企業(yè)質(zhì)量風(fēng)險管理中英文對照

Tablef1敏抖，WORD文檔，目錄編輯修改】1.INTRODUCTION引言2.SCOPE范圍3.PRINCIPLESOFQUALITYRISKMANAGEMENT質(zhì)量風(fēng)險管理原理4.GENERALQUALITYRISKMANAGEMENTPROCESS質(zhì)量風(fēng)險管理基本程序4.1Responsibilities職責(zé)分配4.2InitiatingaQualityRiskManagementProcess質(zhì)量風(fēng)險管理的啟動4.3RiskAssessment風(fēng)險評估4.4RiskControl風(fēng)險控制4.5RiskCommunication風(fēng)險交流4.6RiskReview風(fēng)險回顧5.RISKMANAGEMENTMETHODOLOGY風(fēng)險管理方法學(xué)6.INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS工業(yè)及監(jiān)管與質(zhì)量風(fēng)險管理的整合

7.DEFINITIONS定義8.REFERENCES參考資料AnnexI:RiskManagementMethodsandTools附件I:風(fēng)險管理方法及工具I.1BasicRiskManagementFacilitationMethodsI.1基本風(fēng)險管理簡易方法I.2FailureModeEffectsAnalysis(FMEA)I.2失誤模式影響分析(FMEA)I.3FailureMode,EffectsandCriticalityAnalysis(FMECA)I.3失誤模式影響及危險程度分析(FMECA)I.4FaultTreeAnalysis(FTA)I.4故障樹型分析(FTA)I.5HazardAnalysisandCriticalControlPoints(HACCP)I.5危害分析及關(guān)鍵控制點(diǎn)(HACCP)I.6HazardOperabilityAnalysis(HAZOP)I.6危害可操作性分析(HAZOP)I.7PreliminaryHazardAnalysis(PHA)I.7初步危害分析(PHA)I.8RiskRankingandFilteringI.8風(fēng)險排序及濾除I.9SupportingStatisticalToolsI.9輔助統(tǒng)計工具

AnnexII:PotentialApplicationsforQualityRiskManagement附件II:質(zhì)量風(fēng)險管理潛在應(yīng)用前景.II.1QualityRiskManagementasPartofIntegratedQualityManagementII.1綜合質(zhì)量管理中的質(zhì)量風(fēng)險管理II.2QualityRiskManagementasPartofRegulatoryOperationsII.2操作優(yōu)化中的應(yīng)用II.3QualityRiskManagementasPartofdevelopmentII.3研發(fā)中的應(yīng)用II.4QualityRiskManagementforFacilities,EquipmentandUtilitiesII.4對工具、設(shè)備和設(shè)施的質(zhì)量風(fēng)險管理II.5QualityRiskManagementasPartofMaterialsManagementII.5物料管理中的應(yīng)用II.6QualityRiskManagementasPartofProductionII.6生產(chǎn)中的應(yīng)用II.7QualityRiskManagementasPartofLaboratoryControlandStabilityStudiesII.7實(shí)驗(yàn)室控制及穩(wěn)定性研究中的應(yīng)用II.8QualityRiskManagementasPartofPackagingandLabellingII.8標(biāo)簽及包裝中的應(yīng)用1.INTRODUCTION引言Riskmanagement principlesare風(fēng)險管理原理在商業(yè)和政府的許多領(lǐng)

effectivelyutilizedinmanyareasofbusinessandgovernmentincludingfinance,insurance,occupationalsafety,publichealth,pharmacovigilance,andbyagenciesregulatingtheseindustries.域都得到了有效應(yīng)用，如：金融、保險、職業(yè)安全、公共衛(wèi)生、藥物監(jiān)測及相應(yīng)的監(jiān)管部門。如今質(zhì)量風(fēng)險管理在藥企中雖有應(yīng)用，但范圍有限，并沒有發(fā)揮出它的全部效用。藥企已經(jīng)意識到了質(zhì)量體系的重要性，而質(zhì)量風(fēng)險管理越來effectivelyutilizedinmanyareasofbusinessandgovernmentincludingfinance,insurance,occupationalsafety,publichealth,pharmacovigilance,andbyagenciesregulatingtheseindustries.域都得到了有效應(yīng)用，如：金融、保險、職業(yè)安全、公共衛(wèi)生、藥物監(jiān)測及相應(yīng)的監(jiān)管部門。如今質(zhì)量風(fēng)險管理在藥企中雖有應(yīng)用，但范圍有限，并沒有發(fā)揮出它的全部效用。藥企已經(jīng)意識到了質(zhì)量體系的重要性，而質(zhì)量風(fēng)險管理越來Althoughtherearesomeexamplesof越明顯地成為有效質(zhì)量體系的重要組theuseofqualityriskmanagement分。inthepharmaceuticalindustrytoday,theyarelimitedanddonotrepresentthefullcontributionsthatriskmanagementhastooffer.Inaddition,theimportanceofqualitysystemshasbeenrecognizedinthepharmaceuticalindustryanditisbecomingevidentthatqualityriskmanagementisavaluablecomponentofaneffectivequalitysystem.Itiscommonlyunderstoodthatrisk根據(jù)常規(guī)理解，風(fēng)險被定義為傷害發(fā)生isdefinedasthecombinationofthe的可能性及嚴(yán)重程度。然而，要在不同probabilityofoccurrenceofharmprobabilityofoccurrenceofharmandtheseverityofthatharm.However,achievingasharedunderstandingoftheapplicationofriskmanagementamongdiversestakeholdersisdifficultbecauseeachstakeholdermightperceivedifferentpotentialharms,placeadifferentprobabilityoneachharmoccurringandattributedifferentseveritiestoeachharm.Inrelation利益集團(tuán)之間尋求風(fēng)險管理應(yīng)用方面的共同認(rèn)識是相當(dāng)困難的，因?yàn)樗麄冋J(rèn)識到的潛在危害、各危害發(fā)生的可能性及嚴(yán)重程度都不同。藥品相關(guān)的利益集團(tuán)很多，如病人、醫(yī)療人員和政府企業(yè)，但是質(zhì)量風(fēng)險管理的首要目的是保護(hù)病人。topharmaceuticals,althoughthereareavarietyofstakeholders,includingpatientsandmedicalpractitionersaswellasgovernmentandindustry,theprotectionofthepatientbymanagingtherisktoqualityshouldbeconsideredofprimeimportance.Themanufacturinganduseofadrug藥品生產(chǎn)、使用過程，包括藥品的成分，(medicinal)product,includingits都會不可避免地引入一定的風(fēng)險。質(zhì)量components,necessarilyentailsomedegreeofrisk.Therisktoitsqualityisjustonecomponentoftheoverallrisk.Itisimportanttounderstandthatproductqualitycomponents,necessarilyentailsomedegreeofrisk.Therisktoitsqualityisjustonecomponentoftheoverallrisk.Itisimportanttounderstandthatproductqualityshouldbemaintainedthroughouttheproductlifecyclesuchthattheattributesthatareimportanttothequalityofthedrug(medicinal)productremainconsistentwiththoseusedintheclinicalstudies.Aneffectivequalityrisk風(fēng)險只是其中的一部分。在產(chǎn)品整個生命周期中，確保產(chǎn)品的質(zhì)量，使得藥品質(zhì)量方面的重要性質(zhì)與臨床研究中的一致，做到這些是非常重要的。一個有效的質(zhì)量風(fēng)險管理方法能通過提供前攝措施，確定控制研發(fā)和生產(chǎn)中潛在的質(zhì)量問題，來進(jìn)一步確保藥品質(zhì)量。當(dāng)質(zhì)量問題出現(xiàn)時，應(yīng)用質(zhì)量風(fēng)險管理還能改善決策過程。有效進(jìn)行質(zhì)量風(fēng)險管理能促使產(chǎn)生更好更正式?jīng)Q策，增強(qiáng)監(jiān)控者對公司處理潛在風(fēng)險能力的信心，積極影響直接監(jiān)理的程度和水平。managementapproachcanfurtherensurethehighqualityofthedrug(medicinal)producttothepatientbyprovidingaproactivemeanstoidentifyandcontrolpotentialqualityissuesduringdevelopmentandmanufacturing.Additionally,useofqualityriskmanagementcanimprovethedecisionmakingifaqualityproblemarises.Effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany'sabilitytodealwithpotentialrisksandcanbeneficiallyaffecttheextentandlevelofdirectregulatoryoversight.Thepurposeofthisdocumentistoofferasystematicapproachtoqualityriskmanagement.Itservesasafoundationorresourcedocumentthatisindependentof,yetsupports,otherICHQualitydocumentsandcomplementsexistingqualitypractices,requirements,standards,andguidelineswithinthepharmaceuticalindustryandregulatoryenvironment.Itspecificallyprovidesguidanceon此文件的目的是提供質(zhì)量風(fēng)險管理方面的系統(tǒng)方法。作為一個基礎(chǔ)性、資源性的文件，它獨(dú)立于卻又支持其它ICHThepurposeofthisdocumentistoofferasystematicapproachtoqualityriskmanagement.Itservesasafoundationorresourcedocumentthatisindependentof,yetsupports,otherICHQualitydocumentsandcomplementsexistingqualitypractices,requirements,standards,andguidelineswithinthepharmaceuticalindustryandregulatoryenvironment.Itspecificallyprovidesguidanceon此文件的目的是提供質(zhì)量風(fēng)險管理方面的系統(tǒng)方法。作為一個基礎(chǔ)性、資源性的文件，它獨(dú)立于卻又支持其它ICH質(zhì)量文件，補(bǔ)充藥企和監(jiān)管機(jī)構(gòu)內(nèi)已有的質(zhì)量措施、要求、標(biāo)準(zhǔn)和指南。特別是它提供了一些質(zhì)量風(fēng)險管理工具的原理指南，這些工具能促使監(jiān)管者和企業(yè)考慮整個產(chǎn)品周期中藥用物質(zhì)和藥品的質(zhì)量，做出更有效、更連續(xù)的基于風(fēng)險的決策，并不想在現(xiàn)有法規(guī)之外提出新的期望。theprinciplesandsomeofthetoolsofqualityriskmanagementthatcanenablemoreeffectiveandconsistentriskbaseddecisions,bothbyregulatorsandindustry,regardingthequalityofdrugsubstancesanddrug(medicinal)productsacrosstheproductlifecycle.Itisnotintendedtocreateanynewexpectationsbeyondthecurrentregulatoryrequirements.Itisneitheralwaysappropriatenoralwaysnecessarytouseaformalriskmanagementprocess(usingrecognizedtoolsand/orinternalprocedurese.g.,standardoperatingprocedures).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsand/orinternalprocedures)canalsobeconsidered應(yīng)用正式的風(fēng)險管理程序并非總是合適的或必要的（用已承認(rèn)的工具或內(nèi)部程序，如標(biāo)準(zhǔn)操作規(guī)程）。有時也允許使用非正式的風(fēng)險管理程序（用經(jīng)驗(yàn)工具或內(nèi)部程序）。恰當(dāng)運(yùn)用風(fēng)險管理能方便但不消除企業(yè)遵守法規(guī)要求的責(zé)任，也不能取代企業(yè)和監(jiān)管者之間必要的溝通交流。Itisneitheralwaysappropriatenoralwaysnecessarytouseaformalriskmanagementprocess(usingrecognizedtoolsand/orinternalprocedurese.g.,standardoperatingprocedures).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsand/orinternalprocedures)canalsobeconsidered應(yīng)用正式的風(fēng)險管理程序并非總是合適的或必要的（用已承認(rèn)的工具或內(nèi)部程序，如標(biāo)準(zhǔn)操作規(guī)程）。有時也允許使用非正式的風(fēng)險管理程序（用經(jīng)驗(yàn)工具或內(nèi)部程序）。恰當(dāng)運(yùn)用風(fēng)險管理能方便但不消除企業(yè)遵守法規(guī)要求的責(zé)任，也不能取代企業(yè)和監(jiān)管者之間必要的溝通交流。acceptable.Appropriateuseofqualityriskmanagementcanfacilitatebutdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirementsanddoesnotreplaceappropriatecommunicationsbetweenindustryandregulators.2.SCOPE2.范圍Thisguidelineprovidesprinciples本指南給出了質(zhì)量風(fēng)險管理工具的原理andexamplesoftoolsforquality和應(yīng)用實(shí)例，這些工具可用于藥品質(zhì)量2riskmanagementthatcanbeapplied［方面，即藥用物質(zhì)、藥品、生物和生物孑todifferentaspectsof術(shù)產(chǎn)品（包括藥品中用到的原料、溶劑、pharmaceuticalquality.These賦形劑、包裝標(biāo)簽材料等）生命周期中taspectsincludedevelopment,研發(fā)、生產(chǎn)、銷售、檢察、提交和復(fù)審彳manufacturing,distribution,and過程。theinspectionandsubmission/reviewprocessesthroughoutthelifecycleofdrugsubstances,drug(medicinal)products,biologicaland

biotechnologicalproducts(includingtheuseofrawmaterials,solvents,excipients,packagingandlabelingmaterialsindrug(medicinal)products,biologicalandbiotechnologicalproducts).3.PRINCIPLESOFQUALITYRISKMANAGEMENT3.質(zhì)量風(fēng)險管理原理Twoprimaryprinciplesofquality質(zhì)量風(fēng)險管理的兩條基本原理是：riskmanagementare:1.評估質(zhì)量風(fēng)險應(yīng)基于科學(xué)知識并最?Theevaluationoftheriskto終同對病人的保護(hù)聯(lián)系起來。qualityshouldbebasedon2.投入的努力程度、管理的正式程度scientificknowledgeandultimately及文件管理水平應(yīng)與風(fēng)險水平相適應(yīng)。linktotheprotectionofthepatient;and?Thelevelofeffort,formalityanddocumentationofthequalityriskmanagementprocessshouldbecommensuratewiththelevelofrisk.4.GENERALQUALITYRISKMANAGEMENT4.質(zhì)量風(fēng)險管理基本過程

PROCESSQualityriskmanagementisa質(zhì)量風(fēng)險管理是對藥品質(zhì)量風(fēng)險進(jìn)行systematicprocessforthe評估，控制，交流和審查的系統(tǒng)過程，assessment,control,communication這一過程貫穿藥品整個生命周期。圖1andreviewofriskstothequality給出了這方面的一個模型，其他模型也ofthedrug(medicinal)product有應(yīng)用。具體情況不同，框架中各組分acrosstheproductlifecycle.A受重視水平會各有差別，可是一個有效modelforqualityriskmanagementis的管理過程會將所有因素納入考慮，各outlinedinthediagram(Figure1).因素受關(guān)注程度會因風(fēng)險的特異而各Othermodelscouldbeused.The有區(qū)別。emphasisoneachcomponentoftheframeworkmightdifferfromcasetocasebutarobustprocesswillincorporateconsiderationofalltheelementsatalevelofdetailthatiscommensuratewiththespecificrisk.Figure1:典型質(zhì)量風(fēng)險管理過程簡介啟動質(zhì)量風(fēng)險管理風(fēng)險評估風(fēng)險鑒定風(fēng)險分析風(fēng)險評估風(fēng)險管風(fēng)險評估風(fēng)險鑒定風(fēng)險分析風(fēng)險評估風(fēng)險管理不工合—具風(fēng)險降低風(fēng)險接受風(fēng)險質(zhì)量管理的效果/結(jié)風(fēng)險質(zhì)量管理的效果/結(jié)■事件審核Decisionnodesarenotshowninthe由于決策行為隨時都可能發(fā)生，上圖就diagramabovebecausedecisionscan沒有顯示決策點(diǎn)。這些決策有可能被反diagramabovebecausedecisionscan沒有顯示決策點(diǎn)。這些決策有可能被反occuratanypointintheprocess.饋到上一步以尋求更多信息，這些信息occuratanypointintheprocess.饋到上一步以尋求更多信息，這些信息Thesedecisionsmightbetoreturn可用于調(diào)整風(fēng)險模型；也可能用于管理Thesedecisionsmightbetoreturn可用于調(diào)整風(fēng)險模型；也可能用于管理tothepreviousstepandseek過程的終止。注解：圖中的“不可接受”tothepreviousstepandseek過程的終止。注解：圖中的“不可接受”furtherinformation,toadjustthe項(xiàng)不僅指違背了法令法規(guī)要求，也表示furtherinformation,toadjustthe項(xiàng)不僅指違背了法令法規(guī)要求，也表示riskmodelsoreventoterminatethe風(fēng)險管理過程需要重頭再來。riskmodelsoreventoterminatethe風(fēng)險管理過程需要重頭再來。riskmanagementprocessbaseduponinformationthatsupportssuchadecision.Note:“unacceptable”intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.4.1Responsibilitiesinformationthatsupportssuchadecision.Note:“unacceptable”intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.4.1ResponsibilitiesQualityriskmanagementactivitiesareusually,butnotalways,undertakenbyinterdisciplinaryteams.Whenteamsareformed,theyshouldincludeexpertsfromtheappropriateareas(e.g.,qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketing,legal,statisticsandclinical)inadditiontoindividualswhoareknowledgeableaboutthequalityriskmanagement4.1.職責(zé)分配質(zhì)量風(fēng)險管理經(jīng)常是但也不總是由交叉學(xué)科團(tuán)隊(duì)執(zhí)行。除了要有風(fēng)險管理方面的經(jīng)驗(yàn)人士，團(tuán)隊(duì)還應(yīng)包括相關(guān)領(lǐng)域的專家（例如：質(zhì)量小組、事業(yè)發(fā)展、工程、管理，生產(chǎn)、行銷、法律、統(tǒng)計和臨床方面等。決策者必須負(fù)責(zé)組織協(xié)調(diào)各部門之間的關(guān)系，保障團(tuán)隊(duì)各項(xiàng)功能的有效發(fā)揮，確保整個管理過程得以合理展開、不斷完善、反復(fù)審查，保障有足夠的資源供團(tuán)隊(duì)使用。process.Decisionmakersshouldtakeresponsibilityforcoordinatingqualityriskmanagementacrossvariousfunctionsanddepartmentsoftheirorganization;andassurethataqualityriskmanagementprocessisdefined,deployedandreviewedandthatadequateresourcesareavailable.4.2InitiatingaQualityRiskManagementProcess4.2質(zhì)量風(fēng)險管理的啟動Qualityriskmanagementshouldincludesystematicprocessesdesignedtocoordinate,facilitateandimprovescience-baseddecisionmakingwithrespecttorisk.Possiblestepsusedtoinitiateancplanaqualityriskmanagementprocessmightincludethe質(zhì)量風(fēng)險管理應(yīng)包括這樣一些系統(tǒng)程序，這些設(shè)計好的程序用來協(xié)調(diào)，推動和改善那些風(fēng)險方面基于科學(xué)認(rèn)識的決定。一項(xiàng)管理程序的發(fā)起和設(shè)計可能要經(jīng)過如下步驟：1.定義存在的難題和風(fēng)險問題，包括識別潛在風(fēng)險的相關(guān)假設(shè)；?收集風(fēng)險評估相關(guān)的關(guān)于潛在危險、危

following:Definetheproblemand/orriskquestion,includingpertinentassumptionsidentifyingthepotentialforrisk;Assemblebackgroundinformationand/ordataonthepotentialhazard,harmorhumanhealthimpactrelevanttotheriskassessment;Identifyaleaderandnecessaryresources;Specifyatimeline,deliverablesandappropriatelevelofdecisionmakingfortheriskmanagementprocess.害或人體健康影響的背景信息和數(shù)據(jù)；?確定領(lǐng)導(dǎo)人和重要資源；?詳細(xì)說明決策的時間表，可交付性和適當(dāng)?shù)臉?biāo)準(zhǔn)。4.3RiskAssessment4.3風(fēng)險評估Riskassessmentconsistsoftheidentificationofhazardsandtheanalysisandevaluationofrisksassociatedwithexposuretothosehazards(asdefinedbelow).Quality風(fēng)險評估：此過程進(jìn)行危險確認(rèn)并對接觸這些危險所帶來的風(fēng)險進(jìn)行分析評價。它以一個定義明確的難點(diǎn)描敘或風(fēng)險問題開始，當(dāng)風(fēng)險明確后，選擇合適而有針對性的管理工具和信息類型將

riskassessmentsbeginwitha會變得更容易。以下三個基本問題將有well-definedproblemdescriptionor助于給出風(fēng)險的清晰定義。.什么可能會出錯？..什么可能會出錯？.出錯的可能性有多大？.出錯的后果和嚴(yán)重性有哪些?Whatmightgowrong?Whatisthelikelihood(probability)itwillgowrong?Whataretheconsequences(severity)?Riskidentificationisasystematicuseofinformationtoidentifyhazardsreferringtotherisk風(fēng)險鑒定：參照風(fēng)險問題或難點(diǎn)描敘，系統(tǒng)利用已有信息去鑒定危險。這些信息包括歷史數(shù)據(jù)、理論分析、多方面觀

questionorproblemdescription.Informationcanincludehistoricaldata,theoreticalanalysis,informedopinions,andtheconcernsofstakeholders.Riskidentificationaddressesthe“Whatmightgowrong?”question,includingidentifyingthepossibleconsequences.Thisprovidesthebasisforfurtherstepsinthequalityriskmanagementprocess.點(diǎn)和風(fēng)險承擔(dān)人的意見。風(fēng)險鑒定時提出“什么會出錯”這一問題，同時還確定可能答案。這一過程為后續(xù)步驟奠定了基礎(chǔ)。Riskanalysis istheestimationoftheriskassociatedwiththeidentifiedhazards.Itisthequalitativeorquantitativeprocessoflinkingthelikelihoodofoccurrenceandseverityofharms.Insomeriskmanagementtools,theabilitytodetecttheharm(detectability)alsofactorsintheestimationofrisk.風(fēng)險分析：估計與已確認(rèn)危險相聯(lián)系的風(fēng)險，這是對危害發(fā)生的可能性和嚴(yán)重程度進(jìn)行定性和定量分析的過程。風(fēng)險評價中同樣也應(yīng)用到某些管理工具檢測危害的能力（檢測能力）。aboutaprocessanditsexpectedoraboutaprocessanditsexpectedor詞的適用范圍都要詳細(xì)規(guī)定，Riskevaluationcomparestheidentifiedandanalyzedriskagainstgivenriskcriteria.Riskevaluationsconsiderthestrengthofevidenceforallthreeofthefundamentalquestions.Indoinganeffectiveriskassessment,therobustnessofthedatasetisimportantbecauseitdeterminesthequalityoftheoutput.Revealingassumptionsandreasonablesourcesofuncertaintywillenhanceconfidenceinthisoutputand/orhelpidentifyitslimitations.Uncertaintyisduetocombinationofincompleteknowledgeunexpectedvariability.Typicalsourcesofuncertaintyincludegapsinknowledgegapsinpharmaceuticalscienceandprocessunderstanding,風(fēng)險評估：將經(jīng)過分析和鑒定的風(fēng)險同給定標(biāo)準(zhǔn)作比較，考慮三個基本問題的證據(jù)力。風(fēng)險評估中，數(shù)據(jù)的有效性決定了評估結(jié)果的質(zhì)量。揭示、設(shè)想、分析不確定性的來源將有助于增強(qiáng)對結(jié)果的信心、識別結(jié)果的局限性。對過程了解不充分、過程中可預(yù)見及不可預(yù)見變動的發(fā)生，都將導(dǎo)致不確定性的發(fā)生。知識結(jié)構(gòu)的不完整，有限的藥學(xué)發(fā)展水平、不充分的過程理解、危險來源（不成功的過程模式、變動的來源）及問題被發(fā)現(xiàn)的可能性都是不確定性的典型來源。評估結(jié)果可以是對風(fēng)險的定量表示，也可以是對分險程度的定性描述。定量表示時可用數(shù)值表示可能性，用高、中、低來給風(fēng)險排序時，各個有時候還用到風(fēng)險評分來進(jìn)一步定義。定量評估能對給定的風(fēng)險衍生環(huán)境中特定結(jié)果發(fā)生的可能性做出判斷。因此，定量評估一次只能評判一個特定結(jié)果。于是一sourcesofharm(e.g.,failuremodesofaprocess,sourcesofvariability),andprobabilityofdetectionofproblems.Theoutputofariskassessmentiseitheraquantitativeestimateof些管理工具用到相對衡量尺度，將多重水平的嚴(yán)重性和可能性結(jié)合起來，以完成對相對風(fēng)險的整體評估。評分過程的中間步驟有時也用到定量風(fēng)險估計方法。riskoraqualitativedescriptionofarangeofrisk.Whenriskisexpressedquantitatively,anumericalprobabilityisused.Alternatively,riskcanbeexpressedusingqualitativedescriptors,suchas“high”,“medium”,or“l(fā)ow”，whichshouldbedefinedinasmuchdetailaspossible.Sometimesariskscore"isusedtofurtherdefinedescriptorsinriskranking.Inquantitativeriskassessments,ariskestimateprovidesthelikelihoodofaspecificconsequence,givenasetof

risk-generatingcircumstances.Thus,quantitativeriskestimationisusefulforoneparticularconsequenceatatime.Alternatively,someriskmanagementtoolsusearelativeriskmeasuretocombinemultiplelevelsofseverityandprobabilityintoanoverallestimateofrelativerisk.Theintermediatestepswithinascoringprocesscansometimesemployquantitativeriskestimation.4.4RiskControl4.4風(fēng)險控制Riskcontrolincludesdecision風(fēng)險控制包括風(fēng)險抑低和風(fēng)險接受兩makingtoreduceand/oraccept方面的決策過程，進(jìn)行控制的目的是將risks.Thepurposeofriskcontrol風(fēng)險降低到可接受水平，投入努力量istoreducetherisktoan應(yīng)與風(fēng)險的嚴(yán)重程度相襯。決策者應(yīng)用acceptablelevel.Theamountofeffortusedforriskcontrolshould包括效益-耗費(fèi)比分析在內(nèi)的不同的程序去理解風(fēng)險控制的最佳水平。beproportionaltothesignificance風(fēng)險控制過程中以下問題會受到關(guān)注：oftherisk.Decisionmakersmight風(fēng)險水平是否高于可接受水平之上？

usedifferentprocesses,including怎樣做才能自降低乃至消除風(fēng)險？benefit-cost analysis, for如何尋求效益、風(fēng)險和資源之間的合適understandingtheoptimallevelof平衡？riskcontrol.對已確定風(fēng)險進(jìn)行控制時是否會引入Riskcontrolmightfocusonthefollowingquestions:Istheriskaboveanacceptablelevel?Whatcanbedonetoreduceoreliminaterisks?Whatistheappropriatebalanceamongbenefits, risksandresources?Arenewrisksintroducedasaresultoftheidentifiedrisksbeingcontrolled?新的風(fēng)險？Riskreductionfocusesonprocesses風(fēng)險抑低：此過程著力于減輕或避免超formitigationoravoidanceof過一定水平（可接受水平）的質(zhì)量風(fēng)險，qualityriskwhenitexceedsa包括為減輕危害嚴(yán)重性和發(fā)生可能性specified(acceptable)level(see而采取的一系列措施，還包括一些致力Fig.1).Riskreductionmight于改善危險及質(zhì)量風(fēng)險可檢測性的程

includeactionstakentomitigate序。風(fēng)險抑低過程可能會給系統(tǒng)帶入新theseverityandprobabilityof的風(fēng)險，其他業(yè)已存在的風(fēng)險的嚴(yán)重程harm.Processesthatimprovethe度也可能增加。因此，完成風(fēng)險抑低程detectabilityofhazardsand序后，有必要再重復(fù)一下質(zhì)量評估過qualityrisksmightalsobeusedas程，來識別和評價風(fēng)險系統(tǒng)的可能變partofariskcontrolstrategy.The化。implementationofriskreductionmeasurescanintroducenewrisksintothesystemorincreasethesignificanceofotherexistingrisks.Hence,itmightbeappropriatetorevisittheriskassessmenttoidentifyandevaluateanypossiblechangeinriskafterimplementingariskreductionprocess.Riskacceptanceisadecisionto風(fēng)險接受：就是接受風(fēng)險的決定。它可acceptrisk.Riskacceptancecanbe能為接受殘留風(fēng)險的正式?jīng)Q定，也可以aformaldecisiontoacceptthe是忽略剩余風(fēng)險的消極決定。有些類型residualriskoritcanbeapassive的風(fēng)險，即使用最好的質(zhì)量風(fēng)險管理手decisioninwhichresidualrisksare段，也不能完全清除。在這種情形下，

notspecified.Forsometypesofharms,eventhebestqualityriskmanagementpracticesmightnotentirelyeliminaterisk.Inthesecircumstances,itmightbeagreedthatanappropriatequalityriskmanagementstrategyhasbeenappliedandthatqualityriskisreducedtoaspecified(acceptable)level.This(specified)acceptablelevelwilldependonmanyparametersandshouldbedecidedonacase-by-casebasis.應(yīng)確認(rèn)使用了合適的風(fēng)險管理策略，且風(fēng)險已被降至特定水平（可接受水平）。這個可接受水平由很多參數(shù)和各例具體情況來確定。4.5RiskCommunication4.5風(fēng)險溝通Riskcommunicationisthesharingof風(fēng)險溝通：決策者和其他人就風(fēng)險和風(fēng)informationaboutriskandrisk險管理方面的信息進(jìn)行溝通、交流，各managementbetweenthedecision利益集團(tuán)間的交流在風(fēng)險管理的任意makersandothers.Partiescan階段都可以進(jìn)行（見圖1虛線部分）。communicateatanystageoftheriskmanagementprocess(seeFig.1:dashedarrows).Theoutput/result質(zhì)量風(fēng)險管理過程的產(chǎn)出和結(jié)果應(yīng)得到合理溝通并存檔。（見圖1實(shí)線部分）各利益團(tuán)體間（如監(jiān)管者同企業(yè)之間，ofthequalityriskmanagementprocessshouldbeappropriatelycommunicatedanddocumented(seeFig.1:solidarrows).Communicationsmightincludethoseamonginterestedparties;e.g.,regulatorsandindustry,industryandthepatient,withinacompany,industryorregulatoryauthority,etc.Theincludedinformationmightrelatetotheexistence,nature,form,probability,severity,acceptability,control,treatment,detectabilityorotheraspectsofriskstoquality.Communicationneednotbecarriedoutforeachandeveryriskacceptance.Betweentheindustryandregulatoryauthorities,communicationconcerningqualityriskmanagementdecisionsmightbeeffectedthroughexistingchannelsasspecifiedin企業(yè)和患者之間，公司、企業(yè)、監(jiān)管機(jī)構(gòu)內(nèi)部），就質(zhì)量風(fēng)險的存在、性質(zhì)、形式、可能性、嚴(yán)重程度、可接受度、控制、處理、可檢測度及其他方面的信息進(jìn)行交流。不需要就每個風(fēng)險承擔(dān)都進(jìn)行風(fēng)險交流。企業(yè)和監(jiān)管機(jī)構(gòu)之間關(guān)于質(zhì)量風(fēng)險管理方面的溝通交流可以通過規(guī)則、指導(dǎo)中給定的渠道來實(shí)現(xiàn)。regulationsandguidances.4.6RiskReviewRiskmanagementshouldbeanongoingpartofthequalitymanagementprocess.Amechanismtoreviewormonitoreventsshouldbeimplemented.Theoutput/resultsoftheriskmanagementprocessreviewedtotakeintoshouldbe4.6RiskReviewRiskmanagementshouldbeanongoingpartofthequalitymanagementprocess.Amechanismtoreviewormonitoreventsshouldbeimplemented.Theoutput/resultsoftheriskmanagementprocessreviewedtotakeintoshouldbeaccountnewknowledgeandexperience.Onceaqualityriskmanagementprocesshasbeeninitiated,thatprocessshouldcontinuetobeutilizedforeventsthatmightimpacttheoriginalqualityriskmanagementdecision,whethertheseeventsareplanned(e.g.,resultsofproductreview,inspections,audits,changecontrol)orunplanned(e.g.,root4.6風(fēng)險回顧風(fēng)險管理伴隨著質(zhì)量管理過程的全程，應(yīng)當(dāng)引入審查和監(jiān)控機(jī)制。在審查風(fēng)險管理過程的結(jié)果時要將新的知識和經(jīng)驗(yàn)納入考慮范圍。一旦一個質(zhì)量風(fēng)險管理過程開始啟動，它便用于管理那些可能會影響最初質(zhì)量風(fēng)險管理決策的事件，不管這些事件是計劃中的（產(chǎn)品回顧結(jié)果，自檢、審計和變更控制管理）還是計劃外的（如失敗調(diào)查的根由，召回）。任何回顧的進(jìn)行頻率都應(yīng)基于風(fēng)險水平，風(fēng)險回顧還可能包括對風(fēng)險接受決定的再審議。causefromfailureinvestigations,recall).Thefrequencyofanyreviewshouldbebaseduponthelevelofrisk.Riskreviewmightincludereconsiderationofriskacceptancedecisions(section4.4).5.RISKMANAGEMENTMETHODOLOGYQualityriskmanagementsupportsascientificandpracticalapproachtodecision-making.Itprovidesdocumented,transparentandreproduciblemethodstoaccomplishstepsofthequalityriskmanagementprocessbasedoncurrentknowledgeaboutassessingtheprobability,severityandsometimesdetectabilityoftherisk.Traditionally,riskstoqualityhavebeenassessedandmanagedina同樣，5.5.RISKMANAGEMENTMETHODOLOGYQualityriskmanagementsupportsascientificandpracticalapproachtodecision-making.Itprovidesdocumented,transparentandreproduciblemethodstoaccomplishstepsofthequalityriskmanagementprocessbasedoncurrentknowledgeaboutassessingtheprobability,severityandsometimesdetectabilityoftherisk.Traditionally,riskstoqualityhavebeenassessedandmanagedina同樣，5.質(zhì)量管理方法學(xué)質(zhì)量風(fēng)險管理中的決策過程用到了一種科學(xué)而實(shí)用的方法，它根據(jù)現(xiàn)有的關(guān)于估計風(fēng)險可能性、嚴(yán)重程度和可檢測性方面的知識，提供一些已形成文件的、透明的和可再生的方法，來完成質(zhì)量風(fēng)險管理各步驟。質(zhì)量風(fēng)險傳統(tǒng)上是用一系列非正規(guī)方法來進(jìn)行評估和控制的，這些方法基于觀測報告，風(fēng)險趨勢以及一些其它信息，在處理投訴，質(zhì)量缺陷，偏差和資源配置方面仍能提供有用的資料。藥品廠家和管理者也可用已承認(rèn)varietyofinformalways(empiricaland/orinternalprocedures)basedon,forexample,compilationof的工具和內(nèi)部程序來進(jìn)行評估和控制，以下就是這樣一些工具（Annex1andsectionVIII中更有詳敘）：observations,trendsandotherinformation.Suchapproachescontinuetoprovideusefulinformationthatmightsupporttopicssuchashandlingofcomplaints,qualitydefects,deviationsandallocationofresources.Additionally,thepharmaceuticalindustryandregulatorscanassessandmanageriskusingrecognizedriskmanagementtoolsand/orinternalprocedures(e.g.,standardoperatingprocedures).Belowisanon-exhaustivelistofsomeofthesetools(furtherdetailsinAnnex1andchapter8):observations,trendsandotherinformation.Suchapproachescontinuetoprovideusefulinformationthatmightsupporttopicssuchashandlingofcomplaints,qualitydefects,deviationsandallocationofresources.Additionally,thepharmaceuticalindustryandregulatorscanassessandmanageriskusingrecognizedriskmanagementtoolsand/orinternalprocedures(e.g.,standardoperatingprocedures).Belowisanon-exhaustivelistofsomeofthesetools(furtherdetailsinAnnex1andchapter8):,Basicriskmanagementfacilitationmethods(flowcharts,checksheetsetc.);基本風(fēng)險管理簡易方法(流程圖，對賬單等)失敗模式影響分析失敗模式，影響，和重要性分析(FMECA)錯誤樹形分析(FTA)危害分析和關(guān)鍵監(jiān)控點(diǎn)(HACCP)危害可操作性分析(HAZOP)危害預(yù)分析(PHA)風(fēng)險排序及濾除輔助統(tǒng)計工具將以上方法加以適當(dāng)改進(jìn)，就可用于藥物、藥品質(zhì)量相關(guān)的一些特殊領(lǐng)域。方法同輔助統(tǒng)計工具結(jié)合，帶來的靈活性能為質(zhì)量風(fēng)險管理原則的應(yīng)用提供便利。質(zhì)量風(fēng)險管理的正式程度及精確程度應(yīng)該反映可用到的知識，并與要反映問題的復(fù)雜性、重要程度相適應(yīng)。?FailureModeEffectsAnalysis(FMEA);

FailureMode,EffectsandCriticalityAnalysis(FMECA);FaultTreeAnalysis(FTA);HazardAnalysisandCriticalControlPoints(HACCP);HazardOperability Analysis(HAZOP);PreliminaryHazard Analysis(PHA);Riskrankingandfiltering;Supportingstatisticaltools.Itmightbeappropriatetoadaptthesetoolsforuseinspecificareaspertainingtodrugsubstanceanddrug(medicinal)productquality.Qualityriskmanagementmethodsandthesupportingstatisticaltoolscanbeusedincombination(e.g.,ProbabilisticRiskAssessment).Combineduseprovidesflexibilitythatcanprovidesflexibilitythatcanfacilitatetheapplicationofqualityriskmanagementprinciples.Thedegreeofrigorandformalityofqualityriskmanagementshouldreflectavailableknowledgeandbecommensuratewiththecomplexityand/orcriticalityoftheissuetobeaddressed.REGULATORYOPERATIONSQualityriskmanagementisaprocessthatsupportsscience-basedandpracticaldecisionswhenintegratedintoqualitysystems(seeAnnexII).Asoutlinedintheintroduction,appropriateuseofqualityriskmanagementdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirements.However,effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canREGULATORYOPERATIONSQualityriskmanagementisaprocessthatsupportsscience-basedandpracticaldecisionswhenintegratedintoqualitysystems(seeAnnexII).Asoutlinedintheintroduction,appropriateuseofqualityriskmanagementdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirements.However,effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,can質(zhì)量風(fēng)險管理與質(zhì)量體系結(jié)合后，它能支持基于科學(xué)研究和實(shí)際情況的決策。(seeAnnexII).正如引言中所述，恰當(dāng)?shù)剡\(yùn)用質(zhì)量風(fēng)險管理雖不能免除企業(yè)遵守法規(guī)要求的義務(wù)，卻能推動更好、更合情合理決策的產(chǎn)生，還能增強(qiáng)監(jiān)管當(dāng)局對企業(yè)處理潛在風(fēng)險能力的信心，影響直接監(jiān)管造成的疏忽的程度和水平，促進(jìn)各方對資源的優(yōu)化利用。對企業(yè)職工和監(jiān)管人員進(jìn)行質(zhì)量風(fēng)險管理方面的培訓(xùn)，能使他們更好的理解決策行為，樹立對管理結(jié)果的信心。6.INTEGRATIONOFQUALITYRISK6.行業(yè)與監(jiān)管同質(zhì)量風(fēng)險管理的綜合MANAGEMENTINTOINDUSTRYANDprovideregulatorswithgreaterassuranceofacompany'sabilitytodealwithpotentialrisks,andmightaffecttheextentandlevelofdirectregulatoryoversight.Inaddition,qualityriskmanagementcanfacilitatebetteruseofresourcesbyallparties.Trainingofbothindustryandregulatorypersonnelinqualityriskmanagementprocessesprovidesforgreaterunderstandingofdecision-makingprocessesandbuildsconfidenceinqualityriskmanagementoutcomes.Qualityriskmanagementshouldbe應(yīng)該將質(zhì)量風(fēng)險管理同已有的工作結(jié)integratedintoexistingoperations合起來，并建立妥善的文檔保管。附件anddocumentedappropriately.Annex2列舉了應(yīng)用此方法為藥品各種生產(chǎn)步IIprovidesexamplesofsituations驟提供信息的幾種情形。列出這些例子inwhichtheuseofthequalityrisk只是用于說明的目的，并不能視作是詳managementprocessmightprovide盡而確定的，也不在現(xiàn)有法規(guī)的要求之informationthatcouldthenbeusedinavarietyofpharmaceuticaloperations.Theseexamplesareprovidedforillustrativepurposesonlyandshouldnotbeconsideredadefinitiveorexhaustivelist.Theseexamplesarenotintendedtocreateanynewexpectationsbeyondtherequirementslaidoutinthecurrentregulations.Examplesforindustryandregulatoryoperations(seeAnnexII):Qualitymanagement.Examplesforindustryoperationsandactivities(seeAnnexII):Development;Facility,equipmentandutilities;Materialsmanagement;Production;Laboratorycontrolandstability外提出新的期望。企業(yè)運(yùn)營和活動中的質(zhì)量管理實(shí)例(seeAnnexII):研發(fā)工具，設(shè)備和設(shè)施物料管理生產(chǎn)實(shí)驗(yàn)室控制和穩(wěn)定性檢測包裝和標(biāo)簽監(jiān)管實(shí)例(seeAnnexII):檢查和評估活動testing;?Packagin