美国FDA验证高级培训

1美国FDA验证高级培训DenisKluba博士吴培栋博士2目录TableOfContents1.验证定义2.CGMP对验证的要求3.验证历史与期望4.验证综述5.验证主方案与规划6.实施验证的方法7.验证的技术内容要求8.执行验证方案9.工作流程10.改变控制11.再验证12.总结3PartOne:WhatisValidation?第一部分：验证定义4WhatisValidation?•ForthisSeminaritreferstotwothings:•1.TheUSAFDArequirementsthatmustbemetinordertosuccessfullyandcontinuallyselldrugproductsintheUSA•2.Activitiesthatwillcontributetothesuccessofthecompanyinthemanufactureofdrugproducts验证的含义？5Validation“Anythingwhichyoucannotunderstandisindistinguishablefrommagic.”•ArthurC.Clark“Validationmaynotbemagic!”•C.Edwards业内对验证的理解6ValidationIs.....“Documentedevidencewhichprovidesahighdegreeofassurancethataspecificprocesswillconsistentlyproduceaproductmeetingitspredeterminedspecificationsandqualityattributes.”FDA对验证的定义7ToConsistentlyProduceADesiredKnownProductWhyDoWeValidate?ConfirmDesignEstablishOperatingBoundariesEstablishBaselinesProductComplianceTestwithinSpecification验证的作用/目的8HowDoWeValidate?DetailsWillFollowButThisistheGeneralModelIdentifyEquipmentSystemsDevelopTestsWriteProtocolsConductTestsEvaluateDataReportResultsResultsOK?yesNoAmendProtocolAmendTestCollectDataValidatedSystemSystemModified?验证流程图9FirstthreestepstoCGMPcompliance•document•document•document符合CGMP要求的头三步10BoundariesofValidationCOMMISSIONINGSTART-UPTROUBLESHOOTINGTRIALRUNSCYCLEDEVELOPMENTPROCESSDEVELOPMENTENGINEERINGSTUDIESVENDORSERVICEREPORTSFACTORYACCEPTANCETEST“AS-BUILT”DRAWINGSSTANDARDOPERATINGPROCEDURESMFGBATCHRECORDSPERSONNELTRAININGCALIBRATIONPREVENTATIVEMTCECHANGECONTROLCOMPLIANCEVENDORAUDITSANNUALREVIEWSCOMPLAINTSSAFETYDOCUMENTEDPROGRAMHIGHDEGREEOFASSURANCECONSISTENTLYMEETSPREDETERMINEDSPECIFICATIONS验证的界限/范围11ValidationLifeCycleApproachProspective/ConcurrentDefineSpecificationsEquipmentProcessRequirementsProceduresDesign/SpecifyEquipmentDefineProcessDevelopProcedureSpec.InstallEquipmentVerifyProcedureSpecificationsQualifyEquipmentDevelopValidationProtocolObtainDataonProcessObtainDataonProcessDataOneLotConcurrentValidationReportThreeLotsProspectiveAcceptanceOngoingEvaluationChangeControlNew/RevisedProcess/Product验证生命周期:新的/修改过的工艺/产品12ValidationLifeCycleApproachRetrospectiveDefineSystemSpecificationsEquipmentProceduresQualifyEquipmentReviewProcessCapability,Specifications,Procedures,OperatingInstructionsDevelopValidationProtocolValidationReportAcceptanceOngoingEvaluationDataConductTesting(IfNeeded)ChangeControlExistingProcess/Product验证生命周期:现有工艺/产品13BenefitsofValidation•IncreasedThroughput•ReductionInRejectionsandReworks•ReductionInUtilityCosts•AvoidanceOfCapitalExpenditures•FewerComplaintsAboutProcessRelatedFailures•ReducedTesting–In-processandFinishedGoods•MoreRapid/AccurateInvestigationsIntoProcessUpsets•MoreRapidandReliableStartupOfNewEquipment•EasierScale-upFromDevelopmentWork•EasierMaintenanceOfTheEquipment•ImprovedEmployeeAwarenessOfProcesses•MoreRapidAutomation验证带来的好处14ElementsOfContemporaryValidationInTheUS•EquipmentCalibration-ProcessandValidationEquipment•EquipmentQualification-InstallationandOperational•ProcessDevelopment•ProcessDocumentation•PerformanceQualification-Validation•MaintenanceofValidation-ProcessandEquipmentChangeControl当今美国验证包含的内容15cGMPandISO-9000-Similarities•AimedatQuality•RequireDocumentation•RequireSpecificQualityProgram•QAandQCIncludedCGMP和ISO9000的相似之处16cGMPandISO-9000-Differences•cGMPAimedatProduct•ISO-9000IncludesDesignandService,aswell•cGMPCoversActivitiesDirectlyRelatedtoManufacturing•ISO-9000CoversBroaderRangeofActivities(e.g..Purchasing)•cGMPRequiresFormalValidation•ISO-9000RequiresApplicableStatisticalMethodsCGMP和ISO9000的不同之处17BenefitsoftheSystemsApproachtoValidation•MoreRigorousControlOverOperations•CentralizedPlanningforallValidationRelatedAspects•TiesExistingSub-elementsintoCohesiveSystem•EstablishesValidationasaProgram,notaProject•ProvidesforContinuityofApproach•AffirmsValidationasaDisciplineMuchlikeOthers•AllowsForPersonnelGrowthwithintheValidationExpertise•UsuallyResultsinCentralizationofValidationExpertise•MoreCompatiblewiththeAccomplishmentofaCorporateObjectiveforValidation系统验证方法的好处18TheValidationProgram•EstablishGoalsandObjectivesastoWhatMustbeValidated•QualifyorRe-qualifytheEquipment•EstablishValidationProtocolsforeach,andobtainApprovaloftheProtocols•EstablishPersonnelRequirementsandTrainingRecordsProcedure•DesignandConductExperiments.CollectData•EvaluatetheData•PrepareSummaryReportsOutliningtheResultsoftheExperiments.ObtaintheNecessaryApprovals•EstablishandMaintainValidationFilesIncludingRawData•InstituteaChangeControlProceduretoInsuretheOngoingAcceptabilityoftheWork验证项目/规划19PartTwo:GMPRequirements第二部分：GMP对验证的要求20GMPrequirements•Part211:Currentgoodmanufacturingpracticeforfinishedpharmaceuticals§211.68-Automatic,mechanical,andelectronicequipment.§211.84-Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.§211.110-Samplingandtestingofin-processmaterialsanddrugproducts.§211.113-Controlofmicrobiologicalcontamination.§211.165-Testingandreleasefordistribution.§211.166-Stabilitytesting.GMP要求21cGMPinthePharmaceuticalIndustryGMPistheabbreviationof“GoodManufac