ICH-Q9質(zhì)量風(fēng)險(xiǎn)管理

ICH-Q9質(zhì)量風(fēng)險(xiǎn)管理ICH-Q9質(zhì)量風(fēng)險(xiǎn)管理ICH-Q9質(zhì)量風(fēng)險(xiǎn)管理ICH-Q9質(zhì)量風(fēng)險(xiǎn)管理編制僅供參考審核批準(zhǔn)生效日期地址：電話(huà)：傳真:郵編:INTERNATIONALCONFERENCEONHARMONISATIONOFTECHNICALREQUIREMENTSFORREGISTRATIONOFPHARMACEUTICALSFORHUMANUSE人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議ICHHarmonisedTripartiteGuideline人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議三方協(xié)調(diào)后的指南QualityRiskManagement質(zhì)量風(fēng)險(xiǎn)管理CurrentStep4version現(xiàn)行第四步版本dated9November20052005年十一月9日ThisGuidelinehasbeendevelopedbytheappropriateICHExpertWorkingGroupandhasbeensubjecttoconsultationbytheregulatoryparties,inaccordancewiththeICHProcess.AtStep4oftheProcessthefinaldraftisrecommendedforadoptiontotheregulatorybodiesoftheEuropeanUnion,JapanandUSA.本指南由人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議專(zhuān)家工作組根據(jù)人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議程序開(kāi)發(fā)并提交各方的藥政部門(mén)咨詢(xún)。根據(jù)人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議程序第四步，推薦給歐盟、日本和美國(guó)藥的政部門(mén)采用的最終文本。DocumentHistory文件歷史Codification最初編碼History歷史ApprovalbytheSteeringCommitteeunderStep2andreleaseforpublicconsultation.指導(dǎo)委員會(huì)批準(zhǔn)第二步文件并發(fā)放用于公開(kāi)咨詢(xún)Date日期Q922March20052005/3/22ApprovalbytheSteeringCommitteeofPostStep2correction指導(dǎo)委員會(huì)在批準(zhǔn)第二步后的訂正文件15June20052005/6/15CurrentStep4version現(xiàn)行第四步版本ApprovalbytheSteeringCommitteeunderStep4andrecommendationforadoptiontothethreeICHregulatorybodies.指導(dǎo)委員會(huì)批準(zhǔn)第四步文件并推薦ICH三方藥政部門(mén)批準(zhǔn)9November20052005/11/9HavingreachedStep4oftheICHProcessattheICHSteeringCommitteemeetingon9November2005,thisguidelineisrecommendedforadoptiontothethreeregulatorypartiestoICH在2005年11月9日的人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議上，本指南已經(jīng)通過(guò)人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議第四步程序，本指南已經(jīng)推薦給人用藥注冊(cè)技術(shù)要求國(guó)際協(xié)調(diào)會(huì)議三方的藥政部門(mén)采用。TABLEOFCONTENTS目錄1.INTRODUCTION簡(jiǎn)介................................................................................12.SCOPE范圍............................................................................23.PRINCIPLESOFQUALITYRISKMANAGEMENT質(zhì)量風(fēng)險(xiǎn)管理的原則............24.GENERALQUALITYRISKMANAGEMENTPROCESS常規(guī)質(zhì)量風(fēng)險(xiǎn)管理程序.....2Responsibilities職責(zé).....................................................................................4InitiatingaQualityRiskManagementProcess啟動(dòng)質(zhì)量風(fēng)險(xiǎn)管理過(guò)程.......4RiskAssessment風(fēng)險(xiǎn)評(píng)估...................................................................4RiskControl風(fēng)險(xiǎn)控制....................................................................5RiskCommunication風(fēng)險(xiǎn)溝通.....................................................................6RiskReview風(fēng)險(xiǎn)評(píng)審..................................................................65.RISKMANAGEMENTMETHODOLOGY風(fēng)險(xiǎn)管理方法學(xué)...................................76.INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS質(zhì)量風(fēng)險(xiǎn)管理與業(yè)界及藥政運(yùn)行整合..................................................87.DEFINITIONS定義.........................................................................98.REFERENCES參考文獻(xiàn).................................................................11Annex附錄I:RiskManagementMethodsandTools風(fēng)險(xiǎn)管理方法與工具...12BasicRiskManagementFacilitationMethods基本風(fēng)險(xiǎn)管理簡(jiǎn)易方法.......12FailureModeEffectsAnalysis故障模式效應(yīng)分析(FMEA)..........................12FailureMode,EffectsandCriticalityAnalysis故障模式影響與嚴(yán)重性分析(FMECA)....................................................13FaultTreeAnalysis故障樹(shù)分析(FTA)........................................13HazardAnalysisandCriticalControlPoints危害分析關(guān)鍵控制點(diǎn)(HACCP)....................................................................14HazardOperabilityAnalysis危害及可操作性分析(HAZOP)..................14PreliminaryHazardAnalysis預(yù)先危險(xiǎn)分析(PHA)...................................15RiskRankingandFiltering風(fēng)險(xiǎn)排序及過(guò)濾........................15SupportingStatisticalTools輔助性統(tǒng)計(jì)工具............................................16Annex附錄II:PotentialApplicationsforQualityRiskManagement實(shí)施質(zhì)量風(fēng)險(xiǎn)管理的潛在機(jī)會(huì).......................................16QualityRiskManagementasPartofIntegratedQualityManagement整合質(zhì)量管理部分的質(zhì)量風(fēng)險(xiǎn)管理....................16QualityRiskManagementasPartofRegulatoryOperations藥政操作部分的質(zhì)量風(fēng)險(xiǎn)管理...........................................18QualityRiskManagementasPartofdevelopment開(kāi)發(fā)部分的質(zhì)量風(fēng)險(xiǎn)管理..................................................................19QualityRiskManagementforFacilities,EquipmentandUtilities廠(chǎng)房，設(shè)備和公用設(shè)施的質(zhì)量風(fēng)險(xiǎn)管理..................19QualityRiskManagementasPartofMaterialsManagement物料管理部分的質(zhì)量風(fēng)險(xiǎn)管理..........................................21QualityRiskManagementasPartofProduction生產(chǎn)部分的質(zhì)量風(fēng)險(xiǎn)管理......................................................................21QualityRiskManagementasPartofLaboratoryControlandStabilityStudies實(shí)驗(yàn)室控制和穩(wěn)定性研究部分的質(zhì)量QualityRiskManagement質(zhì)量風(fēng)險(xiǎn)管理風(fēng)險(xiǎn)管理....................................22QualityRiskManagementasPartofPackagingandLabelling包裝和標(biāo)簽部分的質(zhì)量風(fēng)險(xiǎn)管理...................................221.INTRODUCTION導(dǎo)言Riskmanagementprinciplesareeffectivelyutilizedinmanyareasofbusinessandgovernmentincludingfinance,insurance,occupationalsafety,publichealth,pharmacovigilance,andbyagenciesregulatingtheseindustries.Althoughtherearesomeexamplesoftheuseofqualityriskmanagementinthepharmaceuticalindustrytoday,theyarelimitedanddonotrepresentthefullcontributionsthatriskmanagementhastooffer.Inaddition,theimportanceofqualitysystemshasbeenrecognizedinthepharmaceuticalindustryanditisbecomingevidentthatqualityriskmanagementisavaluablecomponentofaneffectivequalitysystem.風(fēng)險(xiǎn)管理原則被有效地應(yīng)用于許多商業(yè)和政府的領(lǐng)域，包括金融、保險(xiǎn)、職業(yè)安全、公共健康、藥物預(yù)警，以及這些行業(yè)的主管部門(mén)。如今，盡管在制藥行業(yè)也有一些運(yùn)用質(zhì)量風(fēng)險(xiǎn)管理的例子，但其非常有限，且沒(méi)有體現(xiàn)出風(fēng)險(xiǎn)管理能提供的全部貢獻(xiàn)。另外，制藥行業(yè)已經(jīng)認(rèn)識(shí)到質(zhì)量體系的重要性，而且，質(zhì)量風(fēng)險(xiǎn)管理對(duì)一個(gè)有效的質(zhì)量體系來(lái)說(shuō)，是一個(gè)有價(jià)值的組成部分這一點(diǎn)越來(lái)越明顯。Itiscommonlyunderstoodthatriskisdefinedasthecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm.However,achievingasharedunderstandingoftheapplicationofriskmanagementamongdiversestakeholdersisdifficultbecauseeachstakeholdermightperceivedifferentpotentialharms,placeadifferentprobabilityoneachharmoccurringandattributedifferentseveritiestoeachharm.Inrelationtopharmaceuticals,althoughthereareavarietyofstakeholders,includingpatientsandmedicalpractitionersaswellasgovernmentandindustry,theprotectionofthepatientbymanagingtherisktoqualityshouldbeconsideredofprimeimportance.通常將風(fēng)險(xiǎn)理解為，風(fēng)險(xiǎn)是由傷害發(fā)生的概率及傷害嚴(yán)重性結(jié)合而成。然而，在不同的風(fēng)險(xiǎn)涉眾中達(dá)成對(duì)風(fēng)險(xiǎn)管理應(yīng)用共識(shí)仍是困難的，因?yàn)槊總€(gè)風(fēng)險(xiǎn)涉眾可能感覺(jué)到不同的潛在傷害，對(duì)每個(gè)所發(fā)生的傷害設(shè)置不同的概率以及傷害不同的嚴(yán)重性屬性。對(duì)于藥品來(lái)說(shuō)，盡管有多種的風(fēng)險(xiǎn)涉眾，包括患者、醫(yī)療從業(yè)人員，以及政府和業(yè)界，運(yùn)用質(zhì)量風(fēng)險(xiǎn)管理都應(yīng)該以保護(hù)病人為基本出發(fā)點(diǎn)。Themanufacturinganduseofadrug(medicinal)product,includingitscomponents,necessarilyentailsomedegreeofrisk.Therisktoitsqualityisjustonecomponentoftheoverallrisk.Itisimportanttounderstandthatproductqualityshouldbemaintainedthroughouttheproductlifecyclesuchthattheattributesthatareimportanttothequalityofthedrug(medicinal)productremainconsistentwiththoseusedintheclinicalstudies.Aneffectivequalityriskmanagementapproachcanfurtherensurethehighqualityofthedrug(medicinal)producttothepatientbyprovidingaproactivemeanstoidentifyandcontrolpotentialqualityissuesduringdevelopmentandmanufacturing.Additionally,useofqualityriskmanagementcanimprovethedecisionmakingifaqualityproblemarises.Effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany’sabilitytodealwithpotentialrisksandcanbeneficiallyaffecttheextentandlevelofdirectregulatoryoversight.藥物(醫(yī)療)產(chǎn)品制造和使用，包括它的組份，必然要承擔(dān)一定程度的風(fēng)險(xiǎn)。其質(zhì)量風(fēng)險(xiǎn)僅是全部風(fēng)險(xiǎn)中的一個(gè)。重要的是要了解到，產(chǎn)品質(zhì)量應(yīng)當(dāng)貫穿產(chǎn)品的生命周期，這個(gè)屬性對(duì)于藥物(醫(yī)療)產(chǎn)品保持與臨床研究時(shí)一致是非常重要的。通過(guò)前瞻意義上辨識(shí)與控制在研發(fā)與制造中的潛在質(zhì)量問(wèn)題，一個(gè)有效的質(zhì)量風(fēng)險(xiǎn)管理方法能進(jìn)一步給患者提供高質(zhì)量藥物(醫(yī)療)產(chǎn)品質(zhì)量的保證。另外，如果出現(xiàn)質(zhì)量問(wèn)題，則采用質(zhì)量風(fēng)險(xiǎn)管理可以改善決策。有效的質(zhì)量風(fēng)險(xiǎn)管理可以促使做出更好，更基于可靠信息的決策，可以為業(yè)界藥政部門(mén)提供更強(qiáng)大應(yīng)對(duì)潛在風(fēng)險(xiǎn)的能力的保證，并且會(huì)對(duì)藥政監(jiān)督的水平和范圍直接產(chǎn)生有利影響。Thepurposeofthisdocumentistoofferasystematicapproachtoqualityriskmanagement.Itservesasafoundationorresourcedocumentthatisindependentof,yetsupports,otherICHQualitydocumentsandcomplementsexistingqualitypractices,requirements,standards,andguidelineswithinthepharmaceuticalindustryandregulatoryenvironment.Itspecificallyprovidesguidanceontheprinciplesandsomeofthetoolsofqualityriskmanagementthatcanenablemoreeffectiveandconsistentriskbaseddecisions,bothbyregulatorsandindustry,regardingthequalityofdrugsubstancesanddrug(medicinal)productsacrosstheproductlifecycle.Itisnotintendedtocreateanynewexpectationsbeyondthecurrentregulatoryrequirements.本文件的目的是提供一個(gè)質(zhì)量風(fēng)險(xiǎn)管理的綜合方法。其作為一個(gè)基礎(chǔ)的或資源性的文件，其獨(dú)立并支撐其它的ICH質(zhì)量文件，并對(duì)現(xiàn)有的質(zhì)量實(shí)踐、要求、標(biāo)準(zhǔn)以及制藥行業(yè)指南與藥政環(huán)境進(jìn)行補(bǔ)充。其將明確提供質(zhì)量風(fēng)險(xiǎn)管理的原理，以及一些工具，其可以確保在藥政部門(mén)和業(yè)界在考慮到貫穿在整個(gè)產(chǎn)品生命周期的原料藥和藥物(醫(yī)療)產(chǎn)品質(zhì)量時(shí)，做出更有效與更一致的基于風(fēng)險(xiǎn)的決策。其并未試圖建立任何超越當(dāng)前管理要求的新的要求。Itisneitheralwaysappropriatenoralwaysnecessarytouseaformalriskmanagementprocess(usingrecognizedtoolsand/orinternalprocedures.,standardoperatingprocedures).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsand/orinternalprocedures)canalsobeconsideredacceptable.Appropriateuseofqualityriskmanagementcanfacilitatebutdoesnotobviateindustry’sobligationtocomplywithregulatoryrequirementsanddoesnotreplaceappropriatecommunicationsbetweenindustryandregulators.使用一個(gè)正式的風(fēng)險(xiǎn)管理過(guò)程(使用公認(rèn)的工具，和/或內(nèi)部程序，例如標(biāo)準(zhǔn)操作程序)既不總是恰當(dāng)?shù)模膊豢偸潜仨毜?。采用非正式的風(fēng)險(xiǎn)管理過(guò)程(使用經(jīng)驗(yàn)的工具，和/或內(nèi)部程序)也是可以考慮接受。恰當(dāng)運(yùn)用質(zhì)量風(fēng)險(xiǎn)管理可以促進(jìn)，但并不能免除業(yè)界遵守藥政要求的責(zé)任，也不能取代業(yè)界和藥政部門(mén)之間適當(dāng)?shù)臏贤ā?.SCOPE范圍Thisguidelineprovidesprinciplesandexamplesoftoolsforqualityriskmanagementthatcanbeappliedtodifferentaspectsofpharmaceuticalquality.Theseaspectsincludedevelopment,manufacturing,distribution,andtheinspectionandsubmission/reviewprocessesthroughoutthelifecycleofdrugsubstances,drug(medicinal)products,biologicalandbiotechnologicalproducts(includingtheuseofrawmaterials,solvents,excipients,packagingandlabelingmaterialsindrug(medicinal)products,biologicalandbiotechnologicalproducts).本指南給出了質(zhì)量風(fēng)險(xiǎn)管理的原理以及一些工具的例子，其可以應(yīng)用于藥品質(zhì)量的不同方面。這些方面包括開(kāi)發(fā)、制造、分銷(xiāo)以及原料藥、藥物(醫(yī)療)產(chǎn)品、生物和生物技術(shù)產(chǎn)品(包括在藥物(醫(yī)療)產(chǎn)品、生物和生物技術(shù)產(chǎn)品中使用到的原料、溶劑、賦形劑、包裝和標(biāo)簽材料)整個(gè)生命周期的檢查和注冊(cè)/評(píng)審過(guò)程。3.PRINCIPLESOFQUALITYRISKMANAGEMENT質(zhì)量風(fēng)險(xiǎn)管理的原則Twoprimaryprinciplesofqualityriskmanagementare:質(zhì)量風(fēng)險(xiǎn)管理的兩個(gè)基本原則為：?Theevaluationoftherisktoqualityshouldbebasedonscientificknowledgeandultimatelylinktotheprotectionofthepatient;and應(yīng)該基于科學(xué)知識(shí)和最終與對(duì)患者的保護(hù)相關(guān)聯(lián)對(duì)質(zhì)量風(fēng)險(xiǎn)進(jìn)行評(píng)價(jià)；以及?Thelevelofeffort,formalityanddocumentationofthequalityriskmanagementprocessshouldbecommensuratewiththelevelofrisk.質(zhì)量風(fēng)險(xiǎn)管理過(guò)程的力度、正式程度和文件化程度都應(yīng)該與風(fēng)險(xiǎn)水平相適應(yīng)。4.GENERALQUALITYRISKMANAGEMENTPROCESS常規(guī)質(zhì)量風(fēng)險(xiǎn)管理程序Qualityriskmanagementisasystematicprocessfortheassessment,control,communicationandreviewofriskstothequalityofthedrug(medicinal)productacrosstheproductlifecycle.Amodelforqualityriskmanagementisoutlinedinthediagram(Figure1).Othermodelscouldbeused.Theemphasisoneachcomponentoftheframeworkmightdifferfromcasetocasebutarobustprocesswillincorporateconsiderationofalltheelementsatalevelofdetailthatiscommensuratewiththespecificrisk.質(zhì)量風(fēng)險(xiǎn)管理指的是對(duì)貫穿于藥物(醫(yī)療)產(chǎn)品生產(chǎn)周期中的風(fēng)險(xiǎn)進(jìn)行評(píng)估、控制、溝通及評(píng)審的系統(tǒng)過(guò)程。圖中概括了質(zhì)量風(fēng)險(xiǎn)管理模式(圖1)。也可以使用其他模式。所強(qiáng)調(diào)的構(gòu)架中每個(gè)組成，可依不同情況而有所不同的，但一個(gè)完善的過(guò)程會(huì)更加詳細(xì)地整合考慮到所有因素，其與具體的風(fēng)險(xiǎn)有相同的水平。Figure1:Overviewofatypicalqualityriskmanagementprocess圖1：典型的質(zhì)量風(fēng)險(xiǎn)管理過(guò)程概述unacceptableunacceptable不接受RiskReview風(fēng)險(xiǎn)評(píng)審RiskControl風(fēng)險(xiǎn)控制InitiateQualityRiskManagementProcess啟動(dòng)風(fēng)險(xiǎn)管理過(guò)程風(fēng)險(xiǎn)控制RiskReduction風(fēng)險(xiǎn)降低RiskAcceptance接受風(fēng)險(xiǎn)Output/ResultoftheQualityRiskManagementProcess質(zhì)量風(fēng)險(xiǎn)管理程序的輸出/結(jié)果風(fēng)險(xiǎn)控制ReviewEvents事件評(píng)審RiskCommunication風(fēng)險(xiǎn)溝通RiskManagementtools風(fēng)險(xiǎn)管理工具RiskAssessment風(fēng)險(xiǎn)評(píng)估RiskIdentification風(fēng)險(xiǎn)辯識(shí)AnalysisRisk風(fēng)險(xiǎn)分析RiskEvaluationun風(fēng)險(xiǎn)評(píng)價(jià)Decisionnodesarenotshowninthediagramabovebecausedecisionscanoccuratanypointintheprocess.Thesedecisionsmightbetoreturntothepreviousstepandseekfurtherinformation,toadjusttheriskmodelsoreventoterminatetheriskmanagementprocessbaseduponinformationthatsupportssuchadecision.Note:“unacceptable”intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.在上圖中并未標(biāo)明判斷結(jié)點(diǎn)，因?yàn)榕袛嗫沙霈F(xiàn)在這個(gè)過(guò)程中的任何一個(gè)點(diǎn)。這些判斷將會(huì)退回到前一步，并尋求進(jìn)一步的信息以調(diào)整風(fēng)險(xiǎn)模型，甚至根據(jù)支持這個(gè)判斷的信息來(lái)終止風(fēng)險(xiǎn)管理過(guò)程。（注：在流程圖中的“不接受”不僅僅是依據(jù)法定、立法或藥政要求，同樣也需要返回風(fēng)險(xiǎn)評(píng)估過(guò)程。）Responsibilities職責(zé)Qualityriskmanagementactivitiesareusually,butnotalways,undertakenbyinterdisciplinaryteams.Whenteamsareformed,theyshouldincludeexpertsfromtheappropriateareas.,qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketing,legal,statisticsandclinical)inadditiontoindividualswhoareknowledgeableaboutthequalityriskmanagementprocess.風(fēng)險(xiǎn)管理活動(dòng)通常，但并不總是，需要多學(xué)科的團(tuán)隊(duì)參與。當(dāng)形成一個(gè)團(tuán)隊(duì)時(shí)，應(yīng)當(dāng)要包括適當(dāng)領(lǐng)域的專(zhuān)家(例如，質(zhì)量部門(mén)、商業(yè)開(kāi)發(fā)、工程、藥政、生產(chǎn)運(yùn)行、銷(xiāo)售和市場(chǎng)、法律和臨床)，及精通質(zhì)量風(fēng)險(xiǎn)管理過(guò)程的個(gè)人。Decisionmakersshould決策者應(yīng)當(dāng)：?takeresponsibilityforcoordinatingqualityriskmanagementacrossvariousfunctionsanddepartmentsoftheirorganization;and負(fù)責(zé)在其組織內(nèi)各職能部門(mén)間協(xié)調(diào)質(zhì)量風(fēng)險(xiǎn)管理；以及，?assurethataqualityriskmanagementprocessisdefined,deployedandreviewedandthatadequateresourcesareavailable.確保明確，開(kāi)展與評(píng)審了質(zhì)量風(fēng)險(xiǎn)管理過(guò)程，并有適當(dāng)?shù)馁Y源。InitiatingaQualityRiskManagementProcess啟動(dòng)質(zhì)量風(fēng)險(xiǎn)管理過(guò)程Qualityriskmanagementshouldincludesystematicprocessesdesignedtocoordinate,facilitateandimprovescience-baseddecisionmakingwithrespecttorisk.Possiblestepsusedtoinitiateandplanaqualityriskmanagementprocessmightincludethefollowing:質(zhì)量風(fēng)險(xiǎn)管理包括那些用于協(xié)調(diào)、促進(jìn)和改善做出與風(fēng)險(xiǎn)相關(guān)的基于科學(xué)的決策系統(tǒng)過(guò)程。可能用于啟動(dòng)和策劃一個(gè)質(zhì)量風(fēng)險(xiǎn)管理過(guò)程的步驟可能包括以下幾點(diǎn)：?Definetheproblemand/orriskquestion,includingpertinentassumptionsidentifyingthepotentialforrisk;明確問(wèn)題和/或風(fēng)險(xiǎn)問(wèn)題，包括辨識(shí)潛在風(fēng)險(xiǎn)相關(guān)假設(shè)；?Assemblebackgroundinformationand/ordataonthepotentialhazard,harmorhumanhealthimpactrelevanttotheriskassessment;收集與風(fēng)險(xiǎn)評(píng)估相關(guān)的潛在危險(xiǎn)、傷害或影響人體健康的背景信息和資料和/或數(shù)據(jù)；?Identifyaleaderandnecessaryresources;辯識(shí)領(lǐng)導(dǎo)與必要的資源；?Specifyatimeline,deliverablesandappropriatelevelofdecisionmakingfortheriskmanagementprocess.指定風(fēng)險(xiǎn)管理程序的時(shí)限、交付日期與決策水平。RiskAssessment風(fēng)險(xiǎn)評(píng)估Riskassessment:consistsoftheidentificationofhazardsandtheanalysisandevaluationofrisksassociatedwithexposuretothosehazards(asdefinedbelow).Qualityriskassessmentsbeginwithawell-definedproblemdescriptionorriskquestion.Whentheriskinquestioniswelldefined,anappropriateriskmanagementtool(seeexamplesinsection5)andthetypesofinformationneededtoaddresstheriskquestionwillbemorereadilyidentifiable.Asanaidtoclearlydefiningtherisk(s)forriskassessmentpurposes,threefundamentalquestionsareoftenhelpful:風(fēng)險(xiǎn)評(píng)估：其包括辨識(shí)危險(xiǎn)因素與暴露在這些危險(xiǎn)因素(定義于后)相關(guān)風(fēng)險(xiǎn)的分析和評(píng)估。質(zhì)量風(fēng)險(xiǎn)評(píng)估開(kāi)始于一個(gè)明確的問(wèn)題或風(fēng)險(xiǎn)問(wèn)題。當(dāng)被討論的風(fēng)險(xiǎn)被明確定義后，則將會(huì)很容易確定適當(dāng)?shù)娘L(fēng)險(xiǎn)管理工具(見(jiàn)第5節(jié)中的例子)和需要用于風(fēng)險(xiǎn)問(wèn)題說(shuō)明的資料類(lèi)型。在風(fēng)險(xiǎn)評(píng)估時(shí)，作為明確定義風(fēng)險(xiǎn)的輔助工具，通常如下這三個(gè)基本問(wèn)題是非常有用的：1.Whatmightgowrong什么可能出錯(cuò)2.Whatisthelikelihood(probability)itwillgowrong會(huì)出錯(cuò)的可能性(概率)是什么3.Whataretheconsequences(severity)結(jié)果(嚴(yán)重性)是什么Riskidentification:isasystematicuseofinformationtoidentifyhazardsreferringtotheriskquestionorproblemdescription.Informationcanincludehistoricaldata,theoreticalanalysis,informedopinions,andtheconcernsofstakeholders.Riskidentificationaddressesthe“Whatmightgowrong”question,includingidentifyingthepossibleconsequences.Thisprovidesthebasisforfurtherstepsinthequalityriskmanagementprocess.風(fēng)險(xiǎn)辨識(shí)：其是指參照風(fēng)險(xiǎn)問(wèn)題或問(wèn)題描述，系統(tǒng)地運(yùn)用信息來(lái)辨識(shí)危險(xiǎn)因素。這些信息可能包括歷史數(shù)據(jù)、理論分析、意見(jiàn)以及風(fēng)險(xiǎn)涉眾的考慮。風(fēng)險(xiǎn)辨識(shí)關(guān)注“什么可能出錯(cuò)”這個(gè)問(wèn)題，包括辨識(shí)可能的結(jié)果。這為進(jìn)一步的質(zhì)量風(fēng)險(xiǎn)管理過(guò)程奠定了基礎(chǔ)。Riskanalysis:istheestimationoftheriskassociatedwiththeidentifiedhazards.Itisthequalitativeorquantitativeprocessoflinkingthelikelihoodofoccurrenceandseverityofharms.Insomeriskmanagementtools,theabilitytodetecttheharm(detectability)alsofactorsintheestimationofrisk.風(fēng)險(xiǎn)分析：其是對(duì)風(fēng)險(xiǎn)所關(guān)聯(lián)已經(jīng)辨識(shí)了的危險(xiǎn)因素進(jìn)行估計(jì)。它是對(duì)發(fā)生事件可能性與及災(zāi)害嚴(yán)重性進(jìn)行定量或定性過(guò)程。在一些風(fēng)險(xiǎn)管理工具中，探測(cè)傷害的能力(可檢測(cè)性)同樣是在估計(jì)風(fēng)險(xiǎn)中的因素。Riskevaluation:comparestheidentifiedandanalyzedriskagainstgivenriskcriteria.Riskevaluationsconsiderthestrengthofevidenceforallthreeofthefundamentalquestions.風(fēng)險(xiǎn)評(píng)價(jià)：其是比較已經(jīng)辨識(shí)和分析的風(fēng)險(xiǎn)與給定的風(fēng)險(xiǎn)標(biāo)準(zhǔn)進(jìn)行比較。風(fēng)險(xiǎn)評(píng)價(jià)考慮到了所有這三個(gè)基本問(wèn)題的證據(jù)強(qiáng)度。Indoinganeffectiveriskassessment,therobustnessofthedatasetisimportantbecauseitdeterminesthequalityoftheoutput.Revealingassumptionsandreasonablesourcesofuncertaintywillenhanceconfidenceinthisoutputand/orhelpidentifyitslimitations.Uncertaintyisduetocombinationofincompleteknowledgeaboutaprocessanditsexpectedorunexpectedvariability.Typicalsourcesofuncertaintyincludegapsinknowledgegapsinpharmaceuticalscienceandprocessunderstanding,sourcesofharm.,failuremodesofaprocess,sourcesofvariability),andprobabilityofdetectionofproblems.在進(jìn)行一個(gè)有效的風(fēng)險(xiǎn)評(píng)估時(shí)，數(shù)據(jù)集的完美性很重要，因?yàn)樗鼪Q定了輸出的質(zhì)量。顯示假設(shè)及合理資源不確定性將會(huì)加強(qiáng)輸出的可靠性，并且/或有助于辨識(shí)其限度。不確定性是由于關(guān)于過(guò)程不完整的知識(shí)以及其期望的或非期望的變異性綜合造成。典型的不確定來(lái)源包括制藥科學(xué)知識(shí)差距、對(duì)過(guò)程理解差距、傷害來(lái)源(如一個(gè)過(guò)程的失效模式，變異行來(lái)源)以及發(fā)現(xiàn)問(wèn)題概率。Theoutputofariskassessmentiseitheraquantitativeestimateofriskoraqualitativedescriptionofarangeofrisk.Whenriskisexpressedquantitatively,anumericalprobabilityisused.Alternatively,riskcanbeexpressedusingqualitativedescriptors,suchas“high”,“medium”,or“l(fā)ow”,whichshouldbedefinedinasmuchdetailaspossible.Sometimesa"riskscore"isusedtofurtherdefinedescriptorsinriskranking.Inquantitativeriskassessments,ariskestimateprovidesthelikelihoodofaspecificconsequence,givenasetofrisk-generatingcircumstances.Thus,quantitativeriskestimationisusefulforoneparticularconsequenceatatime.Alternatively,someriskmanagementtoolsusearelativeriskmeasuretocombinemultiplelevelsofseverityandprobabilityintoanoverallestimateofrelativerisk.Theintermediatestepswithinascoringprocesscansometimesemployquantitativeriskestimation.風(fēng)險(xiǎn)評(píng)估的輸出既是一個(gè)對(duì)風(fēng)險(xiǎn)定量估計(jì)也是一個(gè)對(duì)風(fēng)險(xiǎn)范圍的定性描述。當(dāng)風(fēng)險(xiǎn)被定量地表達(dá)，則運(yùn)用數(shù)值表達(dá)它的概率。另外，風(fēng)險(xiǎn)還可以運(yùn)用如“高”、“中”或“低”等定性描述詞來(lái)表達(dá)，對(duì)其應(yīng)該盡可能詳細(xì)地確定。一些時(shí)候，使用“風(fēng)險(xiǎn)記分”來(lái)進(jìn)一步確定描述風(fēng)險(xiǎn)的排列。在定量風(fēng)險(xiǎn)評(píng)估中，對(duì)一個(gè)風(fēng)險(xiǎn)估計(jì)能提供一個(gè)特定結(jié)果的可能性，給出一系列產(chǎn)生風(fēng)險(xiǎn)狀況。因此，定量風(fēng)險(xiǎn)評(píng)估對(duì)于在某個(gè)時(shí)間的特定后果非常有用。另外，一些風(fēng)險(xiǎn)管理工具采用了相對(duì)的風(fēng)險(xiǎn)度量將多種級(jí)別的嚴(yán)重性和概率合并到一個(gè)完整的相對(duì)風(fēng)險(xiǎn)估計(jì)中。在一個(gè)記分過(guò)程的中間步驟有時(shí)候可以使用定量風(fēng)險(xiǎn)評(píng)估。RiskControl風(fēng)險(xiǎn)控制Riskcontrol:includesdecisionmakingtoreduceand/oracceptrisks.Thepurposeofriskcontrolistoreducetherisktoanacceptablelevel.Theamountofeffortusedforriskcontrolshouldbeproportionaltothesignificanceoftherisk.Decisionmakersmightusedifferentprocesses,includingbenefit-costanalysis,forunderstandingtheoptimallevelofriskcontrol.風(fēng)險(xiǎn)控制：其包括做出的降低和/或接受風(fēng)險(xiǎn)的決定。風(fēng)險(xiǎn)控制的目的是降低風(fēng)險(xiǎn)到一個(gè)可接受的水平。用于風(fēng)險(xiǎn)控制所作工作量應(yīng)該與風(fēng)險(xiǎn)的顯著性相稱(chēng)。決策者可能會(huì)采用不同的過(guò)程，包括收益成本分析，來(lái)了解最佳的風(fēng)險(xiǎn)控制水平。Riskcontrolmightfocusonthefollowingquestions:風(fēng)險(xiǎn)控制可能會(huì)集中在下列問(wèn)題：?Istheriskaboveanacceptablelevel是否風(fēng)險(xiǎn)超過(guò)了一個(gè)可接受的水平?Whatcanbedonetoreduceoreliminaterisks什么方法可以用來(lái)降低或消除風(fēng)險(xiǎn)?Whatistheappropriatebalanceamongbenefits,risksandresources效益、風(fēng)險(xiǎn)和資源之間的恰當(dāng)?shù)钠胶恻c(diǎn)是什么?Arenewrisksintroducedasaresultoftheidentifiedrisksbeingcontrolled控制已經(jīng)所辨識(shí)的風(fēng)險(xiǎn)是否引入新的風(fēng)險(xiǎn)Riskreduction:focusesonprocessesformitigationoravoidanceofqualityriskwhenitexceedsaspecified(acceptable)level(seeFig.1).Riskreductionmightincludeactionstakentomitigatetheseverityandprobabilityofharm.Processesthatimprovethedetectabilityofhazardsandqualityrisksmightalsobeusedaspartofariskcontrolstrategy.Theimplementationofriskreductionmeasurescanintroducenewrisksintothesystemorincreasethesignificanceofotherexistingrisks.Hence,itmightbeappropriatetorevisittheriskassessmenttoidentifyandevaluateanypossiblechangeinriskafterimplementingariskreductionprocess.風(fēng)險(xiǎn)降低：其是著眼于當(dāng)風(fēng)險(xiǎn)超過(guò)了某個(gè)特定(可接受)水平(見(jiàn)圖1)后緩和或避免質(zhì)量風(fēng)險(xiǎn)的過(guò)程。風(fēng)險(xiǎn)降低可能包括用于減緩傷害的嚴(yán)重性和概率所采取的行動(dòng)。改善危險(xiǎn)因素和質(zhì)量風(fēng)險(xiǎn)可檢測(cè)性的過(guò)程也可能作為一個(gè)風(fēng)險(xiǎn)控制策略中的一個(gè)部分。通過(guò)實(shí)施風(fēng)險(xiǎn)降低措施，新的風(fēng)險(xiǎn)可能被引入到系統(tǒng)中或者顯著增加其它已經(jīng)存在的風(fēng)險(xiǎn)。因此，在實(shí)施風(fēng)險(xiǎn)降低過(guò)程后，可能會(huì)適當(dāng)?shù)胤祷氐斤L(fēng)險(xiǎn)評(píng)估中對(duì)風(fēng)險(xiǎn)中任何可能的改變進(jìn)行辯識(shí)和評(píng)價(jià)。Riskacceptance:isadecisiontoacceptrisk.Riskacceptancecanbeaformaldecisiontoaccepttheresidualriskoritcanbeapassivedecisioninwhichresidualrisksarenotspecified.Forsometypesofharms,eventhebestqualityriskmanagementpracticesmightnotentirelyeliminaterisk.Inthesecircumstances,itmightbeagreedthatanappropriatequalityriskmanagementstrategyhasbeenappliedandthatqualityriskisreducedtoaspecified(acceptable)level.This(specified)acceptablelevelwilldependonmanyparametersandshouldbedecidedonacase-by-casebasis.接受風(fēng)險(xiǎn)：其是一個(gè)接受風(fēng)險(xiǎn)的決定。風(fēng)險(xiǎn)接受可以是一個(gè)接受剩余風(fēng)險(xiǎn)的正式?jīng)Q定或者是當(dāng)剩余風(fēng)險(xiǎn)不具體時(shí)的被動(dòng)接受。對(duì)于一些類(lèi)型的傷害，甚至最好的質(zhì)量風(fēng)險(xiǎn)實(shí)踐也未必能全部消除風(fēng)險(xiǎn)。這些情況下，可以認(rèn)為已應(yīng)用了恰當(dāng)?shù)馁|(zhì)量風(fēng)險(xiǎn)管理策略，并且質(zhì)量風(fēng)險(xiǎn)已降低到一個(gè)特定(可接受)的水平。這個(gè)(特定)可接受的水平將會(huì)取決于許多參數(shù)，并且具體情況具體判斷定。RiskCommunication風(fēng)險(xiǎn)溝通Riskcommunication:isthesharingofinformationaboutriskandriskmanagementbetweenthedecisionmakersandothers.Partiescancommunicateatanystageoftheriskmanagementprocess(seeFig.1:dashedarrows).Theoutput/resultofthequalityriskmanagementprocessshouldbeappropriatelycommunicatedanddocumented(seeFig.1:solidarrows).Communicationsmightincludethoseamonginterestedparties;.,regulatorsandindustry,industryandthepatient,withinacompany,industryorregulatoryauthority,etc.Theincludedinformationmightrelatetotheexistence,nature,form,probability,severity,acceptability,control,treatment,detectabilityorotheraspectsofriskstoquality.Communicationneednotbecarriedoutforeachandeveryriskacceptance.Betweentheindustryandregulatoryauthorities,communicationconcerningqualityriskmanagementdecisionsmightbeeffectedthroughexistingchannelsasspecifiedinregulationsandguidances.風(fēng)險(xiǎn)溝通：是在決策者和其它人員之間分享有關(guān)風(fēng)險(xiǎn)和風(fēng)險(xiǎn)管理的信息。各方之間可以在任何風(fēng)險(xiǎn)管理過(guò)程階段進(jìn)行溝通(見(jiàn)圖1的點(diǎn)劃線(xiàn)箭頭)。質(zhì)量風(fēng)險(xiǎn)管理過(guò)程的輸出/結(jié)果應(yīng)當(dāng)進(jìn)行適當(dāng)?shù)臏贤ê痛鏅n(見(jiàn)圖1的實(shí)線(xiàn)箭頭)。溝通有可能包括這些相關(guān)方，例如，藥政與業(yè)界、業(yè)界與患者、在一個(gè)公司、業(yè)界或藥政當(dāng)局內(nèi)部等。所包括的信息應(yīng)該與質(zhì)量風(fēng)險(xiǎn)的存在性、性質(zhì)、形式、概率、嚴(yán)重性、可接受性、控制、處理、可檢測(cè)性或其它有關(guān)方面。溝通不需要對(duì)每個(gè)風(fēng)險(xiǎn)接受都進(jìn)行。如果在業(yè)界和藥政當(dāng)局之間，就可能受影響進(jìn)行質(zhì)量風(fēng)險(xiǎn)管理決策溝通，則這些溝通可能通過(guò)現(xiàn)有的規(guī)章或指南中所說(shuō)明的渠道來(lái)進(jìn)行。RiskReview風(fēng)險(xiǎn)評(píng)審Riskmanagementshouldbeanongoingpartofthequalitymanagementprocess.Amechanismtoreviewormonitoreventsshouldbeimplemented.質(zhì)量風(fēng)險(xiǎn)管理應(yīng)當(dāng)是質(zhì)量管理過(guò)程中的一個(gè)進(jìn)行部分。應(yīng)當(dāng)實(shí)施一個(gè)評(píng)審或?qū)κ录M(jìn)行監(jiān)控的機(jī)制。Theoutput/resultsoftheriskmanagementprocessshouldbereviewedtotakeintoaccountnewknowledgeandexperience.Onceaqualityriskmanagementprocesshasbeeninitiated,thatprocessshouldcontinuetobeutilizedforeventsthatmightimpacttheoriginalqualityriskmanagementdecision,whethertheseeventsareplanned.,resultsofproductreview,inspections,audits,changecontrol)orunplanned.,rootcausefromfailureinvestigations,recall).Thefrequencyofanyreviewshouldbebaseduponthelevelofrisk.Riskreviewmightincludereconsiderationofriskacceptancedecisions.對(duì)風(fēng)險(xiǎn)管理過(guò)程輸出/結(jié)果進(jìn)行評(píng)審應(yīng)當(dāng)考慮采用新的知識(shí)和經(jīng)驗(yàn)。一旦開(kāi)始了某個(gè)質(zhì)量風(fēng)險(xiǎn)管理過(guò)程，則該過(guò)程應(yīng)該一直應(yīng)用于可能影響初始質(zhì)量風(fēng)險(xiǎn)管理決策的事件，而不管那些事件是已被計(jì)劃的(如產(chǎn)品評(píng)審、檢查、審計(jì)、變更控制結(jié)果)或未計(jì)劃的(如從失敗調(diào)查的根本原因、檢查、召回)。評(píng)審頻率應(yīng)該取決于風(fēng)險(xiǎn)水平。風(fēng)險(xiǎn)評(píng)審可能包括對(duì)風(fēng)險(xiǎn)接受決策重新考慮節(jié))。5.RISKMANAGEMENTMETHODOLOGY風(fēng)險(xiǎn)管理方法學(xué)Qualityriskmanagementsupportsascientificandpracticalapproachtodecision-making.Itprovidesdocumented,transparentandreproduciblemethodstoaccomplishstepsofthequalityriskmanagementprocessbasedoncurrentknowledgeaboutassessingtheprobability,severityandsometimesdetectabilityoftherisk.質(zhì)量風(fēng)險(xiǎn)管理支持科學(xué)和實(shí)際方法來(lái)進(jìn)行決策。在現(xiàn)有關(guān)于風(fēng)險(xiǎn)概率，嚴(yán)重性和一些事件的可檢測(cè)性評(píng)估知識(shí)的基礎(chǔ)上，其提供文件的，透明的和可重復(fù)的方法來(lái)實(shí)現(xiàn)質(zhì)量風(fēng)險(xiǎn)管理程序的步驟。Traditionally,riskstoqualityhavebeenassessedandmanagedinavarietyofinformalways(empiricaland/orinternalprocedures)basedon,forexample,compilationofobservations,trendsandotherinformation.Suchapproachescontinuetoprovideusefulinformationthatmightsupporttopicssuchashandlingofcomplaints,qualitydefects,deviationsandallocationofresources.傳統(tǒng)上，對(duì)于質(zhì)量的風(fēng)險(xiǎn)的評(píng)估和管理是基于多種非正式的方式(經(jīng)驗(yàn)的，和/或，內(nèi)部程序)，例如，現(xiàn)象匯總、趨勢(shì)和其它資料。此類(lèi)方法繼續(xù)提供有用的信息，這些信息可以支持諸如處理投訴、質(zhì)量缺陷、偏差與資源分配。Additionally,thepharmaceuticalindustryandregulatorscanassessandmanageriskusingrecognizedriskmanagementtoolsand/orinternalprocedures.,standardoperatingprocedures).Belowisanon-exhaustivelistofsomeofthesetools(furtherdetailsinAnnex1andchapter8):此外，制藥業(yè)界與藥政可以使用公認(rèn)的風(fēng)險(xiǎn)管理工具，和/或，內(nèi)部程序(例如，標(biāo)準(zhǔn)操作程序)來(lái)評(píng)估和管理風(fēng)險(xiǎn)。以下并非是這些工具的一個(gè)詳盡的列表(詳細(xì)在附件1和第8章)：?Basicriskmanagementfacilitationmethods(flowcharts,checksheetsetc.);基本風(fēng)險(xiǎn)管理簡(jiǎn)易方法(流程圖，核對(duì)單等)；?FailureModeEffectsAnalysis(FMEA);故障模式效應(yīng)分析(FMEA)；?FailureMode,EffectsandCriticalityAnalysis(FMECA);故障模式影響與嚴(yán)重性分析(FMECA)；?FaultTreeAnalysis(FTA);故障樹(shù)分析(FTA)；?HazardAnalysisandCriticalControlPoints(HACCP);危害分析關(guān)鍵控制點(diǎn)(HACCP)；?HazardOperabilityAnalysis(HAZOP);危害及可操作性分析(HAZOP)；?PreliminaryHazardAnalysis(PHA);預(yù)先危險(xiǎn)分析(PHA)；?Riskrankingandfiltering;風(fēng)險(xiǎn)排行與過(guò)濾；?Supportingstatisticaltools.輔助性統(tǒng)計(jì)工具。Itmightbeappropriatetoadaptthesetoolsforuseinspecificareaspertainingtodrugsubstanceanddrug(medicinal)productquality.Qualityriskmanagementmethodsandthesupportingstatisticaltoolscanbeusedincombination.,ProbabilisticRiskAssessment).Combineduseprovidesflexibilitythatcanfacilitatetheapplicationofqualityriskmanagementprinciples.在原料藥和藥物(醫(yī)療)產(chǎn)品質(zhì)量的特定領(lǐng)域運(yùn)用這些工具可能是恰當(dāng)?shù)摹Ｙ|(zhì)量風(fēng)險(xiǎn)管理方法以及輔助統(tǒng)計(jì)工具可以聯(lián)合使用(如，概率性風(fēng)險(xiǎn)評(píng)估)。聯(lián)合使用提供了靈活性，而這種靈活性可以促進(jìn)質(zhì)量風(fēng)險(xiǎn)管理原則的應(yīng)用。Thedegreeofrigorandformalityofqualityriskmanagementshouldreflectavailableknowledgeandbecommensuratewiththecomplexityand/orcriticalityoftheissuetobeaddressed.質(zhì)量風(fēng)險(xiǎn)管理的嚴(yán)格程度與和形式應(yīng)當(dāng)反映可利用的知識(shí)和所關(guān)注問(wèn)題的復(fù)雜性，和/或嚴(yán)重性相當(dāng)。6.INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS質(zhì)量風(fēng)險(xiǎn)管理與業(yè)界及藥政運(yùn)行整合Qualityriskmanagementisaprocessthatsupportsscience-basedandpracticaldecisionswhenintegratedintoqualitysystems(seeAnnexII).Asoutlinedintheintroduction,appropriateuseofqualityriskmanagementdoesnotobviateindustry’sobligationtocomplywithregulatoryrequirements.However,effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany’sabilitytodealwithpotentialrisks,andmightaffecttheextentandlevelofdirectregulatoryoversight.Inaddition,qualityriskmanagementcanfacilitatebetteruseofresourcesbyallparties.質(zhì)量風(fēng)險(xiǎn)管理是一個(gè)過(guò)程，當(dāng)將其整合到質(zhì)量體系中時(shí)(見(jiàn)附錄II)可以支持基于科學(xué)和實(shí)踐的決策。正如在簡(jiǎn)介中所簡(jiǎn)述的，恰當(dāng)?shù)剡\(yùn)用質(zhì)量風(fēng)險(xiǎn)管理并不能免除業(yè)界遵守藥政的要求。然而，有效的質(zhì)量風(fēng)險(xiǎn)管理可以促使做出更好和更有遠(yuǎn)見(jiàn)的決策，它可以為管理者提供業(yè)界更多的應(yīng)對(duì)潛在風(fēng)險(xiǎn)能力的保證并且可能會(huì)影響直接監(jiān)管的范圍和水平。另外，質(zhì)量風(fēng)險(xiǎn)管理可以促使資源能被所有部門(mén)更好地運(yùn)用。Trainingofbothindustryandregulatorypersonnelinqualityriskmanagementprocessesprovidesforgreaterunderstandingofdecision-makingprocessesandbuildsconfidenceinqualityriskmanagementoutcomes.對(duì)業(yè)界以及藥政人員進(jìn)行質(zhì)量風(fēng)險(xiǎn)管理的培訓(xùn)可以更好地了解決策過(guò)程，并且對(duì)質(zhì)量風(fēng)險(xiǎn)管理的結(jié)果建立信心。Qualityriskmanagementshouldbeintegratedintoexistingoperationsanddocumentedappropriately.AnnexIIprovidesexamplesofsituationsinwhichtheuseofthequalityriskmanagementprocessmightprovideinformationthatcouldthenbeusedinavariety