PDA TR54質(zhì)量風(fēng)險管理在制藥和生物技術(shù)生產(chǎn)操作中的應(yīng)用-2012（中英文-校對版）

Thistechnicalreportprovidesdetailedguidanceforimplementationofqualityriskmanagement(QRM)principlesthroughouttheproductlifecycle.ThereportemphasiandintegratingQRMintothedocumentsprovidedetailedexamplesofcharacteristicoperationsandhowQRMprinciplesandtoolscanbeappliedforbiotAPIs,drugproduct(liPDATechnicalReportNoQRMisintegraltoaneffecmanagement)thatcanprovideaproactive(whilealsosupportingareactive)qualityandpatientsafety.QRMfacilitatescontinuperformanceandproductqualitythroughouttheproductlifecycle(1).PerICHQ9,QualityRiskapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicating,andreviewingrisk."(2)Itisimportanttounderstandthatriskassessmentisnotsynonymouseffective，riskmanagementshouldholisticallyencompasstheenQRMisalivingprocessandshouldbemanagedbasedonknowledthroughouttheproductlifecycle.ICHQ9specificallyprovidesguidanceontheprinciplesandtoolsofQRM(2).ImplementationofQRMoffersmanybenefitstoindustryandregulators.Whenrisk-baseddecision-making(byregulatorsandindustry')regardingthequalityofdrugsuccessfullyintegratedintoacompany’sPQSICHQ10,whichdiscussesthepotentialopportProspectivePreventiveQualityRiskManagementProspectivePreventiveQualityRiskManagementMostlyRetrospective/CorrectiveQualityRiskManagementIntegratedQualityRiskManagementNoQualityAiskManagement前瞻性的預(yù)防性的質(zhì)量風(fēng)險管理的/補救的質(zhì)量風(fēng)險管理完整的質(zhì)量風(fēng)險管理無質(zhì)量風(fēng)險管理QRMintermsofrisk-basedapproaches.Effectiunderstandingoftheproductandproceenableacompanytoprioritizeandfocusresourcesappropriately.），sectors.Overthelastfewyears,thepharmaceuticalandbiotechnologyindustrieshavebeguntoimplementtheprinciplesandtoolssafeandefficaciousdrugproductsareconsistentlydeliveredtoev生物技術(shù)工業(yè)已經(jīng)使用ICHQ9的原則和工具確保每位患者能夠使用到安全有效RealizationofQRMisanevolutionaryprocess.Itrequiresaparadigmshiftinmindset，質(zhì)量風(fēng)險管理是不斷完善發(fā)展的。在人們的工作中需要轉(zhuǎn)變觀念和行為。圖1-1Figure1-1Exampleofa?Risksmanagedfromearlyoninthelifecycle?Increasedcompliance?Higherefficiency?Knowledgemanagement?FewersurprisesInformalQualityRiskManagement非正式的質(zhì)量風(fēng)險管理Thetaskforcethatdevelopedthisreportwascomprisedofexperiencedprofessionalsfromriskmanagement，manufacturing,tauthorities.Thebroaddiversityinexperienceandexpertiseinthetaskforceenabledrich,balanceddiscussionsfromindustryandregucontentinthisreportdoesnotrepresenttheQRMpThetaskforcerecognizesthattherearemanyapproachesthatcanbeusimplementationoftheICHQ9guideline.ThisreportisintendedtoalignwithICHandpresentsinformationthQRM..Theobjectiveisnottorepresentorreplaceregulatoryrequireguidance;nordoesitestablishlegallyenforceablerequir工作組認識到有許多種途徑能夠用來貫徹執(zhí)行ICHQ9的指導(dǎo)方針。報告的目的ThistechnicalreportwasdistributedforpublicreviewandcommepublicationtoensureitssuitabilityasavaluableguidTheglossaryoftermsisbasedondefinitionsprovidedincurrentICH,FDandotherregulatoryguidelines,standards,orindustrypublications.Insomeavailableinsuchsources,thebestavailabledefinitiobythetaskforce.RefertoICHQ9forasummaryofthecommonriskmanagementtools.Thefollowingtermsanddefinitionshavebeenusedinthistechnical用，工作組會采納或發(fā)展最合適的定義。適用于ICHQ9的普通風(fēng)險管理工具的AsLowAsReasonablyPracticable(ALTheabilitytoreducerisk.ALARPhaspracticabilityreferstotheabilitytoreduceriskregardlessofcost.Economicpracticabilityreferstotheabilitytoreduceriskwithoutmakingtheproducttoocostlyturnoveroffacilities,systems,andequipmenttotheenduserthaexpectations.(ISPEActiveP設(shè)計要求和系統(tǒng)責(zé)任人的預(yù)期（ISPE原料藥指南第二Recurringactivitytoincreasetheabilitytofulfillrequi提高滿足需求的能力的反復(fù)性活動(ICHQ10,ISO9Aplannedsetofcontrols,derivedfromcurrthatensuresprocessperformanceandproductquality.Thecomponents,facilityandequipmentoperatingconditions,in-processcontrolproductspecifications,andthcontrol.(ICHQ10)源自現(xiàn)行產(chǎn)品和工藝理解的一組規(guī)劃過的控成品質(zhì)量標準，和監(jiān)控與控制的關(guān)聯(lián)方法與頻次的相關(guān)參數(shù)與屬性(ICHQ10)。Actiontoeliminatethecauseofadetectednon-conformityorotherundesirableNOTE:Correctiveactionistaketakentopreventoccurrence.(ISO9000:20注意：糾正措施是用來預(yù)防重復(fù)發(fā)生而不是預(yù)防措施用來預(yù)防發(fā)生(ISOAclassificationofanitem(e.g.,procsignificancegiventotheimpactmonitoredtoensureproductCriticalProcessParameAprocessparameterwhosevariabilityhasanimpactonacriticalquathereforeshouldbemonitoredorcontrolledtoensuretheprocessproducesthedesiredCriticalQualityAttrAphysical,chemical,biological,ormicrobioCurrentGoodManufacturingPractiPracticesandsystemsthatarerequiredtobefollowedforpharmaceutimanufacturingtoensurethattheprodriskmanagementdecisions.(ICHTheabilitytodiscoverordeterminetheexisAtoolorprocesswhichprovidesthemeanstoachieveanobjectrepresentationofconsequencesresultingfromaninitiatingevent.FailureModeandEffectsApotentialfailuremodes,theireffectsonsystem,productandprocessperfthepossiblecausesoffai1ureinordertopreventdefectsfromoccurring.Adeductivetechniqueusedtoanalyzethecausvisuallymodelshowlogicalrelationshipsbetweenfailures,humanerrors,andexternalDamagetohealth,includingthedamagethatcanoccurfromlossofproductqualityorThepotentialsourceofharm.(ISO/IECGuide51,ICHQ9)傷害的潛在來源(ISO/IEC指南5HazardAnalysisandCriticalControlPoints(Asystematic,proactive,andpreventivetoolforassuringproductquality,reliabilHazardandOperabilityAnalysisAstructured,systemarepresentriskstopersonnelorequipment,orpreventefficientopeIntendedUse/Intendeinstructionsandinformationprovidedbythemanufacturelatedtoproducts,manufacturingprocessesandcomponents.(ICHAllphasesinthelifeofaproduuntiltheproduct'sdiscontinuation(ICHQ8).Probabi1itythataneventpotentiallyleadingtoharmwilloccPreliminaryHazardAnalysiAtoolofanalysisbasedonapplyingpriorexperienceorknowlharm,aswellastoestimatetheirActiontoeliminatethecauseofapotentialnon-confopotentialsituation.NOTE:Preventiveactitakentopreventrecurrence.(ISO9000:2Confirmingthatthemanufacturingprocessasdesig確認所設(shè)計的商業(yè)生產(chǎn)工藝在商業(yè)化生產(chǎn)階段是能夠再現(xiàn)的(FDA工藝驗證指Collectionandevaluationofdata,production,whichestablishesconsistentlydeliveringqualityproducts.Allphasesinthelifeofaproduuntiltheproduct'sdiscontinuation.(ICHQ8[R2])installed,workcorrectlyandactuallyleadtotheexpectedresults.Quofvalidation,buttheindividua1qualificationstepsalonedonoThedegreetowhichasetofinherentfulfillsrequirementstermincludessuchattQualityRiskManagemAsystematicprocessfortheassessment,cotothequalityofthedrug(medicinal)productacrosstheproductlifecycle.(ICHQ9)Atargetproductprofileisaprospectiveanddynamicsummaryofthequalitycharacteristicsofadrugproductthatideallywillbeachievedtargetproductprofileformsthebasisofdesignforthedevelopmentoftheproduct.Riskremainingafterriskc在采取風(fēng)險控制措施后殘留的風(fēng)險（來自ISOThecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm.(ISO/ECGuide51)傷害發(fā)生的概率和嚴重性的組合（ISO/Theestimationoftheriskassociatedwiththeidentifiedhazards.(ICHQ9)Asystematicprocessoforganizinginformationtosupportariskdecisiontobemwithinariskmanagementprocess.ItconsistsoftheidentificationofhazardsandtanalysisandevaluationofrisksassociatedwithexpThesharingofinformationaboutrActionsimplementingriskmanagementdecisions.(ISOGuide73)Adeterminationofacceptanceorrejectionofrisk.qualitativescaletodeterminethesignificanceoftherisk.(ICHQ9)Thesystematicuseofinformationtoidentifypotentireferringtotheriskquestionorproblemdescription.(ICHQ9)Thesystematicapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicatingandreviewingrisk.(ICHQ9)ReportthatsummarizestheoutcomesoftheQRMprocess.ActionstakentolessentheprobabilityofoccurrenceofharmandtheseverityofthatReviewormonitoringofoutput/resultsoftheriskmanagementprocessconsidering(ifappropriate)newknowledgeandexperienceabouttherisk.(ICHQ9)Ameasureofthepossibleconsequencesofahazard.(ICHQ9)itselftobeaffectedbyarisk.Decisionmakersmightpurposesofthisguideline,theprimarystakeholdersarethepatient,healthcareprofessional,regulatoryauAstatisticaltermreferringtothedirectionorrateofchangeofavariable(s).(ICHQ9)3.0GeneralPrinciplesOnQualityRiskManagementApplication質(zhì)量風(fēng)AcombinedapplicationofICHQ8[enhancedknowledgeofproductperformanceoverarangeofmaterialattributes,manufacturingprocessoptions,andprocessparameterstofurthersuppandrisk-basedmanagementoftheproductlifecycle.），OneofthecharacteristicsofamaturePQSistheeffectiveintegrationrelevantprocessesthroughouttheproductandprocesslifecycles.Ateachphaseinthelifecycle,QRMshouldbeappliedatalevelthatiscommensuratewavailableduringthatphase,andcomplexiproductdesignandprogresstoprocessdesignastheproductadvancestoclinicommercialproduction.Riskassessmentsshouldberevilifecycle(Figure3.1-available.Additionally,QRMcanbeusefulinidentifyingaforotherproductstofacilitatecontinualimprovement.到整個生命周期（圖表3.1-1）中。除此之外，質(zhì)量Figure3.1-1ProductLifecycle3.1.1QualityRiskManagementApplicationDuringPharmaceuticalDevelopment藥productanditsmanufacturingprocesstoconsistentlyperformanceandmeettheneedsofpatients,healthcareprofessionals,regulatoryauthorities,andinternalknowledgeandunderstandingoftheproduct.applicationofQRMcanfsystematicunderstandingofproductsandprocessesbTheappropriateuseofQRMprinciplescanservethefollowingobjectives:?Designtheproductandprocesstoreducerisktoproductqualityandt?Prioritizethepharmaceuticalproductknowledge.Attributes(CQA)(perICHQ8[R2]).ExamplesofhowtoapplyQRMprinciplesduringthedevelopmentphaseinclude:?Developingaprocessthatroutinelymeetscriticalqualityattr?Identifyingcriticalprocessparameters(CPP)andmateri?SupportingtheselectionandsubsequentqualificationofsupplierRiskmanagementtoolssuchasRiskRankingandFilterinanalyzedusingaqualitative/semi-quantitativeriskmanagPreliminaryHazardAnalysis(PHA).FailureModeandEffectsAnalysis(alsobeuseful,particular1yduringthelaterstagesofdevelopment.PerICHQI0,thegoaldevelopmentandmanufacturingorbefollowingobjectives:?AssessandmanageriskstoprocessandproductqualityasaresmanufacturingscaleTheoutcomesoftheQRMprocesscanbeusedtopreventiveactionstoappropriatelymanageidentifmanagementofprocesscontrolsduringthetechnologytransferprocess.QRMcanbeusedtodevelopariskbasedvalidationmasterplantodqualificationandvalidationactivities.DuririskmanagementtoolssuchasanFMEAorHazardandO(HAZOP)are0ftenused.3.1.3QualityRiskManagementApplicationDurinrealizationwithsuitableprocessperformance，establishandmaintainastateofcontrol,faciliitatecontinualimprovementan?Establishrobustconimprovement，toensureconsistentprocessperformaDuringcommercialmanufacturing,QRMcanbeausefulprocessdecision-makingas-sociatedwithchangecontrintheselectionandmanagementofsuppliersandvendors,andmanagingrisksrelatedtointernalandcontractmanufacturingoperations,toproductavailabilitythroughouttheproductldistribution,transportation,chainofgeopoliticalissues,complianceSection5.4,QRMApplicationinMaterialsManagemen3.1.4QualityRiskManagementApplicatPerICHQlO,thegoalofProductDiscontinuationactivitiesisto"managetheterminalstageoftheproductlifecycleeffecdiscontinuationactivitiescanservethefollowingobjec?Ensureriskstopatientsaremainsonthemark?Identifyandmanagerisksrelatedtotransitioningpatientstoalternat3.2ProactiveandReactiveApplicationofQualityRiskManagement質(zhì)量風(fēng)險管andmanagementofrisks.Retrospectiveorreactiveapplicatiolngeneral,theearlierrisksareidentified,themoreeffectivetheirmanagForexample,ifariskisidentifiedduringthedevelopmentofdesignspecificationsforasystem,thesystemcanbedesignedtoreduceoreveneliminatetheristhesameriskisnotidentifieredesignofthesystemcanbechallengingandlikelybemorecostlythanifthesystemhadinitiallybeendesignedtomanagetheriskappropriately.Thiswouladditiontothecostofmanagingpotentialharmtoproductquaduetothatriskduringcommercialoperation.prospectivelyandriskassessmentsmayneedtoberetrospectively.Exampleswouldbenmanufacturingprocess.lntheseinstances,deductiveriskmanagementtoolslikeFaultdeterminethecontributiqualitywillconsequentlyneedtobemanagedretrospe然而,某些情況下,并非所有的風(fēng)險都可以如預(yù)期般識別，這樣就需要執(zhí)行回顧性的潛在風(fēng)險。在這些實例中,演繹的風(fēng)險管理工具如失效和事件樹分析(FTA/ETA),FMEA,或魚骨圖分析可以用來確定事件的相關(guān)因素,接下來任何影響產(chǎn)品existingoperationsandappropriatdeviatefromregulations,justifybadpractices,defendpracticesthatneedtobecorrected,orasasuManufacturingPractices(cGMPs)isam質(zhì)量風(fēng)險管理不是獨立于質(zhì)量系統(tǒng)的元素，而應(yīng)該整合到現(xiàn)存的規(guī)程中，作為3.3FormalityoftheQualityRiskManagementProcess質(zhì)量風(fēng)險管理程序的正式流程OneoftheprinciplesofQRMasperlCHQ9isthatthelevelofeffort,formalityanddocumentationoftheQRMprocessshouldbecommensuratewiththelevelofrisk.ltisneitheralwaysapproprprocess(2).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsorfframeworkforpreviouslyundocinformalriskmanagementprisk-basedapproachcanrangefromadocumeassessmentmethodology(SeeFigure3.3-1).Figure3.3-1RigorandFormalityofQRMApproaches如：過程危險分析逐漸嚴謹&正式化decisiontree)Thedegreeofriskmanagementrigorandformalityrequiredisinfluencedbyacombinationofmanyfactors,including(butnotlimitedto):?Criticality(e.g.,impactonpatientsafetyorproductquality)ofthe?Complexityoftheissue,proce?Availabilityofrelevanthistoricaldataandrelated?LevelofavailableprocessknowledgeandexperienceTheriskassessmentformalityspectrumcanrangeintherigorandformalityoffacilitation,subjectmatterexperts(SMshowninFigure3.3-Figure3.3-2RigorandFoMaybeexistingteam,group,組成專門的相關(guān)項目專家組Recongnizedmethodoptio隨意選取或定制被承認的方法單獨的報告，或者跟其他受package)可能整合到現(xiàn)存的受控GMP文件中（不包括：變更控制3.4EstablishingaQualityRiskManagementPolicyQRMpolicyestablishesthecompany'sQRMphilosophyandguidestheincorpofQRMrequirementsandprinciplesintotheQualitySystemrelatedto:ICHQ10闡述了質(zhì)量風(fēng)險管理作為一種有用的工具合并到質(zhì)量系統(tǒng)中的重?Applicabilityofriskmanagement?Accountabilityandresponsibilityformanaginganddeterminingris?Riskreviewsand3.5ManagementCommitmentessential.TopmanagementendorsestheincorporationofQRMintotheorganizaimplementationofQRMprinciplesandactivities,andprovreceivedtheapplicabletraining.useofQRMisencouraged,itsbenefitsunderstood,itstoolsappliedappropriately,andvariousfunctionsanddepartmentsoftheirorganization.TheultimategoalistoincorporateQRMintoeverydaypractices,integratedintothesafety,heaTofacilitateachievingthisgoaltheo?Havetheresponsibilitytocreateandmaintain?Canperformri?Canreviewandapprovetheassessreductionandriskacceptancedecision?Areresponsibleforcommunicatingtheoutputoftheriskassessments.3.6UnderstandingtheOrganizationandHowitContextualizesRiskTodevelopasharedunderstandingoftheapplicationofQRMstakeholders,organizationsneedtodeandregulatoryexpectationsAnevaluationofthecurrentunderstandingofQRMintheorganwrittenpoliciesandprocedures,practexistingorrelatedQRMactivitiesshouldbereviewedforevidenceofQRMintothecompany'sQualitySydeviationmanagement，productdevelopment將當前組織對質(zhì)量風(fēng)險管理的理解進行評估3.7IntegrationintoOrganizationalProcIntegrationofQRMintoanorganizprocess.PracticalrecommendationsrelatedtoimplementationofQRMmaythefollowing:?Performingagapanalysisoncurrentguidelines,identifywheresystemsarecurrentlyemployingQRMmeasurementofthelevelofrisk?對當前指導(dǎo)原則、程序和操作規(guī)程執(zhí)行差距分析，可以識別什么系統(tǒng)當前需要?CreatingQRMpoliciesandproceduresbaseduponthegapanalyincludingQRMmethodsandsupportingstatisti?Pilotingthepoliciesandacceptabilityprocess,andreportingmechanismsfittheneedsoftheorganization.?Deployingthepoliciesmulti-leveltrainingstrateg?High-levelawareness/QRMoverviewtrainingforgeneralemployincludehands-ontrainingwithreallifeappl?集中對方針，規(guī)程和風(fēng)險管理的基本工具進行培訓(xùn)。其中包括對真實的案例進?Creationofinternalauditprodecisionscomplywiththeestablishedstandardsand?建立識別質(zhì)量風(fēng)險管理活動的內(nèi)部審計規(guī)程，得到符合已建立標準和規(guī)程的決Attitude沒有正式的規(guī)程FearOfBlame沒有意識到不AdHocUseof臨時使用獨立Belief被動的，處理&理解并應(yīng)用階段標記盒子的方法依賴法規(guī)符合性納入和整合階段風(fēng)險管理納入RobustRisk穩(wěn)定的風(fēng)險管常規(guī)審核并改善創(chuàng)新的，自信和合適的風(fēng)險3.8EstablishingCommunicationandReportingMechanismsTofullyintegrateQRMintothcommunicationandrepimplementationofQRMwhentheyareabletoqumanywaystoaccomplishthis,includingtheuseomemoranda.Companiesshouldconsidertheadditionofriskmanagementasanagendatopicfortheirperiodicmanagementmeetingsatallleve的信息流進行識別和溝通新風(fēng)險的發(fā)展變化。有很多方法可以做到這一點,包括Feedbackloopsaretwo-wayinthatasnewrisksareidentifiedtheyarecinternallyandthatproductbaseduponthatinformation.externalcommunicationswiththepublicandregulataoryagencies,ifrequired.反饋循環(huán)都是雙向的,隨著新的風(fēng)險得到識別會引起內(nèi)部溝通,而產(chǎn)品和工藝會根Thereshouldbeamethodtocaptureproductandprocessriskthrochoosestocapturetheoverallresidualriskshouldbculture,documentationpracticesandthepotentialimpactofproductand3.9RolesandResponsibilitieFormalQRMactivitiesareusuallyundertakenbymulti-disciplinaryteamsandshouldincludeSMEsrepresentingrelevantfunctions(e.g.qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketinstatistics,clinicalsafety).Asinglepersonm?Facilitatorswhoareknowledgeableabout,andwillfacilitatetheQ?Asmuchaspossible,facilitatorsshouldbeindependentfromtheprocessbeingriskassessedinordertomaintainobjectivityinfacilitation(expertsshouldnotfacilitateifpossibleinordertomaintainobjectiviKnowledgeofcognitiveandotherfactors,suchashumanheuristics,mayaffectdecision-makingduringQRMactivities(suchasbrainstormingandprobabilityofoccurrenceestimation);thisunderstandingandabilitytomanageitappropriatelycanbeparticularlyusefulforfacilitators.?當進行工藝風(fēng)險評估時，促進者應(yīng)盡可能保持獨立，以在促進過程中保持客觀?QRMLeadwhomaybeindependentfromthefa?Leadingthedevelopmentandcompmanagementplansandrepo?EnsuringthattheoutcomesoftheQRMprocessareapprovedappropriatedecisionmakersandimp?SubjectmatterexpsupportQRMactivities，includingriskassessment,determicontrolmeasuresandtheirimplemendecisions(2).Decisionmakersshouldbeaccountab?EnsuringthataQRMprocessisdefined,includingtheimplementationofidentifiedriskcontrolmeasures.?Reviewingandapprovingtheomakingriskcontrol(riskreductionandriskacceptance)decision?回顧和批準風(fēng)險管理活動的結(jié)果，包括制定風(fēng)險控制（降低風(fēng)險和接受風(fēng)險）見Heuristicsarecognitivebehaviorsthatcomeintoplaywinthepresenceofuncsignificantbiasanderrorsinjudgment.Humanheuristicsgreatlyinfluenceaperceptionofrisk(4)andinevitablytheiropinionofthemagnitudeofthecontributingprobabilitiesandseverities.Agreatdealofresearchhasbeenperexperimentalpsychologistsintohowrisksarepercfactors(5)seemtocontroutputofriskanalysisexercises:偏見和錯誤的來源。人類啟發(fā)極大地影響一個人的風(fēng)險感知（4）和不可避免地知做了大量的研究。在這方面，有三個主要因素（5）似乎有助于這種啟發(fā)式的1.Degreeof"dreadfulnes2.Degreetowhichtheriskwasunders3.Numberofpeopleexposedtotheriskinquestion.perceived.Therearevarioustypesofheuristics,butthreeofthemare:Theheuristicofavailabilityrelatestothefactthatpeopletendtojudgethelikelihoodofaneventintermsofhoweasilytheycanrecall(orimagine)examplesofthatevent.Aperson'sjudgmentconcerninganevent(intermsofitsprobabilityofoccurrenceanditsseverity)maytherefsimilarscenarios(6,7).Thismayleadtoasystematicbiasandothererrorsinjudgment.Researchhasshownthatpeopletendtounderestimatethefrequencyofverycommonhazardsandoverestimatethefrequencyofveryrarehazards(68).Theheuristicofrepresentativenessisrelatedtoaperson'sprobabilityjudgmentbeingthelarge."Inthisinstanceonecanpaymoreaignoringorpayinginsufficientattentionthatisrelevanttotheproblem(8).啟發(fā)式的典型代表與被影響的人的概率判斷有關(guān)，如他們“預(yù)計某種小概率行為Theheuristicofanchoringandadjustmentcomesintoplaywhenpeople'sjudgmcanbeheavilyinfluencedbythefirstapproximationofthevalueorquantitythatthey"anchor"(6,7).隨后的價值偏向于“錨”Biasandvariabilityinriskperceptionareinherentlyhumantraitsandcanbebrcategorizedintothreerecognizableanthropomorphicbehaviors.Eachoftheseperceptionsshouldberecognized,andappropriatebias-mitigationstrategiesandprocessesestablishedwithintheQRMsystem.thatcouldbeconsideredvolu(i.e.withoutourowndewhicharecalculatedtobesignificantlylowerthaninvoluntaryrisks(10).Thephenomenonofhumanheuristics(unconsciousrulesofthumb)hasprofoundcapacitytobiasriskmanagementprocesses.Othatpeopletendtoassignlikelihoodintermsofhoweasilytheycanrecall(orimagine)thatorexamplesofthatevent.ofverycommonhazardsmayinfluencehowtheoutputsofQRMexmaybejudgedandacceptedbydecisionmakers,stAnexpert'sperceptionofriskcandiffermarkedlyfrpersonnellessfamiliarwiththeGenerally,laypeopletendtorthem,unfamiliar,orbeyondtheircontrol.SuchfindingsareprobablyimportanttoandstakeholderstowhomrtechnicalnatureofGMPactivitiesingeneral.Thehumancognitiveandbehavioralorigins,whichmaybiasjudgmentinthisrespect,togetherwithdetailedmeansofaddressingQRM,havebeenpreviouslydescribed(11,12).Effectivecommunicationparticularlyimportantbecausestakeholdersformjudgmentsaboutrisksbasedontheirownperceptions,andthoseperceptionsmaydifferincorporatestrategiestoaddressriskperceptionbiases.non-conformancesandtrendscontributegreatlyinreducingsubjethatheuristicsmayexertonQRMactivities.Toaddressofseveralsimple,practicalstrategieQRMexercisesandthatshouldbefeaturedinQBias?培訓(xùn)和教育可使決策者意識到這種偏見，包括案例學(xué)習(xí)和?如部分決策者不熟悉風(fēng)險場景（例如臨床藥學(xué)，銷售學(xué)，個別人類的啟發(fā)?培訓(xùn)和教育可使決策者意識到主要啟發(fā)的出現(xiàn)，包括案例學(xué)習(xí)和演示啟發(fā)如何被掌握的例子。?如部分決策者不熟悉風(fēng)險場景（例如臨床藥學(xué)，銷售學(xué)，個別?只要數(shù)據(jù)被認為是可靠的，支持定量風(fēng)險管理工具提供盡可能多?為旨在最大限度地減少啟發(fā)的不利影響采用預(yù)先定義的規(guī)則的頭腦風(fēng)暴（例如，當風(fēng)腦風(fēng)暴作為風(fēng)險評估的一部分練習(xí)時，團隊的成員不應(yīng)用語言表達他或她的估計得分概率，直到每個參與者有時間思考和記錄自己的估計）專家層級的偏見?培訓(xùn)和教育可讓決策者意識到這種偏見：包括學(xué)習(xí)案例和偏見演示例子。?如部分決策者不熟悉風(fēng)險場景（例如臨床藥學(xué)，銷售學(xué)，個別4.0ImplementationOfTheQualityRiskManagementProcess質(zhì)量風(fēng)險管理的實施PerICHQ9,themainstepsinth?Initiatingaqualityriskmanagementproce?Output/resultoftheQRMprocess(Section4.4)4.1InitiatingaQualityRiskManagementProcess啟動質(zhì)量風(fēng)險QRMshouldincludesystematicprocessesdesignedtimprovesciencebaseddecisionmakingwithrespecttorisk.AllQRMactiwhethertheyareprospectiveorretrospectiveinnature,shouldbeadequatelyplanpriortoinitiatinganyriskassessments.Therigorinplanningshouldbecowiththeimpactofthepotentialrisksonproductqu