USP30_1208-无菌实验----隔离系统的验证(摘译)

1、USP30-NF25（1208）STERILITYTESTINGVALIDATIONOFISOLATORSYSTEMS无菌实验隔离系统的验证（摘译可供全自动无菌检查系统参考的部分）PerformanceQualifications（PQ）性能确认ThePQphaseverifiesthatthesystemisfunctioningincompliancewithitsoperatorrequirementspecifications.AtthecompletionofthePQphase,theefficacyofthedecontaminationcycleand,ifappropriat

2、e,theadequacyofdecontaminatingchemicalventingareverified.AllPQdataareadequatelysummarized,reviewed,andarchived.PQ阶段要确认的是系统的运行功能符合操作人员所要求的标准。PQ完成时，净化循环的效验以及在适当的情况下化学物品通风净化的适用性被确认。所有的PQ数据应该进行充分地总结、回顾及归档。CleaningVerificationIngeneral,cleaningisnotcriticalforsterilitytestingapplications.However,residual

3、productsareaconcerninmultiproducttesting,particularlyforaggressiveantimicrobialagents,becausethesematerialscouldinterferewiththeabilityofsubsequentteststodetectlowlevelsofcontaminationintheproduct.清洁确认一般而言，清洁对于无菌检测的实施并不关键。然而，在多批产品检测中残留产品是一个值得注意的问题，特别是具有强烈抑菌性的试剂，这些物质可能影响到后续检测实验对产品中低水平污染的检测能力。Concerns

4、aboutcontaminationwiththeproductareheightenedwhenitisaninherentlyantimicrobialpowder,becausepowdersaremorereadilydisseminated.Cleaningtoalevelatwhichnovisiblecontaminationispresentisadequateforsterilitytestisolatorsystemsandisasuitableoperatorrequirementspecification.Thecleaningmethod,frequency,equi

5、pment,andmaterialsusedtocleantheisolatoraredocumented.如果产品本身是一种抑菌性的粉末，由于粉末容易散布，那么应该提高对产品带来的污染的关注。清洁程度达到无肉眼可见污染物的水平，对于无菌检测隔离系统是足够的，也适合于操作规范要求。应用于隔离系统的清洁方法、清洁频次、所使用的设备和材料都应有文件记录。DecontaminationValidationTheinteriorsurfacesoftheisolator,theequipmentwithintheisolator,andthematerialsbroughtintotheisolato

6、raretreatedtoeliminateallbioburden.净化验证对隔离器内表面、隔离器内部设备以及被携带入隔离器的物质都应进行处理以清除所有的生物负载。Thedecontaminationmethodsusedtotreatisolators,testarticles,andsterilitytestingsuppliesarecapableofreproduciblyyieldinggreaterthanathree-logreductionagainsthighlyresistantbiologicalindicators(seeBiologicalIndicatorsfor

7、Sterilization匚1035；：_),asverifiedbythefractionnegativeortotalkillanalysismethods.用于处理隔离器、检测物品以及无菌性检测供应品的净化方法对于高抗性的生物指示剂能够产生超过3个对数值的削减作用(见BiologicalIndicatorsforSterilization1035；：_),asverifiedbythefractionnegativeortotalkillanalysismethods.这已通过部分阴性或全杀灭分析方法确认TotalkillanalysisstudiesaresuitableforBIsw

8、ithapopulationof103spores)perunit,whilefractionnegativestudiesaresuitableforBIswithapopulationof105orgreater.全杀灭分析研究适用于数量为103个抱子每单位的Bls,而fractionnegativestudies适用于105或更高。AsufficientnumberofBlsareusedtoprovestatisticalreproducibilityandadequatedistributionofthedecontaminatingagent.Particularattention

9、isgiventoareasthatposeproblemsrelativetotheconcentrationoftheagent.AlargernumberofBlsmayberequiredinisolatorsthatareheavilyloadedwithequipmentandmaterials.Theabilityoftheprocesstoreproduciblydelivera)greaterthanthree-logkillisconfirmedinthreeconsecutivevalidationstudies.足够的Bls数量用于证明数据的重复性以及净化剂足够的分布。

10、应特别关注由于试剂浓度引起问题的区域。装备了大量设备和物料的隔离器可能需要更大量的Bls。三次连续验证研究确定了重复产生一个大于three-log杀灭过程的能力。Theoperatorestablishesafrequencyforre-decontaminationofthe1S(USP30)isolator.Thefrequencymaybeasshortasafewdaysoraslongasseveralweeks,dependingonthesterilitymaintenanceeffort(seeMaintenanceofAsepsiswithintheIsolatorEnvir

11、onment).操作员应设立隔离器重复净化的频次。根据灭菌的持续效果其频次可以短至几天也可以长至几周。Changetoread:PACKAGEINTEGRITYVERIFICATION包装完整性验证Somematerialsareadverselyaffectedbydecontaminatingagents,whichcanresultininhibitionofmicrobialgrowth.Ofconcernarethepenetrationofdecontaminatingagentsintoproductcontainers;accessorysuppliessuchasfilter

12、setsandtubing;oranymaterialthatcouldcomeincontactwithproduct,media,ordilutionfluidsusedinthesterilitytest.ltistheresponsibilityoftheoperatortoverifythatcontainers,media,andsuppliesareunaffectedbythedecontaminationprocess.净化剂对某些材料的作用是有害的，这会抑制微生物的生长。值得关注的是净化剂对产品包装的穿透；诸如过滤装置和管道等附件物品；以及任何可能与无菌检测用产品、培养基和

13、稀释掖接触的材料。操作人员有责任确定容器、培养基和配备物品不受净化程序的影响。Screw-cappedtubes,bottles,orvialssealedwithrubberstoppersandcrimpoversealshaveprovenveryresistanttothepenetrationofcommonlyuseddecontaminatingagents.Wrappingmaterialsinmetalfoilorplacingtheminasealedcontainerwillpreventcontactwiththedecontaminatingagent;however

14、,theseproceduresmayalsoresultinsomesurfacesnotbeingdecontaminated.Insomecases,theuseofshorterdurationdecontaminationcyclesandreducedconcentrationsmaybenecessarytominimizepenetrationofdecontaminatingagentsintothepackageorcontainer.Cyclesthatprovidealessthanthree-logkillofresistantBIsmaybeacceptablepr

15、ovidedmicrobiologicalanalysisoftheenvironmentprovesthattheisolator(s)arefreeofrecoverablebioburden.在一般情况下，使用带螺纹帽试管，瓶子、采用橡胶塞的小瓶以及多重折叠封口的方法都被证明对穿透有很好的阻抗。采用金属薄膜包装材料或将物品放入密封容器中可以避免其与净化剂接触，然而这样也可能造成某些表面无法净化到。某些情况下，采用短时间的净化循环以及降低净化剂浓度可以减少净化剂穿透包装或容器中。Inmanycases,theoperatorwillchoosetotreatthesurfacesofpro

16、ductcontainersundertestwiththedecontaminatingagentinordertominimizethelikelihoodofbioburdenenteringtheisolator.Itistheresponsibilityoftheoperatortodemonstrate,viavalidationstudies,thatexposureofproductcontainerstothedecontaminatingagentdoesnotadverselyaffecttheabilityofthesterilitytesttodetectlowlev

17、elsofcontaminationwithinthesetestarticles.Itissuggestedthattheabilityofthepackagetoresistcontaminationbeexaminedusingbothchemicalandmicrobiologicaltestprocedures.在多数情况下，操作员会采用净化剂处理通过测验的产品容器的表面来降低微生物进入隔离器的可能性。操作员有责任通过验证研究来论证产品包装物接触净化剂不会影响到无菌检测中对这些物品内低水平污染的检测。建议对包装抗污染的能力应该采用化学和微生物的检测程序。Bacteriostasisandfungistasisvalidationtestsmustbeperformedusingactualtestarticlesthathavebeenexposedtoallphasesofthedecontaminationprocess(seeSterilityTestS71；：_).Thisappliestomedicinaldevicepackagesaswellaspharmaceuticalcontainerandclosuresystems.Validationstudiesdeter