Q9 質(zhì)量風(fēng)險(xiǎn)管理 中英文對照

QUALITYRISKMANAGEMENTQ9工業(yè)指南Q9質(zhì)量風(fēng)險(xiǎn)管理美國健康與公眾服務(wù)部食品藥品監(jiān)督管理局（FDA）

藥品評價(jià)與研究中心（CDER）

生物評價(jià)與研究中心（CBER）2006年6月人用藥物注冊技術(shù)要求國際協(xié)調(diào)會議（ICH）

TableofContents目錄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.RISKMANAGEMENTMETHODOLOGY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8.REFERENCES參考資料AnnexI:RiskManagementMethodsandTools附件I:風(fēng)險(xiǎn)管理方法及工具I.1BasicRiskManagementFacilitationMethodsI.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.3FailureMode,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(HAZOP)I.7PreliminaryHazardAnalysis(PHA)I.7初步危害分析(PHA)I.8RiskRankingandFilteringI.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.1QualityRiskManagementasPartofIntegratedII.1綜合質(zhì)量管理中的質(zhì)量風(fēng)險(xiǎn)管理

QualityManagementII?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,EquipmentandUtilitiesn.4對工具、設(shè)備和設(shè)施的質(zhì)量風(fēng)險(xiǎn)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?INTRODUCTIONRiskmanagementprinciplesareeffectivelyutilizedinmanyareasofbusinessandgovernmentincludingfinance,insurance,occupationalsafety,publichealth,pharmacovigilance,andbyagenciesregulatingtheseindustries.Althoughtherearesomeexamplesoftheuseofqualityriskmanagementinthepharmaceuticalindustrytoday,theyarelimitedanddonotrepresentthefullcontributionsthatriskmanagementhastooffer.Inaddition,theimportanceofqualitysystemshasbeenrecognizedinthepharmaceuticalindustryanditisbecomingevidentthatqualityriskmanagementisavaluablecomponentofaneffectivequalitysystem.Itiscommonlyunderstoodthatriskisdefinedasthecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm.However,achievingasharedunderstandingoftheapplicationofriskmanagementamongdiversestakeholdersisdifficultbecauseeachstakeholdermightperceivedifferentpotentialharms,placeadifferentprobabilityoneachharmoccurringandattributedifferentseveritiestoeachharm.Inrelationtopharmaceuticals,althoughthereareavarietyofstakeholders,includingpatientsandmedicalpractitionersaswellasgovernmentandindustry,theprotectionofthepatientbymanagingtherisktoqualityshouldbeconsideredofprimeimportance.引言風(fēng)險(xiǎn)管理原理在商業(yè)和政府的許多領(lǐng)域都得到了有效應(yīng)用，如：金融、保險(xiǎn)、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(xiǎn)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(xiǎn)管理越來越明顯地成為有效質(zhì)量體系的重要組分。Themanufacturinganduseofadrug(medicinal)藥品生產(chǎn)、使用過程，包括藥品的成分，都會不可避根據(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(xiǎn)管理的首要目的是保護(hù)病人。Themanufacturinganduseofadrug(medicinal)藥品生產(chǎn)、使用過程，包括藥品的成分，都會不可避ContainsNonbindingRecommendationsContainsNonbindingRecommendationsproduct,includingitscomponents,necessarilyentailsomedegreeofrisk.Therisktoitsqualityisjustonecomponentoftheoverallrisk.Itisimportanttounderstandthatproductqualityshouldbemaintainedthroughouttheproductlifecyclesuchthattheattributesthatareimportanttothequalityofthedrug(medicinal)productremainconsistentwiththoseusedintheclinicalstudies.Aneffectivequalityriskmanagementapproachcanfurtherensurethehighqualityofthedrug(medicinal)producttothepatientbyprovidingaproactivemeanstoidentifyandcontrolpotentialqualityissuesduringdevelopmentandmanufacturing.Additionally,useofqualityriskmanagementcanimprovethedecisionmakingifaqualityproblemarises.Effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany'sabilitywithpotentialrisksandcanbeneficiallyaffecttheextentandlevelofdirectregulatoryoversight.Thepurposeofthisdocumentistoofferasystematicapproachtoqualityriskmanagement.Itservesasafoundationorresourcedocumentthatisindependentof,yetsupports,otherICHQualitydocumentsandcomplementsexistingqualitypractices,requirements,standards,andguidelineswithinthepharmaceuticalindustryandregulatoryenvironment.Itspecificallyprovidesguidanceontheprinciplesandsomeofthetoolsofqualityriskmanagementthatcanenablemore免地引入一定的風(fēng)險(xiǎn)。質(zhì)量風(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)控者對公司處理潛在風(fēng)險(xiǎn)能力的信心，積極影響直接監(jiān)理的程度和水平。todeal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。effectiveandconsistentriskbaseddecisions,bothbyregulatorsandindustry,regardingthequalityofdrugsubstancesanddrug(medicinal)productsacrosstheproductlifecycle.Itisnotintendedtocreateanynewexpectationsbeyondthecurrentregulatoryrequirements.Itisneitheralwaysappropriatenoralwaysnecessaryto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useaformalriskmanagementprocess(using（用已承認(rèn)的工具或內(nèi)部程序，如標(biāo)準(zhǔn)操作規(guī)程）。recognizedtoolsand/orinternalprocedurese.g.,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standardoperatingprocedures).Theuseofinformalrisk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managementprocesses(usingempiricaltoolsand/or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internalprocedures)canalsobeconsideredacceptable.間必要的溝通交流。Appropriateuseofqualityriskmanagementcanfacilitatebutdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirementsanddoesnotreplaceappropriatecommunicationsbetweenindustryandregulators.2.SCOPE2.范圍Thisguidelineprovidesprinciplesandexamplesof本指南給出了質(zhì)量風(fēng)險(xiǎn)管理工具的原理和應(yīng)用實(shí)例，toolsforqualityriskmanagementthatcanbeappliedto這些工具可用于藥品質(zhì)量各方面，即藥用物質(zhì)、藥品differentaspectsofpharmaceuticalquality.These生物和生物技術(shù)產(chǎn)品（包括藥品中用到的原料、溶劑aspectsincludedevelopment,manufacturing,賦形劑、包裝標(biāo)簽材料等）生命周期中的研發(fā)、生產(chǎn)distribution,andtheinspectionandsubmission/review銷售、檢察、提交和復(fù)審各過程。processesthroughoutthelifecycleofdrugsubstances,drug(medicinal)products,biologicalandbiotechnologicalproducts(includingtheuseofrawmaterials,solvents,excipients,packagingandlabelingmaterialsindrug(medicinal)products,biologicalandbiotechnologicalproducts).PRINCIPLESOFQUALITYRISKMANAGEMENTTwoprimaryprinciplesofqualityriskmanagementare:Theevaluationoftherisktoqualityshouldbebasedonscientificknowledgeandultimatelylinktotheprotectionofthepatient;andThelevelofeffort,formalityanddocumentationofthequalityriskmanagementprocessshouldbecommensuratewiththelevelofrisk.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：評估質(zhì)量風(fēng)險(xiǎn)應(yīng)基于科學(xué)知識并最終同對病人的保護(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)。GENERALQUALITYRISKMANAGEMENTPROCESSQualityriskmanagementisasystematicprocessfortheassessment,control,communicationandreviewofriskstothequalityofthedrug(medicinal)productacrosstheproductlifecycle.Amodelforqualityriskmanagementisoutlinedinthediagram(Figure1).Othermodelscouldbeused.Theemphasisoneachcomponentoftheframeworkmightdifferfromcasetocasebutarobustprocesswillincorporateconsiderationofalltheelementsatalevelofdetailthatiscommensuratewiththespecificrisk.質(zhì)量風(fēng)險(xiǎn)管理基本過程質(zhì)量風(fēng)險(xiǎn)管理是對藥品質(zhì)量風(fēng)險(xiǎn)進(jìn)行評估，控制，交流和審查的系統(tǒng)過程，這一過程貫穿藥品整個(gè)生命周期。圖1給出了這方面的一個(gè)模型，其他模型也有應(yīng)用。具體情況不同，框架中各組分受重視水平會各有差別，可是一個(gè)有效的管理過程會將所有因素納入考慮，各因素受關(guān)注程度會因風(fēng)險(xiǎn)的特異而各有區(qū)別。ContainsNonbindingRecommendationsContainsNonbindingRecommendationsprocessFigure1:Overviewof5爲(wèi)z杳n“?!■HimTffftuRiskAssessmentiRiskIdsntifjcati-DnVRiskAnalysisJRiskEvaluationRiskControlrRiskReductioHiIRiskAcceptanceFigure1:典型質(zhì)量風(fēng)險(xiǎn)管理過程簡介ContainsNonbindingRecommendationsContainsNonbindingRecommendations風(fēng)險(xiǎn)管理工具風(fēng)險(xiǎn)交流Decisionnodesarenotshowninthediagramabovebecausedecisionscanoccuratanypointintheprocess.Thesedecisionsmightbetoreturntothepreviousstepandseekfurtherinformation,toadjusttheriskmodels由于決策行為隨時(shí)都可能發(fā)生，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oreventoterminatetheriskmanagementprocessbaseduponinformationthatsupportssuchadecision.Note: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?！皍nacceptable"intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.

4.1Responsibilities4.1.職責(zé)分配Qualityriskmanagementactivitiesareusually,butnotalways,undertakenbyinterdisciplinaryteams.Whenteamsareformed,theyshouldincludeexpertsfromtheappropriateareas(e.g.,qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketing,legal,statisticsandclinical)inadditiontoindividualswhoareknowledgeableaboutthequalityriskmanagementprocess.Decisionmakershouldtakeresponsibilityforcoordinatingqualityriskmanagementacrossvariousfunctionsanddepartmentsoftheirorganization;andassurethataqualityriskmanagementprocessisdefined,deployedandreviewedandthatadequateresourcesareavailable.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。4.2InitiatingaQualityRiskManagementProcess4.2質(zhì)量風(fēng)險(xiǎn)管理的啟動(dòng)Qualityriskmanagementshouldincludesystematicprocessesdesignedtocoordinate,facilitateandimprovescience-baseddecisionmakingwithrespecttorisk.Possiblestepsusedtoinitiateandplanaqualityriskmanagementprocessmightincludethefollowing:Definetheproblemand/orriskquestion,includingpertinentassumptionsidentifyingthepotentialforrisk;Assemblebackgroundinformationand/ordataonthepotentialhazard,harmorhumanhealthimpactrelevanttotheriskassessment;質(zhì)量風(fēng)險(xiǎn)管理應(yīng)包括這樣一些系統(tǒng)程序，這些設(shè)計(jì)好的程序用來協(xié)調(diào)，推動(dòng)和改善那些風(fēng)險(xiǎn)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(jì)可能要經(jīng)過如下步驟：?定義存在的難題和風(fēng)險(xiǎn)問題，包括識別潛在風(fēng)險(xiǎn)的相關(guān)假設(shè)；?收集風(fēng)險(xiǎn)評估相關(guān)的關(guān)于潛在危險(xiǎn)、危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(shí)間表，可交付性和適當(dāng)?shù)臉?biāo)準(zhǔn)。

Identifyaleaderandnecessaryresources;Specifyatimeline,deliverablesandappropriatelevelofdecisionmakingfortheriskmanagementprocess.4.3RiskAssessment4.3風(fēng)險(xiǎn)評估Riskassessmentconsistsoftheidentificationofhazards風(fēng)險(xiǎn)評估：此過程進(jìn)行危險(xiǎn)確認(rèn)并對接觸這些危險(xiǎn)所andtheanalysisandevaluationofrisksassociatedwith帶來的風(fēng)險(xiǎn)進(jìn)行分析評價(jià)。它以一個(gè)定義明確的難點(diǎn)exposuretothosehazards(asdefinedbelow).Quality描敘或風(fēng)險(xiǎn)問題開始，當(dāng)風(fēng)險(xiǎn)明確后，選擇合適而有riskassessmentsbeginwithawell-definedproblem針對性的管理工具和信息類型將會變得更容易。以下descriptionorriskquestion.Whentheriskinquestionis三個(gè)基本問題將有助于給出風(fēng)險(xiǎn)的清晰定義。welldefined,anappropriateriskmanagementtool(see1.什么可能會出錯(cuò)？examplesinsection5)andthetypesofinformation2.出錯(cuò)的可能性有多大？neededtoaddresstheriskquestionwillbemorereadily3.出錯(cuò)的后果和嚴(yán)重性有哪些？identifiable.Asanaidtoclearlydefiningtherisk(s)forriskassessmentpurposes,threefundamentalquestionsareoftenhelpful:Whatmightgowrong?Whatisthelikelihood(probability)itwillgowrong?Whataretheconsequences(severity)?Riskidentificationisasystematicuseofinformationto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identifyhazardsreferringtotheriskquestionor信息去鑒定危險(xiǎn)。這些信息包括歷史數(shù)據(jù)、理論分析、problemdescription.Informationcanincludehistorical多方面觀點(diǎn)和風(fēng)險(xiǎn)承擔(dān)人的意見。風(fēng)險(xiǎn)鑒定時(shí)提出data,theoreticalanalysis,informedopinions,andthe“什么會出錯(cuò)”這一問題，同時(shí)還確定可能答案。這concernsofstakeholders.Riskidentificationaddresses一過程為后續(xù)步驟奠定了基礎(chǔ)。the“Whatmightgowrong?"question,includingidentifyingthepossibleconsequences.Thisprovidesthebasisforfurtherstepsinthequalityriskmanagementprocess.Riskanalysisistheestimationoftheriskassociatedwiththeidentifiedhazards.Itisthequalitativeorquantitativeprocessoflinkingthelikelihoodofoccurrenceandseverityofharms.Insomeriskmanagementtools,theabilitytodetecttheharm(detectability)alsofactorsintheestimationofrisk.

風(fēng)險(xiǎn)分析：估計(jì)與已確認(rèn)危險(xiǎn)相聯(lián)系的風(fēng)險(xiǎn)，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(xiǎn)評價(jià)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）。Riskevaluationcomparestheidentifiedandanalyzedriskagainstgivenriskcriteria.Riskevaluationsconsiderthestrengthofevidenceforallthreeofthefundamentalquestions.Indoinganeffectiveriskassessment,therobustnessofthedatasetisimportantbecauseitdeterminesthequalityoftheoutput.RevealingassumptionsandreasonablesourcesofuncertaintywillenhanceTOC\o"1-5"\h\zconfidenceinthisoutputand/orhelpidentifyitslimitations.Uncertaintyisduetocombinationofincompleteknowledgeaboutaprocessanditsexpectedorunexpectedvariability.Typicalsourcesofuncertaintyincludegapsinknowledgegapsinpharmaceuticalscienceandprocessunderstanding,sourcesofharm(e.g.,failuremodesofaprocess,sourcesofvariability),andprobabilityofdetectionofproblems.Theoutputofariskassessmentiseitheraquantitativeestimateofriskoraqualitativedescriptionofarangeofrisk.Whenriskisexpressedquantitatively,anumerical

風(fēng)險(xiǎn)評估: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(dòng)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(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。評估結(jié)果可以是對風(fēng)險(xiǎn)的定量表示，也可以是對分險(xiǎn)程度的定性描述。定量表示時(shí)可用數(shù)值表示可能性，用高、中、低來給風(fēng)險(xiǎn)排序時(shí)，各個(gè)詞的適用范圍都要詳細(xì)規(guī)定，有時(shí)候還用到風(fēng)險(xiǎn)評分來進(jìn)一步定義。定量評估能對給定的風(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，定量評估一次只能評判一個(gè)特定結(jié)果。于是一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(xiǎn)的整體評估。評分過程的中間步驟有時(shí)也用到定量風(fēng)險(xiǎn)估計(jì)方法。probabilityisused.Alternatively,riskcanbeexpressedusingqualitativedescriptors,suchas“high",“medium",or“l(fā)ow",whichshouldbedefinedinasmuchdetailaspossible.Sometimesa"riskscore"isusedtofurtherdefinedescriptorsinriskranking.Inquantitativeriskassessments,ariskestimateprovidesthelikelihoodofaspecificconsequence,givenasetofrisk-generatingcircumstances.Thus,quantitativeriskestimationisusefulforoneparticularconsequenceatatime.Alternatively,someriskmanagementtoolsusearelativeriskmeasuretocombinemultiplelevelsofseverityandprobabilityintoanoverallestimateofrelativerisk.Theintermediatestepswithinascoringprocesscansometimesemployquantitativeriskestimation.4.4RiskControl4.4風(fēng)險(xiǎn)控制Riskcontrolincludesdecisionmakingtoreduceand/or風(fēng)險(xiǎn)控制包括風(fēng)險(xiǎn)抑低和風(fēng)險(xiǎn)接受兩方面的決朿過acceptrisks.Thepurposeofriskcontrolistoreducethe程，進(jìn)行控制的目的是將風(fēng)險(xiǎn)降低到可接受水平，risktoanacceptablelevel.Theamountofeffortusedforriskcontrolshouldbeproportionaltothesignificanceoftherisk.Decisionmakersmightuse投入努力量應(yīng)與風(fēng)險(xiǎn)的嚴(yán)重程度相襯。決策者應(yīng)用包括效益-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。differentprocesses,includingbenefit-costanalysis,for風(fēng)險(xiǎn)控制過程中以下問題會受到關(guān)注：understandingtheoptimallevelofriskcontrol.風(fēng)險(xiǎn)水平是否咼于可接受水平之上？Riskcontrolmightfocusonthefollowingquestions:怎樣做才能降低乃至消除風(fēng)險(xiǎn)？?Istheriskaboveanacceptablelevel?如何尋求效益、風(fēng)險(xiǎn)和資源之間的合適平衡？Whatcanbedonetoreduceoreliminaterisks?Whatistheappropriatebalanceamongbenefits,risks對已確定風(fēng)險(xiǎn)進(jìn)行控制時(shí)是否會引入新的風(fēng)險(xiǎn)？andresources?Arenewrisksintroducedasarestihetidentifiedrisksbeingcontrolled?Riskreductionfocusesonprocessesformitigationoravoidanceofqualityriskwhenitexceedsaspecified(acceptable)level(seeFig.1).Riskreductionmightincludeactionstakentomitigatetheseverityandprobabilityofharm.Processesthatimprovethedetectabilityofhazardsandqualityrisksmightalsobeusedaspartofariskcontrolstrategy.Theimplementationofriskreductionmeasurescanintroducenewrisksintothesystemorincreasethesignificanceofotherexistingrisks.Hence,itmightbeappropriatetorevisittheriskassessmenttoidentifyandevaluateanypossiblechangeinriskafterimplementingariskreductionprocess.

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)可檢測性的程序。風(fēng)險(xiǎn)抑低過程可能會給系統(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)量評估過程，來識別和評價(jià)風(fēng)險(xiǎn)系統(tǒng)的可能變化。Riskacceptanceisadecisiontoacceptrisk.Riskacceptancecanbeaformaldecisiontoaccepttheresidualriskoritcanbeapassivedecisioninwhichresidualrisksarenotspecified.Forsometypesofharms,eventhebestqualityriskmanagementpracticesmightnotentirelyeliminaterisk.Inthesecircumstances,itmightbeagreedthatanappropriatequalityriskmanagementstrategyhasbeenappliedandthatqualityriskisreducedtoaspecified(acceptable)level.This(specified)acceptablelevelwilldependon

風(fēng)險(xiǎn)接受：就是接受風(fēng)險(xiǎn)的決定。它可能為接受殘留風(fēng)險(xiǎn)的正式?jīng)Q定，也可以是忽略剩余風(fēng)險(xiǎn)的消極決定。有些類型的風(fēng)險(xiǎn)，即使用最好的質(zhì)量風(fēng)險(xiǎn)管理手段，也不能完全清除。在這種情形下，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。manyparametersandshouldbedecidedonacase-by-casebasis.4.5RiskCommunication4.5風(fēng)險(xiǎn)溝通Riskcommunicationisthesharingofinformation風(fēng)險(xiǎn)溝通：決朿者和其他人就風(fēng)險(xiǎn)和風(fēng)險(xiǎn)管理方面的aboutriskandriskmanagementbetweenthedecision信息進(jìn)行溝通、交流，各利益集團(tuán)間的交流在風(fēng)險(xiǎn)管makersandothers.Partiescancommunicateatanystageoftheriskmanagementprocess(seeFig.1:dashedarrows).Theoutput/resultofthequalityriskmanagementprocessshouldbeappropriatelycommunicatedanddocumented(seeFig.1:solidarrows).Communicationsmightincludethoseamonginterestedparties;e.g.,regulatorsandindustry,industryandthepatient,withinacompany,industryorregulatoryauthority,etc.Theincludedinformationmightrelatetotheexistence,nature,form,probability,severity,acceptability,control,treatment,detectabilityorotheraspectsofriskstoquality.Communicationneednotbecarriedoutforeachandeveryriskacceptance.Betweentheindustryandregulatoryauthorities,communicationconcerningqualityriskmanagementdecisionsmightbeeffectedthroughexistingchannelsasspecifiedinregulationsandguidances.理的任意階段都可以進(jìn)行（見圖1虛線部分）。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，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)。4.6RiskReview4.6風(fēng)險(xiǎn)回顧Riskmanagementshouldbeanongoingpartofthequalitymanagementprocess.Amechanismtoreviewormonitoreventsshouldbeimplemented.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Theoutput/resultsoftheriskmanagementprocessshouldbereviewedtotakeintoaccountnewknowledgeandexperience.Onceaqualityriskmanagementprocesshasbeeninitiated,thatprocessshouldcontinuetobeutilizedforeventsthatmightimpacttheoriginalqualityriskmanagementdecision,whethertheseeventsareplanned(e.g.,resultsofproductreview,inspections,audits,changecontrol)orunplanned(e.g.,rootcausefromfailureinvestigations,recall).Thefrequencyofanyreviewshouldbebaseduponthelevelofrisk.Riskreviewmightincludereconsiderationofriskacceptancedecisions(section4.4).RISKMANAGEMENTMETHODOLOGYQualityriskmanagementsupportsascientificandpracticalapproachtodecision-making.Itprovidesdocumented,transparentandreproduciblemethodstoaccomplishstepsofthequalityriskmanagementprocessbasedoncurrentknowledgeaboutassessingtheprobability,severityandsometimesdetectabilityoftherisk.Traditionally,riskstoqualityhavebeenassessedandmanagedinavarietyofinformalways(empiricaland/orinternalprocedures)basedon,forexample,compilationofobservations,trendsandotherinformation.Suchapproachescontinuetoprovideusefulinformationthatmightsupporttopicssuchashandlingofcomplaints,qualitydefects,deviationsandallocationofresources.程開始啟動(dòng)，它便用于管理那些可能會影響最初質(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)回顧還可能包括對風(fēng)險(xiǎn)接受決定的再審議。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，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(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。同樣，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)行評估和控制，以下就是這樣一些工具（Annex1andsectionVIII中更有詳敘）：基本風(fēng)險(xiǎn)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(cuò)誤樹形分析（FTA）Additionally,thepharmaceuticalindustryandregulatorscanassessandmanageriskusingrecognizedriskmanagementtoolsand/orinternalprocedures(e.g.,standardoperatingprocedures).Belowisanon-exhaustivelistofsomeofthesetools(furtherdetailsinAnnex1andchapter8):?Basicriskmanagementfacilitationmethods(flowcharts,checksheetsetc.);FailureModeEffectsAnalysis(FMEA);FailureMode,EffectsandCriticalityAnalysis(FMECA);FaultTreeAnalysis(FTA);HazardAnalysisandCriticalControlPoints(HACCP);HazardOperabilityAnalysis(HAZOP);PreliminaryHazardAnalysis(PHA);Riskrankingandfiltering;Supportingstatisticaltools.Itmightbeappropriatetoadaptthesetoolsforuseinspecificareaspertainingtodrugsubstanceanddrug(medicinal)productquality.Qualityriskmanagementmethodsandthesupportingstatisticaltoolscanbeusedincombination(e.g.,ProbabilisticRiskAssessment).Combineduseprovidesflexibilitythatcanfacilitatetheapplicationofqualityriskmanagementprinciples.Thedegreeofrigorandformalityofqualityriskmanagementshouldreflectavailableknowledgeandbecommensuratewiththecomplexityand/orcriticalityoftheissuetobeaddressed.危害分析和關(guān)鍵監(jiān)控點(diǎn)(HACCP)危害可操作性分析(HAZ0P)危害預(yù)分析(PHA)風(fēng)險(xiǎn)排序及濾除輔助統(tǒng)計(jì)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(jì)工具結(jié)合，帶來的靈活性能為質(zhì)量風(fēng)險(xiǎn)管理原則的應(yīng)用提供便利。質(zhì)量風(fēng)險(xiǎn)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)。INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS行業(yè)與監(jiān)管同質(zhì)量風(fēng)險(xiǎn)管理的綜合Qualityriskmanagementisaprocessthatsupportsscience-basedandpracticaldecisionswhenintegratedintoqualitysystems(seeAnnexII).Asoutlinedintheintroduction,appropriateuseofqualityriskmanagementdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirements.However,effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany'sabilitytodealwithpotentialrisks,andmightaffecttheextentandlevelofdirectregulatoryoversight.Inaddition,qualityriskmanagementcanfacilitatebetteruseofresourcesbyallparties.Trainingofbothindustryandregulatorypersonnelinqualityriskmanagementprocessesprovidesforgreaterunderstandingofdecision-makingprocessesandbuildsconfidenceinqualityriskmanagementoutcomes.Qualityriskmanagementshouldbeintegratedintoexistingoperationsanddocumentedappropriately.AnnexIIprovidesexamplesofsituationsinwhichtheuseofthequalityriskmanagementprocessmightprovideinformationthatcouldthenbeusedinavarietyofpharmaceuticaloperations.Theseexamplesareprovidedforillustrativepurposesonlyand質(zhì)量風(fēng)險(xiǎn)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(xiǎn)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(dòng)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(xiǎn)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(xiǎn)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。應(yīng)該將質(zhì)量風(fēng)險(xiǎn)管理同已有的工作結(jié)合起來,并建立妥善的文檔保管。附件2列舉了應(yīng)用此方法為藥品各種生產(chǎn)步驟提供信息的幾種情形。列出這些例子只是用于說明的目的，并不能視作是詳盡而確定的，也不在現(xiàn)有法規(guī)的要求之外提出新的期望。?企業(yè)運(yùn)營和活動(dòng)中的質(zhì)量管理實(shí)例(seeAnnexII):shouldnotbeconsideredadefinitiveorexhaustivelist.Theseexamplesarenotintendedtocreateanynewexpectationsbeyondtherequirementslaidoutinthecurrentregulations.Examplesforindustryandregulatoryoperations(seeAnnexII):Qualitymanagement.Examplesforindustryoperationsandactivities(seeAnnexII):Development;Facility,equipmentandutilities;Materialsmanagement;Production;Laboratorycontrolandstabilitytesting;Packagingandlabeling.Examplesforregulatoryoperations(seeAnnexII):Inspectionandassessmentactivities.?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(dòng)Whileregulatorydecisionswillcontinuetobetakenonaregionalbasis,acommonunderstandingandapplicationofqualityriskmanagementprinciplescouldfacilitatemutualconfidenceandpromotemoreconsistentdecisionsamongregulatorsonthebasisofthesameinformation.Thiscollaborationcouldbeimportantinthedevelopmentofpoliciesandguidelinesthatintegrateandsupportqualityriskmanagementpractices.盡管監(jiān)管決策依舊是被區(qū)域性的采納,但對質(zhì)量風(fēng)險(xiǎn)管理原則的普遍理解和應(yīng)用能增進(jìn)監(jiān)管者同企業(yè)之間的相互信任，促使監(jiān)管者基于同樣的信息做出更易于讓企業(yè)接受的決策。這種合作在發(fā)展整合支持質(zhì)量風(fēng)險(xiǎn)管理的政策、指導(dǎo)原則方面非常重要。DEFINITIONSDecisionMaker(s):Person(s)withthecompetenceandauthoritytomakeappropriateandtimelyqualityriskmanagementdecisions.

定義決策者：有能力和權(quán)力在質(zhì)量風(fēng)險(xiǎn)管理中做出適當(dāng)及及時(shí)決策的人員Detectability:Theabilitytodiscoverordeterminetheexistence,presence,orfactofahazard.

探測能力：發(fā)現(xiàn)并確定危害存在事實(shí)的能力Harm:Damagetohealth,includingthedamagethatcanoccurfromlossofproductqualityoravailability.

損傷:產(chǎn)品質(zhì)量及有效性降低引起對健康的損害Hazard:Thepotentialsourceofharm(ISO/IECGuide51).

危險(xiǎn)：危害的可能來源(ISO/IECGuide51).ProductLifecycle:Allphasesinthelifeoftheproductfromtheinitialdevelopmentthroughmarketinguntiltheproduct'sdiscontinuation.Quality:Thedegreetowhichasetofinherentpropertiesofaproduct,systemorprocessfulfillsrequirements(seeICHQ6Adefinitionspecificallyfor"quality"ofdrugsubstanceanddrug(medicinal)products.)

產(chǎn)品生命周期：產(chǎn)品從最初的開發(fā)到銷售，直至最終停產(chǎn)的各個(gè)階段質(zhì)量：產(chǎn)品、系統(tǒng)和過程的一整套內(nèi)在性質(zhì)與已有規(guī)定、要求的符合程度。(seeICHQ6Adefinitionspecificallyforqualityofdrugsubstanceanddrugproducts).QualityRiskManagement:

質(zhì)量風(fēng)險(xiǎn)管理：在產(chǎn)品生命周期中，系統(tǒng)地對產(chǎn)品質(zhì)Asystematicprocessfortheassessment,control,communicationandreviewofriskstothequalityofthedrug(medicinal)productacrosstheproductlifecycle.量相關(guān)的風(fēng)險(xiǎn)進(jìn)彳丁評估、控制、父流及審查。QualitySystem:Thesumofallaspectsofasystemthatimplementsqualitypolicyandensuresthatqualityobjectivesaremet.質(zhì)量體系：一個(gè)能貫徹質(zhì)量方針并確保質(zhì)量目標(biāo)的達(dá)到的體系各方面的總和Requirements:Theexplicitorimplicitneedsorexpectationsofthepatientsortheirsurrogates(e.g.,healthcareprofessionals,regulatorsandlegislators).Inthisdocument,“requirements"refersnotonlytostatutory,legislative,orregulatoryrequirements,butalsotosuchneedsandexpectations.要求：病人及他們的代理人(衛(wèi)生從業(yè)人員，管理者，立法者)的明晰或隱性要求、期望。此文件中，要求不僅是法定和規(guī)定的要求，還包括這些需要和期望Risk:Thecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm(ISO/IECGuide51).風(fēng)險(xiǎn):損害發(fā)生的可能性及其可能嚴(yán)重程度(IS0/IECGuide51).RiskAcceptance:Thedecisiontoacceptrisk(ISOGuide73).風(fēng)險(xiǎn)承擔(dān)：決定承擔(dān)風(fēng)險(xiǎn)(ISOGuide73).RiskAnalysis:Theestimationoftheriskassociatedwiththeidentifiedhazards.風(fēng)險(xiǎn)分析：對與已確定危險(xiǎn)相聯(lián)系的風(fēng)險(xiǎn)進(jìn)行評估RiskAssessment:Asystematicprocessoforganizinginformationto風(fēng)險(xiǎn)評估：系統(tǒng)地組織信息以支持風(fēng)險(xiǎn)管理過程中做出的決策。這一過程包括對危害的辨別，及分析、

supportariskdecisiontobemadewithinariskmanagementprocess.Itconsistsoftheidentificationofhazardsandtheanalysisandevaluationofrisksassociatedwithexposuretothosehazards.評估接觸這些危害所帶來的風(fēng)險(xiǎn)。RiskCommunication:Thesharingofinformationaboutriskandriskmanagementbetweenthedecisionmakerandotherstakeholders.風(fēng)險(xiǎn)溝通：決策者冋其他風(fēng)險(xiǎn)承擔(dān)人就風(fēng)險(xiǎn)和風(fēng)險(xiǎn)管理方面的信息進(jìn)行父流。RiskControl:Actionsimplementingriskmanagementdecisions(ISOGuide73).風(fēng)險(xiǎn)控制：貫徹執(zhí)行風(fēng)險(xiǎn)管理決策(ISOGuide73).RiskEvaluation:Thecomparisonoftheestimatedrisktogivenriskcriteriausingaquantitativeorqualitativescaletodeterminethesignificanceoftherisk.風(fēng)險(xiǎn)評價(jià)：用定量或是定性方法，將預(yù)計(jì)風(fēng)險(xiǎn)冋已有風(fēng)險(xiǎn)標(biāo)準(zhǔn)進(jìn)行比較，以判定風(fēng)險(xiǎn)的大小程度。RiskIdentification:Thesystematicuseofinformationtoidentifypotentialsourcesofharm(hazards)referringtotheriskquestionorproblemdescription.風(fēng)險(xiǎn)鑒定：參考風(fēng)險(xiǎn)問題及問題描述,系統(tǒng)地運(yùn)用其提供的信息來判定危害(危險(xiǎn))來源。RiskManagement:Thesystematicapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicatingandreviewingrisk.風(fēng)險(xiǎn)管理：系統(tǒng)地運(yùn)用質(zhì)量管理方針，程序，實(shí)踐，來進(jìn)行風(fēng)險(xiǎn)評估，控制，交流及審查。

RiskReduction:Actionstakentolessentheprobabilityofoccurrenceofharmandtheseverityofthatharm.風(fēng)險(xiǎn)抑減：米取措施來減少風(fēng)險(xiǎn)帶來的危害及降低危害的嚴(yán)重性。RiskReview:Reviewormonitoringofoutput/resultsoftheriskmanagementprocessconsidering(ifappropriate)newknowledgeandexperienceabouttherisk.風(fēng)險(xiǎn)審核：借鑒風(fēng)險(xiǎn)方面的新知識和經(jīng)驗(yàn)，對風(fēng)險(xiǎn)管理結(jié)果進(jìn)行審核和跟蹤監(jiān)測Severity:Ameasureofthepossibleconsequencesofahazard.嚴(yán)重性：度量危害后果可能程度的尺度Stakeholder:Anyindividual,groupororganizationthatcanaffect,beaffectedby,orperceiveitselftobeaffectedbyarisk.Decisionmakersmightalsobestakeholders.Forthepurposesofthisguideline,theprimarystakeholdersarethepatient,healthcareprofessional,regulatoryauthority,andindustry.風(fēng)險(xiǎn)承擔(dān)者：風(fēng)險(xiǎn)波及或能感受到奉獻(xiàn)影響的個(gè)人，集體，或組織。決策者可被稱為風(fēng)險(xiǎn)承擔(dān)者。再此指南中，風(fēng)險(xiǎn)承擔(dān)者主要是指病人，衛(wèi)生事業(yè)從業(yè)人員，管理機(jī)構(gòu)和工業(yè)。Trend:Astatisticaltermreferringtothedirectionorrateofchangeofavariable(s).趨勢：一個(gè)關(guān)于各種變化的方向和頻率的統(tǒng)計(jì)學(xué)術(shù)語。8.REFERENCESICHQ8PharmaceuticalDevelopment.ISO/IECGuide73:2002-RiskManagement-Vocabulary-GuidelinesforuseinStandards.ISO/IECGuide51:1999-SafetyAspects-Guidelinefortheirinclusioninstandards.

ProcessMappingbytheAmericanProductivity&QualityCenter,2002,ISBN1928593739.IEC61025-FaultTreeAnalysis(FTA).IEC60812AnalysisTechniquesforsystemreliability—Proceduresforfailuremodeandeffectsanalysis(FMEA).FailureModeandEffectAnalysis,FMEAfromTheorytoExecution,2ndEdition2003,D.H.Stamatis,ISBN0873895983.GuidelinesforFailureModesandEffectsAnalysis(FMEA)forMedicalDevices,2003DyademPress,ISBN0849319102.TheBasicsofFMEA,RobinMcDermott,RaymondJ.Mikulak,MichaelR.Beauregard1996,ISBN0527763209.WHOTechnicalReportSeriesNo908,2003,Annex7ApplicationofHazardAnalysisandCriticalControlPoint(HACCP)methodologytopharmaceuticals.IEC61882-HazardOperabilityAnalysis(HAZOP).ISO14971:2000-ApplicationofRiskManagementtoMedicalDevices.ISO7870:1993-ControlCharts.ISO7871:1997-CumulativeSumCharts.ISO7966:1993-AcceptanceControlCharts.ISO8258:1991-ShewhartControlCharts.WhatisTotalQualityControl?;TheJapaneseWay,KaoruIshikawa(TranslatedbyDavidJ.Liu),1985,ISBN0139524339.AnnexI:RiskManagemen