企業(yè)質(zhì)量風(fēng)險(xiǎn)管理 中英文對(duì)照

1、TableOfM，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(xiǎn)管理原理4.GENERALQUALITYRISKMANAGEMENTPROCESS質(zhì)量風(fēng)險(xiǎn)管理基本程序4.1Responsibilities職責(zé)分配4.2InitiatingaQualityRiskManagementProcess質(zhì)量風(fēng)險(xiǎn)管理的啟動(dòng)4.3RiskAssessment風(fēng)險(xiǎn)評(píng)估4.4RiskControl風(fēng)險(xiǎn)控制4.5RiskCommunication風(fēng)險(xiǎn)交流4.6RiskReview風(fēng)險(xiǎn)回顧5.RISKMA

2、NAGEMENTMETHODOLOGY風(fēng)險(xiǎn)管理方法學(xué)6.INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS工業(yè)及監(jiān)管與質(zhì)量風(fēng)險(xiǎn)管理的整合7.DEFINITIONS定義&REFERENCES參考資料AnnexI:RiskManagementMethodsandTools附件I:風(fēng)險(xiǎn)管理方法及工具I1BasicRiskManagementFacilitationMethodsI.1基本風(fēng)險(xiǎn)管理簡易方法I.2FailureModeEffectsAnalysis(FMEA)I.2失誤模式影響分析(FMEA)I.3F

3、ailureMode,EffectsandCriticalityAnalysis(FMECA)I.3失誤模式影響及危險(xiǎn)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(HAZ0P)I.7PreliminaryHazardAnalysis(PHA)I.7初步危害分析(PHA)I.8RiskRankingandFilter

4、ingI.8風(fēng)險(xiǎn)排序及濾除I.9SupportingStatisticalToolsI.9輔助統(tǒng)計(jì)工具AnnexII:PotentialApplicationsforQualityRiskManagement附件II:質(zhì)量風(fēng)險(xiǎn)管理潛在應(yīng)用前景.II.lQualityRiskManagementasPartofIntegratedQualityManagementII.1綜合質(zhì)量管理中的質(zhì)量風(fēng)險(xiǎn)管理II.2QualityRiskManagementasPartofRegulatoryOperationsII.2操作優(yōu)化中的應(yīng)用II.3QualityRiskManagementasPartofde

5、velopmentII.3研發(fā)中的應(yīng)用II.4QualityRiskManagementforFacilities,EquipmentandUtilitiesII.4對(duì)工具、設(shè)備和設(shè)施的質(zhì)量風(fēng)險(xiǎn)管理II.5QualityRiskManagementasPartofMaterialsManagementII5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

6、的應(yīng)用II.8QualityRiskManagementasPartofPackagingandLabellingII.8標(biāo)簽及包裝中的應(yīng)用1.INTRODUCTION引言principlesareRiskmanagement風(fēng)險(xiǎn)管理原理在商業(yè)和政府的許多領(lǐng)effectivelyutilizedinmanyareas域都得到了有效應(yīng)用，女口：金融、保險(xiǎn)、ofbusinessandgovernment職業(yè)安全、公共衛(wèi)生、藥物監(jiān)測及相應(yīng)includingfinance,insurance,的監(jiān)管部門。如今質(zhì)量風(fēng)險(xiǎn)管理在藥企occupationalsafety,publichealth,中雖有應(yīng)用，

7、但范圍有限，并沒有發(fā)揮pharmacovigilance,andbyagencies出它的全部效用。藥企已經(jīng)意識(shí)到了質(zhì)regulatingtheseindustries.量體系的重要性，而質(zhì)量風(fēng)險(xiǎn)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.Inadditi

8、on,theimportanceofqualitysystemshasbeenrecognizedinthepharmaceuticalindustryanditisbecomingevidentthatqualityriskmanagementisavaluablecomponentofaneffectivequalitysystem.Itiscommonlyunderstoodthatriskisdefinedasthecombinationofthe根據(jù)常規(guī)理解，風(fēng)險(xiǎn)被定義為傷害發(fā)生的可能性及嚴(yán)重程度。然而，要在不同probabilityofoccurrenceofharmandthes

9、everityofthatharm.However,achievingasharedunderstandingoftheapplicationofriskmanagementamongdiversestakeholdersisdifficultbecauseeachstakeholdermightperceivedifferentpotentialharms,placeadifferentprobabilityoneachharmoccurringandattributedifferentseveritiestoeachharm.Inrelation利益集團(tuán)之間尋求風(fēng)險(xiǎn)管理應(yīng)用方面的共同認(rèn)識(shí)是

10、相當(dāng)困難的，因?yàn)樗麄冋J(rèn)識(shí)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(xiǎn)管理的首要目的是保護(hù)病人。topharmaceuticals,althoughthereareavarietyofstakeholders,includingpatientsandmedicalpractitionersaswellasgovernmentandindustry,theprotectionofthepatientbymanagingtherisktoqualityshouldbeconsideredofprimeimportance.Them

11、anufacturinganduseofadrug藥品生產(chǎn)、使用過程，包括藥品的成分，(medicinal)product,includingits都會(huì)不可避免地引入一定的風(fēng)險(xiǎn)。質(zhì)量components,necessarilyentailsomedegreeofrisk.Therisktoitsqualityisjustonecomponentoftheoverallrisk.Itisimportanttounderstandthatproductqualityshouldbemaintainedthroughouttheproductlifecyclesuchthattheattribute

12、sthatareimportanttothequalityofthedrug(medicinal)productremainconsistentwiththoseusedintheclinicalstudies.Aneffectivequalityrisk風(fēng)險(xiǎn)只是其中的一部分。在產(chǎn)品整個(gè)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(gè)有效的質(zhì)量風(fēng)險(xiǎn)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(shí)，應(yīng)用質(zhì)量風(fēng)險(xiǎn)管理還能改善決策過程。有效進(jìn)行質(zhì)量風(fēng)險(xiǎn)管理能促使產(chǎn)生更好更正式?jīng)Q策，增強(qiáng)監(jiān)控者對(duì)公

13、司處理潛在風(fēng)險(xiǎn)能力的信心，積極影響直接監(jiān)理的程度和水平。managementapproachcanfurtherensurethehighqualityofthedrug(medicinal)producttothepatientbyprovidingaproactivemeanstoidentifyandcontrolpotentialqualityissuesduringdevelopmentandmanufacturing.Additionally.useofqualityriskmanagementcanimprovethedecisionmakingifaqualityproblem

14、arises.Effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompanysabilitytodealwithpotentialrisksandcanbeneficiallyaffecttheextentandlevelofdirectregulatoryoversight.Thepurposeofthisdocumentistoofferasystematicapproachtoqualityriskman

15、agement.Itservesasafoundationorresourcedocumentthatisindependentof,yetsupports,otherICHQualitydocumentsandcomplementsexistingqualitypractices,requirements,standards,andguidelineswithinthepharmaceuticalindustryandregulatoryenvironment.Itspecificallyprovidesguidanceon此文件的目的是提供質(zhì)量風(fēng)險(xiǎn)管理方面的系統(tǒng)方法。作為一個(gè)基礎(chǔ)性、資源性

16、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(xiǎn)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(gè)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(xiǎn)的決策，并不想在現(xiàn)有法規(guī)之外提出新的期望。theprinciplesandsomeofthetoolsofqualityriskmanagementthatcanenablemoreeffectiveandconsistentriskbaseddecisions,bothbyregulatorsandindustry,regardingthequalityof

17、drugsubstancesanddrug(medicinal)productsacrosstheproductlifecycle.Itisnotintendedtocreateanynewexpectationsbeyondthecurrentregulatoryrequirements.Itisneitheralwaysappropriatenoralwaysnecessarytouseaformalriskmanagementprocess(usingrecognizedtoolsand/orinternalprocedurese.g.,standardoperatingprocedur

18、es).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsand/orinternalprocedures)canalsobeconsidered應(yīng)用正式的風(fēng)險(xiǎn)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(shí)也允許使用非正式的風(fēng)險(xiǎn)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(xiǎn)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.Appropriateuseofqualityriskmanagementcanfacilitatebutdoesno

19、tobviateindustrysobligationtocomplywithregulatoryrequirementsanddoesnotreplaceappropriatecommunicationsbetweenindustryandregulators.2.范圍Thisguidelineprovidesprinciples本指南給出了質(zhì)量風(fēng)險(xiǎn)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SCOPEriskmanagementthatcanbeapplied方面，即藥用物質(zhì)、藥品、生物和生物todifferentaspectso

20、f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aspectsincludedevelopment,研發(fā)、生產(chǎn)、銷售、檢察、提交和復(fù)審各manufacturing,distribution,and過程。theinspectionandsubmission/reviewprocessesthroughoutthelifecycleofdrugsubstances,drug(medicinal)products,biologicalandbiotechnologicalproducts(includingtheuseof

21、rawmaterials,solvents,excipients,packagingandlabelingmaterialsindrug(medicinal)products,biologicalandbiotechnologicalproducts).PRINCIPLESOFQUALITYRISKMANAGEMENTTwoprimaryprinciplesofqualityriskmanagementare:Theevaluationoftherisktoqualityshouldbebasedonscientificknowledgeandultimatelylinktotheprotec

22、tionofthepatient;andThelevelofeffort,formalityanddocumentationofthequalityriskmanagementprocessshouldbecommensuratewiththelevelofrisk.3.質(zhì)量風(fēng)險(xiǎn)管理原理質(zhì)量風(fēng)險(xiǎn)管理的兩條基本原理是:評(píng)估質(zhì)量風(fēng)險(xiǎn)應(yīng)基于科學(xué)知識(shí)并最終同對(duì)病人的保護(hù)聯(lián)系起來。投入的努力程度、管理的正式程度及文件管理水平應(yīng)與風(fēng)險(xiǎn)水平相適應(yīng)。GENERALQUALITYRISKMANAGEMENT4.質(zhì)量風(fēng)險(xiǎn)管理基本過程PROCESSQualityriskmanagementisa質(zhì)量風(fēng)險(xiǎn)管理是對(duì)藥品

23、質(zhì)量風(fēng)險(xiǎn)進(jìn)行systematicprocessforthe評(píng)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(gè)生命周期。圖1andreviewofriskstothequality給出了這方面的一個(gè)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(huì)各有差別，可是一個(gè)有效modelforqualityriskmanagementis的管理過程會(huì)將所有因素納入考慮，各outlinedinthediagram(Fig

24、ure1).因素受關(guān)注程度會(huì)因風(fēng)險(xiǎn)的特異而各Othermodelscouldbeused.The有區(qū)別。emphasisoneachcomponentoftheframeworkmightdifferfromcasetocasebutarobustprocesswillincorporateconsiderationofalltheelementsatalevelofdetailthatiscommensuratewiththespecificrisk.Figure1:典型質(zhì)量風(fēng)險(xiǎn)管理過程簡介風(fēng)險(xiǎn)管理工具Decisionnodesarenotshowninthe由于決策行為隨時(shí)都可能發(fā)生,di

25、agramabovebecausedecisionscanoccuratanypointintheprocess.Thesedecisionsmightbetoreturntothepreviousstepandseekfurtherinformation,toadjusttheriskmodelsoreventoterminatethe上圖就沒有顯示決策點(diǎn)。這些決策有可能被反饋到上一步以尋求更多信息，這些信息可用于調(diào)整風(fēng)險(xiǎn)模型；也可能用于管理過程的終止。注解：圖中的“不可接受”項(xiàng)不僅指違背了法令法規(guī)要求，也表示風(fēng)險(xiǎn)管理過程需要重頭再來。riskmanagementprocessbasedup

26、oninformationthatsupportssuchadecision.Note:“unacceptable”intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.4.1ResponsibilitiesQualityriskmanagementactivitiesareusually,butnotalways,undertakenbyinterdisciplinaryteams.Whent

27、eamsareformed,theyshouldincludeexpertsfromtheappropriateareas(e.g.,qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketing,legal,statisticsandclinical)inadditiontoindividualswhoareknowledgeable4.1職責(zé)分配質(zhì)量風(fēng)險(xiǎn)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(xiǎn)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

28、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(jì)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(gè)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。aboutthequalityriskmanagementprocess.Decisionmakersshouldtakeresponsibilityforcoordinatingqualityriskmanagementacrossvariousfunctionsanddepartmentsoftheirorganization;andassurethataqualityris

29、kmanagementprocessisdefined,deployedandreviewedandthatadequateresourcesareavailable.4.2InitiatingaQualityRisk4.2質(zhì)量風(fēng)險(xiǎn)管理的啟動(dòng)ManagementProcessQualityriskmanagementshould質(zhì)量風(fēng)險(xiǎn)管理應(yīng)包括這樣一些系統(tǒng)程includesystematicprocesses序，這些設(shè)計(jì)好的程序用來協(xié)調(diào)，推動(dòng)designedtocoordinate,facilitate和改善那些風(fēng)險(xiǎn)方面基于科學(xué)認(rèn)識(shí)的andimprovescience-baseddecisi

30、on決定。一項(xiàng)管理程序的發(fā)起和設(shè)計(jì)可能makingwithrespecttorisk.要經(jīng)過如下步驟：Possiblestepsusedtoinitiateand1定義存在的難題和風(fēng)險(xiǎn)問題，包括識(shí)別planaqualityriskmanagement潛在風(fēng)險(xiǎn)的相關(guān)假設(shè)；processmightincludethe收集風(fēng)險(xiǎn)評(píng)估相關(guān)的關(guān)于潛在危險(xiǎn)、危following:害或人體健康影響的背景信息和數(shù)據(jù)；Definetheproblemand/orrisk確定領(lǐng)導(dǎo)人和重要資源；question,includingpertinent詳細(xì)說明決策的時(shí)間表，可交付性和適assumptionsidentif

31、yingthe當(dāng)?shù)臉?biāo)準(zhǔn)。potentialforrisk;Assemblebackgroundinformationand/ordataonthepotentialhazard,harmorhumanhealthimpactrelevanttotheriskassessment;Identifyaleaderandnecessaryresources;Specifyatimeline,deliverablesandappropriatelevelofdecisionmakingfortheriskmanagementprocess.4.3RiskAssessment4.3風(fēng)險(xiǎn)評(píng)估Riskass

32、essmentconsistsofthe風(fēng)險(xiǎn)評(píng)估：此過程進(jìn)行危險(xiǎn)確認(rèn)并對(duì)接identificationofhazardsandthe觸這些危險(xiǎn)所帶來的風(fēng)險(xiǎn)進(jìn)行分析評(píng)analysisandevaluationofrisks價(jià)。它以一個(gè)定義明確的難點(diǎn)描敘或風(fēng)associatedwithexposuretothose險(xiǎn)問題開始，當(dāng)風(fēng)險(xiǎn)明確后，選擇合適hazards(asdefinedbelow).Quality而有針對(duì)性的管理工具和信息類型將riskassessmentsbeginwithawell-definedproblemdescriptionorriskquestion.Whentheris

33、kinquestioniswelldefined,anappropriateriskmanagementtool(seeexamplesinsection5)andthetypesofinformationneededtoaddresstheriskquestionwillbemorereadilyidentifiable.Asanaidtoclearlydefiningtherisk(s)forriskassessmentpurposes,threefundamentalquestionsareoftenhelpful:會(huì)變得更容易。以下三個(gè)基本問題將有助于給出風(fēng)險(xiǎn)的清晰定義。什么可能會(huì)出錯(cuò)

34、？出錯(cuò)的可能性有多大？出錯(cuò)的后果和嚴(yán)重性有哪些？1.Whatmightgowrong?2.Whatisthelikelihood(probability)itwillgowrong?3.Whataretheconsequences(severity)?Riskidentificationisasystematicuseofinformationtoidentifyhazardsreferringtotherisk風(fēng)險(xiǎn)鑒定：參照風(fēng)險(xiǎn)問題或難點(diǎn)描敘，系統(tǒng)利用已有信息去鑒定危險(xiǎn)。這些信息包括歷史數(shù)據(jù)、理論分析、多方面觀questionorproblemdescription.點(diǎn)和風(fēng)險(xiǎn)承擔(dān)人的意見。風(fēng)

35、險(xiǎn)鑒定時(shí)提Informationcanincludehistorical出“什么會(huì)出錯(cuò)”這一問題，同時(shí)還確data,theoreticalanalysis,定可能答案。這一過程為后續(xù)步驟奠定informedopinions,andtheconcerns了基礎(chǔ)。ofstakeholders.Riskidentificationaddressesthe“Whatmightgowrong?”question,includingidentifyingthepossibleconsequences.Thisprovidesthebasisforfurtherstepsinthequalityriskma

36、nagementprocess.Riskanalysisistheestimationof風(fēng)險(xiǎn)分析：估計(jì)與已確認(rèn)危險(xiǎn)相聯(lián)系的theriskassociatedwiththe風(fēng)險(xiǎn)，這是對(duì)危害發(fā)生的可能性和嚴(yán)重identifiedhazards.Itisthe程度進(jìn)行定性和定量分析的過程。風(fēng)險(xiǎn)qualitativeorquantitativeprocess評(píng)價(jià)中同樣也應(yīng)用到某些管理工具檢oflinkingthelikelihoodof測危害的能力（檢測能力）。occurrenceandseverityofharms.Insomeriskmanagementtools,theabilitytodet

37、ecttheharm(detectability)alsofactorsintheestimationofrisk.aboutaprocessanditsexpectedor詞的適用范圍都要詳細(xì)規(guī)定,Riskevaluationcomparestheidentifiedandanalyzedriskagainstgivenriskcriteria.Riskevaluationsconsiderthestrengthofevidenceforallthreeofthefundamentalquestions.Indoinganeffectiveriskassessment,therobustne

38、ssofthedatasetisimportantbecauseitdeterminesthequalityoftheoutput.Revealingassumptionsandreasonablesourcesofuncertaintywillenhanceconfidenceinthisoutputand/orhelpidentifyitslimitations.Uncertaintyisduetocombinationofincompleteknowledgeunexpectedvariability.Typicalsourcesofuncertaintyincludegapsinkno

39、wledgegapsinpharmaceuticalscienceandprocessunderstanding.風(fēng)險(xiǎn)評(píng)估：將經(jīng)過分析和鑒定的風(fēng)險(xiǎn)同給定標(biāo)準(zhǔn)作比較，考慮三個(gè)基本問題的證據(jù)力。風(fēng)險(xiǎn)評(píng)估中，數(shù)據(jù)的有效性決定了評(píng)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(duì)結(jié)果的信心、識(shí)別結(jié)果的局限性。對(duì)過程了解不充分、過程中可預(yù)見及不可預(yù)見變動(dòng)的發(fā)生，都將導(dǎo)致不確定性的發(fā)生。知識(shí)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(xiǎn)來源（不成功的過程模式、變動(dòng)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(píng)估結(jié)果可以是對(duì)風(fēng)險(xiǎn)的定量表示，也可以是對(duì)分險(xiǎn)程度的定性描述。定量表示時(shí)可

40、用數(shù)值表示可能性，用高、中、低來給風(fēng)險(xiǎn)排序時(shí)，各個(gè)有時(shí)候還用到風(fēng)險(xiǎn)評(píng)分來進(jìn)一步定義。定量評(píng)估能對(duì)給定的風(fēng)險(xiǎn)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(píng)估一次只能評(píng)判一個(gè)特定結(jié)果。于是一sourcesofharm(e.g.,failuremodes些管理工具用到相對(duì)衡量尺度，將多重ofaprocess,sourcesof水平的嚴(yán)重性和可能性結(jié)合起來，以完variability),andprobabilityof成對(duì)相對(duì)風(fēng)險(xiǎn)的整體評(píng)估。評(píng)分過程的detectionofproblems.中間步驟有時(shí)也用到定量風(fēng)險(xiǎn)估計(jì)方Theoutputofariskassessmentis法。ofeithe

41、raquantitativeestimateriskoraqualitativedescriptionofarangeofrisk.Whenriskisaexpressedquantitatively.numericalprobabilityisused.Alternatively,riskcanbeexpressedusingqualitativedescriptors,suchas“high”，“medium”，or“l(fā)ow”，whichshouldbedefinedinasmuchdetailaspossible.Sometimesariskscoreisusedtofurtherdef

42、inedescriptorsinriskranking.Inquantitativeriskassessments,ariskestimateprovidesthelikelihoodofaspecificconsequence,givenasetofrisk-generatingcircumstances.Thus,quantitativeriskestimationisusefulforoneparticularconsequenceatatime.Alternatively,someriskmanagementtoolsusearelativeriskmeasuretocombinemu

43、ltiplelevelsofseverityandprobabilityintoanoverallestimateofrelativerisk.Theintermediatestepswithinascoringprocesscansometimesemployquantitativeriskestimation.4.4RiskControl4.4風(fēng)險(xiǎn)控制Riskcontrolincludesdecision風(fēng)險(xiǎn)控制包括風(fēng)險(xiǎn)抑低和風(fēng)險(xiǎn)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(xiǎn)降低到可

44、接受水平，投入努力量istoreducetherisktoan應(yīng)與風(fēng)險(xiǎn)的嚴(yán)重程度相襯。決策者應(yīng)用acceptablelevel.Theamountofeffortusedforriskcontrolshoulc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(xiǎn)控制的最佳水平。beproportionaltothesignificance風(fēng)險(xiǎn)控制過程中以下問題會(huì)受到關(guān)注：oftherisk.Decisionmakersmight風(fēng)險(xiǎn)水平是否高于可接受水平之上？usedifferentprocesses,includingbenefit-costanalysis,forunderstandingthe

45、optimallevelofriskcontrol.Riskcontrolmightfocusonthefollowingquestions:Istheriskaboveanacceptablelevel?Whatcanbedonetoreduceoreliminaterisks?Whatistheappropriatebalanceamongbenefits,risksandresources?Arenewrisksintroducedasaresultoftheidentifiedrisksbeingcontrolled?Riskreductionfocusesonprocessesfor

46、mitigationoravoidanceofqualityriskwhenitexceedsaspecified(acceptable)level(seeFig.1).Riskreductionmight怎樣做才能降低乃至消除風(fēng)險(xiǎn)？如何尋求效益、風(fēng)險(xiǎn)和資源之間的合適平衡？對(duì)已確定風(fēng)險(xiǎn)進(jìn)行控制時(shí)是否會(huì)引入新的風(fēng)險(xiǎn)？風(fēng)險(xiǎn)抑低：此過程著力于減輕或避免超過一定水平（可接受水平）的質(zhì)量風(fēng)險(xiǎn),包括為減輕危害嚴(yán)重性和發(fā)生可能性而采取的一系列措施，還包括一些致力于改善危險(xiǎn)及質(zhì)量風(fēng)險(xiǎn)可檢測性的程qualityrisksmightalsobeusedas程,partofariskcontrolstrategy.

47、Theimplementationofriskreductionincludeactionstakentomitigatetheseverityandprobabilityofharm.Processesthatimprovethedetectabilityofhazardsand化。序。風(fēng)險(xiǎn)抑低過程可能會(huì)給系統(tǒng)帶入新的風(fēng)險(xiǎn)，其他業(yè)已存在的風(fēng)險(xiǎn)的嚴(yán)重程度也可能增加。因此，完成風(fēng)險(xiǎn)抑低程序后，有必要再重復(fù)一下質(zhì)量評(píng)估過來識(shí)別和評(píng)價(jià)風(fēng)險(xiǎn)系統(tǒng)的可能變measurescanintroducenewrisksintothesystemorincreasethesignificanceofotherexi

48、stingrisks.Hence,itmightbeappropriatetorevisittheriskassessmenttoidentifyandevaluateanypossiblechangeinriskafterimplementingariskreductionprocess.Riskacceptanceisadecisionto風(fēng)險(xiǎn)接受：就是接受風(fēng)險(xiǎn)的決定。它可acceptrisk.Riskacceptancecanbe能為接受殘留風(fēng)險(xiǎn)的正式?jīng)Q定，也可以aformaldecisiontoacceptthe是忽略剩余風(fēng)險(xiǎn)的消極決定。有些類型residualriskoritcanb

49、eapassive的風(fēng)險(xiǎn)，即使用最好的質(zhì)量風(fēng)險(xiǎn)管理手decisioninwhichresidualrisksare段，也不能完全清除。在這種情形下,notspecified.Forsometypesofharms,eventhebestqualityriskmanagementpracticesmightnotentirelyeliminaterisk.Inthesecircumstances,itmightbeagreedthatanappropriatequalityriskmanagementstrategyhasbeenappliedandthatqualityriskisreduce

50、dtoaspecified(acceptable)level.This(specified)acceptablelevelwilldependonmanyparametersandshouldbedecidedonacase-by-casebasis.應(yīng)確認(rèn)使用了合適的風(fēng)險(xiǎn)管理策略，且風(fēng)險(xiǎn)已被降至特定水平（可接受水平）。這個(gè)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(xiǎn)溝通Riskcommunicationisthesharingof風(fēng)險(xiǎn)溝通：決策者和其他人就風(fēng)險(xiǎn)和風(fēng)informationaboutriskandrisk險(xiǎn)管理方面的信息進(jìn)行溝通、交

51、流，各managementbetweenthedecision利益集團(tuán)間的交流在風(fēng)險(xiǎn)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(xiǎn)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，ofthequalityriskmanagementprocessshouldbeappropriatelycommunicatedanddoc

52、umented(seeFig.1:solidarrows).Communicationsmightincludethoseamonginterestedparties;e.g.,regulatorsandindustry,industryandthepatient,withinacompany,industryorregulatoryauthority,etc.Theincludedinformationmightrelatetotheexistence,nature,form,probability,severity,acceptability,control,treatment,detec

53、tabilityorotheraspectsofriskstoquality.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(xiǎn)的存在、性質(zhì)、形式、可能性、嚴(yán)重程度、可接受度、控

54、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(gè)風(fēng)險(xiǎn)承擔(dān)都進(jìn)行風(fēng)險(xiǎn)交流。企業(yè)和監(jiān)管機(jī)構(gòu)之間關(guān)于質(zhì)量風(fēng)險(xiǎn)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/resultsoftheriskmanagementprocessreviewedtotakeintos

55、houldbeaccountnewknowledgeandexperience.Onceaqualityriskmanagementprocesshasbeeninitiated,thatprocessshouldcontinuetobeutilizedforeventsthatmightimpacttheoriginalqualityriskmanagementdecision,whethertheseeventsareplanned(e.g.,resultsofproductreview,inspections,audits,changecontrol)orunplanned(e.g.,r

56、ootcausefromfailureinvestigations.4.6風(fēng)險(xiǎn)回顧風(fēng)險(xiǎn)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(xiǎn)管理過程的結(jié)果時(shí)要將新的知識(shí)和經(jīng)驗(yàn)納入考慮范圍。一旦一個(gè)質(zhì)量風(fēng)險(xiǎn)管理過程開始啟動(dòng)，它便用于管理那些可能會(huì)影響最初質(zhì)量風(fēng)險(xiǎn)管理決策的事件，不管這些事件是計(jì)劃中的（產(chǎn)品回顧結(jié)果，自檢、審計(jì)和變更控制管理）還是計(jì)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(xiǎn)水平，風(fēng)險(xiǎn)回顧還可能包括對(duì)風(fēng)險(xiǎn)接受決定的再審議。recall).Thefrequencyofanyreviewshouldbebaseduponthelevelofrisk.Ris

57、kreviewmightincludereconsiderationofriskacceptancedecisions(section4.4).havebeenassessedandmanagedin彳同樣,varietyofinformalways(empiricalRISKMANAGEMENTMETHODOLOGYQualityriskmanagementsupportsascientificandpracticalapproachtodecision-making.Itprovidesdocumented,transparentandreproduciblemethodstoaccomp

58、lishstepsofthequalityriskmanagementprocessbasedoncurrentknowledgeaboutassessingtheprobability,severityandsometimesdetectabilityoftherisk.Traditionally,riskstoqualityand/orinternalprocedures)basedon,forexample,compilationof5.質(zhì)量管理方法學(xué)質(zhì)量風(fēng)險(xiǎn)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(jì)風(fēng)險(xiǎn)可能性、嚴(yán)重程度和可檢測性方面的知識(shí)，提供一些已形成文件的、透

59、明的和可再生的方法，來完成質(zhì)量風(fēng)險(xiǎn)管理各步驟。質(zhì)量風(fēng)險(xiǎn)傳統(tǒng)上是用一系列非正規(guī)方法來進(jìn)行評(píng)估和控制的，這些方法基于觀測報(bào)告，風(fēng)險(xiǎn)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)的工具和內(nèi)部程序來進(jìn)行評(píng)估和控制，以下就是這樣一些工具（Annex1andsectionVIII中更有詳敘）：observations,trendsandotherinformation.Suchapproachescontinuetoprovideusefulinformationthatmightsupporttopicssuchashandlingofco

60、mplaints,qualitydefects,deviationsandallocationofresources.Additionally,thepharmaceuticalindustryandregulatorscanassessandmanageriskusingrecognizedriskmanagementtoolsand/orinternalprocedures(e.g.,standardoperatingprocedures).Belowisanon-exhaustivelistofsomeofthesetools(furtherdetailsinAnnex1andchapt