì)組裝過濾器元熱阻、化學(xué)相容性和抗氧化性和力學(xué)性能。用戶應(yīng)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(jié)構(gòu)，構(gòu)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(yīng)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(duì)于這樣的應(yīng)用，必須挑選合適的結(jié)構(gòu)材料或者應(yīng)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(shí)上，一些應(yīng)用的經(jīng)濟(jì)性視蒸汽滅菌However,mostelementssThesetestsinvolveastatimembraneandsupportmaterialsdonotadverselyaffectthesafetyoftheproduct.FiltersupplitothestandardUnitedStatesPharmacop件的評(píng)估。進(jìn)行這些測(cè)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(yīng)商提供毒性數(shù)據(jù)，依據(jù)標(biāo)準(zhǔn)Particlesheddingneedslinesandbreakingthevacuumattheendoffreeze-drparticles,thepossibilityofmediamigrationshouldbeconsideredatheliquidisconsideredtoprovideamorestringenttest慮媒介移動(dòng)的可能性并評(píng)估那些被認(rèn)為是重要的應(yīng)用。用液體評(píng)估顆粒脫落，液體的高粘度被認(rèn)為是提4.4.5Gas/FilterIncompatibilitiesbetweenthefilterandthExcessivetemperaturescanresult(underflowconditions),cancaususceptiblesupportcomponentslongbeforethereisanyloss或者可能導(dǎo)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(shí)間的氧化氣體Duetoflammabilityissuall-fluoropolymermaterialsofconstructiverifythatthefiltefwatervaporcanoccurwithinthefiltrationsystem.Accinterferingwithfilterperformance.Theaccumulaabove,reducestheseadverseef在許多的應(yīng)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(jié)會(huì)在過濾系統(tǒng)中發(fā)生體的流動(dòng)，因此干擾過濾器性能。積聚的水會(huì)促進(jìn)細(xì)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(jié)預(yù)過濾達(dá)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(duì)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(guān)管道是Whenusingsteam-jacketedorheat-tracedhousings,itshouldbenotedthatmanymaterialsofconstruction(especificationsfrommanymanufacturerswillstatealomaterials(suchasspeciallyformulatedpolypropylene同高氣流會(huì)加速對(duì)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(yīng)該具有耐高溫和機(jī)械抗力，足以承受?Thefiltershouldwithstandmul?Thefiltershould?Themembraneshouldbehydrophobictoresis?Thefiltermustbeintegritytestablewitha?Thefilter'smaterialsofconstructionshouldbecompatiblewithtTherelativeimportanceorneedforsuThebroadest,mostcriticaluseofsterilizinggradehydrophobicmembranefiltefilledproducts.Thisincludesprocessgasesusedintanksorheadspacegasesus無菌等級(jí)疏水膜過濾器的最廣泛、最關(guān)鍵的應(yīng)用是對(duì)于那些直接接觸醫(yī)減少降解。接觸溶液的任何氣體應(yīng)該是無菌的，以保持滅菌產(chǎn)品的低生物負(fù)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(yīng)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(yīng)該能夠?yàn)檫^程的過濾器應(yīng)該滿足高微生物滯留標(biāo)準(zhǔn)，以及在相對(duì)低壓條件下提供高流速。對(duì)于這種應(yīng)積，表明可靠的微生物滯留能力。優(yōu)化過濾器濾芯的構(gòu)造以避免水封阻。元件也要求耐高溫inturn,canresultinanundesirableincreaseoftheheadpressurewicanbeavoidedbychoosingthreachingthefilter.Thisisoftenaccomplishedbyhavingtheof膜過濾器應(yīng)用于發(fā)酵尾氣。這個(gè)應(yīng)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(dāng)氣水封。應(yīng)該設(shè)計(jì)尾氣系統(tǒng)防止冷凝和氣溶膠達(dá)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(dǎo)致過濾器封阻。因此，系統(tǒng)應(yīng)該設(shè)計(jì)并防止泡沫產(chǎn)生減少泡沫。在復(fù)雜的工藝中，可能需要安裝分離器以消除泡沫5.4VentFiltersonCompendialWaterandProducontaminationofthecontentsincriticalapplications,tadditiontotherigorofthesteamcycle,anotherchallengepresentedbythisapplicationisblockageofflowduetoentrapmentofmois儲(chǔ)存罐或傳輸罐也要蒸汽滅菌，因?yàn)闇缇h(huán)末期進(jìn)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(shí)被封阻，在蒸汽循環(huán)末期尤其重要。當(dāng)容器冷卻后，蒸汽凝結(jié)產(chǎn)生真定律或者蒸汽表測(cè)定。例如，100°C，每升蒸汽凝結(jié)后為0.6毫升，體積減小幾乎1700倍。因?yàn)榇罅坷淠l(fā)生迅速短時(shí)間內(nèi)傳遞與容器體積等量的空氣。如果沒有適當(dāng)?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(fēng)險(xiǎn)是產(chǎn)品損失，存在明顯的故障停機(jī)時(shí)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(jìn)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(jìn)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(duì)蒸汽或滅菌的建議應(yīng)該上要求蒸汽。由于過濾器會(huì)經(jīng)歷重復(fù)蒸汽滅菌循環(huán)，過濾器應(yīng)該耐用且通過完整性測(cè)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(zhuǎn)移到灌裝生產(chǎn)線。通過在儲(chǔ)存器的shouldberoutinelysterilizedandintegrity-testedtoassuretheexpectedmi這種關(guān)鍵應(yīng)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(jìn)行吹風(fēng)-填充-密封操作。通常，設(shè)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(gè)過程步驟，例如鑄造主要容器或保護(hù)設(shè)備的關(guān)鍵部位以防止帶有細(xì)菌和微粒的環(huán)境空氣進(jìn)入。耐用并可靠。過濾器必須無菌且通過完整性測(cè)試以5.8EnvironmentalAirin15Isolatortechnologyhandweighingandhandlingofsterileandevennon-sterilepotentcompounds.Dependingonthornegativepressurerelativetothesurroundingenvironment.Whicheverthemodeofoperation,filtrationofmake-upandexhaustairaccomplishtheairexchangretentionoftoxicpowdersfromtheexhaustortheadmissiprogramthatshouldbeimplement在過去的幾十年中，分離技術(shù)在關(guān)鍵應(yīng)用中已經(jīng)普及了，例如無菌測(cè)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(yīng)用，分離器可以在與周圍環(huán)境呈正壓或負(fù)壓下運(yùn)行。無論何種運(yùn)行模式，過濾器無論是有毒粉末滯留或無菌空氣進(jìn)入，就越應(yīng)該進(jìn)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(duì)疏水膜過濾器滅菌的最普通方法是一傳導(dǎo)特性、濾孔內(nèi)大量空氣、蒸汽滲透、和構(gòu)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(guān)的壓力，這個(gè)滅菌過程要求無菌并不存在物理完整性損失。在許多的應(yīng)用中，“無菌等級(jí)”疏水膜過濾器重復(fù)使用或長期使用。因此，應(yīng)該承受多重滅菌循環(huán)。通常，使用者應(yīng)該按過多暴露，因?yàn)槿绻麥缇磺‘?dāng)，過濾器膜或者其他元件可能被破壞。使用者應(yīng)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(duì)物理完整性測(cè)試帶來不利影響。然而，如果能夠證明過濾器不會(huì)受suitablemicrobialbarrierthatpreventscontaminationofthesterilefiltercomponentspost-sterilization.Thebarriermustallowpenetration.Thefiltercartridgeshouldbeproperlysupportedduringsterilizaticycleinitiationbyaseriesofvacuumcyclesorflushingthechamberwithpulsesofsteafiltershouldbeorientedhorizontally,orwiththeoutletpointeddownward,tosterilizationparameters.Forallapplications,theautoclavecycleshouldbevalidatedtoyieldthed使用高壓滅菌法，過濾器的準(zhǔn)備是非常關(guān)鍵的。重要的是要保護(hù)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(jìn)入滅菌器，以充分滅菌。至關(guān)重要的是，過濾器進(jìn)，汽滲透。該濾芯在消毒期間應(yīng)有適當(dāng)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(jié)。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(shè)備的過濾器可能需要調(diào)整殺菌參數(shù)。對(duì)于所Dryingofthesterilizedfilterisgenerallyaccomplishedbyapplyingapperformedoff-linepriortoinstallationofthefilter.Ifthesecases,theintegritytestsh消毒過濾器的干燥通常是通過應(yīng)用完成后循環(huán)真空和空的位置。在這類應(yīng)用中，過濾器安裝前，完整性測(cè)試也可進(jìn)行。這些情況下，完整性測(cè)試應(yīng)在適當(dāng)?shù)沫h(huán)境進(jìn)行，如工作的HEPAe