分析成果大四上-optimize nff consolidated-ecust

OptimizeOptimizeNormalFlowFiltrationSelectfiltersforafiltrationprocess---5412PresentationPresentationHowaFilterKeyMembraneandDepthFilter FilterFoulingIntroductiontoFilterSizingandScalingMilliporeTraining-OptimizeNormalFlowFiltration CellCellCulture/PurificationFilterViral清CellMediaPrepFinal发MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore 去澄清FinalMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. HowHowaFilterMicroporousMicroporous膜ReverseOsmosis反渗透MilliporeTraining-OptimizeNormalFlowFiltration s ParticleParticleRetentionSizeExclusion–Sieving筛分（表面Entrapment滞留（深度吸AttractionforcesbetweenparticlesandfilterMolecularand/orNotsize-ParticleSolutionFiltermaterialandMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore ExamplesExamplesofAdsorptiveDepthFilterMedia过滤介质的poresize层析介Abilitytoperformhighresolution优点/缺SEMofDepth深度层析介质的紫外吸%Retentionisnotsize-RetentioncanbeaffectedbyfluidandprocessMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. ExamplesExamplesofSizeManytypesofManycommon0.22umDuraporeSurfaceMembraneRigidCriticalSterilizingfilter-common(legal0.22umDuraporeCross-section••截MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore RetentionRetentionDescribehowfilterscapture(retain)描述过滤器怎样捕获（截留）颗Mechanismscanbeaffected可影响机理的因素有Fluid流体特Operating操作条Particle颗粒类Filter过滤器类Retentionmechanismsformthefoundationoffilterfoulingmodels截留机理构成了过滤器堵塞模型的基MilliporeTraining-OptimizeNormalFlowFiltration KeyKeyMembraneandDepthFilter膜式 过滤器关键特WhatWhatdoMembraneFilterslookMainlymadebycastingCanbeeitherhydrophilicorRatedonthesizeofthesmallestparticleitVerythin(100-260(100260AdsorptiondependsonNottheprimaryretentionCelluloseMilliporeTraining-OptimizeNormalFlowFiltration HowHowareMembraneFiltersProducedbyNylon,Cellulose(mixedester,PVDF,Producedby膜铸 MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore 0.22Symmetric0.22Asymmetric对称结 不对称结MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. WhatWhatdoStretchedfilterslookSlotshapedVeryOftenbondedtoasupportCanhavehighproteinUsuallyPTFE-NaturallyMosthydrophobic KeyKeyMembraneFilterStrong,RigidNOT坚固、刚性，非Veryhighinternal65-75%孔隙率为65-Sizeexclusion-particlewithfloworpressureandsterilefiltrateIntegritytestable(diffusion&/orbubble可测试完整性（扩散和/或泡点MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. MicrofiltrationMicrofiltrationMembraneMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore Lowdirtholdingcapacity污垢保持能力adsorptionandentrapment）Feature特）Verythintypically0.010.2mm)很薄（通常为0.010.2NarrowdefinedporeRigiddefinedstructureNote:RigidNOTBrittle)刚性、确定的结构-（注：刚性，非脆性）Castpolymericmembranes铸造聚合膜Non-fiberreleasingstructure 纤维的结Retentionisindependentoffluidhydraulics(flow,differentialpressure)截留不取决于流体水力学（流量、压差Goodoperatingdifferential

Result Insignificanthold-upvolumeCanbegivenatruerretentionrating,canbenon-destructivelyintegritytestedusingliquidpropertybasedtestsRetentiondoesnotchangewithenvironmenti.eheatpressure)截留不受环境（即热/压力）影响IncreasedmanufacturingconsistencyVerycleanfiltrateVeryefficientfiltertypically99.9999.9999999%)过滤器非常高效（通常达99.9999.9999999%)）Filtercanblockquickerthanothertypesterblockseasily”0-30psig(0-2bar)fortypicalbiologicalfiltration,0-45psig(0-3bar)fortypicalparticulatefiltration对于典型的生物过滤：030psig02bar粒过滤：045psig03MilliporeTraining-OptimizeNormalFlowFiltrationProcesses ）What）WhatdoSurface(Pre-)FilterslookFiberslockedtogetherbyheatormembraneGivenanominalratingorratedbythefilterit 定等级，或根据其保护的过滤器划分等Thin(1mmorless)&Slightly薄（1mm或以下），轻微吸附Giveapercentage(90-99.9%)particle实Celluloseestercoatedcelluloseorpolyester s Non-fiberreleasing(orverylowfiber structure 纤维（或很 MediumdirtholdingcapacityHybriddepth/membraneRetentiondoesnotchangewithflowrateorpressure截留不受流速或压力影响Goodoperatingdifferential"Reasonable"filterlifeParticlesretainedbyphysicalentrapmentinsidethematrix,adsorptionontothefiltermatrix,andsizeexclusionofparticlesinandonthefilter Canbeusedinunsteadyorchanging0-30psig(0-2bar)fortypicalbiologicalfiltration,0-45psig(0-3bar)fortypicalparticulatefiltration对于典型的生物过滤：030psig02bar颗粒过滤：045psig03MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. gherqualityfiltratewithoutmatrixBetterconsistencyinperformanceandminimalfiltervariations更好的性能一致性，最小的过滤器差异MoredefinedpolymericBetterestimationofretention(usually90-99.9%),Cannotbereliablyintegritytestedusingliquidbasednon-destructivetestmethodsThintypicallylessthan1mm)薄（通常小于1mmNegligibleholduplossResultCommentFeatureWhatWhatdoDepthFilterslookFibrous(canshed由纤维构成（可脱落纤维DifficulttogiveanaccurateporesizeThick(3-30mm)&often厚(3-30mm)，常具有吸附Giveapercentage(i.e.30-70%)particleHavethegreatest生产能力最实微玻璃纤缠线型过滤Sheet/pad板状/垫状过滤 DepthDepthfilter纤维素 DE(DiatomaceousDE（硅藻土RefinedLargesurfaceEntrapmentResinFilterMatrixCross-Section@3656过滤基质横截面@3656MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. 内）内）DepthDepthFilterFeatureThicktypically320mm)厚（通常为3–20BroadporeRandomMatrixcanmoveunderdynamicResult Oftenhighproducthold-uplossNominalparticlerating.Virtuallyimpossibletoreliablyintegritytestusingliquidbasednon-destructivetests颗粒截留概率（通常为30–Highprobabilitythatparticlesandfiberscanbereleasedintothefiltrate颗粒和纤维被 颗粒截留：吸附到过滤基质上，或物理滞留在过滤基质部Highdirtholdingcapacity污垢保持能力高RetentionchangeswithflowandorpressureLowoperatingdifferentialmatrixandphysicalentrapmentinsidethefiltermatrixparticlesmigratethroughtheParticlescanbleedthroughafterfilterisoverloaded,”Long”lifeFilterisbestusedinsteadyorun-pulsed0-15psig(0-1bar)fortypicalbiologicalfiltration,0-30psig(0-2bar)fortypicalparticulate粒过滤：030psig02MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore TypicalTypicalFiltration-DiskFilterDisksplacedonsupportscreenandsealedwith2-3盘放置于支撑滤网上，用2-3个O形圈密Rangeofdiameters13-293直径范围为13293Inusefor>50使用历史>50Canusedepth/surfacefiltersinthesame可在相同的支架中使用深度/表面过滤Oftenusedforsmallvolume经常用于小体积批Lowunit沉难以装Many部件很Oftennottruly往往并不真正卫

c.1960s-MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. -StackedMembranebondedtobothsidesofasupportdiskwhicharethenbondedtogether.Allfiltersworkinparallel膜与支撑盘两侧粘合，然后粘合在一起。所有过滤器Easytouse&更换过滤器， 装Non-c. toback对背压的抵抗力MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. -PleatedAllcomponentsthermoplasticallyweldedtogether.Usuallyhas2-5materialsof膜处于支撑材料之间。所有部件热塑焊接在一起。通常有5Goodforward&reverseRangeofsurfacearea150–10,000表面积范围为150–10,000 Varietyofsizes,surfaceareasando-ring各种尺寸、表面积和OCanhaveprefilter/finalfilterinthesamec.1990s-MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore TypicalDepthFilter典 Plateandc.rigid,reusablemanuallyreplacecutsheetsofhighincidenceofby-c.1950-robust,simplifiedc.robust,scalable,reducelaborandexposuretonoby-MilliporeTraining-OptimizeNormalFlowFiltration FilterFilterFoulingAnIntroductiontoFilterBiologicalBiologicalFluidSolids(>1固体(>1Easilyremovedbydepthentrapment,cakebuild-upCellsandorganisms(0.2-50细胞和有机体(0.250–Delicate,canlyseunderstressandreleasepluggingmaterials••–••••Bacteria,yeast,insect,Colloids(0.01-1.0胶体(0.011.0DeformableandPlugdownstream••CellculturePlasma盐CellculturePlanthydrolysate&CellcultureMilliporeTraining-OptimizeNormalFlowFiltration TypesTypesofParticlesinBiologicalNon-deformableResinbeadsorDrugCarbonDiatomaceousEarth硅藻土FormporouspermeableCanmovethroughthefilter,break-upcompressintoimpermeableMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore CakeCakeHappenswithhard发生于硬颗Particlesbuilduponthesurfaceofthe颗粒在过滤器表面上堆Ifparticlesarerigid, linearwithcakethickness若颗粒为刚性，随着滤饼厚度增加，阻性增MilliporeTraining-OptimizeNormalFlowFiltration s CompleteCompletePoreHappenswithdeformablePressureforcesparticlestocompleyblockthe“pore”CommonwhenthereispoorornoprefiltrationORwhensoftparticlesslightlylargerthanthefilterratedporesizeMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore GradualGradualPoreHappenswithhardordeformable硬颗粒或可变形颗粒均可发Particlesbuilduponthe“pore”throator颗粒堆积在“孔隙 或开Filterslowly过滤器缓慢阻Mostcommonwithbiological最常见于生物流MilliporeTraining-OptimizeNormalFlowFiltration ImpactImpactonFilterGradualblockagemost"Everythingwasgoingalright,thenallofasuddenthefilterplugged“Constantflowfiltration–filterfoulsGradualandcompleteblockingdonothavealinearrelationshipbetween∆PandMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore FilterFilterPerformanceFilterperformanceisdefinedbytwokey生产能Volumethatcanbeprocessperfilterarea单位过滤面积可处理的体积How多少流••••••••••Volumeprocessedpertimeperarea(L/m2/hr=单位时间、单位面积处理的体积(L/m2/hr=HowPerformancedepends性能取决于Filterselection-thecorrectfilterforthe过滤器选择–适合于应用的正Process工艺参Optimizingpressure,flowrate,time,优化压力、流速MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Pdoesnot△P不过滤期间，△PChoosingaFilterSizingFoulingMechanism恒SizeExclusion尺寸排阻机MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Modeof测试模Small-ScaleSmall-ScaleTestConstantPressure恒压FluidisheldatconstantpressureandthroughfilterConstantFlowRate恒定流速Fluidisonstantflow在恒定压 体通过过滤介Filterpluggingisobservedbythedecreaseinflowrateovertimepluggingmodelthroughthefilterdifferentialpressureovertime或Filterpluggingisobservedbyanincreaseinfiltrateturbidityovertime过滤器堵塞的表现：withempiricaldatafittingMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore SizingVolumePressureTurbidityChoosingChoosingaFilterSizingTechnique:FilterTypeBasis(ApplicationFocus)Pmax（应用焦点Pmax(Applicable,butlessPmax（适用，但不太常见MembraneFiltersMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore FiltrationFiltrationTherearetwomajorretentionmechanismsinAdsorption,SizeDepth, dindifferentDisc,StackedDisc,PleatedCartridgefor透镜状和 过滤Filtersperformanceischaracterizedbyflowand过滤能力由堵塞机理决Understandingandcharacterizingoffilterfoulingmechanismformthebasisforfiltersizingandscaling理解和表征过滤器堵塞机理，构成了过滤器尺寸分析和缩放的基MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. OptimizeOptimizeNormalFlowFiltrationPerformVmaxsizingformembrane对膜式过滤器执行Vmax••••••ReviewtheVmaxtestmethodforsmall-scalefilterBrieflydefinethescopeoftheVmaxmethodologyDescribetheimplementationofaVmax说明Vmax试验ExplainysisofVmax解释Vmax数据Other其Selectingsafety选择安全“Beyond“VmaxWrap-总MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. andVmaxMethod恒MeasuresdecreaseinflowasafunctionEndpointisdeterminedbyflowrateor

ConstantFlow恒定流Measuresincreaseinpressureanddecreasefiltratequalityasafunctionofdesiredfiltratequality

flowflowMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. FilterFilterPluggingMechanismoffilterdt/dV=t=过滤时间=kconstantwhosedimensionsaredependentonnk=常数，其大小取决于nn1.5forgradualpluggingn=1.5（对于逐渐堵塞）H.P.Grace,"StructureandPerformanceofFilterAICHEJournal2(3),307-336Inpracticalt/v=t/V+V= umvolumethatcanbefilteredattimeinfinityV=时间无限时，可过滤的最大体积QinstantaneousinitialflowQ=瞬时初始流量MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore TheTheVmaxConstantPressureTestAcceleratedscreeningtechniquetoestimatescaled-upfiltersizeHelpstooptimizefiltrationtrainEstimates umfluidvolumefilterablethroughaPredictsCapacity,Vmax[=]L/m(@VmaxL/m2@PredictsFluxDecayProfile,Q[=]通量衰减曲线，QVmax–VBasedonthegradualporepluggingPlott/VversustatconstantVmax=1/Slope,Qi=Vmax1/斜率，Qi1/MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Simple,rapid&easytoEstablishesoptimizedfiltrationtrainandpreliminaryinformationforscale-up,confirmatorypilotscaletrials••••um‘filterable’fluidvolumebeforeplugging,Vmax–Qi–初始滤液通量，L/min/m2Requiresonlylimitedfluidvolumetoperformthe<11MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore ItdoesnotlyouwhichfiltertoExperience&historicalrecordsareDoesnotlyouanythingaboutfiltrate不会告诉您滤液质IndirectlyVmax,withatighterfilter,onthefiltrateisameasureoffiltrate对于更紧密的过滤器，滤液Vmax是滤液质量的间接量DoesnotsimulatetheentireNeedforintermediatepilotOnlyappliestogradualporepluggingMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. VmaxTestVmax:Vmax:HowtoSelecttheTestFilterTypeEvaluatethefeedstreamandtheifturbidity>20NTU,aprefilterislikelyMilligard,PolySepII,Milligard,PolySepIIifturbidity10-20NTU,aguardedsterilefiltermaybe若浊度为10-20NTU，可使用防护无菌过滤Durapore0.45/0.22µm,ExpressSHC(0.5/0.2µm),ExpressSHRP(0.5/0.1ifturbidity<10NTU,asterilefilteralonecanbe<Durapore0.22µm,ExpressSHF(0.2µm),ExpressSHR(0.1Thereisnosimplecriteria,howeverweUsetheMilliporeFilterSelectionGuideforgeneralAskaMilliporeProcessDevelopmentUsehistoricalWhereappropriate,useotherfluidCell细胞密度/ProteinParticlesize Vmax:ChoosingtheRightVmax:ChoosingtheRightCat.No.:HP01MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Cat.No.:Cat.No.:XX40047Cat.No.:号 XX40047FeedsolutionisaddedtothepressureThetestfilterisattachedtothepressureThevesselispressurizedandflowisTotalfiltrateweightisrecordedatregulartimeMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore Fluid流体体mended>500upusingapressurevessel,gauge&balance100-500UseOptisealhousingorsmallvolumeVmaxcontainer使用Optiseal外壳或小体Vmax<100Usesmallvolumecontainer:Holder”100mL力过滤器支架”100mLVmax:Vmax:HowtoSelecttheTestPressureAlwaystrytotestatumexpectedpressureduringfull-scaleIfprocess-pressureisunknown,arule-of-thumbmaybeForfinalfilters(e.g.Durapore,对于终滤器（例如Durapore、Select20-30psiforaqueous对于水相流体，选择20-30Use30psiorhigherforfluidswithhigher对于粘度较高的流体，使用30psiForprefilters(PolysepII,Milligard,Lifegard,对于预滤器（PolysepII、Milligard、Lifegard、Select5-10选择5-10MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore Vmax:Vmax:TheEffectofTestPressure••••••••Foraqueous对于水溶液TestpressuredoesnothaveastrongeffectonVmaxsizing试验压力对VmaxHowever,recentworkbyMillipore’sBioprocessEngineeringGroupsuggeststhathighertestpressuresmimicconstantflowprocessesbetterForotherfluids,theimpactoftestpressureis对于其他流体，试验压力的影响是可变ForViscous对于粘性流体Higherpressurehasbeenfoundtogiveahigher已发现：当压力更高时，Vmax也更例如多种ForNon-ViscousNotcompley不完全透明Dependsonfluid&filter取决于流体和过滤器类Ifpossible,runhigh&lowpressuresto如可能，在高压和低压下运行，以进行MilliporeTraining-OptimizeNormalFlowFiltration Vmax:TheVmax:TheEffectofAutoclaving&IrradiationEffectofGammaIrradiationonCapacity(0.1Durapore)伽马辐射对生产能力的影响(0.10feedNon-Gamma非伽 Gamma伽Autoclaving&gammairradiationhavenosignificanteffectonthroughput(i.e.Observeddifferencesoftenarerelatedtoautoclavecycleswhichoperateoutsideofthe mendedrangeforagivenmembranetypeMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Autoclaved高压灭Non-Autoclaved非高压灭EffectofAutoclavingonCapacity(0.22高压灭菌对生产能力的影响(0.220feedVmaxandMinimumAreaVmax:ResultVmax:Result–r2>r2>Whathappenswhenr2<当r2<0.99PredictionofCapacity(Vmax)basedon10mineslesst基于10min试验 生产能力(Vmax)，变得不太可RemoveearlierpointstoseeiffitisNeedatleast6pointsinthestraightlineforreliablecorrelation为了可靠关联，直线上需要至少6Runtestto80%plugging(flow运行试验至80%堵塞（流量衰减r2<tMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore Vmax:Vmax:ApproachestoFilterSizingThreeprocessscenariosorcasesareusually三个工艺情景或案例通常相关Case1:BatchVolumeoffluidtobefilteredis案例1：给出流体过滤批体Case2:BatchVolumeoffluidtobefilteredata案例2：给出在最大容许处理时间时的流体过滤批体umallowableprocesstimeCase3:BatchVolumeoffluidtobefilteredwithaspecifiedminimumallowableflowrateisgiven案例3：给出在规定的最小容许流速下的流体过滤批Largestsurfaceareathatfulfillsallprocessrequirementsisselected,选择满足所有工艺要求的最大表面积MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Vmax:Vmax:Sizing Case1.OnlyV(BatchVolumeisgiven;Nobatchtime,minimumAminVEq.givestheminimumarearequired(nosafetyfactoris方程给出所需最小面积（不包括安全系数EnsurethatAleadstorespectablebatchCase2.V(BatchVolume)andt(Batchtime)areVB V QCase3.V(BatchVolume),t(Batchtime)&Q(minimumflowrate)are.1Qi Vmax UsinganIterativeMethod,SolveEq.For‘Case2’cangiveareasonableinitial VmaxVmaxVmax尺寸分析：若Vmax/Qi低，会发LetusinspectthesizingWhathappenswhenVmax/QiisA V1 BV1QWhenVmax/Qiislowthen1/(QitB)0若Vmax/Qi低，则1/(QitB0，AmintBdoesnotsignificantlyaffecttBTypicalexamplesincludeserumor典型实例包 或消泡MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Low低实例Vmax=60Qi=20L/m2VB=Vmax/Qi=0.05High高实例Vmax=20,000Qi=20L/m2VB=Vmax/Qi=16.7tbislessonly3%!差异仅3VmaxislessDifferenceisonly6差异仅6%！MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. VmaxVmax WhathappenswhenVmax/Qiis V 1 BV QForhighVmax/Qi,AminVB/Qi‘Vmax’contributesverylittletoMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore SizingSizing尺寸分析准tBatch=4tBatch=1tBatch=4hrVmax=Sizing尺寸分析准tBatch=4tBatch=1tBatch=4hrVmax=OtherOtherImplicationsofHighLeadstoahighvariabilityin导致VmaxResultsfromdifficultyinaccuraymeasuringtheslopeoft/Vversus由于难以准确测量t/V对tThevariabilityisdisconcerting;itmayundermineourconfidenceinthedata(i.e.IsitokforVmaxtovarybetween20,000-30,000?)（即：Vx在之间变化，是否可接受？）ItisimportanttorememberthatsincehighVmaxvaluesdoesnotsignificantlyaffectsizing,theimpactonfiltertraindesignisminimalMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore HowHowRepeatableisVmax?Repeatabilityneedstobecarefully需评价可重复性••••••Keepthefilter&fluidlot保持过滤器和流体批相Testsmustbecarriedoutwithinclosetimeintervalstopreventchangesinfeedwith进行试验的时间间隔必须较近，以防止进料随时间推移而发生变Formoderatetohigh‘plugging’对于中等或高‘堵塞AppliestoproductswithlowtomediumVmax(50-2000适用于具有低或中等Vmax(50-2000L/m)的产Repeatabilitycouldbewithin20-35%dependingonthefilterandproducttype;forcarefullycontrolledtests,repeatabilitycanbewithin15%•••视过滤器和产品类型而定，可重复性可在20-35%以内；对LowPlugging低堵塞料液AppliestoproductwithhighVmax(>5000适用于具有高Vmax(>5000L/m)的产控制的试验 可重复性可在15%以 eslessrelevant,Sizingemphasisshiftstoflowrate;LargedifferencesmaybeseeninVmaxwithoutanyimpactonsizingVmax变得不太相关，尺寸分析重点转移到流速；即使Vmax的差异很大，也可能对尺寸分析没有影MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Vmax Vmax范 意>5,000>5,000500–2000500–2000Ex:Moderate(ModerayEx:MostSolutionsafter中等（中等堵塞实例：在充分的预过滤之后的大多数溶液–‘100-200100-200Low(Highlymembranefilters低（高度堵塞MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore SafetySafetyandOther#10"SafetyUsingacost ysisbasedonasampleofsterile分析基于无菌过滤器样butincreasesriskofafailedbatchHighermembraneareaincreasesoverallcostbutriskoflostbatchisExistenceofaminimumvalueforafailedbatchvs.overallcostisthebasecasefordeterminingasafetyfactor失败批相对于总成本，存在最小值，这是确定安全系数的基础案MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. 4"O123456789SafetySafetyGeneralruleis1.5Xbut…Itdepends!AmountandqualityofExpectedvariabilityofExpectedvariabilityofExistingScalingMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore SafetyChoosingarobustsafety••••rangeof每个单元操作都有自己的下述范itsownrangeofsafetyfactors“标准”安全 CostratioFinalBulksterilization$500-1500K1-7sqm$0.4-0.6Growthmedia1-7sqm$0.4-0.6400-1-7sqm$0.4-0.6$100-1000K1-30sqm$0.3-0.5$500-1500K1-7sqm$2.8-7.550-MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. Vmaxisapowerfultoolforselectingandsizingfilters,butotherconsiderationscanbeequallyimportantinselectingafilterBroadchemicalIntegritytesting TimeEveryAbroadrangeofsizesmuchexistforagivenfilterThesedevicesmustscaleinapredictable rVendorsupplymustbestablewithbusinesscontinuityTechnicalsupportmustbeavailable&MilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore Goodfiltersizingstartswithwell-designedsmall-scaleMultipleTherighttestProperunderstandingofsizingIntermediate(pilot-scale)trialswillensuresmoothscale-中间（中试规模）Implementingthe“right”filterinvolvesmorethancapacity;otherconsiderationsTherightsafetyProcessHardwareSIPSIPRobustIT稳健的ITMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009Millipore RandyWilkins(BioprocessTrainingCenterDirector)RandyWilkins（生物工艺培训中心 Generalfiltersizing&“beyond一般过滤器尺寸分析和“生产能力以外BalaRaghunath(NABioprocessEngineeringManager)BalaRaghunath（NA生物工艺工程经理）Vmaxbackground& Vmax背景和数据分HerbLutz（顾问生物工艺工程师） ysisofsafety安全系数的成本分MilliporeTraining-OptimizeNormalFlowFiltration s OptimizeOptimizeNormalFlowFiltrationPerformPmaxsizingexperimentsforpre-filterclarificationConstantflowPmax/Tmax umpressureorPmax/Tmax ysis&SelectionoftheProperSafetyMilliporeTraining-OptimizeNormalFlowFiltrationProcessesCopyright©2009MilliporeCorporation. TheThePmax/TmaxConstantFlowTestUsingaperistaltic(orotherpositivedisplacemen