美国FDA验证高级培训资料

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1、美国美国FDA验证高级培训验证高级培训Denis Kluba 博士博士吴培栋吴培栋 博士博士驼一譬心凉忘砚遵沁氖臀帅锹撼创厘模阵抚照凯炮锁凿窟草数酶译坛衍憾美国FDA验证高级培训资料美国FDA验证高级培训资料1目录TableOfContents1.验证定义验证定义2.CGMP对验证的要求对验证的要求3.验证历史与期望验证历史与期望4.验证综述验证综述5.验证主方案与规划验证主方案与规划6.实施验证的方法实施验证的方法7.验证的技术内容要求验证的技术内容要求8.执行验证方案执行验证方案9.工作流程工作流程10.改变控制改变控制11.再验证再验证12.总结总结尧骂维诵帖壁炸哭劣纤甸惨裴吧炬惕铱梧漏

2、只子糟阵缄昆尉杨敞柱花锤迭美国FDA验证高级培训资料美国FDA验证高级培训资料2PartOne:WhatisValidation?第一部分：验证定义凶湖次储棱退碾束芭镇尚味戊辐枝谱箕城针哲酝捞逢候裸胸宾删肖附徊泵美国FDA验证高级培训资料美国FDA验证高级培训资料3WhatisValidation?ForthisSeminaritreferstotwothings:1.TheUSAFDArequirementsthatmustbemetinordertosuccessfullyandcontinuallyselldrugproductsintheUSA2.Activitiesthatwillc

3、ontributetothesuccessofthecompanyinthemanufactureofdrugproducts验证的含义？诞费谈状驴寨辰褒爬鹿裹琶鹃泅欺芥力溅如洞拓典治寡岸晰剃疮庆耳失深美国FDA验证高级培训资料美国FDA验证高级培训资料4Validation“Anything which you cannot understand is indistinguishable from magic.” Arthur C. Clark“Validation may not be magic!” C. Edwards业内对验证的理解壮蹋做筷泛呸杨荔浓永遗拜瞻蚂谴胚站丸纬钮引问核介炕雷

4、督肿阀踌闹伏美国FDA验证高级培训资料美国FDA验证高级培训资料5Validation Is.“Documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.”FDA对验证的定义舔萄侈戳硼抿茸课砚谰消幂桨氢村呕徐膛晚绥鼎笨歇仲速猪厄剁晶恩橙诡美国FDA验证高级培训资料美国FDA验证高级培训

5、资料6ToConsistentlyProduceADesiredKnownProductWhy Do We Validate?ConfirmDesignEstablish OperatingBoundariesEstablish BaselinesProductComplianceTest withinSpecification验证的作用/目的汲岔摇亭斑垫毡蟹伏靶捂带牲班设舒写败碑袜银邢淌谐壶酞梨仓箔肤爪糠美国FDA验证高级培训资料美国FDA验证高级培训资料7How Do We Validate?DetailsWillFollowButThisistheGeneralModelIdentify

6、 EquipmentSystemsDevelop TestsWrite ProtocolsConduct TestsEvaluate DataReport ResultsResults OK?yesNoAmendProtocolAmendTestCollect DataValidated SystemSystem Modified?验证流程图啄藻恫弗估深折覆额楞敝僵邓砌竹遂耪木农抱锑咬捶墒轧童舍溉差倾山衬美国FDA验证高级培训资料美国FDA验证高级培训资料8FirstthreestepstoCGMPcompliancedocumentdocumentdocument符合CGMP要求的头三步娠荒

7、歹师狭琢毯遵蝎作丛恶京广目寥窍梁展剑洁窘孙天燕友棘憨耸埃甥盘美国FDA验证高级培训资料美国FDA验证高级培训资料9BoundariesofValidationCOMMISSIONING START-UP TROUBLE SHOOTING TRIAL RUNS CYCLE DEVELOPMENT PROCESS DEVELOPMENT ENGINEERING STUDIES VENDOR SERVICE REPORTS FACTORY ACCEPTANCE TEST “AS-BUILT” DRAWINGS STANDARD OPERATING PROCEDURES MFG BATCH RECOR

8、DS PERSONNEL TRAINING CALIBRATION PREVENTATIVE MTCE CHANGE CONTROL COMPLIANCE VENDOR AUDITS ANNUAL REVIEWS COMPLAINTS SAFETYDOCUMENTEDDOCUMENTED PROGRAM PROGRAM HIGH DEGREE OF HIGH DEGREE OFASSURANCEASSURANCECONSISTENTLYCONSISTENTLYMEETSMEETSPREDETERMINEDPREDETERMINEDSPECIFICATIONSSPECIFICATIONS验证的界

9、限/范围又洗雁衷消墒佛兑舅绎流赐估切航磕吊拉惭脂塘土妙燥晃食炽秉戮中此煌美国FDA验证高级培训资料美国FDA验证高级培训资料10ValidationLifeCycleApproachProspective / ConcurrentDefine SpecificationsEquipment Process RequirementsProceduresDesign/Specify EquipmentDefine Process Develop Procedure Spec.Install Equipment Verify Procedure SpecificationsQualify Equip

10、ment Develop ValidationProtocol Obtain Data on Process Obtain Data on Process Data One LotConcurrent Validation ReportThree LotsProspectiveAcceptanceOngoingEvaluationChange ControlNew / Revised Process / Product验证生命周期:新的/修改过的工艺/产品枪蓟粒埋面胆疯着犁歌时蝗疑绥潘案惫味能拦办搪曲厢秸衬褂星尊馈戒激美国FDA验证高级培训资料美国FDA验证高级培训资料11Validation

11、LifeCycleApproachRetrospectiveDefine SystemSpecificationsEquipment ProceduresQualifyEquipmentReview Process Capability,Specifications, Procedures,Operating InstructionsDevelop ValidationProtocol Validation ReportAcceptanceOngoingEvaluation Data Conduct Testing(If Needed)Change ControlExisting Proces

12、s / Product验证生命周期:现有工艺/产品腕摈拌噪禁婉馒仰绳例拒把亮冠钙约绵肉则酥始昂宵榨残玖豢湿已棉募曲美国FDA验证高级培训资料美国FDA验证高级培训资料12Benefits of ValidationIncreased ThroughputReduction In Rejections and ReworksReduction In Utility CostsAvoidance Of Capital ExpendituresFewer Complaints About Process Related FailuresReduced Testing In-process and F

13、inished GoodsMore Rapid / Accurate Investigations Into Process UpsetsMore Rapid and Reliable Startup Of New EquipmentEasier Scale-up From Development WorkEasier Maintenance Of The EquipmentImproved Employee Awareness Of ProcessesMore Rapid Automation验证带来的好处彼倦籍祖捡涧如屯莱沏弊庄把亚竣裁抬箍犬亡淖笔字锚稀嚎万蕴麓详甲拷美国FDA验证高级培训

14、资料美国FDA验证高级培训资料13ElementsOfContemporaryValidationInTheUSEquipmentCalibration-ProcessandValidationEquipmentEquipmentQualification-InstallationandOperationalProcessDevelopmentProcessDocumentationPerformanceQualification-ValidationMaintenanceofValidation-ProcessandEquipmentChangeControl当今美国验证包含的内容悬接牌夜赁

15、诽圃镀板饶五绅惰移钧腮峰散蝴桥叠莹怂增逼沃郑脓较捐盘晕美国FDA验证高级培训资料美国FDA验证高级培训资料14cGMPandISO-9000-SimilaritiesAimedatQualityRequireDocumentationRequireSpecificQualityProgramQAandQCIncludedCGMP和ISO9000的相似之处备活援单抖归艺朵寅菌筏庄分髓琼亦称比订棒轰厘乡搁嫁宰贷弧含攘履铝美国FDA验证高级培训资料美国FDA验证高级培训资料15cGMPandISO-9000-DifferencescGMPAimedatProductISO-9000IncludesD

16、esignandService,aswellcGMPCoversActivitiesDirectlyRelatedtoManufacturingISO-9000CoversBroaderRangeofActivities(e.g.Purchasing)cGMPRequiresFormalValidationISO-9000RequiresApplicableStatisticalMethodsCGMP和ISO9000的不同之处吭颂溺畦滞送筛臼决六院片搐丹罗荔骇椒茬褐疮绍喉劲尾滓昭莲自鞠妊患美国FDA验证高级培训资料美国FDA验证高级培训资料16BenefitsoftheSystemsAppro

17、achtoValidationMoreRigorousControlOverOperationsCentralizedPlanningforallValidationRelatedAspectsTiesExistingSub-elementsintoCohesiveSystemEstablishesValidationasaProgram,notaProjectProvidesforContinuityofApproachAffirmsValidationasaDisciplineMuchlikeOthersAllowsForPersonnelGrowthwithintheValidation

18、ExpertiseUsuallyResultsinCentralizationofValidationExpertiseMoreCompatiblewiththeAccomplishmentofaCorporateObjectiveforValidation系统验证方法的好处表刚袁口黍宴渗医虱夯黍甄煞何胯重依鞘穷摧夏莹酸楼苔淹耿缺犹脏阴铬美国FDA验证高级培训资料美国FDA验证高级培训资料17TheValidationProgramEstablishGoalsandObjectivesastoWhatMustbeValidatedQualifyorRe-qualifytheEquipmentE

19、stablishValidationProtocolsforeach,andobtainApprovaloftheProtocolsEstablishPersonnelRequirementsandTrainingRecordsProcedureDesignandConductExperiments.CollectDataEvaluatetheDataPrepareSummaryReportsOutliningtheResultsoftheExperiments.ObtaintheNecessaryApprovalsEstablishandMaintainValidationFilesIncl

20、udingRawDataInstituteaChangeControlProceduretoInsuretheOngoingAcceptabilityoftheWork验证项目/规划臃跃角田败眉竹产系卫障撅倘骗陨萧丁飞袭探峻沦目福奎榆刁制应萨抑肇美国FDA验证高级培训资料美国FDA验证高级培训资料18PartTwo:GMPRequirements第二部分：GMP对验证的要求沿迭受盾奶佐辩寂敢网女位彪配抨陵豺硒贩剧泻脆裕井偷炭选扁疡阵呈虫美国FDA验证高级培训资料美国FDA验证高级培训资料19GMPrequirementsPart 211: Current good manufacturing

21、practice for finished pharmaceuticals211.68-Automatic,mechanical,andelectronicequipment.211.84-Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.211.110-Samplingandtestingofin-processmaterialsanddrugproducts.211.113-Controlofmicrobiologicalcontamination.211.165-Testingandre

22、leasefordistribution.211.166-Stabilitytesting.GMP要求俺颖酌伏洱岛癌俊燎掷铂芝笑忱嘉事纺抒当睹版娥雨绥螟玲络唆桂均或梳美国FDA验证高级培训资料美国FDA验证高级培训资料20cGMPinthePharmaceuticalIndustryGMPistheabbreviationof“GoodManufacturingPractice”whichisadoptedbythemedicalandhealthrelatedindustriesincludingthepharmaceuticalindustryinanefforttomaintainthe

23、higheststandardsofqualityinthedevelopment,manufactureandcontrolofmedicinalproducts.Sincetheindustrystandardsaresubjecttocontinuousimprovement,thelettercintheabbreviation“cGMP”refersmorespecificallytothecurrentorthelatestversionoftheGMPrequirements.制药行业的cGMP奸齿吝夜黑季肢钉苛衙饼由惕陆械伯餐墨摔柬脖硫谅窄司弃敖闪愚者钢沥美国FDA验证高级培训

24、资料美国FDA验证高级培训资料21RegulatoryRequirementsforValidation.The requirement of process validation is implicit in the language of 21 CFR 211.100 of the Current Good Manufacturing regulations which states:“There shall be written procedures for product and process control to assure that drug products have the

25、 identity, strength, quality, and purity they purport or are represented to possess.监管部门对验证的要求疟合钎搅挨简泞卓牙刃尸撮驯攻侈认团焦词袍状正卒向守羊争咳蔽是屑姑美国FDA验证高级培训资料美国FDA验证高级培训资料22GMPRegulatoryRequirementsforCleaningValidation1978 cGMP Regulations (part 211.67(a) Equipment cleaning and maintenance states:“Equipmentandutensil

26、sshallbecleaned,maintained,andsanitizedatappropriateintervalstopreventmalfunctionsorcontaminationthatwouldalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements”.GMP条例对清洗验证的要求令弹随蛊晓攀樊熄棵啃墟抨蚌港檄朽终瓢容恩臼锄历滚讨彼枣柒郝峨炮绒美国FDA验证高级培训资料美国FDA验证高级培训资料23GMPRegu

27、latoryRequirementsforTestMethodValidationLaboratory Controls 21 CFR 211.165(e) states:Theaccuracy,sensitivity,specificityandreproducibilityoftestmethodsemployedbythefirmshallbeestablishedanddocumented.SuchvalidationanddocumentationmaybeaccomplishedinaccordancewithPart211.194(a)(2).GMP条例对化验方法验证的要求佛萝琴

28、骆竿的寿茎私源戳隙榜庸媚跨腥沃觅吉椿荷潜编砖吹似起捕孺滩侯美国FDA验证高级培训资料美国FDA验证高级培训资料24GMPRegulatoryRequirementsforTestMethodValidationPart 211.194(a)(2) states: Astatementofeachmethodused.shallindicatethelocationofdatathatestablishthatthemethodsusedinthetestingofthesamplemeetproperstandardsofaccuracyandreliabilityasappliedtothe

29、producttested.Thesuitabilityofalltestingmethodsusedshallbeverifiedunderactualconditionsofuse.GMP条例对化验方法验证的要求称贫央屁组稠戳娠械号喊踩姻墓自盔鄙匠软殉扭贵兼弯请韵则器江绝唤城美国FDA验证高级培训资料美国FDA验证高级培训资料25GMPRegulatoryRequirementsforTestMethodValidationU.S. Federal Court decision:UnitedStatesvsBarrLabsCleaningValidation:.itwasruledforc

30、leaningtobeeffective,thespecifictestmethodshadtobeshowntobeeffective.GMP条例对化验方法验证的要求腊相笆羹卡讯毡喘蛾什术隘胰盐脉远疹炉乍坍趋达翱装暗涡肾鸵弟胸清磐美国FDA验证高级培训资料美国FDA验证高级培训资料26PROCESS VALIDATION21 CFR 211.110“such control procedures shall be established to monitor the output and to validate the performance of those manufacturing p

31、rocesses that may be responsible for causing variability in the characteristics of in-process material and the drug product” 工艺验证钝猾帖藩惨孺媳涤拎路灯牵铲熬含硼寇势斌娄鞭莲虎望煤恩航介焙标煮漾美国FDA验证高级培训资料美国FDA验证高级培训资料27PartThree:HistoryandExpectationsAsappliedbytheFDAandImplementedbyIndustry第三部分：验证历史与FDA和制药行业对验证的期望卒警腻恼钙肝滞挺袱玄舟迁减鹃

32、燕朝形涤首妈钨舔仇姓劈器拆桌泛掩炬逃美国FDA验证高级培训资料美国FDA验证高级培训资料28HistoryandexpectationsLearnfortheexperiencesoftheUSAmanufacturersandindustryorganizationsCurrentapplicationsPastcitationsIndustryguidelinesICHQ7AISPEPDAEtc.历史与期望讥释讲累钎孤凿资稠柜幢滁藐灸宛溃影匹犊沽迄健熔撂荒恼尿连这籽眩渔美国FDA验证高级培训资料美国FDA验证高级培训资料29ValidationTargetsEarlyYearsSteril

33、izationAsepticOperationsMiddleYearsNon-sterileProcessesOralDosageFormsRecentYearsBiologicalProcessesBulkOrganicSynthesisDevelopmentalandPilotOperationsSupportingServicesCurrentlyTotalOperationsReviewbySystemsQualitySystemProductionSystemLaboratoryControlsPackagingandLabeling,MaterialsandFacilitiesEq

34、uipmentManufacturing.验证目标纱描而昏求话雪掘觉沉拣蘑蜕赐距脑辟厩掂济宠周坪获将幅赵漓送板许栗美国FDA验证高级培训资料美国FDA验证高级培训资料30HistoryofValidationValidationinTheEarlyYears-1972to1978RegulatoryBasedtoSatisfyFDAPressuresDefensivetoProtectProductLineValidationinItsAdolescence-1978To1983PrimarilyDefensiveSomeEffortsatProcessOptimizationIncludes

35、SomePeripheralConcernsValidationintheUSToday-1983toPresentNon-RegulatoryinManyAreasGearedTowardsOptimizationandfocusedonSystems验证历史剧捶往袜卿赫音撂蹈捣米刃氛袜首藕涧侯顶蹬垦蕉获侦闭亲税狸第脖弗阿美国FDA验证高级培训资料美国FDA验证高级培训资料31validationvs.VALIDATIONvalidationDefensiveTestingOrientedCostlyQualityControlNarrowFocusVALIDATIONOptimizatio

36、nTotal Process ControlCost EffectiveQuality AssuranceDiverse Application如何正确理解验证二胳熔缉寸饮姑缚慎瑟作潜氏嗽做犊目布森非刮馒继砰挎偶厉俺郡冬砧窗美国FDA验证高级培训资料美国FDA验证高级培训资料32ElementsofContemporaryValidationintheUSEquipmentCalibration-ProcessandValidationEquipmentEquipmentQualification-InstallationandOperationalProcessDevelopmentProc

37、essDocumentationPerformanceQualification-ValidationMaintenanceofValidation- ProcessandEquipmentChangeControl当今美国验证所包含的内容/要素怯脉槛讼头倚倪页瞩豆荔宰简于爪挛拷介踪峦播瓢惭隋尔钉瑞外润壬抱泥美国FDA验证高级培训资料美国FDA验证高级培训资料33ExpectationsValidationisaProgramnotaProjectValidationContributestotheStabilityoftheOperationsValidationisnotSomeoneEl

38、sesJob!对验证的期望厦荡吉房拎该艰碾繁垄由矣妻冬挨笼捏库客捆务萨赡抉卷柜刃狭秘蔬乍黄美国FDA验证高级培训资料美国FDA验证高级培训资料34PartFour:ValidationAnOverview第四部分：验证概述沟咽卷冷纹氦轩影唤未县劲长冯墟瘁拼松砒迷酪车圭恼讼枯缉容杨究融裕美国FDA验证高级培训资料美国FDA验证高级培训资料35Who Validates?Validation StaffEngineeringQuality AssuranceQuality ControlManufacturing谁进行验证？恢蜜固陕写细寞瘟妮晨就咎铅卿漂侦骚蔗忽挤窑蝎宦滇薄悬淖薯发辈姻线美国FDA

39、验证高级培训资料美国FDA验证高级培训资料36ValidationvDesignTestingOperation验证运作积缮俯弛捡戮使抖怎手菌互揩梅迎菌喊丫豌蔓猿兽绰而异狐沟伎俗鲍丘筒美国FDA验证高级培训资料美国FDA验证高级培训资料37ValidationvVendorSystemsIntegratorOwner/User验证系统集成者眯蚕榴么零莎惠榨罩卡移踏已券事鲸峦囤秽摸姬庞漂饱绳叮逻缉希慎沽浓美国FDA验证高级培训资料美国FDA验证高级培训资料38ValidationvEngineeringR&DValidation TeamMaintenanceManufacturingQuali

40、ty Assurance验证制造质量保障街祟戮魏财戊冶骡谜尼防伸定泄弊望盘服麓抢辊枝友港迄玲疡印蒸逝南刮美国FDA验证高级培训资料美国FDA验证高级培训资料39WriteProtocols起草方案身呵姿够装良局暂也泰锭掂遣仓挪焰释困鬼扫摊踢镭擅郑啪檄阶素鸯擂碗美国FDA验证高级培训资料美国FDA验证高级培训资料40Example Data Sheets数据单样品姐婶娥骏跑俊咎湖裴茄恃找殿哭嘴师丽尖昼腑晌席卫傅硷哄驳殿为瘟骆册美国FDA验证高级培训资料美国FDA验证高级培训资料41ConductTestingChemical TestsCareful Review andMarkup of Pr

41、ints, SpecsMicrobiologicalTestsPhysical Tests(Temp., Press., Flow)Computer Tests进行测试志翘底彪锰颖碗戊劝蒋蛆俺蜗振醉缩俩肥丸虫刑关禁滁晋图丽矗计溯时羡美国FDA验证高级培训资料美国FDA验证高级培训资料42InstallationQualification(IQ)IQdocumentsthatsystemisinstalledinaccordancewithapproveddesign,specificationandregulatorycodesmanufacturersinstallationrecommen

42、dationhavebeentakenintoconsiderationIQsimplementedconcurrentlywithconstructionofeachsystem安装合格确认淆娃强拆池浆巳异历钮磁醚庄盗采耻授下股俊郁疙泣紧捧光社钠玫噬枫限美国FDA验证高级培训资料美国FDA验证高级培训资料43OperationalQualification(OQ)OQdocumentsthattheequipment:canoperateasdesignedandintendediscapableofrepeatableoperationovertheentireoperatingrange

43、ofprocessvariablesOQexecutedwhenequipmentcanbestartedup运转/运作合格确认你篓刃讫且兜丰症迅邪概昨雌摇矽胁丛捡墓氦几船羌胳恨腮盂莲淘侄芍篙美国FDA验证高级培训资料美国FDA验证高级培训资料44ProcessQualification(PQ)PQdocumentscriticalsystemswhichcanbechallengedtestproceduresproductqualityattributestobeevaluatedacceptancecriteriaalert/actionlevelssystemvalidatedunde

44、rworstcaseconditionsgenerally3consecutivesuccessfulrunsrequired工艺合格确认它窜开弥族漾或柬乏酮紧晃闯蝶互跨蓖累纷辣钉脂蜗佯汞弊勋柬僳疟忠圾美国FDA验证高级培训资料美国FDA验证高级培训资料45DefinitionofProcessValidation 1978Validation is: Documented evidence that provides a high degree of assurance that a specific process will consistently produce a product o

45、f a certain predetermined quality.工艺验证定义咯针玲韶烧战寨腾窘同组憎汾赵卜杠停梧皮坑乃蘸二佑增修习照贰蕊惟排美国FDA验证高级培训资料美国FDA验证高级培训资料46Definition of Process ValidationIn addition to documented evidence that a process will perform reliably and repeatedly, validation, in its highest form, provides an understanding of why.1993工艺验证定义骄契坤部

46、圆仍逸伪推僧琳炎吵谜勒仙栽振窿刁椅挖婆擞菏疵缕株命洗畔粤美国FDA验证高级培训资料美国FDA验证高级培训资料47StagesoftheLife-CycleR&DDesignConstructionTestingSOPs/MaintenanceChange Control生命周期的阶段辣煽条玩鸿基卸便柠稽寥孜钱就拂矫破放蚊新棠瘁耽止诈套幅轧翻椭殴爬美国FDA验证高级培训资料美国FDA验证高级培训资料48BenefitsofValidationIncreasedThroughputReductioninRejectionsandReworksReductioninUtilityCostsAvoid

47、anceOfCapitalExpendituresFewerComplaintsAboutProcessRelatedFailuresReducedTestingIn-processandFinishedGoodsMoreRapid/AccurateInvestigationsIntoProcessUpsetsMoreRapidandReliableStartupOfNewEquipmentEasierScale-upFromDevelopmentWorkEasierMaintenanceOfTheEquipmentImprovedEmployeeAwarenessOfProcessesMor

48、eRapidAutomation验证的好处瘤厩陛之爹骇蓟恐东莫歌钝么粉筛咽验旱烧菇抵凉祟琐伟廊褪催玩灶吕捏美国FDA验证高级培训资料美国FDA验证高级培训资料49DocumentationofValidationMasterPlanProtocolDataSheetsReportProcedures验证文件错褂隘在业州槛锗幕彝仪膛寿悯汕异舱刁钱迂龟埔猛卷蟹及拢便瘩尤盛痔美国FDA验证高级培训资料美国FDA验证高级培训资料50ValidationProtocolsProvideanOutlineoftheValidationEffortIncludeaClearDefinitionofWhatW

49、illBeValidatedIsUniquelyIdentifiedIsDatedApprovedByCompetentIndividualsInResponsibleAreasAreSuitableForReviewByRegulatoryAgencies验证方案警晴桅衬炕功冶圆灌称瘁饯攀五禾盏些犊于辨恩媳宵养帚俘灾洁性咐宦跌美国FDA验证高级培训资料美国FDA验证高级培训资料51ValidationProtocolEssentialElementsIntroduction/AbstractDescriptionofProcessorSystemTestPlanResponsibilitie

50、sAcceptanceCriteriaApprovalsAppendDataSheets,Etc.验证方案的核心要素舰硅白卉陕共园拐丘卧机环拖睦裤岭橡殃台阅涝街桨屋嫁退亲势獭毖阐锅美国FDA验证高级培训资料美国FDA验证高级培训资料52ValidationReportsFunctionsRestricttoOneTaskorSubjectHasaUniqueIdentificationIsDatedFormallyReviewedandApprovedIdentifiesProtocol(s)UsedintheStudyIsSuitableforReviewbyFDA验证报告功能运咖教研云靛儒

51、宰腕卞筑傅飞蹭财妓记鼠吴拣卸懦流淆呈喜昭嘱贡阴垃裂美国FDA验证高级培训资料美国FDA验证高级培训资料53ValidationReport-ContentsAbstractOrSummaryConclusionPlanOfStudyExperimentalResultsConclusionsProtocolReferenceDiagramsAnyMiscellaneousInformationApprovals验证报告内容赤莱菠肖潜枣垄魏骚哨拳撵羚韶衅菱息撮馁驭涉辱嵌炼蕾豪蔑御钝慰慷副美国FDA验证高级培训资料美国FDA验证高级培训资料54InstallationQualification(I

52、Q)IQDocumentsThatThe:SystemisInstalledinAccordancewithApprovedDesign,SpecificationsandRegulatoryCodesManufacturersInstallationRecommendationshavebeentakenintoConsiderationIQisImplementedConcurrentlywithConstructionofEachSystem安装合格确认偷炙誉违吨罪盆返记兜但根幢润沿势派芭湖角训恩尧榔酪褒病臂阿藉矿分美国FDA验证高级培训资料美国FDA验证高级培训资料55DesignDo

53、cumentationDesignandProcurementDocumentationSupportofIQ:PFDs/P&IDsCriticalSystemInstallationDrawings(E.G.WaterSystemIsometrics,SanitaryDuctDrawings)PurchaseandInstallationSpecificationsVendorManualsandPrintsComputerSoftwareDocumentation设计文件宰京晚纸宠盔蘸畅未戮凄揭狼竟授苞百昂士授卿约泉舒苑植吏锥诡死菱赏美国FDA验证高级培训资料美国FDA验证高级培训资料56

54、ConstructionDocumentationConstructionDocumentsInSupportOfIQ:SlopeChecksPipingPressureTestReportsMotorCheckoutReportsWeldInspectionReportsCleaning,PassivationandSanitizationProceduresandReportsHVACTestandBalanceReportsOtherAppropriateConstructionDocumentation建造文件腿岳喉辽硼婉违越蛙饺娠怒乳别煽遏彩拼防芦性芍懂貌张褥径仰雨拖巫系美国FDA验

55、证高级培训资料美国FDA验证高级培训资料57TheP&ID(Piping & Instrumentation Diagram, Engineering Flow Diagram)ProcessEquipmentSupportVesselsInterconnectingLinesUtilityLinesInstruments/InstrumentFunctionsSchematicNoScale-NotSpatiallyPreciseShowsRelationshipsandRelativePosition管线和仪器图损峡免雌抖权符资获愿堂棚容计三蕉吻咏警硕淮森如跳泄拂视每贱甜裤媳美国FDA验证

56、高级培训资料美国FDA验证高级培训资料58OperationalQualification(OQ)OQDocumentsThatTheEquipment:CanOperateasDesignedandIntendedIsCapableofRepeatableOperationOvertheEntireOperatingRangeofProcessVariablesOQImplementedAfterEquipmenthasbeenStartedUporCommissioned运作合格确认幽疥侧喘夺盅膛葛张橇先频灾着琉阎劳垢流噎鼎吸讫萨万轧词刻蝎蚁算炭美国FDA验证高级培训资料美国FDA验证高级

57、培训资料59ProcessQualification(PQ)PQDocumentsThat:ProcessesOperateasRequiredattheNormalOperatingLimitsofCriticalParametersSystemsOperateConsistentlyandReliablyAppropriateChallengesAreEmployed工艺合格确认亚撤蝶愧磐峰守渗枝收振曼酬辆猜了旧蛋勇祥留螺哼系蛮跑杯魁脂堵奴直美国FDA验证高级培训资料美国FDA验证高级培训资料60ReviewandApprovalsDesignDrawingsandSpecificatio

58、nsMasterPlanProtocolsReportsProcedures审阅和批准辨痉挛壁乎搐理糖状耀鸯赖悲搁飞沽栈妊荚吸喻经奥钱跨揪厚蕉籍附缓鲤美国FDA验证高级培训资料美国FDA验证高级培训资料61PartFive:ValidationMasterPlanning第五部分：主验证规划书船赋词麦个粱粪僻臼缠敞张矾教塑难赂固粘渗夷墒悉找痛渣襄摔讽苞楚美国FDA验证高级培训资料美国FDA验证高级培训资料62Planning“Ifyoudontknowwhereyouaregoing,youarelikelytoendupsomeplaceelse!”-LewisCarrollLikeanyo

59、therimportantactivityinacomplexorganizationvalidationmustbemanaged.Thisisespeciallytruegiventhemulti-disciplinednatureofmanyvalidationactivities.规划纷盔喧联当协蹭料钳疙滔陀替拼滑丰疡乏瘪哈齿插哆墅轻格图会荫抚康孝美国FDA验证高级培训资料美国FDA验证高级培训资料63ExistingPlantsThesamelevelofmanagementisnecessaryforthevalidationofanexistingfacility,whether

60、fullyvalidatedornot.Validationiseasierwhenitisanintegralpartoftheday-to-dayoperationofthefacility.现有工厂撰坏哪骆缘台俐喀迟荣岳沼切凡拾润笑庭臼恋刮昭谴厚卯祖鹊摧惰散泛崇美国FDA验证高级培训资料美国FDA验证高级培训资料64MasterPlanDefines and Establishes the Validation Approach and the Acceptance Criteriaand more!主方案蕊好豪梯镀救郎帜毫萄凤嘿知淤猩丙坎枣挣券晾却意规细物浦崎妻蜡陋彦美国FDA验证高级

61、培训资料美国FDA验证高级培训资料65Facilities,ProcessesorProductsWhatneedstobedone?Whowilldoit?Howwilltheydoit?Howlongwillittake?Howmuchwillitcost?设施，工艺或产品厩暗牡谅驮柴甫凸耶姓食款森督盟死聂阉刷缸星储勉蒲辕痪己舶安桥箔壹美国FDA验证高级培训资料美国FDA验证高级培训资料66MasterPlan-GeneralIntroductiontoFacilityPurposeandDesignIntentFacility/ProcessDescriptionProcessContr

62、olConsiderationsSystemDefinitionsPlanning/Scheduling主方案概述益嚼附丘缘凸趁谨寝靠赌狈朽廖溜拟彭惰镜毁撬卡彭草亦掀陀低太脑药扩美国FDA验证高级培训资料美国FDA验证高级培训资料67MasterPlan-WhyProjectFamiliarization/TrainingManagementIntroductionFDAIntroduction/FamiliarizationValidationProgramFoundationBasicProceduresProtocolOutlines/BasesResourcePlanning/Sche

63、dulingContractExecutionInteractionCodifiesPriorDecisionsStructuresValidationActivitiesFacilitatesRegulatoryComplianceUsefulinRegulatoryandClientInteractionsUseWith3rdPartiesConvertibleIntoDrugMasterFileInternalAuditPreparation为什么需要主方案？摔袒缸泼眷毋柞獭顷社爆帧酸惫嚏臀苯肯畴粱瓷兵先描佬诈逻沧充茄偶售美国FDA验证高级培训资料美国FDA验证高级培训资料68Maste

64、rPlan-WhatIntroductionFacility/Process/ProductDescriptionProcessControlConsiderationsSystemDefinitionProtocolOutlines/AcceptanceCriteriaFormatsSOPsPlanning/Scheduling什么是主方案？埠酸拼造搅少常负坊页宪懊轨滥拂晤吻已挽烦钱潍碧氓目挤镣惺咕妈嫌热美国FDA验证高级培训资料美国FDA验证高级培训资料69MasterPlan-GettingStartedFacilityLayoutProcessDescription(s)Product

65、Description(s)EquipmentListUtilityListControlledEnvironmentRequirementsControlPhilosophySchedule主方案的起点庆燕垛牌侈寝遇介济域刃考侨喝缴捆爬亩伸屿削惦野评纵寥淑些劣崇莲策美国FDA验证高级培训资料美国FDA验证高级培训资料70MasterPlanFacilityDescriptionLayout/EquipmentArrangementPeople/Material/ComponentFlowControlledEnvironmentsMaterialsofConstructionSketches

66、主方案中的设施描述褂涤廓笛猫册咀郎银赁座狸湃歇汰踞椅评雹蒸坯宰虱宛崔酉势烁德褒护厦美国FDA验证高级培训资料美国FDA验证高级培训资料71MasterPlan-ProcessDescriptionMajor Process StepsBlock DiagramProcess Flow Diagram(s)Utilities (WFI, DI, CIP, Etc.)Major Support Equipment (Autoclaves, Ovens, Etc.)主方案中的工艺描述膛畜报鲤罢揣诧雌他拽后疤辖膏谤切嫡一拣肖海毛悔芳观焕插搭韭冲义学美国FDA验证高级培训资料美国FDA验证高级培训资料7

67、2MasterPlan-ProcessControlGeneralArchitectureCentral/DistributedControlSystemPLCs/IndividualControlSystemsBuildingAutomationSystemHigherLevelSystems(LIMS,EBR,Etc.)IntegrateintootherSectionsifMinimal主方案中的工艺控制仲昭诸筹爹卸况凡调僚晒疗隶扎惟兑啡掂诉缴盘帆贼撂孵蛆惶楞队馋原播美国FDA验证高级培训资料美国FDA验证高级培训资料73MasterPlan-ValidatedSystemsListsO

68、fSystemsToBeValidatedGeneralAcceptanceCriteriaSpecificAcceptanceCriteriaBasicProtocolOutlines主方案中验证过的系统位秉蜗奶渠冶怖迷人悟枚逛浊漠巧呐凯桔阉肃慨窘确深毖惶敬圃部拙桌爷美国FDA验证高级培训资料美国FDA验证高级培训资料74MasterPlan-ProceduresandFormatsProtocol Format SOP FormatBasic Procedures Validation ProgramResponsibilitiesCalibrationChange ControlList

69、 Of SOPs主方案的流程和格式锰嚣最贪为侣银寸镶揣郸北齐蒲妹摔捍挟骡驯鞋毯痛爽付呕红叭邻境徊伺美国FDA验证高级培训资料美国FDA验证高级培训资料75Master Plan - Planning and Scheduling ManpowerResourcesDocumentPreparationFieldExecutionCalibrationLabSupportTest&Balance/FilterCertificationStart-Up/Commissioning主方案的规划与计划可尺袋华银孩捐撩词几亚贤非甜睫役量揖储胺帐量毗侧二绸由讫哨骡核纬美国FDA验证高级培训资料美国FDA验

70、证高级培训资料76MasterPlan-FocusSterileProductsFacilityEmphasisOnFacilityandEnvironmentPeople,Component,ProductFlowsAutomationMayOrMayNotBeCentralSupportSystemsCritical(Autoclaves,Ovens,WFI,Etc.)主方案的集中点曹牵蝇供捆脚资源舰世脾汀昔诵瓶滞史瑚坤膝锡令幢鞍斯靖仙嗓又骸骆弄美国FDA验证高级培训资料美国FDA验证高级培训资料77MasterPlan-FocusSolidsFacilityIn-processContr

71、olsTestsExaminationstobeConductedonAppropriateSamplesofIn-processMaterialsofEachBatch主方案的集中点绸替浮霞管秦趋载有屑咒朔鹊憋侮洽亮透鹿轴搂隘窑蔓枢爹愿得锻谍做潘美国FDA验证高级培训资料美国FDA验证高级培训资料78MasterPlan-FocusAPIFacilityEmphasisOnChemicalProcessIdentifyAPIStepCross-contaminationControl,ifAppropriateAutomationCriticalCleaningCriticalInMulti

72、-productFacilities主方案的集中点闭刀忿第怒阳逃恐围订兽吵该除迭绦胖醇臃息叛侩栏售持滚仙吓满邦漂弥美国FDA验证高级培训资料美国FDA验证高级培训资料79MasterPlan-FocusCIMSystemsEmphasisonFunctionalRequirementsSystemStructureCommunicationRouting主方案的集中点谰经俩恃话怒航嘻送诱碗酮武样跟屡鳖惊佑服糟熔舆弹乏旦壶眼歉俱哄祭美国FDA验证高级培训资料美国FDA验证高级培训资料80MasterPlan-FocusAnythingUnusualAreasthatareUniquetoYour

73、ProcessEmphasesonthePhilosophyforControls(ProceduralandAutomation)主方案的集中点摊瓷者舶货胜丢釜轻萎衙氮足妮断捅兰枣沏秆做新浑挛惫粗庄牧啊脸渡祖美国FDA验证高级培训资料美国FDA验证高级培训资料81PartSix:MethodsofPerformingValidationIncludingDocumentRequirements,FormatsandApprovals第六部分：设施验证的方法包括文件要求，格式，和批准段婶吠朋路厄砰谐唬撒颈贩现陶孩菊祝胳吨恢谭虫败细贩原穴例慌驰锡人美国FDA验证高级培训资料美国FDA验证高级培训

74、资料82QualificationCombineI/OQintoSingleDocumentAddPQforSmallerProjectsI/OQisSometimes90%oftheOverallEffort,butReceivesOnly10%oftheInvestigatorsAttentionReviewContractorProposalsClosely合格确认迂友疲变亭樊乘汞瓮荆炊王鹊拈逻绣溶仪秃睡凡筷雍语儿一茸睫隐粤墓恭美国FDA验证高级培训资料美国FDA验证高级培训资料83DesignQualificationUsefulonLargerProjectsCritiquesDes

75、ignfromanOperability&ValidationPerspectiveReducesCostsofCorrectingErrorsRequiredinDeviceRegulations设计合格确认雇乃穷老系痒漾袄洁纫幸搐淮畦纠渗绽迫嗡箍怕钠稳絮子帮射广疚杜惠凳美国FDA验证高级培训资料美国FDA验证高级培训资料84Installation/OperationalQualificationChecklistFormatPreferredAvoidArbitraryCriteriaConveyRequirementstoSuppliersinSpecificationsCheckat

76、VendorandReconfirmonSiteFocusonAccuracyofCollectedDocumentationTesttoManufacturersSpecificationsiftheDetailedProcessNeedsareVague安装/运作合格确认契淄控求两资般或哭戊柬欢绸埠火滨功疡辆呐篆苛剃溯方棕铱寸辱烙啪秦美国FDA验证高级培训资料美国FDA验证高级培训资料85PerformanceQualificationUseGenericProtocols“TerminalSterilization”ratherthan“SterilizationofxxxxxVials

77、,Autoclave6,Building4”UseQuantitativeCriteria“RSDMaximumof4.5%”RatherThan“MustDemonstrateaUniformMix”UseMeaningfulCriteria“3LogReductioninEndotoxin”RatherThan“8MinutesAt300C”性能合格确认邯果由困蹬胁龙慕肚楚讶磅炸横渣亦齐耻配伍峪梦涅嫁韩粳官惋怖彪峰栋美国FDA验证高级培训资料美国FDA验证高级培训资料86ValidationasdiscussedinQ7AShouldextendtothoseoperationsdeter

78、minedtobecriticaltothequalityandpurityoftheAPICriticalparameters/attributesarenormallyidentifiedduringthedevelopmentstageorfromhistoricaldata,alongwithrangesnecessaryforreproducibleoperationsQ7A要求的验证暖绍殷嗡删戴沼傀钨领儒龙备拼它钱慰致坚夏仅瞒蔑杂栅敝幻旗提勤颊梧美国FDA验证高级培训资料美国FDA验证高级培训资料87ProspectiveValidationQ7ANormallyperformed

79、forallAPIprocessesValidationofAPIprocessshouldbecompletedbeforecommercialdistributionofthefinaldrugproductmanufacturedfromthatAPI从Q7A角度看验证帖囤扦帅笑骡貉碌舰恨闸哑委邵窗碴惦敢思嘱禁畏则糯改航棘豌寸胰咖洲美国FDA验证高级培训资料美国FDA验证高级培训资料88ConcurrentValidationQ7AConductedwhendatafromreplicateproductionrunsareunavailable:LimitednumberofAPIba

80、tchesproducedAPIbatchesproducedinfrequentlyAPIbatchesproducedbyavalidatedprocessthathasbeenmodifiedQ7A中的同步验证总铺践纽擦见嘿敏仁厘隅芒毙励劣幕砖狗绩踊汛果嘘裂蝴喧史胃酚漓炮妊美国FDA验证高级培训资料美国FDA验证高级培训资料89ConcurrentValidationQ7ABatchescanbereleasedandusedinproductionofdrugproductsforcommercialdistributionbasedonthoroughmonitoringandtes

81、tingoftheAPIbatchesQ7A中的同步验证眩职竟且努俞难饭掺送椭如浸遍施投清惦泻叠炕烙晶袜蒋洼寨瞎来忻疙宜美国FDA验证高级培训资料美国FDA验证高级培训资料90RetrospectiveValidationQ7AExceptionforwell established processesusedwithoutsignificantchangestoAPIqualityduetochangesin:RawmaterialsEquipmentSystemsFacilitiesProductionProcessQ7A中的回顾性验证具撮科陵歪乘定阑孤姥将簧阵口玛沃龙夺贮基铁臃怖纯杏打坷

82、垂具行帮禁美国FDA验证高级培训资料美国FDA验证高级培训资料91RetrospectiveValidationQ7AMaybeusedwhere:CriticalqualityattributesandcriticalprocessparametershavebeenidentifiedAppropriatein-processacceptancecriteriaandcontrolshavebeenestablishedQ7A中的回顾性验证匝俺凿己参衅甫沮桅绪述珐姻冀峨泽渗荚荐扩桂婿陪步坏旺鼻饥进浸竣春美国FDA验证高级培训资料美国FDA验证高级培训资料92RetrospectiveVal

83、idationQ7AMaybeusedwhere(Continued):Process/productfailuresattributedmostlytooperatorerrororsporadicequipmentfailuresunrelatedtoequipmentsuitabilityImpurityprofileshavebeenestablishedforexistingAPIQ7A中的回顾性验证器位皖获射遂春飘癣谤颤掖冉概迫舜鸵节贞仆阵季绦驭砍的安肛舱噬撒淮美国FDA验证高级培训资料美国FDA验证高级培训资料93ValidationQ7AValidationisNOTforex

84、plorationtodesignaprocess.Itisforshowingthatanalreadyestablishedprocessdoeswhatitissupposedtodo.Validationapproaches,protocols,execution,andreportsarefullydescribed.Differentfromdrugmanufacturing:Onlycriticalprocessesareusuallyvalidated,e.g.atthefollowingpointsoftheprocessing:-significantimpuritiesm

85、aybeintroducedorremoved-nosignificantimpuritieswillberemoved-allessentialstructuralelementsoftheAPIarepresentQ7A中的验证要求拔匙争抚乱氨稍毛慨琢豢吩肩拍喘遥谦桓晾凳专韵伐找苍碧赠这灰罕款站美国FDA验证高级培训资料美国FDA验证高级培训资料94NewEquipment/SystemMilestones新设备/系统里程数怯悍甩罢境裤竟校甲辞摧坟瞩阐脖第巡虑侯尹亮奇甲丁灸哪父寅具婚抓美国FDA验证高级培训资料美国FDA验证高级培训资料95Commissioning/Qualificati

86、on TransformationMechanical CompletionCommissioningQualification调试/合格确认的转变某搽冶星挝汰珠彩慌挺揉疏孔叫壁譬酌衙恃厅跟龋狮华吟爵兵骂沤考医井美国FDA验证高级培训资料美国FDA验证高级培训资料96QualificationProgram合格确认项目遮吨糟侮碎肄曹尘欢涩惯播闸衙辞歹峭肠斟侗敦腹踌析抚佰史院奴甚移屎美国FDA验证高级培训资料美国FDA验证高级培训资料97QualificationProgramAttributesCompletionOfCommissioning.TestProtocol(s)WithPre-d

87、eterminedAcceptanceCriteriaCoveringInstallationandOperation.ExecutionUnderPre-approvedProceduresFor:ProtocolandReportDevelopmentDocumentationPracticesChangeControl(Pre-approvalOfChanges)Investigations(Deviations)Approvals合格确认项目的特征生沧扭恐蔡州另汁瑚鼎佬沽祁念澈荤争痊筒颈耸拼汗绣迪竖嘿耶啼般闹玛美国FDA验证高级培训资料美国FDA验证高级培训资料98Commission

88、ing Program AttributesAbilitytoFixEquipment/SystemasRequired(DesignIntent).DocumentedActivities.TestsThatHavePre-determinedExpectations.ExecutionUnderPre-approvedProceduresFor:TestPlanDevelopmentTestExecutionDocumentationPracticesChangeManagement(DocumentedAuditTrailforChanges,includingApprovals)App

89、rovals调试项目的特征兜绦佛咖泣奎眨步瓣速攘美程浚哆诗株饱啪偶簇炕隔羔摄替域俄棠铃撩郁美国FDA验证高级培训资料美国FDA验证高级培训资料99ProposedQualificationProgram建议的合格确认项目己隘注吴古盲值床恒舅著釜榷奖屿彦诵助应塑症眯经倚悍骆兹张蝉盆俗惺美国FDA验证高级培训资料美国FDA验证高级培训资料100TestDocumentation测试文件盆剿拱怀版鸣零拖绢攒姜透曝轧砒漳伐众锨邯蘸透正樟钉框时词豹愚航狮美国FDA验证高级培训资料美国FDA验证高级培训资料101PROJECTRESPONSIBILITIESTHERESPONSIBILITIESOFTHE

90、VALIDATIONTEAMWriting and approving the Master Plan.Writing protocolsProviding validation engineersProviding supervisory assistance Generation of summary reportsPreparation of designated Standard Operating Procedures (SOP).Training to construction and operation personnel as needed for the validation

91、 activities.Review, assistance and support as outlined in the project approach section of this Master Plan for the Engineering/Construction/Validation interface.验证项目组职责鞋团同帖祁甩课钾烧邢脓蹋找轻刨演容令拐去缴拣氓苍匣般帽佩冷碌牛聋美国FDA验证高级培训资料美国FDA验证高级培训资料102PROJECTRESPONSIBILITIESTHERESPONSIBILITIESOFTHEGENERALCONTRACTORReviewi

92、ng and approving the Master Plan and appropriate protocols.Review, approval and implementation of Validations checklists.Establish and maintain the document control procedures and administration for this project.Transmission of all design drawings, specifications, purchase documents and vendor liter

93、atureExecution of the Protocols as defined.Assembly of the turn-over and construction support documentation. Coordination of Calibration, certification activities and supervision of the subcontractors execution of validation activities.Support activities as outlined in the project approach section o

94、f the Master Plan for the Engineering/Construction/Validation interface.总承包商职责驻铃蓖京珠东悟鹏陇痈黔渡翠姥磁木袄沂瓤目狰武吧钟分拖挡抉英染诧子美国FDA验证高级培训资料美国FDA验证高级培训资料103PROJECTRESPONSIBILITIESTHERESPONSIBILITIESOFENGINEERINGCONTRACTORWriteuptheBasisofDesignforallsystemsandsectionsofthefacilityandhavethemapprovedbytheresponsibleo

95、perationspersonnel.PreparationofalldesigndrawingsandspecificationsnecessaryforthecompletionofthescopeofworkbyValidation.SupportactivitiesasoutlinedintheprojectapproachsectionoftheMasterPlanfortheEngineering/Construction/Validationinterface.ReviewingandapprovingtheMasterPlan.工程承包商职责吼词癌划耪歼渴泪误接散俄帧曝滩邯詹卤

96、佳农毁肿毅率区撇氖苑始隆赔亮美国FDA验证高级培训资料美国FDA验证高级培训资料104PROJECTRESPONSIBILITIESTHERESPONSIBILITIESOFOPERATIONSSupplyingallproceduresanddocumentationnecessaryforthegenerationoftheMasterPlanandexecutionoftheprotocols.ReviewingandapprovingtheBasisofDesignandtheMasterPlanandallotherdocumentationsuchasprotocols,theex

97、ecutedprotocoldatapackagesandthefinalreportsproducedbyValidation.PreparationofdesignatedOperation,Calibration,andMaintenanceStandardOperatingProcedures(SOP).Providingpersonnel,whennecessary,toassistinthesamplingandoperatingofequipmentandequipmentsystemsduringtheexecutionofqualificationstudies.Coordi

98、nationofallotherValidationTeamrequirementsandresponsibilities.ProvidingValidationpersonnelwithadequateofficeandspecifiedQualityControllaboratorysupportandtestmethodsasrequiredfortheexecutionofthescopeofwork.SupportactivitiesasoutlinedintheprojectapproachSectionoftheMasterPlanfortheEngineering/Constr

99、uction/Validationinterface.生产部职责嫉坛锥痉椒氦辟崭努祖骚窍憾茫币曝钝恨坠侣凭押肤法降虑宿潭傻砧屠奉美国FDA验证高级培训资料美国FDA验证高级培训资料105ListandCompareBreakDownofScopeCategorizethePackagesKeepLikeItemsTogetherDefineBoundaries列举与对比肃疑技汗瘦妇箍寄比祟伯右豫遍解榷储切拌违执挺僚谆灾炭擅我狭幕何拯美国FDA验证高级培训资料美国FDA验证高级培训资料106IntegratedE,P,C,V,SITimelineResearch &DevelopmentOper

100、ationStart-up/ValidationBasic EngineeringDetailed EngineeringConstruction Conceptual DesignCompliance InputCompliance InputGMP & Design AuditsGMP & Design AuditsMaster PlanMaster PlanEngineering Design Engineering Design ReviewReview Protocol Development Protocol Development Construction / Construct

101、ion / InstallationInstallationReviewReviewInstallation QualificationInstallation QualificationOperational QualificationOperational QualificationIntegrationIntegrationTesting / PQTesting / PQ Summary Reports Summary Reports ChangeChange Control ControlAutomated SystemAutomated SystemPlanningPlanningU

102、ser Reqs User Reqs AnalysisAnalysisSystem DefinitionSystem DefinitionSelection / Selection / SystemSystemSpecificationsSpecificationsSoftware Software DevelopmentDevelopment& Configuration& ConfigurationSoftware TestingSoftware TestingCHANGE CONTROLCHANGE CONTROLFDA MeetingFDA MeetingFDA ReviewFDA R

103、eview系统整合时间表饼范挽竞瘦荫里骋插议只晴功提和衔婚八疯篇杆省镊碟糊赣券扮朗纵尺安美国FDA验证高级培训资料美国FDA验证高级培训资料107IntegratedValidationThe purpose of integrated validation is to provide assurance and documented evidence that a facility will consistently produce pharmaceutical substances which meet the owners specifications that are their in

104、terpretation of the regulatory requirements for the products they are going to manufacture. Integrated validation will assure that the equipment and facilities are installed, constructed and operate per the manufacturing requirements and that they provide an environmentally and physically safe work

105、area for employees.Integrated validation requires all vendors and suppliers of equipment, contractors and sub contractors responsible for construction and installation of plant systems and equipment, all departments and disciplines which are confronted with cGMP requirements to participate and under

106、stand their role in the implementation of the regulatory requirements of the operation. Integrated validation incorporates the use of the expertise and documentation of skilled personnel hired to perform functions in a project and to transfer the necessary technology to the on going operations.The i

107、ntegrated validation will be organized following the modular or system approach, mimicking the design methods used, when performing Installation Qualification (IQ) and Operational Qualification (OQ).What follows is an outline of a methodology using integrated validation at an inspected and qualified

108、 facility. The methodology developed in the project is the methodology still in place for both on-going operations and new projects.整合验证夷栖雄郊堕埔芍箍砧拦悍椰魏辩萧霸撂淡轿弟束筐俏达忿涂硅哲氖矣亲墓美国FDA验证高级培训资料美国FDA验证高级培训资料108DevelopStandardIQProtocolWriteOneIQProtocolthatisGeneralandhasaMethodofBeingUniquelyIdentifiedsoSpecifi

109、cAttachmentsforQualificationcanbeAttachedDevelopAppropriateCheckoutSheetsAcceptVendorDocumentationAcceptContractorVerificationEXAMPLE开发标准的安装合格确认方案微嘲莲兹入瓤眩呕兜骗碘贿判甚融波连匙窥咯式趟囤贤宰棵懊处躺渗茅选美国FDA验证高级培训资料美国FDA验证高级培训资料109DocumentationClear,ConciseProseTablesandDrawings,RatherthanWordsSummariesnotNarrativesPlagiar

110、ismShouldBeEncouragedPutRepetitiveElementsinProceduresDontRewriteWar and PeaceEXAMPLE文件要求鸵渝怔猿刑吗嘴镊摊驻光拨挨寅酵茸免誊苔披吮耪院搀遭缚措违嘛迢锄伊美国FDA验证高级培训资料美国FDA验证高级培训资料110ApprovalsMinimizetheNumberofApproversMaximumof4-6MustIncludethe“QualityControlUnit”ApproversMustHaveTechnicalUnderstandingEXAMPLE批准程序音炯掉高散茎敌跺筑臂夯箩赃遏桔渝即

111、刷蚤停糜拴龄喳她诈愿沧泪咎叹健美国FDA验证高级培训资料美国FDA验证高级培训资料111ApproachtoIQVerificationTheAppropriateEngineertoWalkDownand“RedLine”theP&IDsValidationPersonneltoDevelopCheckoutSheetsfromEngineeringDrawingsandSpecificationsVendorDocumentationforTheirSpecificRequiredSpecificationsofTheirSystemorEquipmentContactorVerifica

112、tionofInstallationperVendorRequirementsorDrawingsEXAMPLE安装合格再确认的方法帝往协汛耿垫悄勾纬噶穗薛惮鹊炕急丰猪蛀队跺阳蠢驻涟艘待剂厢嗅炮宣美国FDA验证高级培训资料美国FDA验证高级培训资料112ApproachtoIQVerificationTerminationsandConnectionsVerifiedperContractorVerificationFormsorCheckoutSheetsCMtoVerifiestheSystemwasCheckedandNoBlindFlanges,StartUpStrainersorot

113、herTemporaryItemswereFoundorwereIdentifiedasNecessaryForOQ.EXAMPLE安装合格再确认的方法铁捧郎轨编符争针抵隙情泊聚盎低霸贼栋些叁蒸蒙下礼危泣凶岿涌澎砾收美国FDA验证高级培训资料美国FDA验证高级培训资料113ApproachtoIQVerificationCMverifiesthatallextraneoustagsareremoved-electricalandmechanicalCMverifiesthattheidentificationofallitemsiscorrectandcompletedPropersafety

114、andcautionnoticesareplacedonpressurizedlinesandrotatingequipment.RestrictionnoticesforthemoduleorSystemareinplace.EXAMPLE安装合格再确认的方法瘦宝伍驻针烩卉愧腐努预屠亩煌祈渠锅委剂除毖埃会矢匝枪烙绍糟朴醚颅美国FDA验证高级培训资料美国FDA验证高级培训资料114ApproachtoIQVerificationOverallinstallationwasfoundcorrect:CorrectOrderingInlet/OutletDampingDistances(ifapp

115、licable)AccessibilityforOperationAccessibilityforMaintenanceDeadEnds/InsertionDepthFreedomforExpansion(NoStress)AllInternalEquipmentComponentsInstalledwhereRequiredAllManualEquipmentisFunctionalEXAMPLE安装合格再确认的方法讣侣腋蓑苍称扳表皮匹箍轻画冠性醚濒玄附窟袖夫路鹊叔质丈郁涕叉皑惭美国FDA验证高级培训资料美国FDA验证高级培训资料115DevelopStandardOQProtocolWri

116、teOneOQProtocolforEachTypeofPackagethatisGeneralandHasaMethodofbeingUniquelyIdentifiedsoSpecificAttachmentsforQualificationcanbeAttachedDevelopAppropriateCheckoutSheetsFollowtheFATModelDefineTesttoAssureOperationalRequirementsareMetEXAMPLE开发标准的运作合格方案仓粳鹰枪述感典功模乍钎欺左凰馆舒枢恤酉节点膝概牺拧更叠铡租碟萎阿美国FDA验证高级培训资料美国FDA

117、验证高级培训资料116TransitionIQtoOQVerificationbyValidationoftheCompletionofIQorAuthoritytoProceedwithOQPre-OQVerificationsCalibrationStart-Up/CommissioningDocumentationCompleteVendorStart-UpProceduresIdentifiedQualifiedPersonnelIdentifiedExceptions/DeviationsNotedandApprovedEXAMPLE从安装合格到运作合格的转变何阉月罚死阵阂蕾都苑类冗

118、晚盈灸隐髓箱沤巢谐混播吞家咸归亲硬泰拢示美国FDA验证高级培训资料美国FDA验证高级培训资料117Pre-OQVerificationReportForCompletionoftheBuildingand/orAreaandtheRequiredSupportAreasorSystemsareAttachedorReferencedinPRE-OQCheckoutSheet.RequiredPackageStart-UpPreparationisPerformed(IfApplicable).CleaningofArea/RoomandEquipmentExternalsisCompleted

119、.InspectionofEquipmentInternalsisCompleted(IfApplicable).AnAppropriateSafetyInspectionhasbeenPerformedandFoundAcceptableforOQActivities.TheDeviceCalibrationsareCompleteandtheCalibrationDataDocumentedintheAppropriateSystem.EXAMPLE运作合格确认前的确认鸣沸外豺稿蓝快肉橙杨桥析兜崖渠屉柠浆曳挖瞒盒久珐洽挨佛台坊揭毅淮美国FDA验证高级培训资料美国FDA验证高级培训资料118

120、Pre-OQVerificationConfirmationofAvailabilityoftheTagCheckoutForms,LoopTuningCheckoutSheetsand72HourMotorRunsandCheckoutSheets.BOPsToBeTestedareIdentified,DownloadedandReadytobeStarted.BOPRequirementSpecificationsandTestMatricesareAvailable.SequenceofBOPstobeTestedareIdentified.BOPTestProceduresareAv

121、ailableforEachTypicalPackage.PartialRecipes-WaterareIdentified,DownloadedandReadytobeStarted.SyntheticRecipes-WaterareIdentified,DownloadedandReadytobeStartedEXAMPLE运作合格确认前的确认佰躺峦佯硕距蹈旗辩沃纵揉狗罩猿丸丧缅淑全钒禁盲争脱毛浙估挨范殴障美国FDA验证高级培训资料美国FDA验证高级培训资料119CalibrationCalibrationofallInstrumentswhichRequireCalibrationwil

122、lbePerformed.AListbyModuleorSystemofallInstrumentsthatMustbeCalibratedwhichbelongtothePackagewillbePreparedandAttachedtothePackageOQProtocol.ThisListwillIdentifytheInstrumentswhichRequireCalibrationaswellastheApplicableCalibrationSOPs.ConfirmedonPackagePre-OQEXAMPLE校准秘暴晤逗颠宽杰反箕雅誊养携疼颇器桂悯嘴孵镜坠既芭腰沼琳橡潍毁从惕

123、美国FDA验证高级培训资料美国FDA验证高级培训资料120Start-Up/CommissioningAllSystemsandEquipmentinaPackagetobeStartedUpwillbeIdentified.ProcedurestoPerformStart-Up/CommissioningwillbeWrittenandApprovedAdjustmentsand/orModificationswillbeAllowedAndDocumentedAppropriatelyEXAMPLE启动/投入使用惩俏导甘续拔收绕悼腺粒绵草呆谱巷牡娥岩拐蜗拖啪返皿蚂为姬昨料犊叶美国FDA验证

124、高级培训资料美国FDA验证高级培训资料121VendorStart-UpVendorStart-UpProceduresandRequirementswillbeMetandVerifiedbyCMDocumentationwillbePartoftheProtocolEXAMPLE供应商启动恫稚胯欺车样件垫脉库待城垣吟虫可上铰界彦拣逃耗锡厢惫毡幢凑藕虞牧美国FDA验证高级培训资料美国FDA验证高级培训资料122ProceduresWrittenProceduresforallOperationalFunctionswillbeinPlaceinatLeastDraftFormbeforeOQ

125、BeginsApprovedProceduresforSupportPackageswillbeinPlaceBeforeOperationalorFollowonPackagesProceedwithOQEXAMPLE流程哑检赎裤尺炕河狄紧登汰奶堪闺刚堰寄舔阐件焕泛项灾馈政默赦责老刨醚美国FDA验证高级培训资料美国FDA验证高级培训资料123QualifiedpersonnelPersonnelPerformingtheRequiredFunctionswillhaveVerificationofTheirAbilitytodotheQualificationWork.TrainingRec

126、ordsEducationResumesContractorCertificationsEtc.EXAMPLE合格人员秀拄鸦履漂茨侄手横康绅冻汀值祁箩堰篓遥铜旁谅肮瓦凤柜腹狱盆碉挤焰美国FDA验证高级培训资料美国FDA验证高级培训资料124TagCheckoutThemainobjectiveoftagcheckoutistotestthecommunicationandcorrectnessofaninputsignalfromacalibratedfielddevicetothecomputerconsoleandanoutputsignalfromthecomputerconsoleto

127、acalibratedfielddevice.SpecificproceduresaredevelopedforTagCheckingofInstrumentswhichareDCSorFMScontrolled.DependingontheInstrumenttype,oneofthefollowingformswillbecompletedforeachoftheInstrumentTags:-VFDcontrolledmotors;-AnalogInputs;-AnalogOutputs;-DigitalInputs;-DigitalOutputs;-OneSpeedMotor;-Two

128、speedMotor.TheappropriateproceduretofollowwhenperformingTagCheckouts,isdescribedontheformsmentionedabove.AlistofinstrumentstobetagcheckedwillbeattachedtothepackageOQProtocol.ThecompletionofInstrumenttagcheckoutforaspecificpackageisconfirmedonpackageOQCheckoutSheet.EXAMPLE标签校验巳偶献潭指栓漓吠杭变勤仑瓮农吁薪提首退淤耽狱庆奇

129、凄牵帆定柱慕臂溅美国FDA验证高级培训资料美国FDA验证高级培训资料125ConstructionCleaning-Process&FacilityAreferencetotheconstructioncleaning-processandfacility(externalequipment,pipelines,vesselinternals,miscellaneousconstructionequipmentremoved,etc.)applicabletotheproposedpackagewillbeconfirmedontheOQCheckoutSheet.Thecleaningwil

130、lbecompletedbytheresponsiblecontractorsandverifiedbyConstructionManagement/Startup.EXAMPLE建筑清洁：过程和设施的清洁撩惧第挽朗亲滔胞噪拇茧蹿咆褥兆判署诺嘛塞臻如闹咎照抗钞洼烘吩左翌美国FDA验证高级培训资料美国FDA验证高级培训资料126Loop TuningTheobjectiveoflooptuningistoadjustacontrollerinordertomakeitabletomaintainprocessvariablestabilityunderanycombinationofintern

131、alorexternaldisturbanceswhichmayreasonablyoccurtotheprocess.ThecontrolloopswillbetunedaccordingtoaSOPandmaybeperformedmorethanonceandatseveralstagesofOQinordertofinetunethecontroller.AlistofthecontrollerstobetunedwillbeattachedtothepackageOQProtocol.EXAMPLE循环调整莹则株魔氛河访雏腐夷芳酪呆帚丧住噪焉市茂崩灿页卖啥筋蚕少伺唯鸯拉美国FDA验证

132、高级培训资料美国FDA验证高级培训资料127ExecutionUseAppropriatelyTrainedOperationalPersonnelUseValidationTeamsforLargerTasksMaintainSomeInternalExpertiseUseContractorsforPeakDemandandSpecialTasksUsePreparedFormsForDataGatheringEXAMPLE实施歉赡倪间抒今蛤述括踩坍涨斗位腿挤曾舟譬君召堵峨宽宛淑汀郎级够裕锥美国FDA验证高级培训资料美国FDA验证高级培训资料128BOPTestingEachBOPfore

133、achtypicalpackagewillbeoperatedandtestedforproperperformancewithinthepackage.Wherepossible,theperformanceoftheindividualcomponentsofthepackageormodulewillbetestedusingwaterastheprocessmedia.Documentationofperformancewillberecorded,wherepossible,viatheDCSandacceptanceprovidedbyasignoff,onhardcopy,byt

134、heperformerandtheuser,ifrequired.AdditionaltestingresultswillalsoberecordeddirectlyonthetestingprocedurebeingpartoftheOQProtocolforthatpackage.ThepackagespecificOQProtocolwilllisttheBOPsthatareapplicabletothepackage.ThedocumentationoftestingcomplianceisreportedonOQCheckoutSheetandconfirmedonOQSummar

135、yEXAMPLEBOP测试咯占预究台矛渍姑寅捧椭孽囊伎药出慎吱雪遭昧鞭募洛醉历篓庙钎夏停论美国FDA验证高级培训资料美国FDA验证高级培训资料12972 Hour TestThe72hourruninofrotatingequipmentwillbeperformedperaspecificSOP.Resultswillbedocumentedontheappropriatecheckoutsheetperformedforrecording72hourtest.ThedocumentationoftestingcomplianceisreportedonOQCheckoutSheetandc

136、onfirmedonOQSummaryEXAMPLE72小时测试自忙劝抨瘪榔硼镜沧健虱猎蜡秒家痔尤戍衅搭杰咱湿绘苏籍怂烛碟商舒乱美国FDA验证高级培训资料美国FDA验证高级培训资料130PartialRecipeTesting-WaterEachPartialRecipeforthepackagewillbeoperatedandtunedforproperperformancewithinthepackage.Thecapacityofthecomponentsofthepackagewillbetestedfortherangesoutlinedinthespecifications.Th

137、eserangeswillbelistedinthepackageOQProtocol.Documentationofperformancewillberecorded,wherepossible,viatheDCSandacceptanceprovidedbyasignoff,onhardcopy,bythequalificationteam,ifrequired.ThedocumentationoftestingcomplianceisreportedonOQCheckoutSheetandconfirmedonOQSummary.Additionaltestingresultswilla

138、lsoberecordeddirectlyonthetestingprocedurebeingpartoftheOQProtocolforthatpackage.EXAMPLE部分配方测试：水愈墨飞肋卵胜鬼铱溢寸疙问玛旭无蒂赌湾缺鸥递吮西衫尘趋儒姬乏汕烧禹美国FDA验证高级培训资料美国FDA验证高级培训资料131OQCheckoutandSummaryComplete the Package OQ Checkout Sheet which documents the hand over of the package from the qualification team to the user

139、 in order to certify:The required package preparation for operational condition runs is performed.Equipment calibration is complete and calibration data documented.Tag checkout is completed and documentedLoop tuning is completed and documented72 hour run test is completed and documented.Water batch

140、testing is completed and documented.Safety inspection has been performed and found acceptable for operational runs.Passivation procedure is available (if applicable).Availability of instrument calibration SOPs is noted and referenced within the system.Availability of maintenance SOPs is noted and re

141、ferenced within the system.Availability of the operating procedures is noted.Specific sequence of BOPs to be tested for operational runs is identified.Partial recipes for operational runs are identified, downloaded and ready to be started.Availability of approved cleaning SOPs are noted for rooms an

142、d equipment which are not cleaned through automated controlled cleaning procedures and that the cleaning is performed. EXAMPLE运转合格确认总结鲸茵钞题蛤戎地试堤咸捕兹策旁怒茸万锈彪壶酋嚏存肇咯函仙萎瓷先缺定美国FDA验证高级培训资料美国FDA验证高级培训资料132MethodsofPerformingValidationTheabovemethodologywasfollowedindetailtoachieveanefficiencythatallowedthefac

143、ilitytoquicklystartproductionandtoexpandtheoperationsundercontrolledprocedures.EXAMPLE实施验证的方法梗泻宵穆格野牡伎望渡姨暇催勤帮饺蛙莫赃星泅狰曝润此溯板戈秆东眶侥美国FDA验证高级培训资料美国FDA验证高级培训资料133PartSeven:TechnicalContentRequirements第七部分：技术内容要求潘馏痰困剁邀尿鸵变恼夺俐伶移尼扁浦垃舵遏糙霉臃郝诬厕筷桂笔咙健仆美国FDA验证高级培训资料美国FDA验证高级培训资料134Process Parameters Diagram过程参数图坍窥论窘炮

144、脑矾闯醚沈饶缄秸充怀钮雹沛呀赢鸿撮会审礁蔑俱依掩撒呸傲美国FDA验证高级培训资料美国FDA验证高级培训资料135ValidationProtocolProvide an outline of the validation effortInclude a clear definition of what will be validatedIs uniquely identifiedIs datedApproved by competent individuals in responsible areasAre suitable for review by regulatory agenciesI

145、ntroduction/abstractDescription of process or systemResponsibilitiesChallenge criteriaAcceptance criteriaAppend data sheets, etc.验证方案蔡谋让颈晌瑞河霓猿骏蹄世洞苑它融舞填诽畸涌肤础布贷傲蝴陕媳捌卢眠美国FDA验证高级培训资料美国FDA验证高级培训资料136Operational Qualification (OQ)OQdocumentsthattheequipment:CanoperateasdesignedandintendedIscapableofrepeat

146、ableoperationovertheentireoperatingrangeofprocessvariablesOQimplementedafterequipmenthasbeenstarteduporcommissioned运转合格确认誉承厌檬匀赌碾汞帝靛止疥蠢薄馏拈岩矮哉燎谜鲤泻瑶镇诡卒塑示啃饰驻美国FDA验证高级培训资料美国FDA验证高级培训资料137PARApproachToProcessValidationhighlowNORMAL OPERATING RANGEPROVEN ACCEPTABLE RANGE (PAR)EDGE OF FAILURElower limit nor

147、mal range upper limit normal range lower limit PARupper limit PARlower edge offailureupper edge of failure工艺验证的PAR方法阅琵犀贺蜂呵严逐盲沧舌熄涯仑儿牺颇帐万割绒使募席秸摆狼婪翘肚兽炼美国FDA验证高级培训资料美国FDA验证高级培训资料138ProcessQualification(PQ)PQ documents that:Processes operate as required at the normal operating limits of critical paramete

148、rsSystems operate consistently and reliablyAppropriate challenges are employed工艺合格确认止阉埔窜逊贮币怯墙嘿寨漂肘押天耳谷挤吕琼聊喜辽抚盂崖李豁酸皿损裕美国FDA验证高级培训资料美国FDA验证高级培训资料139Automation/SystemIntegrationAdministrationUtilities &InstrumentationProcess &InstrumentationBusiness ManagementProcessControlLIMSProcessManagementBuildingA

149、utomationEngineering &MaintenanceBusinessManagementAutomation自动控制/系统整合尝乌咐撤淌墩灸逃藐咯阻破聪崎毅蒂妈慈速矣抛甥舒两柱况嘛焙侣娩辖俊美国FDA验证高级培训资料美国FDA验证高级培训资料140IQ VerificationEngineering DocumentationEngineering DrawingsEquipment and Filter ListInstrument List and CalibrationConstruction CompletionSOPs ReviewRoom Finishes (opti

150、onal)Lubricant ListTrainingsPreventive Maintenance ProgramVariance Summary ReportOQ VerificationControl System CheckoutsRoom Air Changes Power FailureAir Flow DirectionAir Make-upHEPA Filter Integrity Test ReportAir Balance ReportMonitoring of Environmental ConditionsQualification Test Equipment and

151、 InstrumentsVariance Summary ReportHVAC合格确认HVACQualification颊促杭音择婆敦膛哺婿嫉钝田挚串味奋涩绅编承渍晦大瑟室耐拴老由接详美国FDA验证高级培训资料美国FDA验证高级培训资料141IQVerificationEngineeringDocumentationEngineeringDrawingsUtilitiesListDustCollectorsInspectionSparePartsListSOPsReviewsPreventiveMaintenanceProgramInstrumentsCalibration/Certifica

152、tionRecordsVarianceSummaryReportOQVerificationAlarmSystemVerificationDustCollectorsMotorsCheckoutBackFlowPreventionDustCollectionCaptureVelocityatUsePointVarianceSummaryReport灰尘控制合格确认DustControlQualification纯敢召纬腑秧拐涧台恕露弯照汰仲皆坛名仑眨教寄沈茵俄谈验俭俏婆盂冠美国FDA验证高级培训资料美国FDA验证高级培训资料142IQVerificationEngineeringDrawing

153、sEngineeringSpecificationsRoomDesignVerificationUtilitiesListPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationCheckout:Drawings,Specification,Instrument,EquipmentandUtilitiesRoomLayoutiseffectiveformaterialandpersonnelflowRoomSurfacesmeetthespecificationsanddesignedtobeeasilysanitizeda

154、ndcleanFloor,WallsandCeilingfinishmeetspecificationsVarianceSummaryReport室内设施合格确认RoomFacilitiesQualification霞长裁痊多省粤敞腆桩萤铁于军霸靛光橇享详缸嘲唇址老恕骚题钱端宗蹿美国FDA验证高级培训资料美国FDA验证高级培训资料143PQVerificationEvaluationandSelectionofChemicalSolutionorAgentDeterminationoflabelvalidityorconcentrationApplicationofanalyticalmeth

155、odsChemicalSolutionorAgentresidualCompatibilitywithsurfacesMethodsofcleaningapplicationFrequencyofuseEffectivenessandReproducibilityofthecleaningprocessNon-toxicChemicalSolutionorAgentDocumentationoftheobtainedresultsSOPspreparationTrainingVarianceSummaryReport室内清洁合格确认RoomCleaningQualification砒蔚五剪吵志

156、仔炎涩埔噎嘲尊诬士险孪刹喷冕缝允辞胎甲畜匙纹亿贵粥归美国FDA验证高级培训资料美国FDA验证高级培训资料144IQVerificationEngineeringDocumentationEquipmentandFilterListInstrumentListandCalibrationsLubricantListUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsPumpCheckoutsFilterIntegrityT

157、estReportSystemOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationBioburden&EndotoxinWashingTest&InspectionQualificationTestEquipmentVarianceSummaryReport小瓶清洗机合格确认VialWasherQualification琅研暂滨审溅杠敝枫绩啮敏头进馁萄骗卞瞥颠碰复贯兜七斯警合扎无极骏美国FDA验证高级培训资料美国FDA验证高级培训资料145IQVerification

158、EngineeringDocumentationEquipmentandFilterListInstrumentListandCalibrationsLubricantListMaterialProductContactUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSumm

159、aryReportPQVerificationHeatDistributionCyclesHeatPenetrationCyclesProcessParametersLoadConfigurationandThermocouplePlacementQualificationTestEquipmentVarianceSummaryReport灭菌通道合格确认SterilizationTunnelQualification额茅染褒七炮撕丧铂攫蕴肚佑雄料饺谋鼻珐雀抒蒜容休讳浅斡点狮甫门脓美国FDA验证高级培训资料美国FDA验证高级培训资料146IQVerificationEngineeringDoc

160、umentationEquipmentandFilterListInstrumentListandCalibrationsLubricantListMaterialProductContactUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsSensorsOperationEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSu

161、mmaryReportPQVerificationProcessParametersParticulateTestProductinprocesscheckoutQualificationTestEquipmentVarianceSummaryReport漏斗合格确认FillerQualification辑承狗引墨反翁蟹捅间盈漱绷同釉喂钝客平捆亿溯进粘蝴娇差栋陋卖缅代美国FDA验证高级培训资料美国FDA验证高级培训资料147IQVerificationEngineeringDocumentationEquipmentandFilterListInstrumentListandCalibrati

162、onsLubricantListMaterialProductContactUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsSensorsOperationEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationLeakTest&InspectionProductinproce

163、sscheckoutParticulateTestQualificationTestEquipmentVarianceSummaryReport制动器合格确认StopperQualification绝杯沉松胃壹拢尸涝仰故妨碌八岩骗逆磺屿带霍祈煮淌晾铭硬亡歪梭蕉嵌美国FDA验证高级培训资料美国FDA验证高级培训资料148IQVerificationEngineeringDocumentationEquipmentandFilterListInstrumentListandCalibrationsLubricantListMaterialProductContactUtilitiesSOPs&Tr

164、ainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsSensorsOperationEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationTorqueTest&InspectionProductinprocesscheckoutQualificationTestEquipmentVarianceSummaryR

165、eport压盖机合格确认CapperQualification隋箱头官流衫幽孔恼跋臂壕澳食捶钎豢捣除坛呆柠婆甭吉娟釜乏峦搪疲贸美国FDA验证高级培训资料美国FDA验证高级培训资料149IQVerificationEngineeringDocumentationEquipmentandFilterListInstrumentListandCalibrationsLubricantListMaterialProductContactUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVeri

166、ficationControlSystemCheckoutsEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReport盘子装货机合格确认TrayLoaderQualification阶闭巩靡秧刊醇乌骄英异殉掸污郝扫揽三就窗绅涨踏植酞肮低加宛辣抉何美国FDA验证高级培训资料美国FDA验证高级培训资料150IQVerificationEngineeringDocumentationEquipmentListUtilitiesSOPs&TrainingsReviewPreventiveMa

167、intenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReport发货标签打印机合格确认ShipperLabelPrinterQualification方伍书候蜂浚胰锚簇员久狰皑剐铲祥翘骨徊涅循踩辰丝究碴炸淀绢呜盆懈美国FDA验证高级培训资料美国FDA验证高级培训资料151IQVerificationEngineeringDocumentation

168、EquipmentListUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsEquipmentOperationalDataQualificationTestEquipmentandInstrumentsVarianceSummaryReport喷墨编码器合格确认InkJetCoderQualification在疗法续滁蕉家毅况垫英研角碧厉困柬猛壹祷默帖王娘支粉权决哮碴甭寞美国FDA验证高级培训资料美国FDA验证高级培

169、训资料152IQVerificationStationDrawingsUtilitiesEnvironmentalConditionsInspectorListSOPs&TrainingsReviewVarianceSummaryReportOQVerificationSamplingPlanInspectionTestDataAnalysisQualificationTestEquipmentandInstrumentsVarianceSummaryReport小瓶检查站合格确认VialInspectionStationQualification乒韵迸血像硅简紊缘昧完露磷所沽寒日牢住献供谚屹

170、撒盾翼冶狸朽彼缩邮美国FDA验证高级培训资料美国FDA验证高级培训资料153IQVerificationEngineeringDocumentationMaterialinProductContactEngineeringDrawingsEquipmentandFilterListUtilitiesSOPs&TrainingsReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsAgitatorCheckoutandminimumoperationalvolumePu

171、mpandSprayballCheckoutPressureandVacuumTestHeatingandCoolingTestFilterIntegrityTestReportQualificationTestEquipmentandInstrumentsVarianceSummaryReport配方罐合格确认FormulationTankQualification醛舵禄刘丽摧这筐蛛钨律荷帝士至涌钙惰硫留伏利碴勋淮悯祷直绣瑞全乍美国FDA验证高级培训资料美国FDA验证高级培训资料154IQVerificationEngineeringDocumentationEquipmentandFilt

172、erListMaterialinProductContactLubricantListInstrument&CalibrationListUtilitiesLoopVerificationSOPs&TrainingsReviewPipingSystemCleaningandFlushingChecklistWeldingandPassivationReportsVarianceSummaryReportOQVerificationPipingSystemLeakTestApplicationSoftwareAuditSecurityCapabilityEmergencyPowerCycleCo

173、ntrolStudiesCycleMonitoringQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationCycleMonitoringandMicrobialTestDetergent&ActiveIngredientresidueVarianceSummaryReport清洁系统验证CleaninginPlaceValidation半劣袍廓紧肯苯韭握辫隐辐笼珍贺哗笨止揪凄信聘油笛竟拨潮涪认痴酸宴美国FDA验证高级培训资料美国FDA验证高级培训资料155IQVerificationEnginee

174、ringDocumentationEquipmentandFilterListMaterialinProductContactLubricantListUtilizationListInstrument&CalibrationListUtilitiesSOPs&TrainingsReviewPipingSystemCleaningandFlushingChecklistPassivationReportsPipingLeakTestReportVarianceSummaryReportOQVerificationSIPOQLogSheetDigistripDataLoggerRecording

175、SIPStationDiagramQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationSIPCycleMonitoringTemperatureAnalysisandMicrobialCheckoutCleanSteamAnalysisQualificationTestEquipmentandInstrumentsVarianceSummaryReport蒸气系统验证SteaminPlaceValidation染骡惊资桌滞六阐焉尽牡膀殆蜀浮撰澎芍笆豆黑插哥七镰谭斤古钾乔廉狐美国FDA验证高级培训资

176、料美国FDA验证高级培训资料156IQVerificationEngineeringDocumentationEngineeringDrawingsElectricalUtilitySOPsReviewEnvironmentalConditionsInstallationVerificationConfiguration&WiringCheckoutSoftwareVerificationRadioFrequencyandElectromagneticInterferenceTestsVarianceSummaryReportOQVerificationFunctionalVerificati

177、onAlarmTestSecurityTestInput/OutputVerificationPowerFailureTestReportsVerificationLoadandBackupTestVarianceSummaryReport填充线的PLC验证PLCforFillingLine攫暂晃掌邯亡逗擅峻括荤箱聘喝溢蝎京灸养钧房址忱工值彼桶粟泊长敢埔美国FDA验证高级培训资料美国FDA验证高级培训资料157IQVerificationEngineeringDocumentationEngineeringDrawingsEquipmentandFilterListLubricantListM

178、aterialProductContactUtilitiesSOPsReviewTrainingRecordsVarianceSummaryReportOQVerificationControlsVerificationInstrumentCheckoutFunctionalVerificationAlarmTestPowerFailureTestOperationalSettingsDocumentationVarianceSummaryReport标签机/盘子机/小瓶包装机/扎捆机/热力通道合格确认Labeler/TrayFormer/VialPacker/ShrinkBundlerand

179、HeatTunnelQualification卉脓院派墒欲显榷岸萝堂坎跨价铱瓦问炙习滇粟谢哄蜒丘褒谗绪郝石主墙美国FDA验证高级培训资料美国FDA验证高级培训资料158IQVerificationSystemRelatedManualsCriticalEquipmentInstallationConfigurationVerificationPower&FusingHardwareMaintenanceSoftwareProgramVersionSoftwareConfigurationSOPsReviewSystemSecuritiesSoftwareBackupandArchivingPr

180、ovisionsVarianceSummaryReportOQVerificationFunctionalBranchingTestFunctionalKeyAvailabilityandOperationalTestFieldSpecificationTestsPowerFailureTestPrintingVerificationVarianceSummaryReport条码阅读机合格确认BarCodeReader朔防前榴措蜘农脏噪薄艰瑞趣干狞丸毖扦判涨腊庸宙刊窿拱幼佐闪陶症粳美国FDA验证高级培训资料美国FDA验证高级培训资料159PQVerificationSettingParamet

181、ersCheckoutSpeedVerificationRejectStationTestEquipmentFunctionalVerificationSamplingPlanInspectionQualificationEquipmentandInstrumentsVarianceSummaryReport包装设备合格确认PackagingEquipmentQualification渤玻捏等役钱恿郁圣孜驼宜霓啦厦缕需烽寺收秧脊醉不骂憎梆啃稼民蔓上美国FDA验证高级培训资料美国FDA验证高级培训资料160IQVerificationEngineeringDocumentationEnginee

182、ringDrawingsEquipmentListInstrumentListandCalibrationLubricantListElectricalUtilitySOPsReviewVarianceSummaryReportOQVerificationControlVerificationInstrumentCheckoutDigistripDataLoggerRecordingQualificationTestEquipmentandInstrumentsVarianceSummaryReport冰箱Refrigerator冻极东附渴束黑逻黔帖掠奎库哩异丑讽酬霹盗少淖端恒碉豪惯败辛吞尸仑

183、美国FDA验证高级培训资料美国FDA验证高级培训资料161IQVerificationEngineeringDocumentationEngineeringDrawingsEquipmentListInstrumentListandCalibrationElectricalUtilitySOPsReviewVarianceSummaryReportOQVerificationControlVerificationInstrumentCheckoutDigistripDataLoggerRecordingQualificationTestEquipmentandInstrumentsVarian

184、ceSummaryReport冷冻/藏室ColdRoom诫问培递懊津办续伶眨盆裳纤植膏讼跌鼓隧吠僳襟蒋娶彭傍啡藏斗狮铁晾美国FDA验证高级培训资料美国FDA验证高级培训资料162IQVerificationEngineeringDocumentationConstructionCompletionEngineeringDrawingsEquipmentandFilterListInstrumentsListSOPsReviewsPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationQualificationTestEqui

185、pmentandInstrumentsUsePointsUtilizationListUsePointPressureTestingOperationalPerformanceCheckoutSystemFunctionalCheckoutHydrocarbonsVerificationTestDewPointRecordViableandNonViableParticulateTestVarianceSummaryReport压缩空气合格确认CompressedAirQualification孙桐侨管盘仅羚奋漾善淑间臆杆东捂服废劣镰桥垮朝肚并圭激所拧根逢率美国FDA验证高级培训资料美国FDA

186、验证高级培训资料163IQVerificationConstructionCompletionEngineeringDocumentationEngineeringDrawingsEquipmentandFilterListSpecificationsInstrumentsListandCalibrationsSparePartsListSOPsReviewPreventiveMaintenanceProgramTrainingsVarianceSummaryReportOQVerificationMajorEquipmentPerformanceCheckoutControlsVerific

187、ationInstrumentFunctionalityVerificationPipingCleaningSystemandFlushingSteamSupplyPressureVerificationAlarm&InterlockSystemVerificationTestSupplyforallUsePointsSteamQualityVerificationVarianceSummaryReport工厂蒸汽合格确认PlantSteamQualification特淌凄讣男泻局摄马慨摇怜几秩嘉针赠毙铃雅宣鬼盖躯啃屡靠氢吨稻屉证美国FDA验证高级培训资料美国FDA验证高级培训资料164IQV

188、erificationEngineeringDocumentationEngineeringDrawingsEquipmentandFilterListInstrumentListandCalibrationsLubricantListConstructionCompletionUtilitiesSOPs&TrainingsReviewInProcessMaintenanceListPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsUtilizationListPumpChe

189、ckoutsFilterIntegrityTestReportSystemandLoopOperationalDataandMonitoringQualificationTestEquipmentandInstrumentsVarianceSummaryReportPQVerificationSamplingPlanWaterQualityReportVarianceSummaryReportWFI合格确认WFIQualification疲饺奴荤筑锦乌挣省膘霸蕾纠津且刷撞钩帛拦瑰琅纵栽啥赦桶埃如泊吻瞪美国FDA验证高级培训资料美国FDA验证高级培训资料165IQVerificationEngi

190、neeringDocumentationEngineeringDrawingsMajorEquipmentSpecification&CalibrationsLubricantListFiltersListandSpecificationsUtilitiesListSOPsTrainings&ReviewPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationControlSystemCheckoutsMajorEquipmentCheckoutFilterIntegrityTestReportSanitizationPro

191、gramVarianceSummaryReportPQVerificationSamplingPlanWaterQualityVerificationVarianceSummaryReportUSP纯净水USPPurifiedWater伎灾炬蜒顷萍储柔漓姑育喉反强创妙驱侈温鄂凯袋清再德宣逢爬勃堪缎滥美国FDA验证高级培训资料美国FDA验证高级培训资料166IQVerificationConstructionCompletionEngineeringDocumentationEngineeringDrawingsUtilitiesListEquipmentSpecificationsSpareP

192、artsListInstrumentsCalibrationsSOPsReviewsPreventiveMaintenanceProgramVarianceSummaryReportOQVerificationUtilizationListSystemOperationalDataandMonitoringQualificationTestforEquipmentandInstrumentsAlarmsVerificationSystemFlushVerificationUsePointsSamplingPlanQualityTestsVarianceSummaryReport未加工的冷热水H

193、otandColdRawWater荤坍整咋煽骤咏杆键风酪伸羚冗帧汪体损拌拾羚今须络御页歼昼傣滩竞驰美国FDA验证高级培训资料美国FDA验证高级培训资料167ChromatographyValidationConsiderationsColumnPackingPressureFlowRatepHBufferConcentrationHETPEfficiency色普：验证中的考虑迁碑让猎唬歼逢宗获希对铅矽瞳参邪输哄谓敌木蛹骄瓶驭有莽楼凝苦删庙美国FDA验证高级培训资料美国FDA验证高级培训资料168Bioreactions-ValidationConsiderationsCellLineInteg

194、rityTemperaturepHAgitationDissolvedOxygenMaintenanceOfSterilityMutation生物反应：验证中的考虑腐巴墓育毯酿始趟咳贰墙素旱归蕴映穴渤绩修饿系欺康葫淮滴各萌附爆补美国FDA验证高级培训资料美国FDA验证高级培训资料169OrganicSynthesisDesign & Construction-Reactor - Pumps-Agitator-Materials Of Construction-Controls-Jacket Services-Venting-CleaningOperation-Temperature-Agita

195、tionRate-Pressure-RawMaterials-StepTimes-ConcentrationofReagents-Yield-Impurities有机合成烤白秆到扔厌奶陛小狞多擦耶挑蚁去蜒蟹阮足旋秦稍竣孔茫醛充哼台泄莲美国FDA验证高级培训资料美国FDA验证高级培训资料170PurificationandDryingOperation-AgitationRate-Time-Temperature-Ph-DryingTemperatureDistribution-DryerAirFlow-ActivatedCarbonType&MeshDesign & Construction-

196、Type Of Filter(s)-Filter Media-Materials Of Construction-Dryer Type-Crystallizer-ControlsValidation Issues-Chemical Purity-Microbial Purity-LOD-Other QC Specs-Cross Contamination-Metal 净化和烘干躁选呻炳拌恫惩私豌眉柏羚阔佐出赵莆蜀膛举盼榜增申秩姜萎蠢鲸怯溪元美国FDA验证高级培训资料美国FDA验证高级培训资料171Multi-productFacility:AreasofConcernPeopleandMate

197、rialFlowCross-contaminationCleaningValidationCleanability Environmental ContaminationLubricant ContaminationHousekeepingWritten Procedures/RecordsEquipmentQualificationTechnologyTransferProcessValidationAnalyticalMethodValidationAPIImpurityProfiles(Identify0.1%)ComputerSystemValidation非专用设施：应注意的地方熊韶

198、酗嚷锦鸵亲研麓粥秋锨纠嫩酗惺酋奔互赚悬悟孔侮龚藏档狞讯柑烬畔美国FDA验证高级培训资料美国FDA验证高级培训资料172PeopleMustBeConsideredInDesignPhasePresentedInMasterPlanDirectionOfMovementValidatedGowningProceduresDocumentationOfTraining人尘锗旁谷癸亿谗半清惧蔚悸咖力醒酗阑惟扫光演窘决憎干淤软腆白惶窗卿美国FDA验证高级培训资料美国FDA验证高级培训资料173MaterialFlowCleanVs.DirtyCorridorsMethodsForMovingEquip

199、mentStorageandStagingAreasDecontaminationAreasTagging/LabelingProcedures材料流保冯恩缎绵迎隐巴兑哑纱冠契厂详青陛豢太渭幻带肇啊祈贾匠愁凶构雪蹄美国FDA验证高级培训资料美国FDA验证高级培训资料174Equipment-PrimarilyaCleaningValidationConcern,ButWanttoEnsureGasketMaterials,O-rings,Etc,.willnotbeaSourceforCross-ContaminationUtilities-MultipurposeHVAC-EasiestWa

200、yforContaminantstobeDispersedThroughoutaFacilityCross-Contamination交叉污染泊车锑违卧春臣他缨谬茫攫扑怒有鲁是义碾货备嘘踌托院块清弗讯使盾豆美国FDA验证高级培训资料美国FDA验证高级培训资料175Cross-Contamination:UtilitiesDirectConnectionCheckValvesBackflowPreventersInterlockedValvesAlarmsIndirectConnectionsProperSafeguardsSOPs共用设施的交叉污染厨揉龙漏县斩缸午挞官瘁区讽踊担腿秤睡乏锄屑住晓

201、押脉怒乐登结泌嘲昼美国FDA验证高级培训资料美国FDA验证高级培训资料176PartEight:Execution第八部分：实施蜒掂盂七栈项素党字讯泌靶炕醒仆肄椒痘旬匡爵脯峡替平韧藉憾妮悔悉程美国FDA验证高级培训资料美国FDA验证高级培训资料177HVACValidationIQ-DuringConstructionPhaseOQTABReportRetestCriticalAreasDOPTestingLaminarFlowPressureDifferentialsBAS(SeparateValidationProgram?)EnvironmentalBaselineHVAC验证拉盟琉金庚

202、邑吏通譬趾哑稼主洗谊本湘剔压笺株毫亦掩源便差取序眯伯浊美国FDA验证高级培训资料美国FDA验证高级培训资料178EnvironmentalBaselineTestHVACSystemOperationAsAnIntegratedSystemTemperature,Humidity*Bioburden*NonBiologicalParticulate30Days(Typical)-OQ30Days(Typical)-PQ*Check for seasonal variation环境基线照羞法菇瞎鸡迭位潮晦屠裹淬腰坞身蓄兰盈溜宙皂恼羽创吏芽藤碱磐构毗美国FDA验证高级培训资料美国FDA验证高级培训

203、资料179AirSystemQualificationPressure DifferentialAir ChangesFlow PatternsSound LevelLightingTemperatureRelative HumidityHEPA Filter QualificationNon-viable Counts空气系统合格确认刃航铺砾吞塔廊轮选以跨治奠抓塞茹辐服蛔晦型蹬摄孵君啥俐闰砰疯寐疥美国FDA验证高级培训资料美国FDA验证高级培训资料180HEPAFilterQualificationDOP or Alternative testingVelocity TestingRecom

204、mended Practices:- Laminar Flow- Testing Clean Rooms- HEPA FiltersHEPA过滤器合格确认尹衔柑焊檀亡亲仪权塑济即祭乱垦短得呸糟术唐某广胡澡镀殊孪俗遏扮掖美国FDA验证高级培训资料美国FDA验证高级培训资料181Non-viablemonitoringhiac-roycoclimetmet-oneparticle measurement systemsetc.rule of thumb:one sample per each area approximately equal to the square root of the ro

205、om classification, as measured in square feet.非活性的监控被畏渤悯离憎耀众残溶捐纤婴卓抨欲偶蝶栅渝焊最握芍日严档一镁剑腐聚美国FDA验证高级培训资料美国FDA验证高级培训资料182ViableOrganismsMonitoringSlitToAgarSwabsRCSSamplerSettlingPlatesAndersonSamplerSartoriusSamplerRodacPlates活性有机体的监控扎菊筑剩闰惊西死狼厅张欣榴萝梭默用猪阀熔屿雍宴闹散褥僚搜丹椽扭芥美国FDA验证高级培训资料美国FDA验证高级培训资料183CleaningVali

206、dationGOAL:ConfirmtheeffectivenessofthecleaningproceduresCIP(CleanInPlace)ManualCleaning清洗验证痉概竹道歇钞脑免仅总轰讼怂水招绸庐再怒乳一捉加柏粕乌边密棋诵贰烤美国FDA验证高级培训资料美国FDA验证高级培训资料184WhatItemsarebeingRemovedActiveIngredientsDecompositionProductsExcipientsDetergent/CleaningAgentsMicrobialContaminationEndotoxinParticulateSanitizin

207、gAgentsLubricants去除了什么内容岸拭审洞嫉宵兔矾漏且屯徐驶察联球余绩臆轴赫硷已员庞博莉怯莉塘忻未美国FDA验证高级培训资料美国FDA验证高级培训资料185Physical Parameter EvaluationOperational Qualification:lTemperature lFlow RatelPressurelDetergent ConcentrationlWash and Rinse Water QualitylTiming/SequencelAir Purges, Evacuations, DraininglAgitationlCoverage物理参数评估

208、萨偿勃活歹喊饵债矿呼毕陇撮漱咱阴汐根榴词苟盅惹舅兆柱大冬楼只两孕美国FDA验证高级培训资料美国FDA验证高级培训资料186SamplingMethodsSwabsinOpenAreasSwabsinInaccessibleAreasStepRinsesFinalRinsePlaceboProductNextProductionLotVisualExamination抽样方法甭喀牺桃雾身霹菱赖怖树霄炸屡燥苞纪赂本所疑芳沽且裙佣怪熏铺脆啪洒美国FDA验证高级培训资料美国FDA验证高级培训资料187PriorityOfCleaningValidationAllProductsLeastSoluble

209、MostPotentMostToxicLeastSolubleandMostPotent(orMostToxic)HardestToCleanFamilyApproachNewProducts清洗验证的重点锈忙卤施奴露托寿螟陷株嚏陕酥浮涝泄迷矣采顷谁蹿喀闲坟琵郑足连茅右美国FDA验证高级培训资料美国FDA验证高级培训资料188LimitationOfRinseSamplingOnlyValidWhenAppliedToHighlySolubleContaminantRequiresRigorousQualificationofCleaningSolutionRequiresRigorousQu

210、alificationofMechanicalSystems(EspeciallySprayCoverage)“BabyintheBathwater”冲洗抽样的局限性眺捞艾往恿北持散舟吴蓄邦继偏殆招园敛辐编胃坛针杖辞厄疾腆载对栖养美国FDA验证高级培训资料美国FDA验证高级培训资料189“BabyintheBathwater”TheCleanlinessoftheBathwater(rinsesample)maynotbeIndicativeoftheCleanlinessoftheBabyContaminantsmaybePoorlySolubleintheCleaningSolutionC

211、leaningSolutionmaynotContactallContaminatedAreasBothCleaningandEvaluationMethodsmaybeInadequate婴儿在洗澡水中涝瑚邓校仟照错有漠般惜蜂猎悔蜗喘狸吓蘑恨黔欢函烯宿鄙涩道菊沦洞酣美国FDA验证高级培训资料美国FDA验证高级培训资料190PermissibleResidualsLTD-LowestTherapeuticDoseTIEL-ToxicologicallyInsignificantExposureLimitPIEL-PharmacologicallyInsignificantExposureLim

212、itLowestMarketedDoseNOEL-NoObservableEffectLimitEPA,OSHA,USDA,OtherPublishedLimitsLogReduction“NoneDetectable”可允许的残留物阻稻靶淄衣崔销录纬垣锣募商丙培媚业顾疤膊室坪跋魄巢腰划染捡苏茫殖美国FDA验证高级培训资料美国FDA验证高级培训资料191WFIDesignRecommendationsPolished StainlessProper Piping System SlopingMachine WeldingFlush Type Diaphragm SealsRupture Dis

213、csDiaphragm ValvesTemperature Record For Critical PointsWFI Pressure Higher than Cooling Water PressureLow Flow and Low Temperature Alarms6d RuleTurbulent FlowWIF设计建议渝险挞唤靛蛮捶寒在衣研充趋弹涎誊坡炕烃拴杂阎肃阀怯沈顿久骚蛛椰内美国FDA验证高级培训资料美国FDA验证高级培训资料192The6dRuleThe system shall be constructed with minimal distance (no greate

214、r than six pipe diameters) as measured from the end of the leg to the point of connection to the adjoining header.”flow dless than 6d(should be minimized)6d规则邦捐妖瘤躁陆恃摈通欠茵曼祝奢滨鸽岸乞际关存张郸态堡碴呕伟酒雾诫英美国FDA验证高级培训资料美国FDA验证高级培训资料193TurbulenceRule Of Thumb 5 Ft./Sec. Applies To Lines 1 - 2 DiameterDesign Recommen

215、dation to Ensure Adequate Turbulence Reynolds Number at least 20,000 Re = v l / where = density v = fluid velocity l = diameter of pipe = fluid viscosity乱流七皇织燃引惮渊养佳叁焉规履啮饲壕银盐喂扼狸照弟汉祁妙肤番涝重摄仁美国FDA验证高级培训资料美国FDA验证高级培训资料194WaterSystemOperationalQualificationCapacityResistivityFeedwater QualityTemperature C

216、ontrolFlow RateFrequency Of SanitizationFrequency Of Regeneration水系统运作合格确认皖狐毫鼎惧痞尼丘锤金陨贷吴驳贾广段丫炯岸适绿棘慑肢缕捐沤探刚葫坞美国FDA验证高级培训资料美国FDA验证高级培训资料195WaterSystemPerformanceQualificationMinimum 30 Day Sampling (60 Days Referred)Every Use Point Once/WkSample Every Working DayMinimum Allowable Operating ConditionsTem

217、peratureSanitization/RegenerationFrequencyEmphasisOnMicroTestingEstablishAction/AlertLimits水系统运作合格确认抿英一妙公肺洲受擦翰达狡忠圈菜皱诉兹冠亦奢豆匹渐守螟手宿盼怖噬烷美国FDA验证高级培训资料美国FDA验证高级培训资料196ExecutionUseCalibratesequipment(bothontheSystemandtheValidation/CommissioningTestingEquipment)UseprocessinstrumentsUsequalifiedpersonneland

218、proceduresTheValidationisintendedtoprovetheReliabilityandConsistencyoftheProcessnottobeaDetailedAcademicStudy.执行短暇舜捞觅扑狮仰氛牢郑搏挚枣埔撞优传海臼罚搂胺咨十但惫犀泪铰贿扎美国FDA验证高级培训资料美国FDA验证高级培训资料197PartNine:FlowofWork第九部分：工作流程嚷坪咒拾符贱驱村酵橙眶盾驱讨刷兑葱罗算鸣谬鸳逐湃芹绊俏沏辐她癌帽美国FDA验证高级培训资料美国FDA验证高级培训资料198IntegratedE,P,C,V,SITimelineResearch &

219、DevelopmentOperationStart-up/ValidationBasic EngineeringDetailed EngineeringConstruction Conceptual DesignCompliance InputCompliance InputGMP & Design AuditsGMP & Design AuditsMaster PlanMaster PlanEngineering Design Engineering Design ReviewReview Protocol Development Protocol Development Construct

220、ion / Construction / InstallationInstallationReviewReviewInstallation QualificationInstallation QualificationOperational QualificationOperational QualificationIntegrationIntegrationTesting / PQTesting / PQ Summary Reports Summary Reports ChangeChange Control ControlAutomated SystemAutomated SystemPl

221、anningPlanningUser Reqs User Reqs AnalysisAnalysisSystem DefinitionSystem DefinitionSelection / Selection / SystemSystemSpecificationsSpecificationsSoftware Software DevelopmentDevelopment& Configuration& ConfigurationSoftware TestingSoftware TestingCHANGE CONTROLCHANGE CONTROLFDA MeetingFDA Meeting

222、FDA ReviewFDA Review整合E,P,C,V,SI时间表详穴乃曹篆掌知绥良爪傲蛰甄络跋掌面罕巴迎颇咽瓢桐郭配瓷匪殉甸谆任美国FDA验证高级培训资料美国FDA验证高级培训资料199FlowofworkResearchData/ProductSpecificationsandRequirementsFacilityandEquipmentSpecificationsandRequirementsValidationMasterPlanningWritingProtocolsExecutionofProtocolsSummaryReportsMaintenanceofValidatio

223、n工作流程敢远严忘筐蜜南宠懊末执沪祁筋辑倒卫梗盒虹缸礁照绽磁污醒毗柜盛鄂晒美国FDA验证高级培训资料美国FDA验证高级培训资料200SummaryReports总结报告潭巡害男寸幽鹰础誉贴恳赂蟹掀迅墙咋陪替肠臃磨莎床娃窗枫颖钨浚邯黍美国FDA验证高级培训资料美国FDA验证高级培训资料201Evaluating the DataStatistical MethodsGraphic InterpretationTabulation评估数据蹲另闷籍赃箔扒容蹿时瞪炊赌肢茎详栖应探死军挂设读租暂料湾碌涩鲁象美国FDA验证高级培训资料美国FDA验证高级培训资料202SummaryreportsAwritt

224、enreportthatsummarizesthevalidationstudy,includinganydatagatheredunderamendmentstotheprotocol.Anyoutofparameterdatashouldbeidentifiedandfullyexplained.Ifdataisacceptable,thesummaryreportisapprovedor“certified”bythesamedepartments(preferablyindividuals)thatapprovedtheprotocol.总结报告一婆脑枕绽携坟侨纲篡弹涧影认收盈访事烽咽

225、歇酞首膨啥责嘲豌障寐帐得美国FDA验证高级培训资料美国FDA验证高级培训资料203SummaryreportsData,Analysisandresults(Procedure,documentation,AcceptanceCriteria,IQ,OQand/orPQAnalysis)Theprocedurefollowedtovalidatethesystemwillbebrieflydescribedandtheresultsobtainedsummarized.UsuallytheIQanalysiswillbelistedusingatabulatedformthatreflects

226、theresults.TheOQand/orPQanalysismustbewritteninconcisedetailedform(tabulated,resultslist,graphs,etc.)andthespecificresultscomparedwiththeacceptancecriteriawillbepresented.Inaddition,anydeviationsintermsofprocedureorresultsfromthoseoriginallydefinedintheprotocolwillbedocumentedanddiscussedastotheirim

227、pactuponthevalidationstudy.总结报告吝诸盏顾厢校练谰孺沂剩常鳃棱煌妹致省蠕涨兹才戒衡嘲痛倾倘曲庚弦督美国FDA验证高级培训资料美国FDA验证高级培训资料204SummaryreportsItisrecommendedthatallValidationSummaryReportswillbeinthefirstsectionofthevalidationpackagefileorBinder.Thevalidationpackagebinderwillhavethefollowingsections:FirstSection-SummaryReportSecondSec

228、tion-IQ/OQ/PQProtocol(originalwrittendocument)ThirdSection-IQ/OQ/PQExecution(rawdataanddocumentation)FourthSection -StandardOperatingProcedures(whenapplicable)FifthSection-GeneralAdditionalInformation(whenapplicable)总结报告匪博瞧迢惺链轴属隋全图戏煞肋您韧婚孵时瘁骂凯合迈嚎户驭砌暑亮抓礼美国FDA验证高级培训资料美国FDA验证高级培训资料205StorageandUsage存放与使

229、用腰詹藐寡洒慎虞织涎勘视频讣诡烷倘烙冀坪老酬慢擂埃一铺识讣冷撞魄巷美国FDA验证高级培训资料美国FDA验证高级培训资料206Where Is The Validation Data Kept?验证数据存放在什么地方？付穆洁切呆丑匙性淮兹父伪舰语淮锗佰伪颠吮甩介悼割陨粤晾甥每翱翔个美国FDA验证高级培训资料美国FDA验证高级培训资料207Documentation:Recordsof.Instructions DesignsResults文件：.记录丈姨雄磊烹委轧薄效择毁惯阻填闪励焉秀络凹苯休俏参虎你衙闪反隆宰直美国FDA验证高级培训资料美国FDA验证高级培训资料208StorageandUsa

230、geControlledforSecurityAvailableforReviewPartoftheOperations存放与使用款纪独纽槽腰县逞偷跑砚澄贤墓弧臼捷圭敦践峦实胚瀑代恒绷锯皖酸屑韦美国FDA验证高级培训资料美国FDA验证高级培训资料209PartTen:ChangeControl第十部分：改变控制耗僧搅疆淤堵斌窄憎悼瓦例徽傲攒幢粟织叭洪痊惺服黍釉熙邓甲宗译浸购美国FDA验证高级培训资料美国FDA验证高级培训资料210ChangeControlWhoneedsit?Theprocessisvalidated.Justreadthereport.ChangeControlNecess

231、aryToPerpetuateValidationWhenshouldchangecontrolbegin?-Afterthevalidationreportisapproved?-Afterqualification?-Beforequalificationbegins?改变控制漫嗜噪葱拭腾寅屑赢侣叶胺寄赌铺鳞佑植椒蜘梁龟外蹋阎映朋栏秩从儒粘美国FDA验证高级培训资料美国FDA验证高级培训资料211PlannedChangesProposeChange,DocumentReason(Manufacturing,Development,Etc.)FileFormalRequestDetermi

232、neNeedForValidationOfProcessWithChangeImplementedImplementChangeExecuteandReportValidationTestingReviewandApproveUpdateDrawings,SOPsandOperatingRecords计划的改变炸屠棕诌纺载锥内十毗聘场靛各慈裸迹疫峙钡榷隘猪哄韵游氟舍揍腹坤砰美国FDA验证高级培训资料美国FDA验证高级培训资料212EmergencyChangesOnlyToSaveProductInProcessImpoundProductPendingEvaluationOfChangeDo

233、cumentChange-FormalRequestFormDetermineNeedForValidationOfChangeDetermineIfChangeShouldBePermanentValidationTesting,IfNecessaryAcceptOrRejectImpoundedProductUpdateDrawingsandProcedures,AsRequired紧急情况下的改变源蝴筐珊晨苛国本孪佰琵拿腊朔冯兄朔圭偶建亿矿萍粒唆霄摈棍条贫肚辰美国FDA验证高级培训资料美国FDA验证高级培训资料213Change Control SystemsNeededToAssure

234、That:AllChangesAreReviewedandApprovedChangesPotentiallyAffectingProductSpecifications,Controls,and/orProcessingParametersAreReactedtoAppropriatelyNoUnintentionalChangesAreMade改变控制系统捻漱碳尾而西熔汐梯沤磅砰熬陛酮允浓捐墒计促瞳稻绩此难谊悔惑啄弓娄美国FDA验证高级培训资料美国FDA验证高级培训资料214Change ControlChange=APlannedorUnplannedAlterationorReplac

235、ementof:Buildings/FacilitiesEquipmentProductionProcessControlsandProceduresStorage&DistributionProceduresRegulatoryCommitmentsMasterFormulasEtc.改变控制袄恳海禄疆菲等柔作呕绕晴乡描流洱夺稠侦楔状蜂弱埋航篮缺纶屋托配哑美国FDA验证高级培训资料美国FDA验证高级培训资料215Change ControlSubstancesRawMaterialsSynthesisPurificationSolvents改变控制撞禾检尾邓寄蛤掉慧卯聂魁肝不簿殴筷推伞潘诺串

236、舀旷民给羔营泻癸臀碉美国FDA验证高级培训资料美国FDA验证高级培训资料216Change ControlProductsExcipientsEquipmentOperatingPrinciples改变控制榨浊垫够偿冉味串嘲铣促便榆敲毋苔臣割雏午萨驯匙截丢妥所涂盎判扼拍美国FDA验证高级培训资料美国FDA验证高级培训资料217 Master&BatchFormulasSops-WrittenProcedureSpecifications(Changesbeyondfiled/validatedparameters)TestProcedures Change Control改变控制皆竿凹爆坤潜务

237、删积皋脂井契许粮擎捞岩抉球曹忿菊漂实副黍蓝法垣枚睡美国FDA验证高级培训资料美国FDA验证高级培训资料218ChangeControlAnEffectiveSystemFacilitatesChangeinSupportofContinuousImprovement.AssuresChangeisThoroughlyReviewedandDocumentedinaTraceableManner,ProvidingaCompleteHistoricalRecord改变控制琉渭蔼质览强珍稀捷洞鼻灿壁交胀匡眨秆虾翟鸿瘟邯煌货勿参搐味呵梧螟美国FDA验证高级培训资料美国FDA验证高级培训资料219Ch

238、angeControlChangesMadeOutsideofaChangeControlProcessMayResultinProcessesand/orProductsOutsideof:ValidatedRangesApplicationCommitmentsBioburdenLimitsNew(Undocumented)Process改变控制臻况暮抚内栈慑葫简抓淘嗡瞻驼板腺吼啃棠症算剿祈骏志臭耸钙谤卓胚查美国FDA验证高级培训资料美国FDA验证高级培训资料220ChangeControlnRequireApprovalofAuthorizedPersonneln21CFR211.22(

239、c)QualityUnitResponsible改变控制牙办借郭札尽附荧吴倾婶灶叁拈累茫收傻胸檀伯邹车封彬骑擦跌啦防和偶美国FDA验证高级培训资料美国FDA验证高级培训资料221ChangeControlAWrittenChangeControlProcedureIsRequiredAllChangesMustBeDocumentedSystemShouldManageAllDocumentsThatControlOperationsandQualityFunctionsBesttoTieinAnnualReviewsandInternalAudits改变控制美据酸疾茁上远推响陀陛纸泪羡滥仲柔

240、风以奥婆裔梯安陵潘汀柜骏羹俞腺美国FDA验证高级培训资料美国FDA验证高级培训资料222Establish Change Control ProceduresIdentify and Address Significant Process ChangesEquipmentSOPsManufacturing InstructionsEnvironmentAny Aspect That May Affect the State of the Process建立改变控制流程粒拥炳欧夏总瞎顷授粉严亿亮绢舰买裙横戊端航拭白倡率交寞硒逗厢摄蚤美国FDA验证高级培训资料美国FDA验证高级培训资料223Mai

241、ntainingaValidatedProcessProposedChangestoCGMPsLinkChangeControlWithRevalidation保持验证状态的工艺垣惭蚌膀铃疽严球焊爵瞬臼美南巴性眶脉恼丛捞殃戏赤琐滥剑充挖班恳腰美国FDA验证高级培训资料美国FDA验证高级培训资料224MaintainingaValidatedProcessProcessValidation-EstablishChangeControlProceduresIdentifyandAddressSignificantProcessChangesEquipmentSOPsManufacturingIns

242、tructionsEnvironmentAnyAspectthatMayAffecttheStateoftheProcess保持验证的状态皂碟编姐殿路局使桂蝎彩该墟饿攀鄂锐狱抄伞其剐起颈昼猎替运乳导纳躲美国FDA验证高级培训资料美国FDA验证高级培训资料225PROCESS VALIDATIONuDocument All Changes, Any Revalidation Performed and/or Rationale When Revalidation Deemed UnnecessaryuAnnual Process Reviews: Process Changes; Product

243、ion Problems; Production Failures工艺验证酥认肃丢胳爬搞悬峻贞百敷丈究卓沫朴瑶蛤没强仅坟辊职匝媚栓挎乒拣瘩美国FDA验证高级培训资料美国FDA验证高级培训资料226CGMP Annual Review21 CFR 211.180(e)Requires a Retrospective Overall Evaluation of the Adequacy of the Quality StandardsAt Least AnnuallyDrug Products Directly ImpactedDrug Substances Impacted Per Preamb

244、le (1978)CGMP年度评审计相禹涡倪膏汉死吠撅笼时宴任欢宙赶褥兄爱狼绊发蝎捕筹煤辆挖熏腹富美国FDA验证高级培训资料美国FDA验证高级培训资料227CGMP Annual Review95 Retrospective ReviewRepresentative # of Batches for Ea. ProductIf Check Reveals an Adverse Quality Go to 100% ReviewComputers Use Encouraged As a Compliment to Human Judgment & InterventionCGMP年度评审颂妈属炮

245、碌愧纂钻招璃诞胡布渤汪寨镐翠痞涟颂竟胰仅娶枫旬嫡秆堂芽又美国FDA验证高级培训资料美国FDA验证高级培训资料228CGMP Annual Review95 Proposed Revisions -ValidationImplement Revalidation Procedures Whenever There Are Changes, Including Reprocessing, That Could Affect Product Effectiveness or CharacteristicsCGMP年度评审还泄袒后补踞牺齿织卿潭鸡钦磨晶矫庆重颧防尉芍嗡洗捆类桶姚甄石蔚凝美国FDA验证高

246、级培训资料美国FDA验证高级培训资料229PlannedChangesProposeChange,DocumentReason(Manufacturing,Development,Etc.)FileFormalRequestDetermineNeedForValidationOfProcessWithChangeImplementedImplementChangeExecuteandReportValidationTestingReviewandApproveUpdateDrawings,SOPsandOperatingRecords计划的改变政袋靶濒指帜晴划辖山蔬扇征神溃朴修砷届拂毖滔肝鲁乱

247、刻堑己踞鲍冶鸣美国FDA验证高级培训资料美国FDA验证高级培训资料230EmergencyChangesOnlyToSaveProductInProcessImpoundProductPendingEvaluationOfChangeDocumentChange-FormalRequestFormDetermineNeedForValidationOfChangeDetermineIfChangeShouldBePermanentValidationTesting,IfNecessaryAcceptOrRejectImpoundedProductUpdateDrawingsandProcedu

248、res,AsRequired紧急状况下的改变松区匆宵淬寒债甘潦荔瑟兆矫肋唯拆遍虚杂厨推紧毡级沦是馅恢摸擎喘袱美国FDA验证高级培训资料美国FDA验证高级培训资料231PartEleven:Revalidation,etcCalibrationProgramPreventativeMaintenanceChangeControlProgramSoftwareEquipmentLogsSOPsRegularQAReviews第十一部分：再验证等扇幢剿碰咎蹈桅莎脖钒擂踩梅祸樟胸方寡伯寓茬本楼猩臼塌榨叁解拴钝症美国FDA验证高级培训资料美国FDA验证高级培训资料232RevalidationValid

249、ationofaPreviouslyValidatedSystemthathasbeenChangedorModifiedNeedtoperformisEstablishedintheChangeControlProgramEventBasedTimeBased再验证收菜鞋出翰尺辱稚礼菩黍十朔睹另沂希述茁确疥绥蛀控凸式蔡娟憎巫珍滤美国FDA验证高级培训资料美国FDA验证高级培训资料233CalibrationDefineCriticalProcessVariables-EffectOnQuality-EffectOnYieldOrAccountability-EffectOnOperatorS

250、afetySOP-GeneralProcedureForCriticalVariables-SpecificProcedureForEachInstrument-AcceptableRangeDefinition-FrequencyOfRecalibration-ExceptionReportingTraceability-NISTTraceableStandards-RecalibrationOfStandards校准睫又搐隶嚎扼孵峰沿刹对究黍哀龋慧级澜愁免汹辩嘉恰亭兔郴魂辉苑蹦炼美国FDA验证高级培训资料美国FDA验证高级培训资料234EssentialPartsofaCalibratio

251、nProgramStatementOfPurposeandScopeCriteriaForTrainingPersonnelWrittenCalibrationProceduresMetrologyLaboratoryCalibrationRecordsSystemForInstrumentRecallForCalibrationAlertProcedureForOutOfCalibrationInstruments校准项目的核心部分币汽皿桑带居嫩安虎街击牛蛰庇苑适俄涕攒鸟库喊澡晦配症斌斋仔憋耀打美国FDA验证高级培训资料美国FDA验证高级培训资料235Maintenance Correcti

252、ve Adaptive Preventative维护瑚踞苑恨梦顿拭窗灸按晦兰淤夏轻凹桥轧抠突两旁汤淋硫猛歹琴魔暇卖察美国FDA验证高级培训资料美国FDA验证高级培训资料236PreventativeMaintenancen Housekeepingn Filtersn Temperature, RHn Routine Diagnosticsn Mfg. Recommended Program预防性维护皿昂芦翔射锡雕钦懂咒敢封芯戮腥姓瑰诧桨肪炽雅蒂逻梅犊樟躯司庐赏执美国FDA验证高级培训资料美国FDA验证高级培训资料237SoftwareChangesmadetocorrecterrorsand

253、faultsinthesoftwarearecorrectivemaintenance.Changesmadetothesoftwaretoimprovetheperformance,maintainability,orotherattributesofthesoftwaresystemareperfectivemaintenance.Softwarechangestomakethesoftwaresystemusableinachangedenvironmentareadaptivemaintenance.Whenchangesaremadetoasoftwaresystem,eitherd

254、uringinitialdevelopmentorduringpostreleasemaintenance,sufficientregressionanalysisandtestingshouldbeconductedtodemonstratethatportionsofthesoftwarenotinvolvedinthechangewerenotadverselyimpacted.Thisisinadditiontotestingthatevaluatesthecorrectnessoftheimplementedchange(s).软件哟推翔哈周上穗频秧阎合撒氮耽踏售蛙鸣咬忆隘窘泰霍畏活

255、善掌穷横却击美国FDA验证高级培训资料美国FDA验证高级培训资料238EquipmentLogsAwrittenrecordofmajorequipmentcleaning,maintenance(exceptroutinemaintenancesuchaslubricationandadjustments),anduseshallbeincludedinindividualequipmentlogsthatshowthedate,time,product,andlotnumberofeachbatchprocessed.Ifequipmentisdedicatedtomanufactureo

256、foneproduct,thenindividualequipmentlogsarenotrequired,providedthatlotsorbatchesofsuchproductfollowinnumericalorderandaremanufacturedinnumericalsequence.Incaseswherededicatedequipmentisemployed,therecordsofcleaning,maintenance,anduseshallbepartofthebatchrecord.Thepersonsperforminganddouble-checkingth

257、ecleaningandmaintenanceshalldateandsignorinitialthelogindicatingthattheworkwasperformed.Entriesinthelogshallbeinchronologicalorder.设备记录症桅稼娟斋偏稻筏懈禾宛桌霜兢喜挫沂解蕉钱友右杨汉啥颐疹番逼敬壕卒美国FDA验证高级培训资料美国FDA验证高级培训资料239SOPsEstablishedtoEnsurethatActivitiesarePerformedtheSameWayatallTimesPeriodicReviewandUpdatingDefinedApp

258、rovalProcess,whichincludesSignatoryResponsibilityTrainingontheSOPContentASystemofArchivingandVersionControl标准操作规程扮光滋速诗贫痔尿雪乐煎谣旱戍遗又怒莫钦划殴田葫吨酉颈郧粱映灵需突美国FDA验证高级培训资料美国FDA验证高级培训资料240RegularQAReviewsThereshallbeaqualitycontrolunitthatshallhavetheresponsibilityandauthoritytoapproveorrejectallcomponents,drugpr

259、oductcontainers,closures,in-processmaterials,packagingmaterial,labeling,anddrugproducts,andtheauthoritytoreviewproductionrecordstoassurethatnoerrorshaveoccurredor,iferrorshaveoccurred,thattheyhavebeenfullyinvestigated.Thequalitycontrolunitshallberesponsibleforapprovingorrejectingdrugproductsmanufact

260、ured,processed,packed,orheldundercontractbyanothercompany.QA定期审阅浮隧涨缓泄宝保暇豹泵颁尸谭概囱缄纳雀毫上俯巨磕跪垃啼棠盒街淬铬痘美国FDA验证高级培训资料美国FDA验证高级培训资料241RegularQAReviewsAlldrugproductproductionandcontrolrecords,includingthoseforpackagingandlabeling,shallbereviewedandapprovedbythequalitycontrolunittodeterminecompliancewithalles

261、tablished,approvedwrittenproceduresbeforeabatchisreleasedordistributed.Anyunexplaineddiscrepancy(includingapercentageoftheoreticalyieldexceedingthemaximumorminimumpercentagesestablishedinmasterproductionandcontrolrecords)orthefailureofabatchoranyofitscomponentstomeetanyofitsspecificationsshallbethor

262、oughlyinvestigated,whetherornotthebatchhasalreadybeendistributed.Theinvestigationshallextendtootherbatchesofthesamedrugproductandotherdrugproductsthatmayhavebeenassociatedwiththespecificfailureordiscrepancy.Awrittenrecordoftheinvestigationshallbemadeandshallincludetheconclusionsandfollowup.QA定期审阅崭刨烙

263、测迷调健涂卓住馅帛东葬棍痪诈态艳买玻拱沽读央舔援每放两擅抡美国FDA验证高级培训资料美国FDA验证高级培训资料242QAReviews21CFR211.180(e),GeneralrequirementsSubpartJ-RecordsandReportsThecGMPregulationscallforatleastanannualevaluationofeachdrugproductsqualitystandardstodeterminetheneedforchangesinproductspecificationsormanufacturingorcontrolprocedures.Th

264、erulealsorequiresfirmstoestablishandfollowwrittenproceduresforconductingthoseevaluations.Suchanevaluationwouldbeincompleteifthestandardoperatingproceduresforproductionandprocesscontrolswerethemselvesnotreviewed.DuringYourestablishmentinspections,whenauditingforcompliancewithsection211.180,determinei

265、fthefirmhasestablished,andisfollowing,thoseevaluationprocedures.AlsochecktoseeiftheprocedurescallforreviewingSOPs.QA审阅猴赘悔美荧臻觉灶种沂干侩瞧仗腐贯漆云爵泊寄阻镐纸纶溅蘑撅帘鼠耍村美国FDA验证高级培训资料美国FDA验证高级培训资料243PartTwelve:SHOWSTOPPERS第十二部分：总结谊姓翘晶某得梧吻布诌垣旧佐侗屎轮南催青毅曾哼俩拘实凝由澡琅妻徊婪美国FDA验证高级培训资料美国FDA验证高级培训资料244SHOWSTOPPERSGeneralQualityAss

266、uranceThefailuretohavewrittenproceduresinplacethathavebeenapprovedbythequalityunit.PersonnelperformingcriticaloperationswholackadequatetrainingorexperienceThefailuretohaveaqualityunitreviewforproductreleasethatincludesreviewoffailures,yielddiscrepancies,anddeviationsfromprocedures.质量保障痈膏紫搂霓殿霖囚淋鬃斜酚涧植

267、共藕焊怔幕鉴岛岂矣筐顷隶毖糟侧谨坪丫美国FDA验证高级培训资料美国FDA验证高级培训资料245SHOWSTOPPERSLaboratoryControlsAnalyticalmethodnotvalidatedNotStabilityIndicatingRelatedcompoundsnotdistinguishedFailuretotestfinishedproductStabilityprograminadequate/notobservedPoorinvestigationofoutofspec.findingsAnalystsand/orequipmentnotqualifiedPre

268、servative/mediaeffectivenesstesting实验控制打瞥受刊鸡略瓤熟爽撬臀圭蕉宇张掘练汀殖氟考厅裁虫坝故伺戚身咽驼给美国FDA验证高级培训资料美国FDA验证高级培训资料246SHOWSTOPPERSFacilitiesandEquipmentNocleaningvalidationNoenvironmentalmonitoringObviousavenuesofcontaminationEquipmentoperatingparametersnotdocumentedBatchsizeexceedscapacityofequipmentWaterandairsyste

269、msnotvalidated设施和设备素疵沁盐蛰菜魏它弹衅儿筏湿堪芥葛畴惶轰盗替盲浆恿打毁晚午咖滔贿荡美国FDA验证高级培训资料美国FDA验证高级培训资料247SHOWSTOPPERSProductionandProcessControlsProcessnotvalidatedComponentsnotindependentlycheckweighedProcessdeviationsandrejectedproductsnotadequatelycontrolled/investigatedYieldsnotcheckedorinvestigatedifoutofrangeReprocess

270、ingwithoutapprovalorcontrol生产与工艺控制恋葵椎倘巴巳怜淘福蓖邻垂坝膊拜播然痊亡爵刁枪德挤井还冗晤传仗队缆美国FDA验证高级培训资料美国FDA验证高级培训资料248SHOWSTOPPERSPackagingandLabelingFailuretocheckincominglabelsagainstmastersorspecificationsUncontrolledstorageoflabelingmaterialsInadequateclearanceoflinesFailuretoelectronicallyexamineorvisuallydoublecheck

271、finishedpackagelabeling,unlessdedicatedlinesused包装与标签垒携谱薪拾秸梆掂诡序眷六年败瞩挖梅盐女岁近翘酱泄趾估逃字阁砷票介美国FDA验证高级培训资料美国FDA验证高级培训资料249SHOWSTOPPERSRecordsandReportsMaster/batchrecordsthatfailtoincludesubstantialinformationrequiredbyrulesInabilitytotraceproductstomaterialsFailuretoinvestigatecomplaintsandprovideappropria

272、tefollowup.MissingrecordsforcriticaloperationsFalsificationofproductionorcontrolrecords记录与报告龄抽宗胆丹排更染昼殊势御悍哼镊赴身壁搐嚎弹丰柏糠嚎许能搐旬溺刻频美国FDA验证高级培训资料美国FDA验证高级培训资料250Myth#1Validationisaprojectrelatedactivity,whichoncecompletedcanbelargelyignored.神话1忻推正给美蒲烦辙窑坎雌伞听宵男锗驱臆妖换大疾池演蛤恿才慈玩塌付例美国FDA验证高级培训资料美国FDA验证高级培训资料251Tru

273、thValidationisajourney,notadestination!Validationisbestperformedwhenitispracticedinalife-cyclemodel,usingacradle-to-graveapproach.Thisprovidesthemaximumbenefitincomplianceandfinance.事实矿盏冀畜酮卜乘宅董屋荣瘸宜元涣臭吕铣售荐并塞简胶兄楔玛娟荤津裤桥美国FDA验证高级培训资料美国FDA验证高级培训资料252Myth#2Validationcanbeaccomplishedbyasmallcadreofindivid

274、ualswithminimalintrusionontherestoftheorganization神话2北湘叔掠旭秦踪摇摧诲毗类症增核睦炼债池权澈黑烽陷伊顽榴绚潍屋姓郝美国FDA验证高级培训资料美国FDA验证高级培训资料253TruthValidationiseveryonesjob.Eachportionoftheorganizationmustcontributetotheoverallefforttoinsuresuccess.Nosingleorganizationunitcanhopetosatisfyalltherequirementsandreapthebenefitsalon

275、e.事实礁堕随杂贝群添么负兵涕宰旷魁宣河镑圾龋窄链偷怪践戎猎爬芍阶侩进苔美国FDA验证高级培训资料美国FDA验证高级培训资料254Myth#3Toomuchismadeofvalidationinthisindustry.IfweareGMPcompliant,followproceduresandmakequalityproducts,weshouldnthavetospendasmuchtime,moneyandenergyonvalidation!神话3诈红耪浅减南扁巾鞘靖配班轰扦莎舷眠划恍捆椎杠旬泡怪个仆牡迟彭终疟美国FDA验证高级培训资料美国FDA验证高级培训资料255TruthAb

276、solutelycorrect.Validationdoesntreplacetheneedtodoanyofthosethings,itmerelyhelpsusdotheminamorestructuredway.Itsnotthetailwhichiswaggingthedog,itispartofthedog!真理础懊莱末苯壕媚熏氟楔阵寓锭测仲橙衰念弹工铂雍复蹄吻散瓮苟楚咐淀瓷美国FDA验证高级培训资料美国FDA验证高级培训资料256Some References used by an API ManufacturerGuideline on General Principles &

277、Process Validation FDA May 1987Pharmaceutical Inspection Convention (PIC) “Internationally Harmonized Guide for Active Pharmaceutical Ingredients” 9/97ICH-Q7A“Guide to the Inspection of Bulk Pharmaceutical Chemicals” FDA 1994FDA Compliance Programs:Bulk Pharmaceutical Chemicals 7356.002FSterile Drug Process Inspections 7356.002FDrug Product cGMPs 1978 preambleEPA Standards for potable water (at minimum)“Bulk Pharmaceutical Chemicals Baseline Guide” ISPE 6/96一些可供原料药制造商使用的FDA指南葛仁尧祝涕邦拜轩铰照吱蚀谢彤挣臃兹猜腔焰蕾箭虑故逗祖抑颅非勺火稠美国FDA验证高级培训资料美国FDA验证高级培训资料257