ISPE-CCPIECHINACONFERENCE2025QualitySystem–KeytotheeffectiveQualityManagementSystem質(zhì)量體系——有效質(zhì)量管理體系的關鍵AnwarulHaque,ValidationDirector,Austar奧星公司驗證總監(jiān)ISPEOctober25-282025Shanghai1RegulatoryPerspective法規(guī)問題?TheholderofaManufacturingAuthorisation(MA)mustmanufacturemedicinalproductsensuringthat:?生產(chǎn)許可證（MA）的持有人所生產(chǎn)的藥品必須保證：?Fitfortheirintendeduse符合預期用途?complywiththerequirementsoftheMA符合MA中的要求?Donotplacepatientsatriskduetoinadequatesafety,qualityorefficacy.不會因安全性、質(zhì)量或功效不當而對患者造成風險?SeniorManagementholdstheresponsibilityforQualityobjective(statedabove)?高級管理層擔負著質(zhì)量目標的責任(如上所述)?Inattainingtheobjectivesitrequiresparticipationandcommitmentbyallstakeholderstothecompany?在達到目標方面要求公司內(nèi)的所有利益相關方的參與和承諾ISPE-CCPIECHINACONFERENCE2025RegulatoryPerspective–Cont’d法規(guī)問題-續(xù)?ToachievethequalityobjectivereliablytheremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQAincorporatingGMP?為可靠地達到質(zhì)量目標，必須有經(jīng)過綜合設計和正確實施且集成了GMP的質(zhì)量保障系統(tǒng)。?Qualityobjectivesfullydocumentedanditseffectivenessmonitored?質(zhì)量目標應有完整的文件記錄并對其有效性進行監(jiān)控。?AllpartsoftheQualityAssurancesystemshouldbeadequatelyresourced?質(zhì)量保證系統(tǒng)的所有部分均應配備有充分的資源。ISPE-CCPIECHINACONFERENCE2025RegulatoryFindings監(jiān)管檢查問題?ZhangAiping(DirectorofCenterforCertificationofDrug,SFDA)?國家食品藥品監(jiān)督管理局藥品認證管理中心主任張愛萍:“…WefoundthatthedefectsareconcentratedintheeffectivenessofsuchqualitysystemsastheQCsystemandtheQAsystem.Theproblemsaremainlyininsufficientunderstanding,inaccurategraspingandtheinexperienceinusingtheelementsofthequalityassurancesystem.Especiallythattherearesuchproblemsasinsufficientlyestablishedproceduresorfailuresincompletingcorrespondingactivitiesasrequiredintheestablishedproceduresinsuchareasaschangecontrol,deviationhandlingandcorrectiveandpreventiveactions(CAPA).Theyareinflexibleinimplementingsuchnewconceptsastrendanalysis,alertlimits,actionlimits,annualproductqualityreview,etc.….Theyarestillatanearlystageintheuseofqualityriskmanagementandtheyarenotfullycombinedwiththeirownexperiencesortheactualproductionsituations.ThesedefectshavereflectedthattheenterpriseshavenotintegratedGMPconceptsintoeachofthestepsoftheirqualitysystemmanagementactivitiesandproductqualityriskmanagementhasnotbeeneffectivelyimplemented.”張愛萍：我們對已進行現(xiàn)場檢查的企業(yè)和進行模擬檢查的企業(yè)做了分析對比發(fā)現(xiàn)，缺陷比較?集中地體現(xiàn)在質(zhì)量控制與質(zhì)量保證等質(zhì)量體系有效性方面，問題突出體現(xiàn)在對質(zhì)量保證體系構(gòu)成要素理解不清楚，把握不準確，使用不熟練等。特別是對變更控制、偏差處理、糾正和預防措施（CAPA)方面，存在程序制定不夠完善，或者未按照制定的程序要求完成相應工作的情況；對于趨勢分析、警戒線、糾偏線、年度產(chǎn)品質(zhì)量回顧分析等新概念的應用較為機械，存在生搬硬套的情況，沒有與自己實際情況結(jié)合起來；對于質(zhì)量風險管理的使用尚處于初期，沒有完全與自己已有的經(jīng)驗以及產(chǎn)品或生產(chǎn)的實際情況結(jié)合。這些缺陷反映出目前企業(yè)尚未完全將藥品GMP的精髓有機地融入到其質(zhì)量體系管理的各個環(huán)節(jié)中，產(chǎn)品質(zhì)量的風險管理還未得到有效貫徹。ISPE-CCPIECHINACONFERENCE2025QualityManagementSystem質(zhì)量管理系統(tǒng)QMSAqualitymanagementsystem(QMS)isanorganizationalstructureimplementedbyacompanyandconsistsofprocedures,processesandresourcesusedforqualitymanagement.QMSisdesignedtoincreaseperformanceandqualitywithinanorganization質(zhì)量管理系統(tǒng)（QMS）是公司為進行質(zhì)量管理而實施的一種組織結(jié)構(gòu)，包括規(guī)程、工藝和資源。QMS設計用于提高組織內(nèi)部的業(yè)績和質(zhì)量。Purpose目的AQMSisimplementedtopromotequalityandefficiencywithinacompany.QMSsrelyoncreatingproceduresfortheprocessesusedinproducingaproductorservice.QMS的實施目的是為了提高公司內(nèi)部的質(zhì)量和效率。QMS依賴于為用于生產(chǎn)產(chǎn)品或提供服務的工藝流程制定相應規(guī)程。ISPE-CCPIECHINACONFERENCE2025ProductLifecycle產(chǎn)品生命周期Thereare4phasesofproductlifecycle:產(chǎn)品生命周期有4個階段：?PharmaceuticalDevelopment制藥研發(fā)?TechnologyTransfer技術轉(zhuǎn)移?CommercialManufacturing商業(yè)化生產(chǎn)?ProductDiscontinuation產(chǎn)品停產(chǎn)?ForeachoftheabovephasestheQMSneedstobeappropriateforthatphase需針對上述每個階段制定適宜的規(guī)定?QMSISPE-CCPIECHINACONFERENCE2025QualityRiskManagement質(zhì)量風險管理?QualityriskmanagementisintegraltoaneffectiveQMS?質(zhì)量風險管理是有效QMS中不可分割的一部分。?Itprovidesaproactiveapproach?它提供了一種積極主動的方法?Itfacilitatescontinualimprovementofprocessperformanceandproductqualitythroughouttheproductlifecycle.?它有助于在產(chǎn)品的整個生命周期過程中對工藝性能和產(chǎn)品質(zhì)量進行持續(xù)改進。ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMSQMS的目的?AchieveProductRealisation實現(xiàn)產(chǎn)品生產(chǎn)??EstablishandMaintainaStateofControl建立并維持受控狀態(tài)??FacilitateContinualImprovement幫助進行持續(xù)改進?ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMSQMS的目的實現(xiàn)?AchieveProductRealisation產(chǎn)品生產(chǎn)Itshouldallowthedeliveryofproductswiththequalityattributesappropriatetomeettheneedsof:應使得可以生產(chǎn)出符合如下方面要求的質(zhì)量屬性的產(chǎn)品：-patients患者要求-healthcareprofessionals醫(yī)療保健專業(yè)人員的要求-regulatoryauthorities法規(guī)當局的要求-internalandexternalcustomers內(nèi)部及外部客戶的要求ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMS(cont’d)QMS的目的（續(xù)）?EstablishandMaintainaStateof建立并維持受控狀態(tài)ControlDevelopanduseeffectivemonitoringandcontrolsystemsforprocessperformanceandproductquality制定并使用用于監(jiān)控工藝性能和產(chǎn)品質(zhì)量的有效監(jiān)視和控制系統(tǒng)Qualityriskmanagementcanbeusefulinidentifyingthemonitoringandcontrolsystems.質(zhì)量風險管理在確定監(jiān)視和控制系統(tǒng)方面非常有用。ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMS(cont’d)QMS的目的（續(xù)）幫助進?FacilitateContinualImprovement行持續(xù)改進Identifyandimplementappropriateproductqualityimprovements,processimprovements,variabilityreduction,innovationsandqualitysystemenhancements確定并實施適宜的產(chǎn)品質(zhì)量改進、工藝改進、可變因素縮減、創(chuàng)新和質(zhì)量系統(tǒng)改進措施Againqualityriskmanagementcanbeusefulforidentifyingandprioritisingareasforcontinualimprovement.同樣，質(zhì)量風險管理在確定持續(xù)改進區(qū)域并確定其優(yōu)先級別方面非常有用。ISPE-CCPIECHINACONFERENCE2025DesignofQSQS的設計?Thedesign,organisationanddocumentationoftheQMSshouldbewellstructuredandclear?QMS的設計、組織和文件編制應具有良好的組織結(jié)構(gòu)且非常明確?QSshouldreflectthesizeandcomplexityofthecompany’sactivities?QS應反映公司業(yè)務的規(guī)模和復雜性?Riskmanagementprinciplesshouldappliedtothedesign?設計中應采用風險管理的原則?QMSaspectscanbecompany-wideandorsomeaspectscanbesite-specific?QMS的某些方面可以是全公司范圍的而某些方面則可以是針對具體廠區(qū)的Note:Effectivenessofthepharmaceuticalqualitysystemisnormallydemonstratedatthesitelevel.備注：制藥質(zhì)量系統(tǒng)的有效性通常是在廠區(qū)層次進行證明的?ISPE-CCPIECHINACONFERENCE2025ContentofQSQS的內(nèi)容?Appropriateprocesses,resourcesand適宜的流程、資源和職責responsibilities管理職責?Managementresponsibilities?QMSincludesthefollowingelements:QMS包括如下成分：?processperformanceandproductqualitymonitoring工藝性能和產(chǎn)品質(zhì)量監(jiān)控?CAPA?changemanagement變更管理?managementreview管理審查?Performanceindicators性能指標ISPE-CCPIECHINACONFERENCE2025ManagementResponsibilities管理職責?Design,implementation,monitorandmaintaintheQS?QS的設計、實施、監(jiān)控和維護?QualityPolicy質(zhì)量方針?QualityPlanning質(zhì)量計劃?EnsureQSimplementationthroughouttheorganisation?保證QS在全公司范圍內(nèi)的實施?Provideescalationprocesstoraisequalityissuesinatimelymanner?提供逐級匯報流程及時報告質(zhì)量問題ISPE-CCPIECHINACONFERENCE2025ManagementResponsibilities(cont’d)管理職責（續(xù)）?Defineroles,responsibilities&atalllevels?界定所有級別的職責、職能?ReviewprocessperformanceandproductqualityandtheQMS?對工藝性能、產(chǎn)品質(zhì)量和QMS進行審查?Managepurchasedmaterials?管理所購置物料?Manageoutsourcedactivities?管理外包工作?Provideappropriateresources?提供適宜的資源ISPE-CCPIECHINACONFERENCE2025QualityManual質(zhì)量手冊?QualityManual(QM)shouldcontainsdescriptionoftheQSaswellas:?質(zhì)量手冊（QM）中應包括有關QS的描述以及：?Thequalitypolicy質(zhì)量方針??Thescopeofthequalitysystem?質(zhì)量系統(tǒng)的范圍?IdentificationoftheQMSprocesses?QMS流程的確定?Managementresponsibilities?管理職責ISPE-CCPIECHINACONFERENCE2025QualityPolicy質(zhì)量方針?QualityPolicyshoulddescribestheoverallintentionsanddirectionofthecompanyrelatedtoquality?質(zhì)量方針應對公司與質(zhì)量相關的整體目的和方向進行描述?Statescompliancewithapplicableregulatoryrequirements?說明所符合的適用法規(guī)要求?ProvidesmechanismforCIofthequalitysystem?提供質(zhì)量系統(tǒng)CI的機制?Understoodbyallstakeholdersofthecompany?為公司的所有利益相關方所理解?Reviewedperiodically?定期審查ISPE-CCPIECHINACONFERENCE2025QualityPlanning質(zhì)量計劃?Qualityobjectivesshouldbedefinedandcommunicated?應制定處質(zhì)量目標并對其進行溝通?AllstakeholdersshouldbuyintoQualityobjectives?質(zhì)量目的應獲得所有利益相關方的同意ISPE-CCPIECHINACONFERENCE2025QualityPlanning(cont’d)質(zhì)量計劃（續(xù)）?Alignsqualityobjectiveswiththecompany’sstrategiesandbeconsistentwiththequalitypolicy?使質(zhì)量目標與公司的策略相符并與質(zhì)量方針保持一致?Appropriateresourcesandtrainingarrangement?適宜的資源和培訓安排?Setperformanceindicatorsagainstqualityobjectivesestablished,monitored&published?針對所建立、監(jiān)控和公布的質(zhì)量目標設定性能指標?ExtendtheQStothecontrolandreviewofanyoutsourcedactivitiesandqualityofpurchasedmaterials?擴展QS至任何外包工作的控制和審查及外購原料的質(zhì)量。ISPE-CCPIECHINACONFERENCE2025QSElementsQS的成分?TheelementsofQSare:?QS的成分為：?Processperformanceandproductqualitymonitoringsystem?工藝性能和產(chǎn)品質(zhì)量監(jiān)控系統(tǒng)?Correctiveactionandpreventiveaction(CAPA)system?糾正和預防措施（CAPA）系統(tǒng)?Changemanagementsystem變更管理系統(tǒng)??Reviewofprocessperformanceandproductquality?工藝性能和產(chǎn)品質(zhì)量的審查ISPE-CCPIECHINACONFERENCE2025Processperformanceandproductquality工藝性能和產(chǎn)品質(zhì)量?Processperformanceandproductqualitytoensureastateofcontrolismaintained?工藝性能和產(chǎn)品質(zhì)量以保證保持受控狀態(tài)?Providetoolsformeasurementandanalysisofparametersandattributes?提供測量工具和參數(shù)及屬性分析?Analyseparametersandattributestoverifystateofcontrol?對參數(shù)和屬性進行分析以檢查確認控制狀態(tài)ISPE-CCPIECHINACONFERENCE2025Processperformanceandproductquality工藝性能和產(chǎn)品質(zhì)量?Continualimprovementactivities-reduceorcontrolvariation?持續(xù)改進工作——降低或控制可變性?Feedbackmechanismonproductquality?產(chǎn)品質(zhì)量的反饋機制?Enhanceprocessunderstanding?促進對工藝的理解?Enableinnovativeapproachestoprocessvalidation?啟用工藝驗證的創(chuàng)新型方法ISPE-CCPIECHINACONFERENCE2025CorrectiveActionandPreventiveAction(CAPA)System糾正和預防措施（CAPA）系統(tǒng)?CAPAresultingfromtheinvestigationof:?CAPA是因如下情況的調(diào)查研究而導致的：?Complaints投訴?productrejections產(chǎn)品剔除?non-conformances不符合?Recalls召回?Deviations偏差?Audits審計?Regulatoryinspectionsandfindings法規(guī)檢查和檢查結(jié)果?Trendsfromprocessperformanceandproductqualitymonitoring?工藝性能和產(chǎn)品質(zhì)量監(jiān)控的趨勢?Thelevelofeffort,formality,anddocumentationoftheinvestigationshouldbecommensuratewiththelevelofrisk?調(diào)查工作量、程序和文件的程度應與風險的程度相匹配ISPE-CCPIECHINACONFERENCE2025ChangeManagementSystem變更管理系統(tǒng)?Aneffectivechangemanagementsystemshouldprovideahighdegreeofassurancetherearenounintendedconsequencesofthechange?有效的變更管理系統(tǒng)應能高度保證變更不會導致預期之外的后果。?OversightofCMbythequalityunit?由質(zhì)量部門對變更管理進行監(jiān)管?Changeassessmentshouldbescienceandriskbased?應以科學和風險為基礎進行變更評估ISPE-CCPIECHINACONFERENCE2025ProcessPerformanceandProductQualityReview工藝性能和產(chǎn)品質(zhì)量的審查?Managementofprocessperformanceandproductqualitytobereviewedoverthelifecycleoftheproduct?應在產(chǎn)品的整個生命周期過程中對工藝性能和產(chǎn)品質(zhì)量的管理進行審查?Shouldbeaformalprocess?應是一種正式的流程?Shouldbedoneperiodically?應定期進行?Reviewincludesbutnotlimitedto:?審查范圍包括但并不僅限于：?MeasurementofachievementofQMSo