藥品生產(chǎn)企業(yè)GMP驗(yàn)證培訓(xùn)巴斯德2管理機(jī)構(gòu)對(duì)制藥企業(yè)檢查展望知識(shí)分享

THEPHARMACEUTICALINDUSTRIESEXPECTATIONSOFINSPECTIONS

BYREGULATORYAUTHORITIES

管理機(jī)構(gòu)對(duì)制藥企業(yè)認(rèn)證檢查展望DavidCDonaldGlobalIndustrialQualityInternationalSites2025/1/251TheExpertiseoftheInspectors

檢查員的專(zhuān)業(yè)技術(shù)Inspectorsshouldhaveprevioustrainingandpracticalexperiencein manufacture,qualitycontrolandqualityassuranceofpharmaceutical products檢查員須經(jīng)培訓(xùn)及具有制藥企業(yè)生產(chǎn)，質(zhì)控及質(zhì)保等方面的實(shí)際工作經(jīng)驗(yàn)Deficienciesinexperienceneedsin-housetraining;attendanceat courses;seminars經(jīng)驗(yàn)上的不足需要加強(qiáng)內(nèi)部培訓(xùn)，上課及參加研討會(huì)Athoroughknowledgeisneededinaspectsofthepharmaceutical industry完整的業(yè)內(nèi)知識(shí)需涉及制藥行業(yè)的所有領(lǐng)域2025/1/252TheRoleoftheInspectors

檢查員的任務(wù)Primeresponsibilitytoproduceafactualreportonthestandardsof GoodManufacturingPractice(GMP)主要職責(zé)是以GMP為標(biāo)準(zhǔn)書(shū)寫(xiě)一份反映實(shí)際情況的報(bào)告AssistManufacturerstocomplywithGMP幫助企業(yè)更好地執(zhí)行GMPIdentifydeficienciesinGMP鑒定GMP執(zhí)行過(guò)程中的缺陷Giveadviceonwaystocorrectdeficiencies對(duì)糾正缺陷的方法提出指導(dǎo)Acceptalternativewaysofcompliance接受與GMP要求相符的其他選擇方法2025/1/253TypesofInspection檢查類(lèi)型RoutineManufacturer’sInspection常規(guī)生產(chǎn)企業(yè)的檢查 -Aninspectiontosatisfythelicensingauthoritythatthemanufacturer isincompliancewithhislicenceandmeetstheGMPrequirements對(duì)生產(chǎn)企業(yè)許可證的檢查以確認(rèn)該證的符合度及是否與GMP要求相一致 -fornewlyestablishedfacilities對(duì)新建設(shè)施的檢查 -newproductlines對(duì)新建生產(chǎn)線的檢查 -changesinkeypersonnelorequipment對(duì)主要人員或設(shè)備變更的檢查2025/1/255TypesofInspection檢查類(lèi)型Follow-upInspection跟蹤檢查 -thefirstinspectionisincomplete第一次檢查不徹底 -theCompanyhasmajordeficiencies發(fā)現(xiàn)企業(yè)存在嚴(yán)重缺陷ProductRelatedInspection與制品相關(guān)的檢查 -toassesscomplianceoftheManufacturers’operationswiththe detailsintheProductLicence確認(rèn)企業(yè)運(yùn)作與產(chǎn)品許可證具體要求是否相符 -eitherprimepurposeorpartofGMPinspection可以是檢查的首要目的，也可以是檢查的一部分2025/1/256TypesofInspection檢查類(lèi)型SpecialistInspections專(zhuān)家檢查 -BulkproductionofBiologicalProductsandBloodProductsuse specialistbiologicalinspectors生產(chǎn)制品原液生產(chǎn)和血制品須由生物學(xué)方面的專(zhuān)家進(jìn)行 -Non-biologicalinspectionsusespecialistprincipalinspectorsto evaluatespecificaspects

microbiologicalaspectswatersystemsetc非生物學(xué)專(zhuān)家組成的檢查應(yīng)由主要檢查人員評(píng)估專(zhuān)業(yè)性的問(wèn)題：如微生物學(xué)方面的問(wèn)題，水系統(tǒng)方面的問(wèn)題2025/1/257TypesofInspection檢查類(lèi)型WholesaleDealers

批發(fā)商 -toassesscompliancewithgoodwholesaledealingpracticeand provisionsofthelicence評(píng)估批發(fā)商運(yùn)作行為是否規(guī)范，所提供的許可證是否與實(shí)際相符 -ImportDealerslicencewitharrangementsforquarantine,QCand finalreleaseofimportedproducts進(jìn)口批發(fā)商許可證及與待檢，QC，進(jìn)口產(chǎn)品的最終發(fā)放的安排等ContractLaboratories委托檢測(cè)的實(shí)驗(yàn)室 -inspectedtoassesscompliancewithGoodLaboratoryPractice Standardsandconfirmthattherelevantprovisionsofthelicenceare observedfortheproductswhicharetested.檢查以評(píng)估GLP的執(zhí)行情況，并確認(rèn)執(zhí)照上所述提供的用以產(chǎn)品檢測(cè)的相關(guān)設(shè)施2025/1/258QualitySystems質(zhì)量系統(tǒng)TheCompanyOrganization公司組織QualityGroup質(zhì)量保證群體Procedures程序ManufacturingProcess生產(chǎn)工藝Records記錄QualityControl質(zhì)控QAactivitiescarriedout貫徹執(zhí)行的質(zhì)量保證2025/1/259FrequencyofInspections檢查頻率ManufacturersLicence:2years生產(chǎn)許可企業(yè)：2年WholesaleDealerImportLicence:2years進(jìn)口產(chǎn)品批發(fā)商：2年WholesaleDealerLicenceHolder:4years批發(fā)商營(yíng)業(yè)執(zhí)照持有人：4年?

Marginal

?companies:12–18months〈邊緣〉企業(yè)：12-18個(gè)月 Follow-up:within6months跟蹤相查：6個(gè)月內(nèi)Overseassites:2–3years海外基地：2-3年2025/1/2510DurationofInspections檢查持續(xù)時(shí)間ProductManufactureSuper+250staffLarge60–249staffMedium10–59staffSmallLessthan10staffSterile10632NonSterile8321Assembly7112025/1/2511PreparationforInspection檢查的準(zhǔn)備工作ReviewtheCompanyfile審核企業(yè)文件Previousreportsandresponses以前的檢查報(bào)告及反饋Anyfollow-upaction任何跟進(jìn)措施ReviewofSiteMasterFile審核企業(yè)自述性文件Licensedmatters–licensesheld,operatingsites,authorisedstaff, limitationsimposedbyspecificprovisions,authorisedproducts有關(guān)許可證事宜：所持許可證，生產(chǎn)基地，授權(quán)員工，特殊產(chǎn)品帶來(lái)的局限性2025/1/2512PreparationforInspection檢查的準(zhǔn)備工作Agreethetimeofthepostinspectionmeeting同意檢查后會(huì)議的時(shí)間Describeitspurpose目的描述Summarizethewaythedeficienciesaretobeclassified概述缺陷的分類(lèi)方式Indicateanydocumentationrequired指出所需的任何文件ReviewManagementstructure審核管理框架2025/1/2513PreparationforInspection檢查的準(zhǔn)備工作ReviewtheCompany’sQualityPolicyandarrangementsfor monitoringthequalitysystem審核公司質(zhì)量政策及質(zhì)量系統(tǒng)監(jiān)控的安排ReviewChanges審核變更情況Reviewprogresswithdeficiencies審核缺陷的跟進(jìn)工作2025/1/2514On-SiteInspection現(xiàn)場(chǎng)檢查WalkthroughtheSite走一遍廠區(qū)Inspecttodeterminethedegreeofconformityoftheoperationstothe requirementsofGMPandcompliancewiththelicenceanddetailsintheapplication檢查確定實(shí)際運(yùn)作與GMP要求的符合程度及實(shí)際運(yùn)用與許可證要求的一致性Itinerarydeterminedbythetypeofinspection確定檢查路線2025/1/2515On-SiteInspection現(xiàn)場(chǎng)檢查T(mén)heinspectionshouldfollowalogicalsequence檢查應(yīng)按一定的邏輯順序Observations,recommendationsanddeficienciesshouldbediscussed withthecompanyrepresentativesatthetime發(fā)現(xiàn)的不到之處，建議和缺陷應(yīng)與及時(shí)與廠房代表溝通Itisimportanttomention?

plus

?points提及《附加》項(xiàng)這點(diǎn)很重要Followtheplanasfaraspossible盡可能多地按計(jì)劃進(jìn)行TheinspectionisbasedonObservations檢查要基于觀察2025/1/2516On-SiteInspection現(xiàn)場(chǎng)檢查Inspectorsmayuseachecklisttoensureallareasofoperationsare investigated檢查員可以使用檢查表來(lái)確認(rèn)所有區(qū)域均列入Experiencehasshownthatrigidadherencetoaverydetailedchecklist developedfromGMPGuidelinescanleadtomissingvulnerableareas經(jīng)驗(yàn)告訴人們嚴(yán)格按照根據(jù)GMP指南上套用下的明細(xì)表來(lái)檢查會(huì)錯(cuò)過(guò)一些簿弱環(huán)節(jié)Inspectorsshouldnotbeconcernedwithnon-GMPaspectsegfinance, H&S檢查員不應(yīng)關(guān)心與GMP無(wú)關(guān)的事宜，例如：財(cái)務(wù)，H&S2025/1/2517On-SiteInspection現(xiàn)場(chǎng)檢查MedicinesTestingScheme:Inspectorssamples醫(yī)學(xué)試驗(yàn)計(jì)劃：檢查員樣品Duringinspectionssamplesofstartingmaterials,workinprogressand finishedproductcanbetakenfortestingiftheInspectorconsiders thatitmightassistinthedetectionofqualitydeficiencies檢查過(guò)程中，如果檢查員認(rèn)為可能對(duì)判斷質(zhì)量缺陷有幫助，則應(yīng)取原材料樣品、過(guò)程中樣及成品來(lái)做試驗(yàn)DocumentationReview文件審核

Anessentialpartoftheinspection.檢查的實(shí)質(zhì)部分Thisisthehistoricalevidenceofcompliance這是說(shuō)明過(guò)往符合要求的依據(jù)Documentscanbereviewedduringthecourseofthesiteinspectionandindetailinthemeetingroom在現(xiàn)場(chǎng)檢查階段應(yīng)審核文件，在會(huì)議室更深入了解2025/1/2518DocumentReview文件審核Manufacturingformulae生產(chǎn)配方BatchManufacturingRecords批記錄Specifications技術(shù)規(guī)格

chemicalrawmaterials化學(xué)原材料

packagingcomponents包裝村料 intermediates中間產(chǎn)物 finishedproducts成品2025/1/2519DocumentReview文件審核Processandequipmentvalidation工藝及設(shè)備驗(yàn)證Environmentalmonitoring環(huán)境監(jiān)控StandardOperatingProcedures標(biāo)準(zhǔn)操作規(guī)程Trainingrecords:jobdescriptions培訓(xùn)記錄：工作職責(zé)描述Releaseprocedures發(fā)放程序DistributionandRecall發(fā)貨及召回TechnicalAgreements技術(shù)協(xié)議2025/1/2520QualityIndicators質(zhì)量顯示器CustomerComplaints–Quantity,Investigation,PreventiveAction用戶投訴—記錄數(shù)量，調(diào)查，防范措施ProductRecalls–defectsreportedtothecompanyortotheDefect ReportingCentreandanyrecallsinstitutedsincetheprevious inspectionshouldbediscussedandrecordsexamined產(chǎn)品召回—報(bào)告至企業(yè)或報(bào)告中心的過(guò)失及任何自上次檢查以來(lái)已經(jīng)展開(kāi)調(diào)查的召回案件都要進(jìn)行討論并檢查記錄HandlingofReturns退貨的處理2025/1/2521QualityIndicators質(zhì)量顯示器Self-Inspectionreports–obtainassurancethatinternalauditsare conductedandfollow-upactionistaken.自查報(bào)告—確認(rèn)企業(yè)執(zhí)行內(nèi)部自查并采取相關(guān)跟進(jìn)措施。Note:Asamatterofpolicytheinternalauditsshouldnotberead作為一項(xiàng)政策，不應(yīng)過(guò)目?jī)?nèi)部自查報(bào)告Non-conformanceprocedure異常情況程序ChangeControlProcedure變更控制程序2025/1/2522ClosingMeeting結(jié)束會(huì)議InspectorconvenesameetingwiththeCompanyRepresentatives檢查員召集企業(yè)代表開(kāi)會(huì)SummarisetheproposedlistofdeficienciestoreporttotheLicensing Authority總結(jié)匯集的缺陷上報(bào)有關(guān)機(jī)構(gòu)AllowCompanytocorrectmisconceptions允許企業(yè)更正誤解Bereadytoexplainyourreasons準(zhǔn)備作出自已的解釋Usefultodiscusspossibleremedialactions討論可能的補(bǔ)救措施是有用的2025/1/2523ClosingMeeting結(jié)束會(huì)議TheCompanyshouldbeencouragedtogiveanundertakingtoresolve thedeficienciesandtoagreeaprovisionaltimetableforcorrective action.應(yīng)鼓勵(lì)企業(yè)承諾拿出針對(duì)這些缺陷的處理方案及糾偏行動(dòng)的時(shí)間表TheReportisin3parts:-報(bào)告包括3部份內(nèi)容 i)Inspector’sInformation檢查員信息 ii)SummaryandConclusions總結(jié)及結(jié)論 iii)TheCompanySiteMasterFile企業(yè)自述性文件2025/1/2524REPORT報(bào)告Inspector’sinformation檢查員信息

Inspectorssummarysheetandintroduction檢查員概述及介紹 Briefreportofinspectionactivities檢查活動(dòng)的大體報(bào)告 Scopeoftheinspection檢查范疇 Personnelmet已會(huì)見(jiàn)人員 Changessincepreviousinspection上次檢查后的變化情況 Futureplannedchanges以后計(jì)劃的變化情況2025/1/2525REPORT報(bào)告i)Inspector’sinformation檢查員信息 Inspector’sfindings檢查員發(fā)現(xiàn)的情況 Samplestakenandresultsifknown所取的樣品及已知的結(jié)果 Assessmentofthesitemasterfile對(duì)自述性文件的評(píng)估 GMPrelatedrecallsmadeinthelast2years在最近2年內(nèi)與GMP相關(guān)的召回案件

2025/1/2526REPORT報(bào)告ii)Summaryandconclusions總結(jié)與結(jié)論 ThelistoffailurestocomplywiththeEuropeanGuidetoGood ManufacturingPractices

withreferencetotheappropriatesectionof theguide.列表陳述與歐洲GMP指南不相符合的事項(xiàng)及相關(guān)參照條例iii)TheCompanySiteMasterFile公司自述性文件Theneed,ifany,toupdatetheCompanySiteMasterFileinlightof theInspection.按檢查結(jié)果是可否更新公司自述性文件2025/1/2527FinalRemarks最后評(píng)論P(yáng)ointsfortheInspector

toconsider檢查員要考慮的幾點(diǎn)內(nèi)容Theconditionofthefacilities廠房的條件Thecleanlinessofthefacilities廠房的潔凈度Theorganisation人員機(jī)構(gòu)組成Thestaffattitude/professionalism員工的敬業(yè)程度及專(zhuān)業(yè)水平Thesitepre