THEPHARMACEUTICALINDUSTRIESEXPECTATIONSOFINSPECTIONS

BYREGULATORYAUTHORITIES

管理機構對制藥企業(yè)認證檢查展望DavidCDonaldGlobalIndustrialQualityInternationalSites2025/1/251TheExpertiseoftheInspectors

檢查員的專業(yè)技術Inspectorsshouldhaveprevioustrainingandpracticalexperiencein manufacture,qualitycontrolandqualityassuranceofpharmaceutical products檢查員須經培訓及具有制藥企業(yè)生產，質控及質保等方面的實際工作經驗Deficienciesinexperienceneedsin-housetraining;attendanceat courses;seminars經驗上的不足需要加強內部培訓，上課及參加研討會Athoroughknowledgeisneededinaspectsofthepharmaceutical industry完整的業(yè)內知識需涉及制藥行業(yè)的所有領域2025/1/252TheRoleoftheInspectors

檢查員的任務Primeresponsibilitytoproduceafactualreportonthestandardsof GoodManufacturingPractice(GMP)主要職責是以GMP為標準書寫一份反映實際情況的報告AssistManufacturerstocomplywithGMP幫助企業(yè)更好地執(zhí)行GMPIdentifydeficienciesinGMP鑒定GMP執(zhí)行過程中的缺陷Giveadviceonwaystocorrectdeficiencies對糾正缺陷的方法提出指導Acceptalternativewaysofcompliance接受與GMP要求相符的其他選擇方法2025/1/253TypesofInspection檢查類型RoutineManufacturer’sInspection常規(guī)生產企業(yè)的檢查 -Aninspectiontosatisfythelicensingauthoritythatthemanufacturer isincompliancewithhislicenceandmeetstheGMPrequirements對生產企業(yè)許可證的檢查以確認該證的符合度及是否與GMP要求相一致 -fornewlyestablishedfacilities對新建設施的檢查 -newproductlines對新建生產線的檢查 -changesinkeypersonnelorequipment對主要人員或設備變更的檢查2025/1/255TypesofInspection檢查類型Follow-upInspection跟蹤檢查 -thefirstinspectionisincomplete第一次檢查不徹底 -theCompanyhasmajordeficiencies發(fā)現(xiàn)企業(yè)存在嚴重缺陷ProductRelatedInspection與制品相關的檢查 -toassesscomplianceoftheManufacturers’operationswiththe detailsintheProductLicence確認企業(yè)運作與產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檢查類型SpecialistInspections專家檢查 -BulkproductionofBiologicalProductsandBloodProductsuse specialistbiologicalinspectors生產制品原液生產和血制品須由生物學方面的專家進行 -Non-biologicalinspectionsusespecialistprincipalinspectorsto evaluatespecificaspects

microbiologicalaspectswatersystemsetc非生物學專家組成的檢查應由主要檢查人員評估專業(yè)性的問題：如微生物學方面的問題，水系統(tǒng)方面的問題2025/1/257TypesofInspection檢查類型WholesaleDealers

批發(fā)商 -toassesscompliancewithgoodwholesaledealingpracticeand provisionsofthelicence評估批發(fā)商運作行為是否規(guī)范，所提供的許可證是否與實際相符 -ImportDealerslicencewitharrangementsforquarantine,QCand finalreleaseofimportedproducts進口批發(fā)商許可證及與待檢，QC，進口產品的最終發(fā)放的安排等ContractLaboratories委托檢測的實驗室 -inspectedtoassesscompliancewithGoodLaboratoryPractice Standardsandconfirmthattherelevantprovisionsofthelicenceare observedfortheproductswhicharetested.檢查以評估GLP的執(zhí)行情況，并確認執(zhí)照上所述提供的用以產品檢測的相關設施2025/1/258QualitySystems質量系統(tǒng)TheCompanyOrganization公司組織QualityGroup質量保證群體Procedures程序ManufacturingProcess生產工藝Records記錄QualityControl質控QAactivitiescarriedout貫徹執(zhí)行的質量保證2025/1/259FrequencyofInspections檢查頻率ManufacturersLicence:2years生產許可企業(yè)：2年WholesaleDealerImportLicence:2years進口產品批發(fā)商：2年WholesaleDealerLicenceHolder:4years批發(fā)商營業(yè)執(zhí)照持有人：4年?

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?companies:12–18months〈邊緣〉企業(yè)：12-18個月 Follow-up:within6months跟蹤相查：6個月內Overseassites:2–3years海外基地：2-3年2025/1/2510DurationofInspections檢查持續(xù)時間ProductManufactureSuper+250staffLarge60–249staffMedium10–59staffSmallLessthan10staffSterile10632NonSterile8321Assembly7112025/1/2511PreparationforInspection檢查的準備工作ReviewtheCompanyfile審核企業(yè)文件Previousreportsandresponses以前的檢查報告及反饋Anyfollow-upaction任何跟進措施ReviewofSiteMasterFile審核企業(yè)自述性文件Licensedmatters–licensesheld,operatingsites,authorisedstaff, limitationsimposedbyspecificprovisions,authorisedproducts有關許可證事宜：所持許可證，生產基地，授權員工，特殊產品帶來的局限性2025/1/2512PreparationforInspection檢查的準備工作Agreethetimeofthepostinspectionmeeting同意檢查后會議的時間Describeitspurpose目的描述Summarizethewaythedeficienciesaretobeclassified概述缺陷的分類方式Indicateanydocumentationrequired指出所需的任何文件ReviewManagementstructure審核管理框架2025/1/2513PreparationforInspection檢查的準備工作ReviewtheCompany’sQualityPolicyandarrangementsfor monitoringthequalitysystem審核公司質量政策及質量系統(tǒng)監(jiān)控的安排ReviewChanges審核變更情況Reviewprogresswithdeficiencies審核缺陷的跟進工作2025/1/2514On-SiteInspection現(xiàn)場檢查WalkthroughtheSite走一遍廠區(qū)Inspecttodeterminethedegreeofconformityoftheoperationstothe requirementsofGMPandcompliancewiththelicenceanddetailsintheapplication檢查確定實際運作與GMP要求的符合程度及實際運用與許可證要求的一致性Itinerarydeterminedbythetypeofinspection確定檢查路線2025/1/2515On-SiteInspection現(xiàn)場檢查Theinspectionshouldfollowalogicalsequence檢查應按一定的邏輯順序Observations,recommendationsanddeficienciesshouldbediscussed withthecompanyrepresentativesatthetime發(fā)現(xiàn)的不到之處，建議和缺陷應與及時與廠房代表溝通Itisimportanttomention?

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?points提及《附加》項這點很重要Followtheplanasfaraspossible盡可能多地按計劃進行TheinspectionisbasedonObservations檢查要基于觀察2025/1/2516On-SiteInspection現(xiàn)場檢查Inspectorsmayuseachecklisttoensureallareasofoperationsare investigated檢查員可以使用檢查表來確認所有區(qū)域均列入Experiencehasshownthatrigidadherencetoaverydetailedchecklist developedfromGMPGuidelinescanleadtomissingvulnerableareas經驗告訴人們嚴格按照根據(jù)GMP指南上套用下的明細表來檢查會錯過一些簿弱環(huán)節(jié)Inspectorsshouldnotbeconcernedwithnon-GMPaspectsegfinance, H&S檢查員不應關心與GMP無關的事宜，例如：財務，H&S2025/1/2517On-SiteInspection現(xiàn)場檢查MedicinesTestingScheme:Inspectorssamples醫(yī)學試驗計劃：檢查員樣品Duringinspectionssamplesofstartingmaterials,workinprogressand finishedproductcanbetakenfortestingiftheInspectorconsiders thatitmightassistinthedetectionofqualitydeficiencies檢查過程中，如果檢查員認為可能對判斷質量缺陷有幫助，則應取原材料樣品、過程中樣及成品來做試驗DocumentationReview文件審核

Anessentialpartoftheinspection.檢查的實質部分Thisisthehistoricalevidenceofcompliance這是說明過往符合要求的依據(jù)Documentscanbereviewedduringthecourseofthesiteinspectionandindetailinthemeetingroom在現(xiàn)場檢查階段應審核文件，在會議室更深入了解2025/1/2518DocumentReview文件審核Manufacturingformulae生產配方BatchManufacturingRecords批記錄Specifications技術規(guī)格

chemicalrawmaterials化學原材料

packagingcomponents包裝村料 intermediates中間產物 finishedproducts成品2025/1/2519DocumentReview文件審核Processandequipmentvalidation工藝及設備驗證Environmentalmonitoring環(huán)境監(jiān)控StandardOperatingProcedures標準操作規(guī)程Trainingrecords:jobdescriptions培訓記錄：工作職責描述Releaseprocedures發(fā)放程序DistributionandRecall發(fā)貨及召回TechnicalAgreements技術協(xié)議2025/1/2520QualityIndicators質量顯示器CustomerComplaints–Quantity,Investigation,PreventiveAction用戶投訴—記錄數(shù)量，調查，防范措施ProductRecalls–defectsreportedtothecompanyortotheDefect ReportingCentreandanyrecallsinstitutedsincetheprevious inspectionshouldbediscussedandrecordsexamined產品召回—報告至企業(yè)或報告中心的過失及任何自上次檢查以來已經展開調查的召回案件都要進行討論并檢查記錄HandlingofReturns退貨的處理2025/1/2521QualityIndicators質量顯示器Self-Inspectionreports–obtainassurancethatinternalauditsare conductedandfollow-upactionistaken.自查報告—確認企業(yè)執(zhí)行內部自查并采取相關跟進措施。Note:Asamatterofpolicytheinternalauditsshouldnotberead作為一項政策，不應過目內部自查報告Non-conformanceprocedure異常情況程序ChangeControlProcedure變更控制程序2025/1/2522ClosingMeeting結束會議InspectorconvenesameetingwiththeCompanyRepresentatives檢查員召集企業(yè)代表開會SummarisetheproposedlistofdeficienciestoreporttotheLicensing Authority總結匯集的缺陷上報有關機構AllowCompanytocorrectmisconceptions允許企業(yè)更正誤解Bereadytoexplainyourreasons準備作出自已的解釋Usefultodiscusspossibleremedialactions討論可能的補救措施是有用的2025/1/2523ClosingMeeting結束會議TheCompanyshouldbeencouragedtogiveanundertakingtoresolve thedeficienciesandtoagreeaprovisionaltimetableforcorrective action.應鼓勵企業(yè)承諾拿出針對這些缺陷的處理方案及糾偏行動的時間表TheReportisin3parts:-報告包括3部份內容 i)Inspector’sInformation檢查員信息 ii)SummaryandConclusions總結及結論 iii)TheCompanySiteMasterFile企業(yè)自述性文件2025/1/2524REPORT報告Inspector’sinformation檢查員信息

Inspectorssummarysheetandintroduction檢查員概述及介紹 Briefreportofinspectionactivities檢查活動的大體報告 Scopeoftheinspection檢查范疇 Personnelmet已會見人員 Changessincepreviousinspection上次檢查后的變化情況 Futureplannedchanges以后計劃的變化情況2025/1/2525REPORT報告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果 Assessmentofthesitemasterfile對自述性文件的評估 GMPrelatedrecallsmadeinthelast2years在最近2年內與GMP相關的召回案件

2025/1/2526REPORT報告ii)Summaryandconclusions總結與結論 ThelistoffailurestocomplywiththeEuropeanGuidetoGood ManufacturingPractices

withreferencetotheappropriatesectionof theguide.列表陳述與歐洲GMP指南不相符合的事項及相關參照條例iii)TheCompanySiteMasterFile公司自述性文件Theneed,ifany,toupdatetheCompanySiteMasterFileinlightof theInspection.按檢查結果是可否更新公司自述性文件2025/1/2527FinalRemarks最后評論PointsfortheInspector

toconsider檢查員要考慮的幾點內容Theconditionofthefacilities廠房的條件Thecleanlinessofthefacilities廠房的潔凈度Theorganisation人員機構組成Thestaffattitude/professionalism員工的敬業(yè)程度及專業(yè)水平Thesitepre