过程确认及方法概述ppt课件

.,ProcessValidationtheinterlockofthecapintothetubewaschangedtoimprovethepullstrengthtesting;andshortcapswereaddedtoaccommodatedifferentsizesyringes.Verificationsand/orvalidations,designreviews,designreleases,anddesignapprovalswerenotperformedforanyofthesechanges.对于这些变更没有实施确认和/或确认，设计评审，设计发布，以及设计批准。Specifically,recordswerenotavailabletoshowthatthebursttestonlot31255wasperformedatthemaximumsterilizationdose.特别是，没有记录可以表明批号为31255的产品按照最大灭菌剂量进行了爆裂测试。Yourfirmfailedtoverify/validateseveralprocessdeviationsasrequiredby21CFR820.75.你们没有按照21CFR820.75的要求进行验证/确认过程偏差。,.,SomeFDAComplianceOfficerCommentsFDA符合官员的一些评论,“Specificationsneedtobedevelopedbeforeyougettothevalidationstage.”“进行确认之前，需要制订技术规范。”“Manufacturerssometimesmissthestepofcompletingadequateprotocolsbeforeproceedingwithvalidationactivities.”“制造商有时会忘记在开始确认之前完成充分的方案。”“Manufacturerssometimesfailtorevisitthevalidationprocesswhenmodificationsaremadeinproductsorprocesses.”“当发生产品或过程变更时，制造商有时没有重新进行过程确认。”,.,SoWhyDontCompaniesJustDoIt?为什么我们不能马上进行过程确认呢？,Misunderstandingoftheregulation对法规的误解Lackofknowledgeinexecution缺乏实施的知识Lackofresourcestoexecute缺乏实施的资源Fearoffailure害怕失败Lackofmanagementsupport缺乏管理层支持Fearofdelaytomarket担心延误了上市Inhibitsprocesschange隐藏了过程变化,.,过程确认的要素,确认,安装鉴定,操作鉴定,性能鉴定,开发,.,何时确认,A过程输出可验证吗？,B验证是充分及成本可接受吗？,C验证并控制过程,D确认,E重新设计产品和/或过程,.,ProcessesWhichShouldBeValidated需要确认的过程,Sterilization灭菌Cleanroomambientconditions净化室周围的环境Asepticfillingprocesses无菌填充过程Sterilepackagingsealingprocesses无菌包装密封过程Lyophilizationprocess（低压）冻干过程Heattreatingprocesses热处理过程Plasticinjectionmoldingprocess注塑成型过程2004GHTF,.,ProcessesThatMayBeVerified可以验证的过程,Manualcuttingprocesses手动切割过程Testingforcolor,turbidity,totalpHforsolutions测试溶液的颜色，混浊度，总的pH值Visualinspectionofprintedcircuitboards印制电路板的目视检验Manufacturingandtestingofwiringharnesses电缆线束的制造和测试2004GHTF,.,WhatisaValidationMasterPlan?什么是确认主计划（VMP）,Amastervalidationplanidentifiesthoseprocessestobevalidated,thescheduleforvalidations,interrelationshipsbetweenprocessesrequiringvalidationandtimingforrevalidations.Oncethesehavebeenestablished,andthepurposeandscopeforvalidationsareclearlystatedandknown,protocoldevelopmentcancommence确认主计划用以明确哪些过程要确认，确认（过程）的进度表，要求确认的过程和再确认（过程）时间选定上的相互关系。一旦确定了上述内容、清楚地规定确认的目的和范围并对外告知，方案的编制便可以着手进行了。Itdocumentsspecificallythevalidationofequipment,processes,software,facilities,etc.它记录了要被确认的设备、过程、软件、设施等。Itsamapoftheprocessvalidationprocessfortheteamtofollow.它是团队要遵守的过程确认主线图。AVMPisanindexthatFDAcanfollowinunderstandingyourvalidations.确认主计划是FDA用来理解你的确认的索引,.,WhyUseaValidationMasterPlan?为什么要用确认主计划,AlthoughthesearenotrequiredbytheFDAregulationsitisoneofthefirstthingsthatanauditormayaskforduringaninspection.尽管这不是FDA法规所要求的，但是它是审核员在检查过程中所要求的首要东西之一。IfacompanyholdstruetoitsVMPanditsdocumentedevidence,credibilityisestablishedandFDAwillhavemoreconfidenceinonesoutcomes.如果公司能够按照VMP做并且记录了证据，信任就建立起来了，FDA对其结果就会更有信心。,.,WhyUseaValidationMasterPlan?为什么要用确认主计划,Allowsonetobeproactiveratherthanreactive.考虑前瞻性而不是事后反应Providesdefinition,scopecreep,andcommitmenttoresponsibilities.提供了定义、范围以及对职责的承诺Itprovidesamaporguidetotheauditordefininghowthecompanyistyingtheirconcepttorealityinordertosuccessfullyachieveuserrequirements.它为审核员提供了公司为了成功的满足用户的要求而如何将公司的观念和实际联系在一起的路线图或指导方向,.,ComponentsofaValidationMasterPlan?确认主计划的组成,Definitionoftheproject项目定义Strategyorapproachtotheproject项目的策略或方法Scopeoftheproject项目的范围Whatprocesseswillbevalidated?将被确认的过程Whatprocesseswillbeverified?将被验证的过程Responsibilities职责,.,ComponentsofaValidationMasterPlan?确认主计划的组成,Arethereanyspecialconsiderations?是否有任何特殊的考虑？Keymilestones关键的里程碑Validationprotocolnumbers确认方案的编号AVMP,perse,isnotthesameasaprojectplan!,.,WhatisinaValidationMasterPlan?确认主计划是什么,.,WhatisRequiredtoBeOutstandinginProcessValidation?过程确认中需要强调什么？,Planning计划CrossfunctionalteamTHATCANWORKTOGETHER!相关职能部门，一起合作Profoundprocessknowledge渊博的过程知识Havingalongtermcommitment长期的承诺Roadmapreflectingregulatoryguidelines能反映法规指导的路标图Metricstomapprogress进展的指标Passionforexcellence追求卓越的激情,.,StepstoValidationofaProcess过程确认的步骤,Formamulti-disciplinaryteam组建一个多功能小组Plantheapproachanddefinerequirements制定步骤并定义要求Identifyanddescribetheprocess识别和描述过程Specifyprocessparametersanddesiredoutput规定过程参数和希望的输出Decideonverificationandorvalidation就验证和（或）确认做出决定CreateaValidationMasterPlan制定一个主要确认方案,.,StepstoValidationofaProcess,Selectmethodsandtoolsforvalidations选择确认的方法和工具Createvalidationprotocols编制确认方案PerformIQ,OQ,PQanddocumentresults执行IQ、OQ、PQ并将结果形成文件Determinecontinuousprocesscontrols确定连续的过程控制Controltheprocesscontinuously连续地控制过程,.,Protocoldevelopment方案编制,Processvalidationprotocolsshouldincludethefollowingelements:过程确认方案应该包括如下元素：Completedescriptionoftheprocess过程的完整描述Identificationoftheprocesstobevalidated要确认的过程标识Selecttheworstcase选择最差条件（产品）Identificationofdevice(s)tobemanufacturedusingthisprocess在这个过程下产出的器械的标识Objectiveandmeasurablecriteriaforasuccessfulvalidation一个成功确认的目标和可测量的标准Lengthanddurationofthevalidation确认的用时和有效期限Shifts,operators,equipmenttobeusedintheprocess过程中采用的轮班制、操作人员和设备Identificationofutilitiesfortheprocessequipmentandqualityoftheutilities过程设备中使用器具(utilities)的标识和质量Identificationofoperatorsandrequiredoperatorqualification操作员识别和要求的操作员资格（证）,.,Protocoldevelopment方案编制,、Relevantspecificationsthatrelatetotheproduct,components,manufacturingmaterials,etc产品、元件、生产材料等的相关规格Anyspecialcontrolsorconditionstobeplacedonprecedingprocessesduringthevalidation在（过程）确认中，对先发生的过程所设置的任何特殊控制或条件Processparameterstobemonitored,andmethodsforcontrollingandmonitoring要监控的过程参数和监控方法Productcharacteristicstobemonitoredandmethodformonitoring监视的产品特性和方法Anysubjectivecriteriausedtoevaluatetheproduct用来评估产品的主观标准Definitionofwhatconstitutesnon-conformanceforbothmeasurableandsubjectivecriteria对于可测量标准和主观标准，定义什么是不合格Statisticalmethodsfordatacollectionandanalysis数据收集和分析的统计方法Considerationofmaintenanceandrepairsofmanufacturingequipment生产设备保养和修理方面的考虑IQ、OQ&PQCriteriaforrevalidation再确认标准,.,Protocoldevelopment方案编制,Forallthreephases,IQ,OQ,andPQ,basedonproduct/processrequirements:对于三个阶段，IQ、OQ和PQ都要基于产品或过程的要求：Determinewhattoverify/measure决定验证或测量什么Determinehowtoverify/measure决定如何验证或测量Determinehowmanytoverify/measure,i.e.statisticalsignificance决定验证或测量多少，如统计量Determinewhentoverify/measure决定何时验证或测量Defineacceptance/rejectioncriteria规定接受或拒绝的标准Definerequireddocumentation规定要求的文件Remember:protocolmustbereviewedandapprovedbeforeexecution记住，在实施前，方案必须被评审和批准。,.,Protocoldevelopment方案编制,Generally,protocolincludes4sections:一般来讲，方案可分为四大部分：The1stsection:validationoverview,includingvalidationscope,processdescription,background,worstcases,lengthanddurationofthevalidation,objectiveetc.第一部分：确认概述部分，包含确认范围，过程描述，背景介绍，最差条件挑选，确认的用时和有效期限，目标等等；The2ndsection:qualificationreadiness,includingtherequirementsforman,machine,material,method,environment,testandlabel&traceability,PFMEAetc.第二部分：鉴定准备阶段，包含所有的人、机、料、法、环、测及标志和追溯,PFMEA等要求和准备；The3rdsection:qualification(IQ,OQ&PQ),includingqualificationplananddeviationdisposaletc.第三部分：鉴定阶段(IQ,OQ&PQ)，包含鉴定计划及偏差处理等；The4thsection:documentrequirements，includingtheinputandoutputdocumentsrequiredbythisprotocol.第四部分：文件要求，包含本方案所需的文件及输出文件要求。,.,QualificationTypes鉴定的类型,Howdorequirementsapply?怎样应用这些要求,.,TheImportanceofGaging量具的重要性,Yourmeasurementmethodismostimportantindeterminingyourprocessparameters.在确定你的过程参数的过程中，你的测量方法是最重要的。Gagesmeasurevariationandprovidesignalsforchangesinvariation.量具用来测量变差并提供变差变化的信号。Gagesarethecompasstohelpnavigatethroughthevalidationprocess.量具是整个确认过程中帮助我们导航的罗盘。,.,InstallationQualification(IQ)安装鉴定（IQ）,Establishingbyobjectiveevidencethatallkeyaspectsoftheprocessequipmentandancillarysysteminstallationadheretothemanufacturersapprovedspecificationandthattherecommendationsofthesupplieroftheequipmentaresuitablyconsidered.用客观证据来支持证明，所安装的过程设备和辅助系统的关键安装方面，能满足制造商已批准的技术规范，且供应商的建议也被恰当的考虑了。2004GHTF,.,InstallationQualification(IQ)安装鉴定（IQ）,“Istheequipmentinstalledcorrectly?”设备已经正确的安装了吗？IQGoal：IQ目的Verifyandproveallkeyaspectsoftheprocessequipmentandancillarysysteminstallationadheretothemanufacturersapprovedspecificationandthattherecommendationsofthesupplieroftheequipmentaresuitablyconsidered.验证并证明所安装的过程设备和辅助系统的关键安装方面，能满足制造商已批准的技术规范，且供应商的建议也被恰当的考虑了。TheIQreducesriskbyreducingthenumberofrootcausessuspectedwhentroubleoccursintheOQandPQ.IQ通过消减在OQ和PQ过程中出现的麻烦的可疑原因数量来减少风险Makesureequipmentstomeetintendeduse.确保设备满足预期用途,.,InstallationQualification(IQ)安装鉴定（IQ）,.,InstallationQualification(IQ)安装鉴定（IQ）,Importantconsiderationsare:IQ考虑事项：Equipmentdesignfeatures(constructionmaterials,cleanability)设备设计特点（如清洁装置的结构材料等）Installationconditions(wiring,utilities)安装条件（布线、实用性、功能性等）Calibration,PreventiveMaintenance,cleaningschedules校准、预防性保养、清洁计划Safety安全特性Supplierdocumentation供应商文件Softwaredocumentation软件文件Sparepartslist零部件清单Environmentalconditions(temperature,humidity)环境条件（如清洁室的要求、温度和湿度）2004GHTF,.,AcceptanceCriteria接受标准,Considerations考虑点:Makethemclearandobjective清晰、客观Bedescriptive可描述的Attributesshouldreferenceastandardwhenpossible.可能时，定性参数应该作为参考标准Specificationscanbeatolerance,maximumorminimum规格应该有公差，最大或最小Theymustmakesense，必须能讲的清楚TheymustkeeptheOQandPQinmind必须一直把OQ和PQ记在心里Acceptancecriteriaarecreatedbeforetheprotocolisapprovednotafterward接受标准要在方案批准之前制定出来而不是之后制定出来,.,InstallationQualification(IQ)安装鉴定（IQ）,Protocolcomponents:方案构成Purpose目的Equipmentdescription设备描述Scope范围Processdescription过程描述Itemstobeverifiedineachinstallationcategory在每个安装类别里所要验证的项目,.,OperationalQualification(OQ)操作鉴定（OQ）,Establishingbyobjectiveevidenceprocesscontrollimitsandactionlevelswhichresultinproductthatmeetsallpredeterminedrequirements用客观证据确定能够生产出满足所有预定要求的产品的过程控制极限和行动标准。-2004GHTF,.,OperationalQualification(OQ)操作鉴定（OQ）,OQGoal：OQ目的：TheOQisintendedtocreateaprocessscope(limits)withinwhichanoperatorcontrolstheprocess.Thiswillchallengetheworstcase(Limits)OQ用于创建过程范围(极限）,操作工可在此过程范围内控制过程。它将会挑战过程的最差条件按（极限）。Usinggoodscienceisessentialtoestablishingreliableprocessparameters.使用正确的科学知识是建立可靠地过程参数的基本条件。,.,OperationalQualification(OQ)操作鉴定（OQ）,Sometime,limitscanbegottenherefromexperienceandothersourceinadvance有时，此处可由经验或其他来源预先获得极限。,.,OperationalQualification(OQ)操作鉴定（OQ）,Importantconsiderationsare:重要的考虑点：Processparameterscontrollimits过程参数控制线Defineproductionrunsbatchqty/productqtyandsequenceforeachgroupofparameters确定每组参数的生产批次/产品的数量以及顺序Acceptancecriteria接受标准Gagingortestmethods测量或测试方法Rawmaterials原材料Processchangecontrol过程变更控制ThelimitsandconditionsestablishedintheOQwillbethesamelimitsandconditionsusedinthePQ.在OQ中建立的极限和条件将是用在PQ中所使用的极限和条件相同的。,.,OperationalQualification(OQ)操作鉴定（OQ）,Importantconsiderations:重要的考虑点：Training培训Methodfordeterminingshorttermstabilityandcapabilityofprocess确定短期稳定性和过程能理的方法Potentialfailuremodes,actionlevels,andworstcaseconditions可能的故障状态、作用程度和最坏情况条件UseofstatisticaltechniquestoidentifykeyprocessvariablesandDOEforoptimization统计学有效技术的使用来识别关键过程变差及用DOE进行优化,.,OperationalQualification(OQ)操作鉴定（OQ）,TheOQmusttestproductattheworsecaseprocessconditions.OQ必须测试在最差过程条件中生产的产品Theworsecaseconditionsmustalsoincludeworsecaseproductwhenmorethanoneproductisinvolved(i.e.aproductfamily).当涉及到不止一个产品时（比如一个产品族）最差条件也要包含最差条件的产品。TheprocessparametersestablishedintheOQwillestablishtherevalidationcriteria.OQ中建立的过程参数要建立再确认标准。,.,DeterminationofProcessScope过程范围的确定,Conventionalapproach:Usebesttechnicaljudgmentstodeterminekeyparametersandoperatingscope传统的方法：使用最好的技术判断来决定关键参数和操作范围。Enhancedapproach:UseDesignofExperimentstodetermineoperationalscope先进的方法：使用DOE来确定操作范围。,.,AdditionalOQConsiderations额外的OQ考虑点,Thisisthetimetofindthelimitsofyourprocess这是发现你们的过程极限的时间。Thisisalsothetimetodemonstrateyouknowhowchangesininputswilleffectyourkeyprocesscharacteristics这是证明你们知道当输入如何变化时会影响你们关键的过程特性的时间。Remember:Oncethekeyprocesscontrolsareestablishedtheycannotbeviolatedbytheoperatorortheengineerwithoutrevalidation!记住：一旦建立了关键的过程控制，如果没有再确认，任何操作工或工程师都不能违背他们。,.,PerformanceQualification(PQ)性能鉴定（PQ）,establishingbyobjectiveevidencethattheprocess,underanticipatedconditions,consistentlyproducesaproductwhichmeetsallpredeterminedrequirements.用客观证据确定，在预期条件下，过程能连续地产出符合所有预定要求的产品。2004GHTF,.,PerformanceQualification(PQ)性能鉴定（PQ）,PQGoal：PQ目标：establishingbyobjectiveevidencethattheprocess,underanticipatedconditions,consistentlyproducesaproductwhichmeetsallpredeterminedrequirements.用客观证据确定，在预期条件下，过程能连续地产出符合所有预定要求的产品。Normally,anticipatedconditionsarethebestconditions(NominalParameters).通常情况下，预期的条件就是最好的条件（名义参数）,.,PerformanceQualification(PQ)性能鉴定（PQ）,Inthisphasethekeyobjectiveistodemonstratetheprocesswillconsistentlyproduceacceptableproductundernormaloperatingconditions.在此阶段，要用关键的目标来证明在正常的操作条件下过程能持续的生产出可接受的产品。2004GHTFThePQmustbeperformedbytheoperator!PQ必须要由操作工来执行！,.,PerformanceQualification(PQ)性能鉴定（PQ）,WhileFDAbelievesthatthreeproductionrunsduringprocessvalidationistheacceptedstandard,FDArecognizesthatallprocessesmaynotbedefinedintermsoflotsorbatches.Thenumberthreeis,however,currentlyconsideredtobetheacceptablestandard.FDA相信在过程确认中三个生产循环是可接受的标准，FDA认识到所有的过程不可能根据批次来进行定义的。然而，三这个数字当前被认为是可接受的标准。FDAPreamble,.,PerformanceQualification(PQ)性能鉴定（PQ）,.,PQconsiderationsinclude:PQ应该考虑：ActualproductandprocessparametersandproceduresestablishedinOQOQ阶段的真实产品、过程参数和建立的程序Acceptabilityoftheproduct产品的可接受性AssuranceofprocesscapabilityasestablishedinOQ就像OQ阶段那样建立的对过程能力的保证Processrepeatability,longtermprocessstability过程的重复能力和长期过程的稳定能力,PerformanceQualification(PQ)性能鉴定（PQ）,.,PQExecutionPQ实施,1.Manufacturethepredeterminednumberoflots.生产预先确定批次数量的产品2.Collectdataoneachlot.收集每一批的数据3.Analyzethedataapplyingtheproperstatisticaltechnique.使用恰当的统计方法分析数据4.Documentallfindings.记录所有的发现5.Dispositiontheprotocol.方案处理Note:Alllotsmustpasstoconsidertheprocessvalidated!注意：所有的批次必须通过将要被确认的过程！,.,TheFinalReport最终报告,Prepareatendofvalidationactivities在确认活动的最后准备Summarizethefindingsandanydeviationstotheprotocol.总结发现和任何对方案的偏离Includeallattachmentsrisenfromprotocol.包含由方案所引起的所有附件ConsiderwhethertheOQisstillvalid.考虑是否OQ仍然有效Deriveconclusionsregardingthevalidationstatusoftheprocess.应得出关于过程确认状态的结论Obtainfinalapprovalsignatures.获得最终的批准签字Releaseprocesstomanufacturing.将过程放行给生产过程,.,FailedStudy失效研究,Summarizethereport.总结报告Investigateanddocumenttherootcauses.调查并记录根本原因DeterminewhethertheOQparametersaretherootcause.确定是否OQ参数是根本原因DeterminewhethertheOQneedstobere-run.决定是否要重新进行OQDeterminewhetherthePQwillberunagain.决定是否再进行PQ,.,FailedStudy失效研究,Deviationsfromtheprotocol对方案的偏离Deviationscanbeacceptable.偏离是否是可接受的Statethedeviation.陈述偏离Statehowitdoesnotaffecttheprotocol陈述偏离不影响方案Havethedeviationapproved.让偏离获得批准,.,DiscussionQuestions问题讨论,Whathappensiftwooutofthreelotsfailduetooperatorerror?Caneachlotbedispositionedoneatatime?Candifferentproductsberunin-betweeneachvalidationlot?Whathappensiftheparametersneedtobetemporarilychangedduetoarawmaterialchange?Doesanewoperatorrequiretheprocesstoberevalidated?Whenequipmentismovedtoanewlocationdoestheprocessneedtoberevalidated?Doesnewgaugingormeasurementmethodrequiretheprocesstoberevalidated?,.,Revalidation再确认,Aslongastheprocessoperatesinastateofcontrolandnochangeshavebeenmadetotheprocessoroutputproduct,theprocessdoesnothavetoberevalidated.一旦过程在受控状态内操作且没有对过程或输出的产品没有变更，过程不需要再确认。FDAConditionsforrevalidationshouldbeclearlydefinedanddocumented.必须清楚地定义出再确认的条件并文件化。,.,WhenisRevalidationappropriateorrequired?什么时候要求再确认,change(s)intheactualprocessthatmayaffectqualityoritsvalidationstatus可能影响质量或其确认状态的真实过程的改变negativetrend(s)inqualityindicators质量指示器的负面动向change(s)intheproductdesignwhichaffectstheprocess对过程有影响的产品设计上的改变transferofprocessesfromonefacilitytoanother从一台装置到另一台装置的过程转换changeoftheapplicationoftheprocess过程应用的改变2004GHTF,.,WhenisRevalidationappropriateorrequir