药品生产企业GMP验证培训巴斯德2管理机构对制药企业检查展望知识分享

THEPHARMACEUTICALINDUSTRIESEXPECTATIONSOFINSPECTIONS

BYREGULATORYAUTHORITIES

管理机构对制药企业认证检查展望DavidCDonaldGlobalIndustrialQualityInternationalSites2025/1/251TheExpertiseoftheInspectors

检查员的专业技术Inspectorsshouldhaveprevioustrainingandpracticalexperiencein manufacture,qualitycontrolandqualityassuranceofpharmaceutical products检查员须经培训及具有制药企业生产，质控及质保等方面的实际工作经验Deficienciesinexperienceneedsin-housetraining;attendanceat courses;seminars经验上的不足需要加强内部培训，上课及参加研讨会Athoroughknowledgeisneededinaspectsofthepharmaceutical industry完整的业内知识需涉及制药行业的所有领域2025/1/252TheRoleoftheInspectors

检查员的任务Primeresponsibilitytoproduceafactualreportonthestandardsof GoodManufacturingPractice(GMP)主要职责是以GMP为标准书写一份反映实际情况的报告AssistManufacturerstocomplywithGMP帮助企业更好地执行GMPIdentifydeficienciesinGMP鉴定GMP执行过程中的缺陷Giveadviceonwaystocorrectdeficiencies对纠正缺陷的方法提出指导Acceptalternativewaysofcompliance接受与GMP要求相符的其他选择方法2025/1/253TypesofInspection检查类型RoutineManufacturer’sInspection常规生产企业的检查 -Aninspectiontosatisfythelicensingauthoritythatthemanufacturer isincompliancewithhislicenceandmeetstheGMPrequirements对生产企业许可证的检查以确认该证的符合度及是否与GMP要求相一致 -fornewlyestablishedfacilities对新建设施的检查 -newproductlines对新建生产线的检查 -changesinkeypersonnelorequipment对主要人员或设备变更的检查2025/1/255TypesofInspection检查类型Follow-upInspection跟踪检查 -thefirstinspectionisincomplete第一次检查不彻底 -theCompanyhasmajordeficiencies发现企业存在严重缺陷ProductRelatedInspection与制品相关的检查 -toassesscomplianceoftheManufacturers’operationswiththe detailsintheProductLicence确认企业运作与产品许可证具体要求是否相符 -eitherprimepurposeorpartofGMPinspection可以是检查的首要目的，也可以是检查的一部分2025/1/256TypesofInspection检查类型SpecialistInspections专家检查 -BulkproductionofBiologicalProductsandBloodProductsuse specialistbiologicalinspectors生产制品原液生产和血制品须由生物学方面的专家进行 -Non-biologicalinspectionsusespecialistprincipalinspectorsto evaluatespecificaspects

microbiologicalaspectswatersystemsetc非生物学专家组成的检查应由主要检查人员评估专业性的问题：如微生物学方面的问题，水系统方面的问题2025/1/257TypesofInspection检查类型WholesaleDealers

批发商 -toassesscompliancewithgoodwholesaledealingpracticeand provisionsofthelicence评估批发商运作行为是否规范，所提供的许可证是否与实际相符 -ImportDealerslicencewitharrangementsforquarantine,QCand finalreleaseofimportedproducts进口批发商许可证及与待检，QC，进口产品的最终发放的安排等ContractLaboratories委托检测的实验室 -inspectedtoassesscompliancewithGoodLaboratoryPractice Standardsandconfirmthattherelevantprovisionsofthelicenceare observedfortheproductswhicharetested.检查以评估GLP的执行情况，并确认执照上所述提供的用以产品检测的相关设施2025/1/258QualitySystems质量系统TheCompanyOrganization公司组织QualityGroup质量保证群体Procedures程序ManufacturingProcess生产工艺Records记录QualityControl质控QAactivitiescarriedout贯彻执行的质量保证2025/1/259FrequencyofInspections检查频率ManufacturersLicence:2years生产许可企业：2年WholesaleDealerImportLicence:2years进口产品批发商：2年WholesaleDealerLicenceHolder:4years批发商营业执照持有人：4年«

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»companies:12–18months〈边缘〉企业：12-18个月 Follow-up:within6months跟踪相查：6个月内Overseassites:2–3years海外基地：2-3年2025/1/2510DurationofInspections检查持续时间ProductManufactureSuper+250staffLarge60–249staffMedium10–59staffSmallLessthan10staffSterile10632NonSterile8321Assembly7112025/1/2511PreparationforInspection检查的准备工作ReviewtheCompanyfile审核企业文件Previousreportsandresponses以前的检查报告及反馈Anyfollow-upaction任何跟进措施ReviewofSiteMasterFile审核企业自述性文件Licensedmatters–licensesheld,operatingsites,authorisedstaff, limitationsimposedbyspecificprovisions,authorisedproducts有关许可证事宜：所持许可证，生产基地，授权员工，特殊产品带来的局限性2025/1/2512PreparationforInspection检查的准备工作Agreethetimeofthepostinspectionmeeting同意检查后会议的时间Describeitspurpose目的描述Summarizethewaythedeficienciesaretobeclassified概述缺陷的分类方式Indicateanydocumentationrequired指出所需的任何文件ReviewManagementstructure审核管理框架2025/1/2513PreparationforInspection检查的准备工作ReviewtheCompany’sQualityPolicyandarrangementsfor monitoringthequalitysystem审核公司质量政策及质量系统监控的安排ReviewChanges审核变更情况Reviewprogresswithdeficiencies审核缺陷的跟进工作2025/1/2514On-SiteInspection现场检查WalkthroughtheSite走一遍厂区Inspecttodeterminethedegreeofconformityoftheoperationstothe requirementsofGMPandcompliancewiththelicenceanddetailsintheapplication检查确定实际运作与GMP要求的符合程度及实际运用与许可证要求的一致性Itinerarydeterminedbythetypeofinspection确定检查路线2025/1/2515On-SiteInspection现场检查Theinspectionshouldfollowalogicalsequence检查应按一定的逻辑顺序Observations,recommendationsanddeficienciesshouldbediscussed withthecompanyrepresentativesatthetime发现的不到之处，建议和缺陷应与及时与厂房代表沟通Itisimportanttomention«

plus

»points提及《附加》项这点很重要Followtheplanasfaraspossible尽可能多地按计划进行TheinspectionisbasedonObservations检查要基于观察2025/1/2516On-SiteInspection现场检查Inspectorsmayuseachecklisttoensureallareasofoperationsare investigated检查员可以使用检查表来确认所有区域均列入Experiencehasshownthatrigidadherencetoaverydetailedchecklist developedfromGMPGuidelinescanleadtomissingvulnerableareas经验告诉人们严格按照根据GMP指南上套用下的明细表来检查会错过一些簿弱环节Inspectorsshouldnotbeconcernedwithnon-GMPaspectsegfinance, H&S检查员不应关心与GMP无关的事宜，例如：财务，H&S2025/1/2517On-SiteInspection现场检查MedicinesTestingScheme:Inspectorssamples医学试验计划：检查员样品Duringinspectionssamplesofstartingmaterials,workinprogressand finishedproductcanbetakenfortestingiftheInspectorconsiders thatitmightassistinthedetectionofqualitydeficiencies检查过程中，如果检查员认为可能对判断质量缺陷有帮助，则应取原材料样品、过程中样及成品来做试验DocumentationReview文件审核

Anessentialpartoftheinspection.检查的实质部分Thisisthehistoricalevidenceofcompliance这是说明过往符合要求的依据Documentscanbereviewedduringthecourseofthesiteinspectionandindetailinthemeetingroom在现场检查阶段应审核文件，在会议室更深入了解2025/1/2518DocumentReview文件审核Manufacturingformulae生产配方BatchManufacturingRecords批记录Specifications技术规格

chemicalrawmaterials化学原材料

packagingcomponents包装村料 intermediates中间产物 finishedproducts成品2025/1/2519DocumentReview文件审核Processandequipmentvalidation工艺及设备验证Environmentalmonitoring环境监控StandardOperatingProcedures标准操作规程Trainingrecords:jobdescriptions培训记录：工作职责描述Releaseprocedures发放程序DistributionandRecall发货及召回TechnicalAgreements技术协议2025/1/2520QualityIndicators质量显示器CustomerComplaints–Quantity,Investigation,PreventiveAction用户投诉—记录数量，调查，防范措施ProductRecalls–defectsreportedtothecompanyortotheDefect ReportingCentreandanyrecallsinstitutedsincetheprevious inspectionshouldbediscussedandrecordsexamined产品召回—报告至企业或报告中心的过失及任何自上次检查以来已经展开调查的召回案件都要进行讨论并检查记录HandlingofReturns退货的处理2025/1/2521QualityIndicators质量显示器Self-Inspectionreports–obtainassurancethatinternalauditsare conductedandfollow-upactionistaken.自查报告—确认企业执行内部自查并采取相关跟进措施。Note:Asamatterofpolicytheinternalauditsshouldnotberead作为一项政策，不应过目内部自查报告Non-conformanceprocedure异常情况程序ChangeControlProcedure变更控制程序2025/1/2522ClosingMeeting结束会议InspectorconvenesameetingwiththeCompanyRepresentatives检查员召集企业代表开会SummarisetheproposedlistofdeficienciestoreporttotheLicensing Authority总结汇集的缺陷上报有关机构AllowCompanytocorrectmisconceptions允许企业更正误解Bereadytoexplainyourreasons准备作出自已的解释Usefultodiscusspossibleremedialactions讨论可能的补救措施是有用的2025/1/2523ClosingMeeting结束会议TheCompanyshouldbeencouragedtogiveanundertakingtoresolve thedeficienciesandtoagreeaprovisionaltimetableforcorrective action.应鼓励企业承诺拿出针对这些缺陷的处理方案及纠偏行动的时间表TheReportisin3parts:-报告包括3部份内容 i)Inspector’sInformation检查员信息 ii)SummaryandConclusions总结及结论 iii)TheCompanySiteMasterFile企业自述性文件2025/1/2524REPORT报告Inspector’sinformation检查员信息

Inspectorssummarysheetandintroduction检查员概述及介绍 Briefreportofinspectionactivities检查活动的大体报告 Scopeoftheinspection检查范畴 Personnelmet已会见人员 Changessincepreviousinspection上次检查后的变化情况 Futureplannedchanges以后计划的变化情况2025/1/2525REPORT报告i)Inspector’sinformation检查员信息 Inspector’sfindings检查员发现的情况 Samplestakenandresultsifknown所取的样品及已知的结果 Assessmentofthesitemasterfile对自述性文件的评估 GMPrelatedrecallsmadeinthelast2years在最近2年内与GMP相关的召回案件

2025/1/2526REPORT报告ii)Summaryandconclusions总结与结论 ThelistoffailurestocomplywiththeEuropeanGuidetoGood ManufacturingPractices

withreferencetotheappropriatesectionof theguide.列表陈述与欧洲GMP指南不相符合的事项及相关参照条例iii)TheCompanySiteMasterFile公司自述性文件Theneed,ifany,toupdatetheCompanySiteMasterFileinlightof theInspection.按检查结果是可否更新公司自述性文件2025/1/2527FinalRemarks最后评论PointsfortheInspector

toconsider检查员要考虑的几点内容Theconditionofthefacilities厂房的条件Thecleanlinessofthefacilities厂房的洁净度Theorganisation人员机构组成Thestaffattitude/professionalism员工的敬业程度及专业水平Thesitepre