PAD TR22无菌工艺模拟中英对照版

2.0Glossaryofterms3.0processsimulationconceptsandpri3.1numberandfrequencyofsimulatio4.0processsimulationfo4.1asepticcompoundingacti 4.3lyophilizedprod4.3.1simulatedload/unloadwithshortenedh4.3.2simulatedlyop4.3.3specialconsiderationsuniquetotheproductionoflyophilizedproductsfreezingofmedia vacuumlevelsandduranaerobiccondit4.5ointments/creams/emulsions/4.6powder4.6.1liquidmediumfilledbythepowderfillingeq4.6.2drypowderfillerwithsupplementaryliquidfillcapab4.6.3on-lineliquidfillfollowedbyon-lin4.6.4on-linepowderfillfollowedbyon-linemed4.6.5specialconsiderationsuniquetothesimulationofasepticfillingofsterilepowders4.7otherdosageformsanddevice/drug4.8otherasepticprocessingtechnologies4.8.1restrictedaccessbarriers4.8.2form-fill-sealandblow-fill4.8.3isolationtechno5.2protocol/procedure5.5processsimulatio6.0microbiologicalenvironment7.0elementsofasepticprocesssimulations7.1facilityandfillingmachineconsid7.3mediaselectionandp7.6container/closureco7.10durationandnumberofunitsfilled7.12pre-incubationcontainerins7.14post-incubationi7.17postsimulation 8.2identifyinginterventionsassociatedwithanase8.5handingofintervention-relatedcontainers9.0personnelquali9.4accesswithoutpriorqu9.5lossofqualification13.1selectionandsterilizationofplacebopowder/mate FiguresandtablesindTable7.10.1durationandnumberofuni ThisdocumentreplacestheoriginalPDATechnicalReportNo.22,ProcessSimulationTestingforAsepticallyFilledProducts,publishedin1996.Theintentofthecurrenteffortistoupdatethatdocumenttoreflectthecontinuingchangesthathaveoccurredinasepticprocessingtechnologynotablecontributionsbyotherorganizations,reguthisarea.Inadditionthereportprovidesguidancewhereriskbasedapproachesmaybeapplied.更新这个文件反映全球产业无菌加工技术在发生不断的变化。我们尽可能的将这个话题覆盖的更加全面，总结其他那些在这个领域工作的著名的组织、管理者、摘要和个人。此外，该报告提供基于Thistechnicalreportwasdisseminatedindraftforpublicreviewandcommentpriortopublicationofthesubmittedcommentshavebeenincludedinthefinaldocument.Webelievethisapproachaccomplishedthewidestpossiblereviewofthedocumentandensuresitssuitabilityasavaluableguidetoindustryintheareaofprocesssimulationforasepticprocessingoperations.这份报告以草案的形式由公众进行了讨论并在出版前征求了公众的意见。一些意见的内终的文件中。我们相信这个方法结合了最广泛的讨论意见，并确保这份文件对于从事无impliedstandard.Thereadermustrecognizethattheremaybeadditionalrequirementsimposedbecauseofneworlocalizedregulatoryexpectationsthatarenotincludedinthisdocument.Thistechnicalreportdoesnotprovideauniversallyappropriatetemplatefortheexecutionofprocesssimulationstudies.Eachcompanymustdeterminetheappropriaterationaleandapproachesapplicabletotheiruniqueoperations.本技术报告应被视为一份指南；它无意于建立任何强制性的或隐含的标准。对于管强制的附加要求，并未涵盖在本文之中，读者应与以充分考虑。本技术报适当执行工艺模拟研究的模板。每一个企业必须根据自己的实际情况选择适当的应用原理及方法。Arecurringthemeinthisreportistheconsiderationofrisktoproductsterilityandpatientsafetyascriteriaforthedesignoftheasepticprocesssimulationstudies.Regulatoryauthoritieshaveissuedrecommendationsforasepticprocessstudydesignandcompaniesshourecommendationswhenplanningtheirstudies.However,thasameanstoprovideinformationusedtomakedecisishouldresultinbetterunderstandingoftheasepticprocessanditscapabilities.Theuseofriskassessmentsandrelatedinformationmayresultinstudieswhichgobeyondtherecommendationsofregulatoryauthorities.Itmayalsoresultinstudieswhichdifferfromresultinstudieswhicharelesseffectivethanthoserecommendedbyregulatoryauthor本报告将产品无菌性风险条件及病人用药安全作为设计无菌工艺模拟研究的标准及科学评估信息有助于对无菌工艺及其能力的充分理解，利于研究设计的决议。含有关信息的研究成果可高于监管建议要求，也可与建议略有差 Thistechnicalreportaddressesprocesscapabilconsistofoneormoreasepticprocesssimulationformulationandfillingactivities(rAsepticoperationsrequiredinthepreparationofsterilebulkmaterialsandbiotechnologyfeedmaterialsarenotapartofthisdocument;refertoPDATechnicalReportNo.28:ProcessSimulationTestingforSterileBulkPharmaceuticalChemicals(1).本报告涉及无菌加工过程能力的评估。本评估由制药，生物制药及灌装活动（世辅助制造）过程中一种以上无菌工艺模拟（APS）构成。有无菌操作的无菌原料药、生物技术种菌Whilethefocusofthisdocumentisonasepticprocessinginthepharmaindustry,applicationoftheconceptsandprinciplestotheprdiagnosticsmaybeappro虽然本文的重点是在制药和生物制药产业的无菌工艺上，将ofAsepticFillingforSolutionDrugProducts;TechnicalReportNo.6:ValidationofAsepticDrugPowderFillingProcesses,andthe1996editionofthisreport.TechnicalReportNo.22:ProcessSimulationTestingforAsepticallyFilledProducts(2,3,4).Sincetheabovereportswereissued,therehavebeencontinuedadvancessuchastheuseofbarrier,isolationandblow-fill-sealtechnologies.Theunderstandingandphilosophiesofasepticprocessqualificatandstandardsauthoritieshaverevisedtheirownguidance'sonasepticprocessing(5,6,7和吹灌封技术。无菌工艺确认理解和理念、验证和控制逐渐成熟。此外,全球法规和标准The2011versionofTechnicalReportNo.22featuresthefollowingneworrevise •RiskManagement:ThisreportfrequentlyreferencestheuseofqualityriskmanagementconceptsinthedesignofAPSprograms风险管理：这份报告频繁的提出在设计无菌模拟工艺方案时使用质量风险分析的•ConceptsandPrinciples:Therehavebeenclarificationsandenhancementsofwithcurrentscientificknowledge,experienceandregulatoryexpectatio•LyophilizedProducts:Thesectionon"LyophilizationofDilAPSapproachisgenerallynotconsideredappropriate.•FreezingofMedia:Forsimilarreasonsreferencestofreezingofmediahavebeenremoved.培养基的冷冻：出于类似的原因在关于培养基冷冻的•PowderFilling:CertainAPSapproachesforpowderfillinghavebeenremove—On-linepowderfillfollowedbyoff-lineliquid—Non-asepticliquidfill,sterilized,andfollowedbyon-linepowder—Off-lineliquidfillfollowedbyon-linepowder•Isolators,restrictedaccessbarriersystems(RABS),blow-fill-seal(BPS):Updatedinform•ElementsofAPS:Enhancedinformationisincludedfor:fillingspeed,interventions,anddunumberofunitsfilled•Interventions:Thisreportdifferentiatesasepticprocessinter"corrective,"adistinctionthatishelpfulinunderstandingtheirrelationshiptomicrobiaandthedesignoftheAPSprogram.APS程序设计的相互关系。•AcceptanceCriteria:Section10includesbackground,currensettingacceptancecriteri可接受标准：在10.0章节包括了背景、当前推荐和设定无•On-goingProcessEvaluation:Formerlyreferredtoas'Validationupdatedtoreflectthatthestateofcontrolisanongoingprocess. Note:This2011revisionofTechnicalReportNo.22representsasignificantupdateofthecontentofthereport.Thisversionshouldbetreatshouldfullyreviewthisedition.Withthepublicationofthe2011versionofTechnicalRPDAnolongersupportsorconsAsepticprocesssimulation(sometimesreferredtoasamediafilcapabilityofasepticprocessingactivities.Fortheresultstobemeaningful,engineeringandmanufacturingcontrols,maintenanceactivities,qualitenvironmentalcontrol,environmecontrolsshouldbeinplace.APSsimulatestheasepticprocessfromtheposterilizationtoclosureofthecontainer(inclumightimpactcontainerintegrity),substitutingamicrobiologicalgrowthmediumfortheTheasepticprocesssimulationalsoprovidesameansfortheevaluationofchangesmadetoanasepticprocessingoperationwhichmightimpactthesterilityofthefinalproduct.Anasepticprocesssimulationcanbeusefulinidentifyingpocontributetothemicrobiologicalcontaminationoftheproductduringprocessing.可有助于识别在无菌过程中产品可能易于被微生物污染的潜在薄弱环节。Thepurposeofanasepticprocesssimulationisto:•Assessthecapabilityofanasepticprocessunderagivenmanufacturingenvironmentandprocess评估一个给定的生产环境和过程控制无菌工艺•Demonstratethatappropriatelydesignedandimplementedprocessc•Evaluatetheproficiencyofasepticprocessingpersonnel•DemonstratecompliancewithcurrentGoodManufacturi•Demonstratetheappropriatenessofoperatingpracticesusedinsupportofasepticprocessing •ChallengetheasepticprocessformicrobialcontaminationvThesuccessfulcompletionofanAPScannotbeconsideredavalidationofasepticsensethataperformancequalificationeffortinvolvingbiologicalchallengeandtemperaturemeasurementcansupportasteamsterilizationprocess.Asepticpropractices,equipmentfeatures,facilitydesign/controlandproceduresthamicroorganismsfromsterilecomponentsandproducts.Theseelementsofasepticprocessingcannotrigorouslycontrolledasasterilizationprocess;resultinginaprocesssimulationisonlyademonstrationofthecapabilityoftheprocesstoproduceasepticallyatthetimeofitsexecutionusingthedefinedprocpersonnel.作依赖于人员干预实践，设备、设施的设计/控制和程序。对无菌操作要素的要求不如灭菌工艺严TheAPSdoesnotprovideinformationwhichrelatesdirectlytothesteriliTherefore,thefactthataspecificAPSdoesnotmeettherequiredacceptancecriteriadoesnotnecindicateasterilityproblemforaeventhasoccurredduringtheAPSleadingtocontaminationofoneormoreunits.Thepotentialimpactoftheeventonproductionmaterialsmustbedetermin表明所有特定产品批存在无菌问题。然而，但它表明APS过程中发生了一Similarly,thesuccessfulperformanceofahigh-riskasepticinterventsimulationdoesnotinitselfjustifyitsuseoracceptabilityduringproduction.Theasepticprocesssimulationisonetoolforevaluatingtheprocessingstepsusedtomanufactureastprovidessupportingdatademonstratingtheon-goingcapabilityofproducingprocessingAholisticapproachmustbeusedtocontrolasepticprocesses.Anasepsystemstoassureandcontrolsterilityofthematerialsproduced.Thesesys•Product,equipmentandcomponents•Personneltrainingandcertificationofasepticgowningandaseptictechniques •Equipmentandfacilitysaniti环境系统：微生物水平、压差、气流组织、风速、温湿度、•Personnel,materialande•Standardoperatingprocedures/workinstruct•AunderlyingqualitysystemapproachtoprThesesystemsmustberoutinelymonitoredtoprovideverificationoftheircontinuedacceptableperformance,bywhichthesterilityassuranceofamanufacturedproductcanbeestablished.Therefore,itisimportanttovalidatealloftherelindependently,suchassterilization/depyrogenationcontactandindirectproductcontactsurfaces(e.g.stoppers,hoppers).这些系统必须定期监测，以提供确认其持续可接受建立一个制造产品的无菌保证的性能。因此， ActionLevel(environmentalmonitAnestablishedmicrobialornon-viableparticlelevelthinvestigationandcorrectiveactionbasedontheinvestigActionPlanAwrittenplanconsistingofelementstobearesponsibilityforeachelementandatargAmicroorganismthatutilizesoxygethatwillgrowprimarilyinthepresenceofoxygen.Forthepurposeofthisreport,thisdefinitionencompassesfacultativeanaerobe微生物在新陈代谢中利用氧作为最终的电子接受体，只有在有氧条件下微生物才能AlertLevel(environmentalmoniEstablishedmicrobialornon-viableparticlelevelgivingearlywarningofpotentoperatingconditions;notnecessarilygroundsfordefinitivecorrectiveactionbuttypicallyre建立的微生物或非活性粒子标准，为正常操作条件下潜在的漂移提供早期的Amicroorganismthatdoesnotutilizemicroorganismthatwillgrowonlyintheabsenceofoxygen.微生物在新陈代谢中不利用氧作为最终的电子受Thepartofasepticprocessingwhereapre-sterilizedproductisfilledand/orpackagedintos 无菌工艺的一部分，即预先灭菌的产品灌和/或装到无菌容Handlingsterilemateriaequipmentandpersonnelareregulatedtocontrolmicrobialandparticulatecontaminationtoacce在对供给空气、设施、物料、设备及人员进行微生物和颗粒物污染严格控制的环境下Controlledenvironment,consistingofseveralzones,andpersonnelareregulatedtocontrolmicrobialandparticulatecontaminationtoaccAsepticProcessingSimulation(Ameansforestablishingthecapabilityofanasepticprocessasperformedusingagrowthmedium.Note:Asepticprocessingsimulationsareunderstoodtobesynonymouswithmediafills,psimulations,simulatedproductfills,brothtrials,brothfil注意：无菌工艺模拟也可称为培养基灌装，工艺模拟，模拟产品灌装，液体培AsystemofphysicalpartitionsthataffordsISO5psurroundingenvironmentutiliz通过气流将内部与外部环境进行部分隔离，以满足ISO5保护的物理分TotalnumberofviablemicroorganismsonorinahealthcareproductpriorAseriesofconsecutiveproductionbatchesmanufacturedwithoutinterveningcleaningandsterilization.过程中无清洁及灭菌活动介入的一系列连续产品批 Aformalprogramthatdescribesevaluationandactionstobetakenifachangeisproposedorcompletedtofacilities,materials,equipment,and/orprocessesusedinthefabricatiooraproposedorcompletedchangethatmayaffecttheoperationofmicrobiologicalmediuAprocessinwhichabulkdrugsubstadrugsubstancetoproduceadrugprod将某种原料药物与其他辅料物和/或原料药物混合，生产药物的工ThepercentageofunitsfilledinaprocesssimulationthatarepositiveformicrobialgrowthaAnareadesignedtomaintainsterilityofsterileequipmentmaybeexposedincritic为无菌物料专门设计的无菌区。无菌产品，容器，封装件，以及设备可暴露于此关键EnvironmentalFlora(iMicroorganismsassociatedwithaprocessingenviroEnvironmentalMonitorintedprogramwhichdescribestheroutineparticulateandmicrobiologicalfprocessingandmanufacturingareas.(Note:Theprogramshouldreferenceacwhereactionlevelsareexc TestperformedtodemonstratethatmediawillsuppoTesttodeterminethefunctionalperformanceofamembranefilterorcontainer/Anasepticmanipulationoractivityperformedbyperstechnicalreportregardsinterventionsaseithercorrectiveorinherent.关键区域内，由人员执行的无菌操作或活动。本技术报告中的干预措施或为Aninterventionthatisincludesuchactivitiesas:clearingcomponentmisfeed,adju执行过程中纠正或调整无菌工艺的干预措施。例如：清Aninterventionthatisanintegralpartoftheasepticprocessandisrequiredforsetand/ormonitoring,e.g.,asepticassembly,containerrepletc.Inherentinterventionsarerequiredbybatchrecconductoftheasepticprocess.样等。根据批记录，规程，或工作指令，计划内介入应对无菌工艺进行适当的指导。EnvironmentaloperatingconditionsdefinedinISO1GMPAnnexl"ManufactureofSterileMedicinalProducts.") AdecontaminatedunitmeetingISO5conditionsthatprovidesuncompromised,continuous,isolationofitsinteriorfromthesurroundingenvironplaceonlythroughmicrobiallyretentivefiltAdecontaminatedunitmeetingISO5conditionsthatprovidesuncompromised,continuous,isolationofitsinteriorfromthesurroundthroughopening?(e.g,"mouseholes")thatprecludetheingressofmicrobialcontamination.MicrobiologicalIdentifBiochemicalcharacterizationofisolatedcoloniestodUnitfilledinanasepticprocesssimulationthatexhibitsdetectablemiRestrictedAccessBarrierSysteRABSareasepticprocessingsystems(ISO5)intendedtosubstantiallyredtheuseofseparativedevicesanddefinedmechanicalfeaturesandoperatingprocedures.封装件及设备的人员带来的污染，确定机械的性能及执行规ShiftScheduledperiodsofworkorproduction,usuallylessthan12hoursinlength,staffedbyofworkers.工作和生产的预定周期，通常少于12小时，工 EstablishedperiodforcollectingsamAbsenceoflife;usuallyreferstoabsenceofviablemicroorganisms.Note:Inpractice,nosuchabsolutestatementregardingtheabsenceofmicroorganismscanbeproven(seesterilization).注意：实际上没有这种状态，不能够实现绝对的没有微生物的状态（见TestperformedtodetermineifviablemicroorganismsarepreseValidatedprocessusedtorenderaproductfreeofviablemicroNote:Inasterilizationprocess,thenatureofmicrobiologicaldeathorreductionisdescribedbyanexponentialfunction.Therefore,thenumberofmineverbereducedtozero.注意：在灭菌过程中，微生物死亡或减少以指数函数形势表示。在灭菌工艺后，仍Establishingdocumentedevidencethatprovidesahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspredeterminedspecificationsandqualityatt(Note:Therehasbeenwide-spreadevolutionintReadersshouldrefertotheU.S.FDA,ECandotherrelatedregulator)'definitionsandguidanceregard建立文件提供高等级的保障，证明某种特定的工艺可以持续生产满足预定标准及质量属性的产品。Asetofconditionsencompassingupperandlowerprocessiwithinstandardoperatingprocedures,thatposethegreatestchance comparedtoidealconditions).Suchconditionsdonotnecessarilyinduceproduct 3.0processsimulationconceThevalidationofanasepticprocessingoperationshouldincludeasepticprocesssimicrobiologicalgrowthmediuminplaceoftheproduct.Tnormallyincludesexposingthemicrobiologicalgrowthmediumtoproductcontactsurfacesofequipment,containerclosuresystpotentialforaunitofdrugproducttobecomecontaminatedduringactualoperations无菌工艺操作验证应包括使用微生物成长培养基替代产品的无菌工艺模拟。无基灌装，正常情况下包括将微生物成长培养基暴露于设备接触表面，容器，封装系统，关键环境，3.1numberandfrequencyofsimulationsThenumberandtypeofasepticprocesssimulationpeposedbytheprocessorsignificantchangestotheprocess.Newfacilitiesandprocessesareregarddifferentlybasedonthedeterminationofthoserisks.无菌工艺模拟的数量和类型应当是建立在工艺或者重大工艺变更的风险评估基Foranewfacilityorproductionprocess,processsimulationsareperformedaspartoftheoverallvalidationactivities.Initialprocesssimulationsaregenerallyconductedaftercompletionof:一个新的设施或生产工艺，工艺模拟应该作为所有验证的一部分。最初的·Implementationofenvironmentaldecontaminationpro·Personneltraining stateofcontrol.Historically,therehasbeenaregulatoryexpectationthatatleastthreeconssuccessfulprocesssimulationsareperformedwhenqThismaybeanappropriateactivitytoutilizeriskmanagementappro无菌工艺模拟是在理想控制状态下，为新的设备、生产线或是工艺操作提供支 模拟。可适当使用风险管理方法。Thereisaregulatoryexpectationfora(6,7,8,9).Additionalprocesssimulevaluationofanymajorchangestoprocedures,practicesorequipmentconfiguration(SeeSection12.0-OngoingProcessEvaluation).Flexibilityinmediafilldesignmaybeappropriatofferrobustseparation(builtinbydesign)andconsistentlyheightenedlevelofproductprotection.装设计应具有灵活性，便于隔离装置提供稳健的分离（专门3.2worstcaseAusefultechniqueinthevalidationofpharmaceuticalprocessistheemploymentof”worstcase”scenarios.Theuseof“worstcase”situationsisintendedtochallengetheprocessunmaybeontheedgeofnormaloperatingconditions.If,underthecircumstanchallenge,acceptableresultsareachieved,thenthereisgreaterconfidenceinthereliabilityofthesystemundermoreroutinecondition.Worstcasedoesnotmeancreationofartificialconditionsorewhichexceedallowedoperatingconditionsandw在制药工业验证中一个有用的技术就是采用“最差条件”。采用“最差条件”意在正常工作条件边缘下对工艺条件进行挑战。如果在“最差条件”的挑战下，仍然能达到预期的接受标准，那么在正常的条件下，系统的可靠性将有更高的信心。最差条件并非意味着人WorstcaseconditionsvarydependingontheoperationsorriskexecutingtheAPSusingthemaximumnumberofpersonnelmaybeworstcaseatcgownedpersonnelarethegreatestsourceofsituationsworstcasemayincludeexecutingtheprocesswithfewerpeopleifthisresultinmoremovementbytheprocessoperato人员更衣可能是在无菌过程中微生物最大的污染源。在其他情况下，最差中，更少的人，如果这样作会导致更多活动在操Otherexamplesof“worstcase”practicesmayinclude:·Usingroom/equipmentatthemaximumtimeperiodaftercompletionofsanitization/ster ·Usingtheslowestfillspeedfo·UsingthehighestfillspeedfortTheworstcaseconditionsselectedforinclusioninancharacteristicsoftheoperation.TheidentificationofappropriateworstcaseconditionsshouldbeaccomplishedbyconductinganassessmentoftheAPScoveringtherelevantvariablesandtheirmicrobiologicalimpactontheprocess.Suchassessmentscanbenefitfromtheapplicationofriskmanagementprincipleandconsiderations/rationalefortheirselecti由此对最差条件进行恰当的识别。评估可借鉴风险管理原理相关内容，评估结Riskisdefinedasthecombinationoftheimpactofahazardorunwantedevenoccurringandharmingthepatient(10,11).Thehazardassocofthistechnicalreportisthelossofsterilityassuranceorpotentialforpyrogens.Theuseassessmentprinciplesshouldbeofbenefitinmakingdecisionsresimulation.ItwouldbebeneficialconfirmingthedesignoftheAPSstudy.风险是指危险或不必要的事件的影响，可能发生事故和危害加工相关的危害是无菌保证或潜在热源的失控。风险评估原则的使用有利于决Anumberofriskassessmentmethodsspecificforasepticprocessinghavebeendefinedasepticprocessstepsandinterventionsthatcanpotentiallyadverselyaffectthesterilityastheproduct.Riskassessmentscanrelatedtocontainersize,configuration,linespeed,batchsize,andoperateffortsshouldbemadetomitigateidecommunicatedtostakeholdersandmanagementintheorganizationincludingtheQ识别和评估无菌工艺步骤和对产品无菌保障有潜在不利影响的干预措施。风险定与容器大小、外形、生产线速度、批量和操作条件相关的最差条件。在努力以减轻确定的风险通过消除或改变工序的风险和完善的设施、设备、和 应记录并传达组织的利益相关者和管理层，包括质量Anassessmentofongoingcontrolsandchangestotheasepticprocescomputerizedsystems,facilityandcriticalutilitiesmaybepchangestotheassuranceofsterility.Thisassessmentmaybeusedtojustifythetypeofresponseorsimulationoftheprocesschangeneededtoassurethatthechangehasnotadverselyaffectedtheasepticprocess.Riskassessmentmaybebeneficialtopresentarationalefortheneeprocesssimulationasaresultofchangecontrol.shouldberecorded,approvedandincorporatedintothechangecontroldocumentat对无菌工艺，人员，设备，计算机系统，设施和关键设施应进行持续控制和变更这些以保证无菌的变更的风险。评估通常可以用来证明反应类型或工艺变更保变更没有对无菌工艺产生不良影响。作为变更控制的结果，风险评估有利需求和范围的呈现。风险评估和风险管理决策应记录、批准，并纳入变更控制 4.0ProcesssimulatTheconductofprocesssimulationsofasepticallyproducedparenteralproductsentailssimulationoftheprocessfromthepointofsterilizationoftheproductandproductcontactsurface,includinandclosures,throughsealingoffilledconcompoundingareanecessarypartoftheAPS.Thefollowinmadeinthedesignandperformanceofprocesssimulationsforasepticallyplyophilizedproducts,suspensions,ointmentsandpowders.对于采用无菌生产工艺的注射药品的工艺模拟，必须模拟从产品和产品容器包括部分。下面的章节总结性的描述了在设计和性能上必须要进行工艺模拟的产品：无菌生产溶液、Theasepticprocessissimulatedthroughtheuseofprand/orplaceboishandledinamanroutineproduction.Theapplicationofthisprincipletoaasepticprocessoradaptationofshouldbeaccomplishedinamannerwhichwillnotreducsimulationand,asaresult,appeartoimprovetheresultsofthesimulationrelativetoroutinepoperations.相近。此项无菌工艺或规程的原理应用要求适当，不能降低模拟的有效挑战ItisimportanttonotethatwheremediaisutilizedintheprocesssimulationitssteForexample,asepticprocesssimulationsdonotsupportthefiltrbeingsimulated,sodifferencesinthefilterarea,fchangesdonotenhancetheasepticprocessoreliminateaprocessstepwhisterilityassuranceoftheproduct.Thisdocu