Q9 質(zhì)量風險管理 中英文對照

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

藥品評價與研究中心（CDER）

生物評價與研究中心（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)量風險管理原理4.GENERALQUALITYRISKMANAGEMENTPROCESS質(zhì)量風險管理基本程序4.1Responsibilities職責分配4.2InitiatingaQualityRiskManagementProcess質(zhì)量風險管理的啟動4.3RiskAssessment風險評估4.4RiskControl風險控制4.5RiskCommunication風險交流4.6RiskReview風險回顧5.RISKMANAGEMENTMETHODOLOGY風險管理方法學6.INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS工業(yè)及監(jiān)管與質(zhì)量風險管理的整合7.DEFINITIONS定義8.REFERENCES參考資料AnnexI:RiskManagementMethodsandTools附件I:風險管理方法及工具I.1BasicRiskManagementFacilitationMethodsI.1基本風險管理簡易方法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(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)量風險管理潛在應用前景.II.1QualityRiskManagementasPartofIntegratedII.1綜合質(zhì)量管理中的質(zhì)量風險管理

QualityManagementII?2QualityRiskManagementasPartofRegulatoryOperationsII.2操作優(yōu)化中的應用II?3QualityRiskManagementasPartofdevelopmentII.3研發(fā)中的應用II.4QualityRiskManagementforFacilities,EquipmentandUtilitiesn.4對工具、設備和設施的質(zhì)量風險管理II?5QualityRiskManagementasPartofMaterialsManagementII.5物料管理中的應用II?6QualityRiskManagementasPartofProductionII.6生產(chǎn)中的應用II.7QualityRiskManagementasPartofLaboratoryControlandStabilityStudiesII.7實驗室控制及穩(wěn)定性研究中的應用II.8QualityRiskManagementasPartofPackagingandLabellingII.8標簽及包裝中的應用1?INTRODUCTIONRiskmanagementprinciplesareeffectivelyutilizedinmanyareasofbusinessandgovernmentincludingfinance,insurance,occupationalsafety,publichealth,pharmacovigilance,andbyagenciesregulatingtheseindustries.Althoughtherearesomeexamplesoftheuseofqualityriskmanagementinthepharmaceuticalindustrytoday,theyarelimitedanddonotrepresentthefullcontributionsthatriskmanagementhastooffer.Inaddition,theimportanceofqualitysystemshasbeenrecognizedinthepharmaceuticalindustryanditisbecomingevidentthatqualityriskmanagementisavaluablecomponentofaneffectivequalitysystem.Itiscommonlyunderstoodthatriskisdefinedasthecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm.However,achievingasharedunderstandingoftheapplicationofriskmanagementamongdiversestakeholdersisdifficultbecauseeachstakeholdermightperceivedifferentpotentialharms,placeadifferentprobabilityoneachharmoccurringandattributedifferentseveritiestoeachharm.Inrelationtopharmaceuticals,althoughthereareavarietyofstakeholders,includingpatientsandmedicalpractitionersaswellasgovernmentandindustry,theprotectionofthepatientbymanagingtherisktoqualityshouldbeconsideredofprimeimportance.引言風險管理原理在商業(yè)和政府的許多領域都得到了有效應用，如：金融、保險、職業(yè)安全、公共衛(wèi)生、藥物監(jiān)測及相應的監(jiān)管部門。如今質(zhì)量風險管理在藥企中雖有應用，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)量風險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，風險被定義為傷害發(fā)生的可能性及嚴重程度。然而，要在不同利益集團之間尋求風險管理應用方面的共同認識是相當困難的，因為他們認識到的潛在危害、各危害發(fā)生的可能性及嚴重程度都不同。藥品相關(guān)的利益集團很多，如病人、醫(yī)療人員和政府企業(yè)，但是質(zhì)量風險管理的首要目的是保護病人。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免地引入一定的風險。質(zhì)量風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，來進一步確保藥品質(zhì)量。當質(zhì)量問題出現(xiàn)時，應用質(zhì)量風險管理還能改善決策過程。有效進行質(zhì)量風險管理能促使產(chǎn)生更好更正式?jīng)Q策，增強監(jiān)控者對公司處理潛在風險能力的信心，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)量風險管理方面的系統(tǒng)方法。作為一個基礎性、資源性的文件，它獨立于卻又支持其它ICH質(zhì)量文件，補充藥企和監(jiān)管機構(gòu)內(nèi)已有的質(zhì)量措施、要求、標準和指南。特別是它提供了一些質(zhì)量風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)的基于風險的決策，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應用正式的風險管理程序并非總是合適的或必要的useaformalriskmanagementprocess(using（用已承認的工具或內(nèi)部程序，如標準操作規(guī)程）。recognizedtoolsand/orinternalprocedurese.g.,有時也允許使用非正式的風險管理程序（用經(jīng)驗工具standardoperatingprocedures).Theuseofinformalrisk或內(nèi)部程序）。恰當運用風險管理能方便但不消除企managementprocesses(usingempiricaltoolsand/or業(yè)遵守法規(guī)要求的責任，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)量風險管理工具的原理和應用實例，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、提交和復審各過程。processesthroughoutthelifecycleofdrugsubstances,drug(medicinal)products,biologicalandbiotechnologicalproducts(includingtheuseofrawmaterials,solvents,excipients,packagingandlabelingmaterialsindrug(medicinal)products,biologicalandbiotechnologicalproducts).PRINCIPLESOFQUALITYRISKMANAGEMENTTwoprimaryprinciplesofqualityriskmanagementare:Theevaluationoftherisktoqualityshouldbebasedonscientificknowledgeandultimatelylinktotheprotectionofthepatient;andThelevelofeffort,formalityanddocumentationofthequalityriskmanagementprocessshouldbecommensuratewiththelevelofrisk.質(zhì)量風險管理原理質(zhì)量風險管理的兩條基本原理是：評估質(zhì)量風險應基于科學知識并最終同對病人的保護聯(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與風險水平相適應。GENERALQUALITYRISKMANAGEMENTPROCESSQualityriskmanagementisasystematicprocessfortheassessment,control,communicationandreviewofriskstothequalityofthedrug(medicinal)productacrosstheproductlifecycle.Amodelforqualityriskmanagementisoutlinedinthediagram(Figure1).Othermodelscouldbeused.Theemphasisoneachcomponentoftheframeworkmightdifferfromcasetocasebutarobustprocesswillincorporateconsiderationofalltheelementsatalevelofdetailthatiscommensuratewiththespecificrisk.質(zhì)量風險管理基本過程質(zhì)量風險管理是對藥品質(zhì)量風險進行評估，控制，交流和審查的系統(tǒng)過程，這一過程貫穿藥品整個生命周期。圖1給出了這方面的一個模型，其他模型也有應用。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)注程度會因風險的特異而各有區(qū)別。ContainsNonbindingRecommendationsContainsNonbindingRecommendationsprocessFigure1:Overviewof5爲z杳n“?!■HimTffftuRiskAssessmentiRiskIdsntifjcati-DnVRiskAnalysisJRiskEvaluationRiskControlrRiskReductioHiIRiskAcceptanceFigure1:典型質(zhì)量風險管理過程簡介ContainsNonbindingRecommendationsContainsNonbindingRecommendations風險管理工具風險交流Decisionnodesarenotshowninthediagramabovebecausedecisionscanoccuratanypointintheprocess.Thesedecisionsmightbetoreturntothepreviousstepandseekfurtherinformation,toadjusttheriskmodels由于決策行為隨時都可能發(fā)生，上圖就沒有顯示決策點。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)整風險模型；也可能用于管理過程的終止。注解：圖中的“不可接受”項不僅指違oreventoterminatetheriskmanagementprocessbaseduponinformationthatsupportssuchadecision.Note:背了法令法規(guī)要求，也表示風險管理過程需要重頭再來?！皍nacceptable"intheflowchartdoesnotonlyrefertostatutory,legislativeorregulatoryrequirements,butalsototheneedtorevisittheriskassessmentprocess.

4.1Responsibilities4.1.職責分配Qualityriskmanagementactivitiesareusually,butnotalways,undertakenbyinterdisciplinaryteams.Whenteamsareformed,theyshouldincludeexpertsfromtheappropriateareas(e.g.,qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketing,legal,statisticsandclinical)inadditiontoindividualswhoareknowledgeableaboutthequalityriskmanagementprocess.Decisionmakershouldtakeresponsibilityforcoordinatingqualityriskmanagementacrossvariousfunctionsanddepartmentsoftheirorganization;andassurethataqualityriskmanagementprocessisdefined,deployedandreviewedandthatadequateresourcesareavailable.質(zhì)量風險管理經(jīng)常是但也不總是由交叉學科團隊執(zhí)行。除了要有風險管理方面的經(jīng)驗人士，團隊還應包括相關(guān)領域的專家（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。決策者必須負責組織協(xié)調(diào)各部門之間的關(guān)系，保障團隊各項功能的有效發(fā)揮，確保整個管理過程得以合理展開、不斷完善、反復審查，保障有足夠的資源供團隊使用。4.2InitiatingaQualityRiskManagementProcess4.2質(zhì)量風險管理的啟動Qualityriskmanagementshouldincludesystematicprocessesdesignedtocoordinate,facilitateandimprovescience-baseddecisionmakingwithrespecttorisk.Possiblestepsusedtoinitiateandplanaqualityriskmanagementprocessmightincludethefollowing:Definetheproblemand/orriskquestion,includingpertinentassumptionsidentifyingthepotentialforrisk;Assemblebackgroundinformationand/ordataonthepotentialhazard,harmorhumanhealthimpactrelevanttotheriskassessment;質(zhì)量風險管理應包括這樣一些系統(tǒng)程序，這些設計好的程序用來協(xié)調(diào)，推動和改善那些風險方面基于科學認識的決定。一項管理程序的發(fā)起和設計可能要經(jīng)過如下步驟：?定義存在的難題和風險問題，包括識別潛在風險的相關(guān)假設；?收集風險評估相關(guān)的關(guān)于潛在危險、危害或人體健康影響的背景信息和數(shù)據(jù)；?確定領導人和重要資源；?詳細說明決策的時間表，可交付性和適當?shù)臉藴省?/p>

Identifyaleaderandnecessaryresources;Specifyatimeline,deliverablesandappropriatelevelofdecisionmakingfortheriskmanagementprocess.4.3RiskAssessment4.3風險評估Riskassessmentconsistsoftheidentificationofhazards風險評估：此過程進行危險確認并對接觸這些危險所andtheanalysisandevaluationofrisksassociatedwith帶來的風險進行分析評價。它以一個定義明確的難點exposuretothosehazards(asdefinedbelow).Quality描敘或風險問題開始，當風險明確后，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三個基本問題將有助于給出風險的清晰定義。welldefined,anappropriateriskmanagementtool(see1.什么可能會出錯？examplesinsection5)andthetypesofinformation2.出錯的可能性有多大？neededtoaddresstheriskquestionwillbemorereadily3.出錯的后果和嚴重性有哪些？identifiable.Asanaidtoclearlydefiningtherisk(s)forriskassessmentpurposes,threefundamentalquestionsareoftenhelpful:Whatmightgowrong?Whatisthelikelihood(probability)itwillgowrong?Whataretheconsequences(severity)?Riskidentificationisasystematicuseofinformationto風險鑒定：參照風險問題或難點描敘，系統(tǒng)利用已有identifyhazardsreferringtotheriskquestionor信息去鑒定危險。這些信息包括歷史數(shù)據(jù)、理論分析、problemdescription.Informationcanincludehistorical多方面觀點和風險承擔人的意見。風險鑒定時提出data,theoreticalanalysis,informedopinions,andthe“什么會出錯”這一問題，同時還確定可能答案。這concernsofstakeholders.Riskidentificationaddresses一過程為后續(xù)步驟奠定了基礎。the“Whatmightgowrong?"question,includingidentifyingthepossibleconsequences.Thisprovidesthebasisforfurtherstepsinthequalityriskmanagementprocess.Riskanalysisistheestimationoftheriskassociatedwiththeidentifiedhazards.Itisthequalitativeorquantitativeprocessoflinkingthelikelihoodofoccurrenceandseverityofharms.Insomeriskmanagementtools,theabilitytodetecttheharm(detectability)alsofactorsintheestimationofrisk.

風險分析：估計與已確認危險相聯(lián)系的風險，這是對危害發(fā)生的可能性和嚴重程度進行定性和定量分析的過程。風險評價中同樣也應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

風險評估:將經(jīng)過分析和鑒定的風險同給定標準作比較，考慮三個基本問題的證據(jù)力。風險評估中，數(shù)據(jù)的有效性決定了評估結(jié)果的質(zhì)量。揭示、設想、分析不確定性的來源將有助于增強對結(jié)果的信心、識別結(jié)果的局限性。對過程了解不充分、過程中可預見及不可預見變動的發(fā)生，都將導致不確定性的發(fā)生。知識結(jié)構(gòu)的不完整，有限的藥學發(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、低來給風險排序時，各個詞的適用范圍都要詳細規(guī)定，有時候還用到風險評分來進一步定義。定量評估能對給定的風險衍生環(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。于是一些管理工具用到相對衡量尺度，將多重水平的嚴重性和可能性結(jié)合起來，以完成對相對風險的整體評估。評分過程的中間步驟有時也用到定量風險估計方法。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風險控制Riskcontrolincludesdecisionmakingtoreduceand/or風險控制包括風險抑低和風險接受兩方面的決朿過acceptrisks.Thepurposeofriskcontrolistoreducethe程，進行控制的目的是將風險降低到可接受水平，risktoanacceptablelevel.Theamountofeffortusedforriskcontrolshouldbeproportionaltothesignificanceoftherisk.Decisionmakersmightuse投入努力量應與風險的嚴重程度相襯。決策者應用包括效益-耗費比分析在內(nèi)的不同的程序去理解風險控制的最佳水平。differentprocesses,includingbenefit-costanalysis,for風險控制過程中以下問題會受到關(guān)注：understandingtheoptimallevelofriskcontrol.風險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險？?Istheriskaboveanacceptablelevel?如何尋求效益、風險和資源之間的合適平衡？Whatcanbedonetoreduceoreliminaterisks?Whatistheappropriatebalanceamongbenefits,risks對已確定風險進行控制時是否會引入新的風險？andresources?Arenewrisksintroducedasarestihetidentifiedrisksbeingcontrolled?Riskreductionfocusesonprocessesformitigationoravoidanceofqualityriskwhenitexceedsaspecified(acceptable)level(seeFig.1).Riskreductionmightincludeactionstakentomitigatetheseverityandprobabilityofharm.Processesthatimprovethedetectabilityofhazardsandqualityrisksmightalsobeusedaspartofariskcontrolstrategy.Theimplementationofriskreductionmeasurescanintroducenewrisksintothesystemorincreasethesignificanceofotherexistingrisks.Hence,itmightbeappropriatetorevisittheriskassessmenttoidentifyandevaluateanypossiblechangeinriskafterimplementingariskreductionprocess.

風險抑低：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)量風險，包括為減輕危害嚴重性和發(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及質(zhì)量風險可檢測性的程序。風險抑低過程可能會給系統(tǒng)帶入新的風險，其他業(yè)已存在的風險的嚴重程度也可能增加。因此，完成風險抑低程序后,有必要再重復一下質(zhì)量評估過程，來識別和評價風險系統(tǒng)的可能變化。Riskacceptanceisadecisiontoacceptrisk.Riskacceptancecanbeaformaldecisiontoaccepttheresidualriskoritcanbeapassivedecisioninwhichresidualrisksarenotspecified.Forsometypesofharms,eventhebestqualityriskmanagementpracticesmightnotentirelyeliminaterisk.Inthesecircumstances,itmightbeagreedthatanappropriatequalityriskmanagementstrategyhasbeenappliedandthatqualityriskisreducedtoaspecified(acceptable)level.This(specified)acceptablelevelwilldependon

風險接受：就是接受風險的決定。它可能為接受殘留風險的正式?jīng)Q定，也可以是忽略剩余風險的消極決定。有些類型的風險，即使用最好的質(zhì)量風險管理手段，也不能完全清除。在這種情形下，應確認使用了合適的風險管理策略，且風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。manyparametersandshouldbedecidedonacase-by-casebasis.4.5RiskCommunication4.5風險溝通Riskcommunicationisthesharingofinformation風險溝通：決朿者和其他人就風險和風險管理方面的aboutriskandriskmanagementbetweenthedecision信息進行溝通、交流，各利益集團間的交流在風險管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行（見圖1虛線部分）。質(zhì)量風險管理過程的產(chǎn)出和結(jié)果應得到合理溝通并存檔。（見圖1實線部分）各利益團體間（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)管機構(gòu)內(nèi)部），就質(zhì)量風險的存在、性質(zhì)、形式、可能性、嚴重程度、可接受度、控制、處理、可檢測度及其他方面的信息進行交流。不需要就每個風險承擔都進行風險交流。企業(yè)和監(jiān)管機構(gòu)之間關(guān)于質(zhì)量風險管理方面的溝通交流可以通過規(guī)則、指導中給定的渠道來實現(xiàn)。4.6RiskReview4.6風險回顧Riskmanagementshouldbeanongoingpartofthequalitymanagementprocess.Amechanismtoreviewormonitoreventsshouldbeimplemented.風險管理伴隨著質(zhì)量管理過程的全程,應當引入審查和監(jiān)控機制。在審查風險管理過程的結(jié)果時要將新的知識和經(jīng)驗納入考慮范圍。一旦一個質(zhì)量風險管理過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，它便用于管理那些可能會影響最初質(zhì)量風險管理決策的事件，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）。任何回顧的進行頻率都應基于風險水平，風險回顧還可能包括對風險接受決定的再審議。質(zhì)量管理方法學質(zhì)量風險管理中的決策過程用到了一種科學而實用的方法，它根據(jù)現(xiàn)有的關(guān)于估計風險可能性、嚴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)量風險管理各步驟。質(zhì)量風險傳統(tǒng)上是用一系列非正規(guī)方法來進行評估和控制的，這些方法基于觀測報告，風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。同樣，藥品廠家和管理者也可用已承認的工具和內(nèi)部程序來進行評估和控制，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）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(HACCP)危害可操作性分析(HAZ0P)危害預分析(PHA)風險排序及濾除輔助統(tǒng)計工具將以上方法加以適當改進，就可用于藥物、藥品質(zhì)量相關(guān)的一些特殊領域。方法同輔助統(tǒng)計工具結(jié)合，帶來的靈活性能為質(zhì)量風險管理原則的應用提供便利。質(zhì)量風險管理的正式程度及精確程度應該反映可用到的知識，并與要反映問題的復雜性、重要程度相適應。INTEGRATIONOFQUALITYRISKMANAGEMENTINTOINDUSTRYANDREGULATORYOPERATIONS行業(yè)與監(jiān)管同質(zhì)量風險管理的綜合Qualityriskmanagementisaprocessthatsupportsscience-basedandpracticaldecisionswhenintegratedintoqualitysystems(seeAnnexII).Asoutlinedintheintroduction,appropriateuseofqualityriskmanagementdoesnotobviateindustry'sobligationtocomplywithregulatoryrequirements.However,effectivequalityriskmanagementcanfacilitatebetterandmoreinformeddecisions,canprovideregulatorswithgreaterassuranceofacompany'sabilitytodealwithpotentialrisks,andmightaffecttheextentandlevelofdirectregulatoryoversight.Inaddition,qualityriskmanagementcanfacilitatebetteruseofresourcesbyallparties.Trainingofbothindustryandregulatorypersonnelinqualityriskmanagementprocessesprovidesforgreaterunderstandingofdecision-makingprocessesandbuildsconfidenceinqualityriskmanagementoutcomes.Qualityriskmanagementshouldbeintegratedintoexistingoperationsanddocumentedappropriately.AnnexIIprovidesexamplesofsituationsinwhichtheuseofthequalityriskmanagementprocessmightprovideinformationthatcouldthenbeusedinavarietyofpharmaceuticaloperations.Theseexamplesareprovidedforillustrativepurposesonlyand質(zhì)量風險管理與質(zhì)量體系結(jié)合后，它能支持基于科學研究和實際情況的決策。(seeAnnexII).正如引言中所述，恰當?shù)剡\用質(zhì)量風險管理雖不能免除企業(yè)遵守法規(guī)要求的義務，卻能推動更好、更合情合理決策的產(chǎn)生，還能增強監(jiān)管當局對企業(yè)處理潛在風險能力的信心，影響直接監(jiān)管造成的疏忽的程度和水平，促進各方對資源的優(yōu)化利用。對企業(yè)職工和監(jiān)管人員進行質(zhì)量風險管理方面的培訓，能使他們更好的理解決策行為，樹立對管理結(jié)果的信心。應該將質(zhì)量風險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)運營和活動中的質(zhì)量管理實例(seeAnnexII):shouldnotbeconsideredadefinitiveorexhaustivelist.Theseexamplesarenotintendedtocreateanynewexpectationsbeyondtherequirementslaidoutinthecurrentregulations.Examplesforindustryandregulatoryoperations(seeAnnexII):Qualitymanagement.Examplesforindustryoperationsandactivities(seeAnnexII):Development;Facility,equipmentandutilities;Materialsmanagement;Production;Laboratorycontrolandstabilitytesting;Packagingandlabeling.Examplesforregulatoryoperations(seeAnnexII):Inspectionandassessmentactivities.?研發(fā)?工具，設備和設施?物料管理?生產(chǎn)?實驗室控制和穩(wěn)定性檢測?包裝和標簽?監(jiān)管實例(seeAnnexII):?檢查和評估活動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)量風險管理原則的普遍理解和應用能增進監(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)量風險管理的政策、指導原則方面非常重要。DEFINITIONSDecisionMaker(s):Person(s)withthecompetenceandauthoritytomakeappropriateandtimelyqualityriskmanagementdecisions.

定義決策者：有能力和權(quán)力在質(zhì)量風險管理中做出適當及及時決策的人員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：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)量風險管理：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)的風險進彳丁評估、控制、父流及審查。QualitySystem:Thesumofallaspectsofasystemthatimplementsqualitypolicyandensuresthatqualityobjectivesaremet.質(zhì)量體系：一個能貫徹質(zhì)量方針并確保質(zhì)量目標的達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).風險:損害發(fā)生的可能性及其可能嚴重程度(IS0/IECGuide51).RiskAcceptance:Thedecisiontoacceptrisk(ISOGuide73).風險承擔：決定承擔風險(ISOGuide73).RiskAnalysis:Theestimationoftheriskassociatedwiththeidentifiedhazards.風險分析：對與已確定危險相聯(lián)系的風險進行評估RiskAssessment:Asystematicprocessoforganizinginformationto風險評估：系統(tǒng)地組織信息以支持風險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險。RiskCommunication:Thesharingofinformationaboutriskandriskmanagementbetweenthedecisionmakerandotherstakeholders.風險溝通：決策者冋其他風險承擔人就風險和風險管理方面的信息進行父流。RiskControl:Actionsimplementingriskmanagementdecisions(ISOGuide73).風險控制：貫徹執(zhí)行風險管理決策(ISOGuide73).RiskEvaluation:Thecomparisonoftheestimatedrisktogivenriskcriteriausingaquantitativeorqualitativescaletodeterminethesignificanceoftherisk.風險評價：用定量或是定性方法，將預計風險冋已有風險標準進行比較，以判定風險的大小程度。RiskIdentification:Thesystematicuseofinformationtoidentifypotentialsourcesofharm(hazards)referringtotheriskquestionorproblemdescription.風險鑒定：參考風險問題及問題描述,系統(tǒng)地運用其提供的信息來判定危害(危險)來源。RiskManagement:Thesystematicapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicatingandreviewingrisk.風險管理：系統(tǒng)地運用質(zhì)量管理方針，程序，實踐，來進行風險評估，控制，交流及審查。

RiskReduction:Actionstakentolessentheprobabilityofoccurrenceofharmandtheseverityofthatharm.風險抑減：米取措施來減少風險帶來的危害及降低危害的嚴重性。RiskReview:Reviewormonitoringofoutput/resultsoftheriskmanagementprocessconsidering(ifappropriate)newknowledgeandexperienceabouttherisk.風險審核：借鑒風險方面的新知識和經(jīng)驗，對風險管理結(jié)果進行審核和跟蹤監(jiān)測Severity:Ameasureofthepossibleconsequencesofahazard.嚴重性：度量危害后果可能程度的尺度Stakeholder:Anyindividual,groupororganizationthatcanaffect,beaffectedby,orperceiveitselftobeaffectedbyarisk.Decisionmakersmightalsobestakeholders.Forthepurposesofthisguideline,theprimarystakeholdersarethepatient,healthcareprofessional,regulatoryauthority,andindustry.風險承擔者：風險波及或能感受到奉獻影響的個人，集體，或組織。決策者可被稱為風險承擔者。再此指南中，風險承擔者主要是指病人，衛(wèi)生事業(yè)從業(yè)人員，管理機構(gòu)和工業(yè)。Trend:Astatisticaltermreferringtothedirectionorrateofchangeofavariable(s).趨勢：一個關(guān)于各種變化的方向和頻率的統(tǒng)計學術(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