ISPE-CCPIECHINACONFERENCE2025QualitySystem–KeytotheeffectiveQualityManagementSystem質(zhì)量體系——有效質(zhì)量管理體系的關(guān)鍵AnwarulHaque,ValidationDirector,Austar奧星公司驗(yàn)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(yù)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(dāng)而對患者造成風(fēng)險(xiǎn)?SeniorManagementholdstheresponsibilityforQualityobjective(statedabove)?高級管理層擔(dān)負(fù)著質(zhì)量目標(biāo)的責(zé)任(如上所述)?Inattainingtheobjectivesitrequiresparticipationandcommitmentbyallstakeholderstothecompany?在達(dá)到目標(biāo)方面要求公司內(nèi)的所有利益相關(guān)方的參與和承諾ISPE-CCPIECHINACONFERENCE2025RegulatoryPerspective–Cont’d法規(guī)問題-續(xù)?ToachievethequalityobjectivereliablytheremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQAincorporatingGMP?為可靠地達(dá)到質(zhì)量目標(biāo)，必須有經(jīng)過綜合設(shè)計(jì)和正確實(shí)施且集成了GMP的質(zhì)量保障系統(tǒng)。?Qualityobjectivesfullydocumentedanditseffectivenessmonitored?質(zhì)量目標(biāo)應(yīng)有完整的文件記錄并對其有效性進(jìn)行監(jiān)控。?AllpartsoftheQualityAssurancesystemshouldbeadequatelyresourced?質(zhì)量保證系統(tǒng)的所有部分均應(yīng)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(rèn)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(jìn)行現(xiàn)場檢查的企業(yè)和進(jìn)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(zhǔn)確，使用不熟練等。特別是對變更控制、偏差處理、糾正和預(yù)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(yīng)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(yīng)用較為機(jī)械，存在生搬硬套的情況，沒有與自己實(shí)際情況結(jié)合起來；對于質(zhì)量風(fēng)險(xiǎn)管理的使用尚處于初期，沒有完全與自己已有的經(jīng)驗(yàn)以及產(chǎn)品或生產(chǎn)的實(shí)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(jī)地融入到其質(zhì)量體系管理的各個(gè)環(huán)節(jié)中，產(chǎn)品質(zhì)量的風(fēng)險(xiǎn)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(jìn)行質(zhì)量管理而實(shí)施的一種組織結(jié)構(gòu)，包括規(guī)程、工藝和資源。QMS設(shè)計(jì)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(shí)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(wù)的工藝流程制定相應(yīng)規(guī)程。ISPE-CCPIECHINACONFERENCE2025ProductLifecycle產(chǎn)品生命周期Thereare4phasesofproductlifecycle:產(chǎn)品生命周期有4個(gè)階段：?PharmaceuticalDevelopment制藥研發(fā)?TechnologyTransfer技術(shù)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(gè)階段制定適宜的規(guī)定?QMSISPE-CCPIECHINACONFERENCE2025QualityRiskManagement質(zhì)量風(fēng)險(xiǎn)管理?QualityriskmanagementisintegraltoaneffectiveQMS?質(zhì)量風(fēng)險(xiǎn)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(dòng)的方法?Itfacilitatescontinualimprovementofprocessperformanceandproductqualitythroughouttheproductlifecycle.?它有助于在產(chǎn)品的整個(gè)生命周期過程中對工藝性能和產(chǎn)品質(zhì)量進(jìn)行持續(xù)改進(jìn)。ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMSQMS的目的?AchieveProductRealisation實(shí)現(xiàn)產(chǎn)品生產(chǎn)??EstablishandMaintainaStateofControl建立并維持受控狀態(tài)??FacilitateContinualImprovement幫助進(jìn)行持續(xù)改進(jìn)?ISPE-CCPIECHINACONFERENCE2025TheObjectivesofQMSQMS的目的實(shí)現(xiàn)?AchieveProductRealisation產(chǎn)品生產(chǎn)Itshouldallowthedeliveryofproductswiththequalityattributesappropriatetomeettheneedsof:應(yīng)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(dāng)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(fēng)險(xiǎn)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(jìn)?FacilitateContinualImprovement行持續(xù)改進(jìn)Identifyandimplementappropriateproductqualityimprovements,processimprovements,variabilityreduction,innovationsandqualitysystemenhancements確定并實(shí)施適宜的產(chǎn)品質(zhì)量改進(jìn)、工藝改進(jìn)、可變因素縮減、創(chuàng)新和質(zhì)量系統(tǒng)改進(jìn)措施Againqualityriskmanagementcanbeusefulforidentifyingandprioritisingareasforcontinualimprovement.同樣，質(zhì)量風(fēng)險(xiǎn)管理在確定持續(xù)改進(jìn)區(qū)域并確定其優(yōu)先級別方面非常有用。ISPE-CCPIECHINACONFERENCE2025DesignofQSQS的設(shè)計(jì)?Thedesign,organisationanddocumentationoftheQMSshouldbewellstructuredandclear?QMS的設(shè)計(jì)、組織和文件編制應(yīng)具有良好的組織結(jié)構(gòu)且非常明確?QSshouldreflectthesizeandcomplexityofthecompany’sactivities?QS應(yīng)反映公司業(yè)務(wù)的規(guī)模和復(fù)雜性?Riskmanagementprinciplesshouldappliedtothedesign?設(shè)計(jì)中應(yīng)采用風(fēng)險(xiǎn)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(jìn)行證明的?ISPE-CCPIECHINACONFERENCE2025ContentofQSQS的內(nèi)容?Appropriateprocesses,resourcesand適宜的流程、資源和職責(zé)responsibilities管理職責(zé)?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(biāo)ISPE-CCPIECHINACONFERENCE2025ManagementResponsibilities管理職責(zé)?Design,implementation,monitorandmaintaintheQS?QS的設(shè)計(jì)、實(shí)施、監(jiān)控和維護(hù)?QualityPolicy質(zhì)量方針?QualityPlanning質(zhì)量計(jì)劃?EnsureQSimplementationthroughouttheorganisation?保證QS在全公司范圍內(nèi)的實(shí)施?Provideescalationprocesstoraisequalityissuesinatimelymanner?提供逐級匯報(bào)流程及時(shí)報(bào)告質(zhì)量問題ISPE-CCPIECHINACONFERENCE2025ManagementResponsibilities(cont’d)管理職責(zé)（續(xù)）?Defineroles,responsibilities&atalllevels?界定所有級別的職責(zé)、職能?ReviewprocessperformanceandproductqualityandtheQMS?對工藝性能、產(chǎn)品質(zhì)量和QMS進(jìn)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(yīng)包括有關(guān)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(zé)ISPE-CCPIECHINACONFERENCE2025QualityPolicy質(zhì)量方針?QualityPolicyshoulddescribestheoverallintentionsanddirectionofthecompanyrelatedtoquality?質(zhì)量方針應(yīng)對公司與質(zhì)量相關(guān)的整體目的和方向進(jìn)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(jī)制?Understoodbyallstakeholdersofthecompany?為公司的所有利益相關(guān)方所理解?Reviewedperiodically?定期審查ISPE-CCPIECHINACONFERENCE2025QualityPlanning質(zhì)量計(jì)劃?Qualityobjectivesshouldbedefinedandcommunicated?應(yīng)制定處質(zhì)量目標(biāo)并對其進(jìn)行溝通?AllstakeholdersshouldbuyintoQualityobjectives?質(zhì)量目的應(yīng)獲得所有利益相關(guān)方的同意ISPE-CCPIECHINACONFERENCE2025QualityPlanning(cont’d)質(zhì)量計(jì)劃（續(xù)）?Alignsqualityobjectiveswiththecompany’sstrategiesandbeconsistentwiththequalitypolicy?使質(zhì)量目標(biāo)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(xùn)安排?Setperformanceindicatorsagainstqualityobjectivesestablished,monitored&published?針對所建立、監(jiān)控和公布的質(zhì)量目標(biāo)設(shè)定性能指標(biāo)?ExtendtheQStothecontrolandreviewofanyoutsourcedactivitiesandqualityofpurchasedmaterials?擴(kuò)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(yù)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(jìn)行分析以檢查確認(rèn)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(jìn)工作——降低或控制可變性?Feedbackmechanismonproductquality?產(chǎn)品質(zhì)量的反饋機(jī)制?Enhanceprocessunderstanding?促進(jìn)對工藝的理解?Enableinnovativeapproachestoprocessvalidation?啟用工藝驗(yàn)證的創(chuàng)新型方法ISPE-CCPIECHINACONFERENCE2025CorrectiveActionandPreventiveAction(CAPA)System糾正和預(yù)防措施（CAPA）系統(tǒng)?CAPAresultingfromtheinvestigationof:?CAPA是因如下情況的調(diào)查研究而導(dǎo)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(jì)?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(yīng)與風(fēng)險(xiǎn)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(yīng)能高度保證變更不會導(dǎo)致預(yù)期之外的后果。?OversightofCMbythequalityunit?由質(zhì)量部門對變更管理進(jìn)行監(jiān)管?Changeassessmentshouldbescienceandriskbased?應(yīng)以科學(xué)和風(fēng)險(xiǎn)為基礎(chǔ)進(jìn)行變更評估ISPE-CCPIECHINACONFERENCE2025ProcessPerformanceandProductQualityReview工藝性能和產(chǎn)品質(zhì)量的審查?Managementofprocessperformanceandproductqualitytobereviewedoverthelifecycleoftheproduct?應(yīng)在產(chǎn)品的整個(gè)生命周期過程中對工藝性能和產(chǎn)品質(zhì)量的管理進(jìn)行審查?Shouldbeaformalprocess?應(yīng)是一種正式的流程?Shouldbedoneperiodically?應(yīng)定期進(jìn)行?Reviewincludesbutnotlimitedto:?審查范圍包括但并不僅限于：?MeasurementofachievementofQMSo