Q9+FMEA失效模式效应分析

AnnexI.2FailureMode

EffectsAnalysis失效模式效应分析

(FMEA)I.2:FailureModeEffectsAnalysis失效模式效应分析(FMEA)(seeIEC60812

见IEC60812)EvaluationofpotentialfailuremodesforprocessesThelikelyeffectonoutcomesand/orproductperformanceOncefailuremodesareestablished,

riskreductioncanbeusedto

eliminate,reduceorcontrolthepotentialfailuresFMEAreliesonprocessunderstandingSummarizetheimportantmodesoffailure,factorscausingthesefailuresandthelikelyeffectsofthesefailures

Howtoperform?

BreakdownlargecomplexprocessesintomanageablestepsICHQ9I.2:FailureModeEffectsAnalysis失效模式效应分析(FMEA)(seeIEC60812

见IEC60812)工艺的潜在失效模式的评估对结果和产品性能的可能的影响一旦失效模式建立，风险降低行动用于来消除、降低或控制潜在的失效依赖于对工艺的理解概述重要的失效模式，引起失效的因数和失效的可能的影响

如何实施?

将大的复杂的工艺分解成易处理的步骤ICHQ9I.2:FailureModeEffectsAnalysis(FMEA)

PotentialAreasofUse(s)PrioritizerisksMonitortheeffectivenessofriskcontrolactivitiesEquipmentandfacilitiesAnalyzeamanufacturingprocess

toidentifyhigh-riskstepsorcriticalparametersRNP:RiskPriorityNumberC.Kingery,TheSixSigmaMemoryJoggerIIICHQ9I.2:失效模式效应分析(FMEA)

可使用的潜在领域：Prioritizerisks优先考虑的风险Monitortheeffectivenessofriskcontrolactivities监控风险控制活动的效力Equipmentandfacilities

设备和设施Analyzeamanufacturingprocesstoidentifyhigh-riskstepsorcriticalparameters为了识别高风险步骤和关键参数分析一个生产工艺RNP:RiskPriorityNumberC.Kingery,TheSixSigmaMemoryJoggerIIICHQ9I.2:FailureModeEffectsAnalysis(FMEA)Howtoperform?1.Establishateam2.Identifytheknownandpotentialfailuremodes:Developlistsofknownproblemsandbrainstormotherpotentials…

e.g.ProductnotmeetingspecificationProcessnotmeetingyieldrequirementsMalfunctioningequipmentSoftwareproblemsNewlyidentifiedfailuremodesshouldbeaddedatanytimeEXAMPLEI.2:失效模式效应分析(FMEA)如何实施?1.成立一个小组2.识别已知和潜在的失效模式生成已知问题和集体讨论的其他潜在问题的列表例如.产品不符合标准工艺不满足收率需要设备故障软件问题新发现的失效问题应该随时加进来。EXAMPLEI.2:FailureModeEffectsAnalysis(FMEA)Howtoperform?3.Characterisetheseverity,probabilityanddetectability

AnequalnumberoflevelsissometimeshelpfulSomepreferenceto3,4,5,6or10levelsBut:anevennumberoflevelsavoidsthemidpointUsedifferentscalesLinear: 1,2,3,4Exponential: 1,2,4,8Logarithmic: 1,10,100,1000Selfmade: 1,3,7,10MultiplyingdifferentscaleswilldifferentiatetheoutcomeTheaimistocomeupwithamethodofprioritisingEXAMPLEI.2:失效模式效应分析(FMEA)如何实施?3.识别严重性、可能性和可检测性一个相当的数字等级常常是很有用的一般优先选择等级3，4，5，6或10但是:一个偶数等级会避免中位数用不同的等级线性的: 1,2,3,4直数的: 1,2,4,8对数: 1,10,100,1000自定义: 1,3,7,10不同的等级的乘积将区分结果目标是提出一个定义优先顺序的方法EXAMPLEI.2:FailureModeEffectsAnalysis(FMEA)Howtoperform?4.Defineactions5.Revisittheranking6.Defineresidualrisk7.PerformashortsummaryScopeDatafromtheassessment&control

(e.g.No.ofidentifiedfailuremodes)Levelofacceptedriskwithoutactionsi.e.residualrisk

(e.g.RiskpriorityNumber<50)Recommendedactions,responsibilitiesandduedates

(includingapproval,ifappropriate)Personinchargeforfollow-upofFMEAEXAMPLEI.2:失效模式效应分析(FMEA)如何实施?4.详细说明行为5.重新评级6.详细说明剩余的风险7.完成一个简短的摘要范围从评估和控制中得到的数据

(例如已识别失效模式的编号)不需要采取措施的可接受的风险的等级即剩余风险

(比如风险优先号<50)建议采取的措施,相关职责和完成日期

(如果需要也包括批准)负责下一步FMEA的责任人EXAMPLESeverity(Consequencesoffailure)10ExtremePredictedtocausesevereimpacttoquality(Productoutofspecifications,noExpertStatementpossible)

7HighPredictedtocausesignificantimpactonquality(Failuretomeetspecifications,noStabilitydata,ExpertStatementpossible)

3ModeratePredictedtocauseminorimpactonquality(Failuretomeetspecifications,Stabilitydataavailable)

1LowPredictedtohaveno/minorimpactonqualityoftheproduct(Qualitywithinspecifications)EXAMPLE严重性(失效的结果)10极高可能会对产品产品产生严重的影响(产品OOS,可能无专家声明)

7高可能对产品质量产生重大的影响(不能满足指标,没有稳定性数据,可能需要专家声明)

3中可能对产品质量产生小的影响(不能满足指标要求,可能没有稳定性数据)

1低可能对产品质量无影响或很微小的影响(质量在指标之内)EXAMPLEProbability(Likelihoodfailurewillhappen)8RegularfailuresExpectedtohappenregularly

4RepeatedfailuresExpectedtohappeninalowfrequency

2OccasionalfailuresExpectedtohappeninfrequently

1UnlikelyfailuresUnlikelytohappenEXAMPLE可能性(失效发生的概率)8经常失效期望有规律的发生

4重复的失效期望以较低频率发生

2偶尔失效期望很少发生

1几乎不会失效不太可能发生EXAMPLEDetectability(Abilitytofindthefailure)4NormallynotdetectedFailureverylikelytobeoverlooked,hencenotdetected

(notechnicalsolution,nomanualcontrol)3LikelynotdetectedFailuremaybeoverseen

(manualcontrol,spotchecks)2RegularlydetectedFailurewillnormallybedetected

(manualcontrol,routineworkwithstatisticalcontrol)1AlwaysdetectedFailurecanandwillbedetectedinallcases

(monitoring,technicalsolutionavailable)EXAMPLE可检测性(发现失效的能力)4通常不能被发现失效非常容易被忽视,因此不能发现

(没有技术解决方法,没有手动控制)3可能发现不了失效可能被检查到

(手动控制,现场检查)2定期检查可以发现失效通常都能发现

(手动控制,

统计控制的例行工作)1随时可以发现失效随时会被发现

(检测器,技术措施有效)EXAMPLEFMEA:QuantitationofRisk:Severity10DangerouslyHighFailurecouldleadtodeathorpermanentinjurytothecustomer.Financial:>$1,000,0009ExtremelyhighFailurecouldleadtoinjurytothecustomer.Failurewouldcreatenon-compliancewithregisteredspecifications.Failurelikelytoleadtorecall.Financial:$1,000,0008VeryHighFailurecouldleadtoadversereactionforcustomer.FailurewouldcreatenoncompliancewithGMPregulationsorproductregistrations.Failurepossibletoleadtorecall.Financial:$500,0007HighFailureleadstocustomerperceptionofsafetyissue.Failurerendersindividualunit(s)unusable.Failurecausesahighdegreeofcustomerdissatisfaction.RecallforbusinessreasonspossiblebutAuthorityrequiredrecallunlikely.Financial:$100,0006ModerateFailurecausesahighdegreeofcustomerdissatisfactionandnumerouscomplaints.Failureunlikelytoleadtorecall.Financial:$50,0005LowFailurelikelytocauseisolatedcustomercomplaints.Financial:$10,0004VeryLowFailurerelatestonon-dosageformissues(likeminorpackagingproblems)andcanbeeasilyovercomebythecustomer.Financial:$5,0003MinorFailurecouldbenoticedbythecustomerbutisunlikelytobeperceivedassignificantenoughtowarrantacomplaint.2VeryMinorFailurenotreadilyapparenttothecustomer.Financial:<$1,0001NoneFailurewouldnotbenoticeabletothecustomer.Financial:noneDr.GaryHarbour,PfizerEXAMPLEFMEA:风险的数值:严重性10高危险失效可能导致消费者死亡或永久的伤害，财产损失：>$1,000,0009极端高失效可能导致消费者的伤害。失效将产生与已注册的标准不符合，失效会导致产品召回财产损失：$1,000,0008很高失效会导致消费者不良反应。可能产生不符合GMP法规或产品注册。可能会导致召回。财产损失：$500,0007高失效会引起客户对安全问题的担心，失效必须给单个单位给与补偿，失效会导致客户高度的不满意，产品召回只是因为商业原因而不会引起强制召回，财产损失:$100,0006中失效会引起客户高度的不满意和大量的投诉。失效未必会引起产品召回，财产损失:$50,0005低失效会引起单个客户投诉，财产损失:$10,0004非常低失效不涉及到剂型等问题（象包装问题），可以很容易被客户接受，财产损失:$5,0003较小失效会被客户注意但是未必会引起客户投诉2非常小失效不容易被客户接受.财产损失:<$1,0001无失效不会引起客户注意。财产损失：无Dr.GaryHarbour,PfizerEXAMPLEFMEA:QuantitationofRisk:Probability10VeryHigh:FailureisalmostinevitableMorethanoneoccurrenceperdayoraprobabilityofmorethanthreeoccurrencesin10units(Cpk<0.33or<1σ).9

Oneoccurrenceeverythreetofourdaysoraprobabilityofthreeoccurrencesin10units(Cpk~0.33or~1σ).8High:RepeatedfailuresOneoccurrenceperweekoraprobabilityof5occurrencesin100units(Cpk~0.67or~2σ).7

Oneoccurrenceeverymonthoroneoccurrencein100units(Cpk~0.83~2.5σ).6Moderate:OccasionalFailuresOneoccurrenceeverythreemonthsorthreeoccurrencesin1,000units(Cpk~1.00or~3σ).5

Oneoccurrenceeverysixmonthstooneyearoroneoccurrencein10,000units(Cpk~1.17or~3.5σ).4

Oneoccurrenceperyearorsixoccurrencesin100,000units(Cpk~1.33or~4σ).3Low:RelativelyfewFailuresOneoccurrenceeveryonetothreeyearsorsixoccurrencesin10,000,000units(Cpk~1.67or~5σ).2

Oneoccurrenceeverythreetofiveyearsor2occurrencesin1,000,000,000units(Cpk~2.00OR~6σ).1Remote:FailureisunlikelyOneoccurrenceingreaterthanfiveyearsorlessthantwooccurrencesin1,000,000,000units(Cpk>2.00OR>6σ).Forbatchfailuresusethetimescaleforunitfailuresusetheunitscale.Dr.GaryHarbour,PfizerEXAMPLEFMEA:风险数值:可能性10非常高:失效几乎不可避免每天发生超过一次或可能性大于3/10(Cpk<0.33or<1σ).9

每三天或四天发生一次或可能性是3/10(Cpk~0.33or~1σ).8高:重复失效每周一次或可能性为5/100(Cpk~0.67or~2σ).7

每月发生一次或可能性为1/100(Cpk~0.83~2.5σ).6中:偶尔失效每三个月发生一次或可能性为3/1000(Cpk~1.00or~3σ).5

每六个月到一年发生一次或可能性为1/10，000(Cpk~1.17or~3.5σ).4

一年发生一次或可能性为6/100，000(Cpk~1.33or~4σ).3低:相对很少失效每一年至三年发生一次或可能性为6/10，000，000(Cpk~1.67or~5σ).2

每三至五年发生一次或可能性为1/1，000，000，000(Cpk~2.00OR~6σ).1微笑:失效几乎不太可能超过五年发生一次或小于2/1，000，000，000(Cpk>2.00OR>6σ).Forbatchfailuresusethetimescaleforunitfailuresusetheunitscale.对于批失效用时间尺度，对于单元失效使用单位尺度Dr.GaryHarbour,PfizerEXAMPLEFMEA:QuantitationofRisk:Detection10AbsoluteUncertaintyTheproductisnotinspectedorthedefectcausedbythefailureisnotdetectable.9VeryRemoteProductissampled,inspected,andreleasedbasedonAcceptableQualityLevel(AQL)samplingplans.8RemoteProductisacceptedbasedonnodefectsinasample.7VeryLowProductis100%manuallyinspectedintheprocess.6LowProductis100%manuallyinspectedusinggo/no-goorothermistake-proofinggauges.5ModerateSomeStatisticalProcessControl(SPC)isusedintheprocessandproductisfinalinspectedoff-line.4ModeratelyHighSPCisusedandthereisimmediatereactiontoout-of-controlconditions.3HighAneffectiveSPCprogramisinplacewithprocesscapabilities(Cpk)greaterthan1.33.2VeryHighAllproductis100%automaticallyinspected.1AlmostCertainThedefectisobviousandthereis100%automaticinspectionwithregularcalibrationandpreventivemaintenanceoftheinspectionequipment.Dr.GaryHarbour,PfizerEXAMPLEFMEA:风险数值:可检测性10绝对不确定产品不检查或失效引起的缺陷检测不到9非常微弱.产品基于可接受的质量平行取样计划进行取样，检查和放行8微弱样品没有缺陷产品就可以被接受。7很低在工艺中产品被100%的人为检查。6低产品使用行/不行或其他防错测量来进行100%的人为检查5中一些统计过程控制（SPC）被用于工艺，产品生产完后做最终检测。4中高使用SPC，对不受控制的条件有中间反应3高用工艺能力大于1.33的一个有效的SPC程序2很高所有产品100%自动检查。1几乎确定缺陷很明显，定期校验的100%的自动检查和检查设备的预防性维护。Dr.GaryHarbour,PfizerEXAMPLESeverity/Probability/Detection(SPD)PhDR.C.Mendson,Menson&Associations,Inc

ICHEWGLondon,March2004EXAMPLEI.2:FailureModeEffectsAnalysis(FMEA)Severity(S)LinktoendproductfunctionalfailureMedicalDepartmentinvolvementProbability(P)UsehistoricaldataSimilarprocessesproductsDetectionMethodvalidationstudiesHistoricaldataEXAMPLETakayoshiMatsumura,EisaiCo.DryingProcessI.2:失效模式效应分析

(FMEA)严重性

(S)联系最终产品功能性失效引入医学部门可能性

(P)使用历史数据类似工艺产品可检测性

方法验证研究历史数据EXAMPLETakayoshiMatsumura,EisaiCo.干燥过程/工艺RankingSeverity(S)Probability(P)Detection(D)10DeathMorethanonceadayImpossibletodetect9↓3–4timesadayRemote8PermanentinjuryOnceaweekVeryslight7↓OnceamonthSlight6TemporaryinjuryOnceinthreemonthLow5↓Onceinhalf–oneyearMedium4Reported/dissatisfiedOnceayearModeratelyhigh3↓Oncein1–3yearsHigh2Notice/noreportOncein3–5yearsVeryHigh1↓Lessthanoncein5yearsVirtuallycertainI.2:FailureModeEffectsAnalysis(FMEA)TakayoshiMatsumura,EsaiCoEXAMPLEDryingProcess级别严重性

(S)可能性

(P)可检测性

(D)10死亡超过一天一次不可能9↓3–4次/每天微弱的8永久伤害1次/周非常微小7↓1次/月微小6暂时伤害1次/3月低5↓1次/6月中4报告的/不高兴1次/年适度高3↓1次/1~3年高2通知/无报告1次/3~5年很高1↓<1次/5年近乎必然I.2:失效模式效应分析

(FMEA)TakayoshiMatsumura,EsaiCoEXAMPLE干燥过程/工艺ProcessPotentialFailureModePotentialCauseSPDRPN1.Setupcontaminationdisheveledgownofoperatorinsufficientcleaningofequipment2.Startdryingcontaminationdamageofinlet-airfilterdegradationofproductdamageofthermometer3.Maintaintemperaturelongdryingtimeunstablesupply-airvolumehighLossOnDrying(LOD)damageoftimerlowLODhighdew-pointnon-uniformityofLODuneventemperaturedistributionDryingProcessI.2:FailureModeEffectsAnalysis(FMEA)TakayoshiMatsumura,EsaiCoEXAMPLERPN:RiskPriorityNumber=S*P*D工艺潜在失效模式潜在原因SPDRPN1.进料污染操作者不洁净的服装设备清洗不充分2.开始干燥污染进口过滤器损坏产品降解温度计损坏3.保持温度长的烘干时间不稳定的供应空气体积高的干燥失重计时器损坏低的干燥失重高露点不均匀的干燥失重不均匀的温度分布干燥过程/工艺I.2:失效模式效应分析

(FMEA)TakayoshiMatsumura,EsaiCoEXAMPLERPN:风险优先因子

=S*P*DExistingcontrols:IPCofLODanddegradationproductafterdryingprocessDryingProcessProcessPotentialFailureModePotentialCauseSPDRPN1.Setupcontaminationdisheveledgownofoperator358120insufficientcleaningofequipment7281122.Startdryingcontaminationdamageofinlet-airfilter736126degradationofproductdamageofthermometer733633.Maintaintemperaturelongdryingtimeunstablesupply-airvolume24540highLODmalfunctionoftimer2228lowLODhighdue-point33327non-uniformityofLODuneventemperaturedistribution35345I.2:FailureModeEffectsAnalysis(FMEA)TakayoshiMatsumura,EisaiCoEXAMPLERPN:RiskPriorityNumber=S*P*D现有的控制:LOD的IPC和

烘干过程后的降解产品干燥过程/工艺工艺潜在失效模式潜在原因SPDRPN1.进料污染操作者不洁净的服装358120设备清洗不充分7281122.开始干燥污染进口过滤器损坏736126产品降解温度计损坏733633.保持温度长的烘干时间不稳定的供应空气体积24540高的干燥失重计时器损坏2228低的干燥失重高露点33327不均匀的干燥失重不均匀的温度分布35345I.2:失效模式效应分析

(FMEA)TakayoshiMatsumura,EisaiCoEXAMPLERPN:风险优先因子=S*P*DTakeactionwhenRPNisover100Takeactionwhenseverityisover5Remainingcriticalparametersaftertakingaction;furthercontrolsrequiredDryingProcessProcessPotentialCauseRPNRecommendedActionSPDRPN1.Setupdisheveledgownofoperator120uselongglovesandgoggles32848insufficientcleaningofequipment112changecleaningprocedure724562.Startdryingdamageofinlet-airfilter126changemaintenanceperiod72684damageofthermometer63changecalibrationperiod723423.Maintaintemperatureunstablesupply-airvolume40―24540malfunctionoftimer8―2228highdew-point27―33327uneventemperaturedistribution45―35345I.2:FailureModeEffectsAnalysis(FMEA)BasedonTakayoshiMatsumura,EsaiCo.EXAMPLERPN:RiskPriorityNumber=S*P*D当RPN大于40采取措施当严重性超过5时采取措施采取措施后保留关键参数;需要进一步控制干燥过程/工艺工艺潜在原因RPN建议措施SPDRPN1.进料操作者不洁净的服装120使用长手套和眼睛32848设备清洗不充分112变更清洗程序724562.开始干燥进口过滤器损坏126变更维护周期72684温度计损坏63变更检验周期723423.保持温度不稳定的供应空气体积40―24540计时器损坏8―2228高露点27―33327不均匀的温度分布45―35345I.2:失效模式效应分析

(FMEA)BasedonTakayoshiMatsumura,EsaiCo.EXAMPLERPN:风险优先因子=S*P*DI.2:FailureModeEffectsAnalysis(FMEA)Analyseagranulationprocessstep

becauseonlyafewparametersareadjustableandmanyproblemscanoccurbymanualoperationsEXAMPLES.Rönninger,RocheI.2:失效模式效应分析(FMEA)分析制粒工艺步骤因为仅仅很少的参数可以调整，手工操作许多问题都可能发生。EXAMPLES.Rönninger,RocheFailureModeEffectsAnalysis(FMEA)

EXAMPLES.Rönninger,RocheI.2FailureModeEffectsAnalysis(FMEA)EXAMPLES.Rönninger,RocheI.2:FailureModeEffectsAnalysis(FMEA)PrepareariskprofileSeverity/Consequencesi negligible

ii marginaliii criticaliv catastrophicProbabilityA frequent

B moderate

C occasionalD rareE unlikelyF veryunlikelyProbabilityConsequencesRisk

protection

levelEXAMPLES.Rönninger,RochePicture:©ZurichInsuranceLtd,SwitzerlandI.2:失效模式效应分析(FMEA)准备一个风险轮廓严重性/重要性i 可以忽略

ii 边际iii 严重的iv 灾难性的可能性A 频繁的B 中等的

C 偶尔的D 很少E 不太可能F 完全不可能可能性重要性风险保护水平EXAMPLES.Rönninger,RochePicture:©ZurichInsuranceLtd,SwitzerlandI.2:FailureModeEffectsAnalysis(FMEA)Prepareariskprofile:ProbabilityEXAMPLES.Rönninger,RocheI.2:失效模式效应分析(FMEA)准备一个风险轮廓:可能性EXAMPLES.Rönninger,RocheI.2:FailureModeEffectsAnalysis(FMEA)RiskEvaluationPrepareariskprofile:ConsequencesEXAMPLES.Rönninger,

RocheI.2:失效模式效应分析(FMEA)风险评估准备一个风险轮廓:重要性（后果）EXAMPLES.Rönninger,

RocheI.2:FailureModeEffectsAnalysis(FMEA)RiskEvaluationPrepareariskprofile:ConsequencesEXAMPLES.Rönninger,

RocheI.2:失效模式效应分析(FMEA)风险评估准备一个风险轮廓:重要性（后果）EXAMPLES.Rönninger,

Roche风险评估:

风险轮廓

Forhighrisks,whicharenotacceptable,riskreductionmeasureshavetobetakenasahighpriorityI.2:失效模式效应分析(FMEA)EXAMPLES.Rönninger,RocheHighriskLowriskRiskEvaluation:RiskProfile

对于不可接受的高风险，因为一个高的风险因子风险消减措施必须实施I.2:FailureModeEffectsAnalysis(FMEA)EXAMPLES.Rönninger,RocheHighriskLowriskI.2:FailureModeEffectsAnalysis(FMEA)Howtoperform?3.Summary(RiskEvaluation)Theeffectsareratedintermsoftheir

consequencesandthe

causesareassessedintermsoftheirprobabilities

a)qualitativeorb)quantitativeBasedontheseresultsariskprofileiscompleted.Inthisprofiletherisksarecomparedwiththe

riskprotectionlevel,whichdeterminestheacceptedprobabilityfordefinedconsequencesUseasanaidtoprioritiseactions!EXAMPLES.Rönninger,RocheI.2:失效模式效应分析(FMEA)如何实施?3.总结(风险评估)效果在术语后果中评估，原因在术语可能性中评估a)定性或

b)定量在这些结果基础上完成一个风险矩阵在这些矩阵中风险使用风险保护水平来比较。为描述的后果来确定可接受的可能性。将预先的措施当作帮助EXAMPLES.Rönninger,RocheI.2:FailureModeEffectsAnalysis(FMEA)QRMforfacilities,equipmentandutilities

Assessanexistingcompressedairsys