完整性测试2

DiffusionTestApplicability扩散测试适用性Forfilterswithgasflowrateof100ml/min过滤器扩散流速大于100ml/minhighsurfaceareafilters大表面积过滤器thinmembranes薄的膜organicsolventwettedfilters有机溶剂湿润的过滤器Diffusionalflowspecifications(andtheS.O.P.)shouldinclude;扩散速率说明(包括SOP)应当包括filtertype过滤器类型wettingliquid湿润液体testgas测试气体Temperature温度maximumacceptableflowrate最大接受流速FactorsAffectingDiffusionTests扩散测试的影响因素Wetting湿润度Lowerorinconsistentfilmthicknessincreasesdiffusion低的和不均匀的薄厚会增加扩散Fluid流体Organicsolventshavehighdiffusionflowrates有机溶剂有较高的扩散流速Gas气体Carbondioxidehashighergasflowthanairornitrogen二氧化碳比空气或氮气有较高的扩散流速Temperature温度80%higherflowrateat60degrees在６０摄氏度流速高80%PoorVentingProperVentingPolypropylenecartridgetestedwithnitrogenat18.8psig(1.3bar)聚丙烯过滤器用氮气(18.8psig)测试–Acetone390ml/min–IPA120ml/minMESSAGE:ChangingsolventschangesdiffusionalflowPureorganicsolventshavehighdiffusionalflow改变溶剂可改变扩散流速,纯溶剂有较高的流速–Canmaskbubblepoints–可能与起泡点相混ExampleofChangedDiffusionalFlow举例Hydrophilicfilteristestedwithbothnitrogenandcompressedairat2.8bar(40psi)–Nitrogen8ml/min–Compressedair10ml/minMESSAGE:Changingthetestgascangiveafalsediffusionalflowrate改变测试气体可以给错误的扩散流速ExampleofChangedDiffusionalFlow举例Whatisthemaximumdiffusionalflowfora5x30pleatedcartridgefiltersystem?–10element13.3ml/min–30element39.9ml/min–5x30elements199.5ml/minMESSAGE:Forthesamedevice,diffusionisdirectlyproportionaltosurfacearea相同的过滤器，扩散与膜面积成正比ExampleofChangedDiffusionalFlow举例“DiffusionTesting”Summary扩散测试总结Diffusiontestingmeasuresgasflow扩散测试测量气体流速Atbubblepoint,gasflowsrapidlythroughthelargestpore(s)在起泡点，气体则快速通过最大的孔Downstreamgasflow(orupstreampressureloss)cancomefrombothdiffusionthroughthewettedporesPLUSthegasflowthroughthe“dry”poreswhichhavereachedtheirbubblepoint下游气流（或上游压力损失）可以由扩散流和达到起泡点时流出“干”孔的气流两者引起Problemsforhydrophobicfilterintegritytestwithalcohol疏水滤膜采用有机溶剂进行完整性测试的问题Alcohol/Watermixturesareoftenuseddueto:酒精/水的混合物使用经常会导致Cost成本高Flammability有燃烧的危险highdiffusion高的扩散流Secureareasandequipmentneeded需要可靠的区域及设备Canbedifficulttoperformin-situ很难在线操作Someconcernswithresidualtestsolutionremaininginfilterholder/pipeworkaftertesting在测试后,测试液体会残存在过滤器/管路中Residualsolutionshouldberemovedbeforefiltersterilization灭菌前需要去除残存的液体HydroCorrTestingHydrocorr测试Forcewaterunderpressureontothesurfaceofthefilter.把水灌在膜表面Appliedpressureisintegralfilterintrusionpressure加压至小于膜的水浸入压Thewaterpressureismaintainedbutnotincreased.压力维持但不再加压Pleatedstructurecompacts折叠式结构进一步压缩Ifintegral,theupstreampressurewillnotdropbelowapresetvalue.膜如果是完整的,上游的压力不会太快下降IntegrityTesterAir/N2WFIHydroCorrTestResistancetowaterintrusion水浸入法测试02.6bar02.6barPatmPatm02.6bar02.6bar01020Time(min.)applypressureandhold加压并保持MeasurepressureDecay测量压力衰减Pressurecausespleatstocompact-resultinginapparentwaterflow压力导致折叠式滤膜进一步压缩—现象是有一定的水流HydroCorrTestResults测试结果•Afterinitialstabilization,“apparent”waterflowforanintegralfilterisverylow•在最初的稳定后,对于完整膜来说,水流是非常小的•Specificationsarecorrelatedtobacterialchallenge•水流指标是与细菌挑战有关•Forintegralfilterthereisno“actual”waterflow•实际上完整膜,没有实际的水流–Filterremainsdryanddoesnotrequiredryingbetweentestinganduse–在测试与使用中,过滤膜维持干燥也不需要干燥WaterFlowml/minTime20minutes0.10.20.30.40.51.0010HydroCorrTestConsiderations测试的注意点Musthavealeak-freesystem必须在一密闭系统内进行Filtersmustbedryandclean过滤芯必须干燥且干净ItisrelativelyeasytoHydrocorrtest“veryhydrophobic”membranessuchasPTFE对于疏水性很强的滤芯,例PTFE材质的膜,水浸入法是相当容易Successfullytesting“lesshydrophobic”membranessuchasPVDFrequiresidealconditionsthatcanbedifficulttoachieveinactualbiopharmaceuticalprocesses在实际的生物制药工艺中,测试一些疏水性不强的滤膜,例PVDF膜是比较困难的Temperaturechangesshouldbeminimized尽量减少温度的变化Referencetestingisimportant相关的参考比较重要Musthaveacompletevalidationpackage必须有一完整的验证文本Valuesmustbecomprehensivelycorrelatedtomicroorganismchallenge数据必须与细菌挑战相关TroubleshootingDecisionTreeforIntegrityTest完整性测试失败处理措施(英文）替换过滤柱并且退回膜去分析再湿润过滤器，使用两倍于初次湿润压或冲洗量或浸泡时间或者使用高压差在过滤器两边再测试过滤器是否通过测试完整性测试评估是否改变否是使用前是否边缘失败是否你能否重装过滤柱用标准程序重装和冲洗过滤器记录价值和程序能否再测试是否使用后测试在使用前还是使用后是否边缘失败冲洗过滤器，使用两倍冲洗量或者浸泡时间再测试过滤器是否通过测试冲洗过滤器，使用两倍于初次湿润压或者使用高压在过滤器两边记录价值和程序完整性测试评估是否接近规范值70/30异丙醇润湿，检测是否是否否是TroubleshootingDecisionTreeforIntegrityTest完整性测试失败处理措施(中文）Repeatwetting再湿润Uselongerwetting使用更长的时间湿润Usehigherpressure使用更高的压力湿润Usehighertemperature使用更高的温度湿润WetwithanAlcohol用酒精湿润Replacestaticsoakwithdynamicflush用动态的冲洗取代静态的浸透WettingSuggestions湿润建议Inlet入口0Outlet出口2Inlet入口38Outlet出口40Summary总结BubblepointandDiffusion(or“Forwardflow”)areBOTHvalidintegritytestsasperregulatoryagencies.起泡点,扩散流（或前向流）和HydroCorr是法规认可的完整性测试方法Thechoiceofanintegritytestdependsonthetestingequipment,thefiltermanufacturer,thecompany‘sphilosophyandthetestingenvironment完整性测试的选择倚赖测试装置，过滤器制造商，公司体系和测试环境Bubblepointprovidesadirectcorrelationtobacterialretention,thecriticalperformancecharacteristic起泡点提供与细菌截留的直接关联，重要的性能特性Diffusiontestingprovidesasensitivewaytodetermineintegrityforlargerareafilters扩散测试提供一个敏感方法来测试大面积过滤器AutomatedIntegrityTesters自动完整性测试仪WhyDoPeopleUseAutomaticTesters为何用户会选用自动测试仪•Abilitytoperformtestwithoutrisktodownstreamsterility•可以在排除下游无菌状态受到影响的情况下操作–PostSIPtesting–可以在蒸气灭菌后操作•Hardcopyprintout•有打印文本•E