FDA檢查相關(guān)要求

PreparingforFDAInspectionsZhejiangApoleaMedicalTechnologyCompanyJanuary,20091RFLAssociatesPurposeofanANDA(DMF)pre-ApprovalInspection

ANDA（DMF）批準(zhǔn)前檢查的目的Ensurethatthefacilities,equipment,andinstrumentsaresuitableforproducingaqualityproduct

確保廠房，設(shè)備和儀器適用于生產(chǎn)合格的產(chǎn)品Ensurethatthequalitysystemisfunctioningcorrectly確保質(zhì)量體系準(zhǔn)確運(yùn)行EnsurethatproductismanufacturedundercGMPs確保產(chǎn)品在cGMP條件下生產(chǎn)2RFLAssociatesPurposeofanANDA(DMF)pre-ApprovalInspectionEnsurethatdatasubmittedintheANDA/DMFsubmissionissupportedbyrawdataatthefacility確保在遞交的ANDA/DMF中的數(shù)據(jù)是依據(jù)工廠的原始數(shù)據(jù)的DataandoriginalrecordsmustbedocumentedaccordingtocGMPstandards數(shù)據(jù)和原始記錄必須根據(jù)cGMP標(biāo)準(zhǔn)記錄存檔EnsurethattheANDA/DMFsubmissionisanaccuratereflectionofwhatisbeingdoneatthefacility確保ANDA/DMF的遞交是準(zhǔn)確地反映工廠中所做的事情3RFLAssociatesTheANDA(DMF)Pre-ApprovalInspection(PAI)ANDA（DMF）批準(zhǔn)前檢查（PAI）WhenistheANDAreviewedbyFDA?FDA什么時(shí)候?qū)徍薃NDA？AftertheANDAholderfilestheANDA在ANDA持有者遞交ANDA之后Becauseofbacklogs,expectatleast6monthdelaybeforereviewing由于文件積壓，在審核之前一般至少有6個(gè)月的延遲WhenistheInspectionscheduled?什么時(shí)候安排檢查？AftertheANDAissatisfactorilyreviewed在對(duì)ANDA審核滿意之后Deficiencylettermaybeissued缺陷信可能已經(jīng)發(fā)布Moreinformationmayberequested可能要求更多的信息4RFLAssociatesFlowofthepre-ApprovalInspection批準(zhǔn)前檢查的流程FDAPersonnelInvolvedFDA涉及的相關(guān)人員

Twopeopleareusuallyinvolved:通常安排兩個(gè)人Investigator調(diào)查員Chemist化學(xué)家Generally,theywillworkseparately通常他們分開(kāi)工作Therefore,preparationfortwopeopleisneeded因此，需要準(zhǔn)備兩組人員5RFLAssociatesFlowofthepre-ApprovalInspectionPreparationfortwopeoplegenerallymeans:兩組人員的準(zhǔn)備TwoInterpreters(providedbythefirm,atpresent)兩個(gè)翻譯人員（目前由公司自己安排）Theinterpretersareextremelyimportanttothesmoothrunningoftheinspection翻譯人員對(duì)于檢查的順利進(jìn)行及其關(guān)鍵Twoadjacentconferencerooms相鄰的兩個(gè)會(huì)議室Investigator調(diào)查員Chemist化學(xué)家6RFLAssociatesFlowofthepre-ApprovalInspectionInspectionwillusuallytakeatleast4fulldays檢查通常至少要滿4個(gè)工作日InitialMeeting(1-1?hours)首次會(huì)議1-1.5小時(shí)WalkthroughofWarehouses,Production,QCLaboratory(5-6hours)倉(cāng)庫(kù)，生產(chǎn)，QC實(shí)驗(yàn)室檢查5-6小時(shí)DocumentReview(3-31/2days)文件審核3-3.5天Closeout(1-2hours)結(jié)束1-2小時(shí)However,theFDAInspectorsmaychangethisschedule但是，F(xiàn)DA檢查官員可能改變這種行程Bepreparedfortheunexpected準(zhǔn)備好應(yīng)對(duì)意外情況7RFLAssociatesFlowofthepre-ApprovalInspectionInitialMeeting(1-11/2hours)首次會(huì)議1-1.5小時(shí)Introductionsandexchangeofbusinesscards介紹和交換名片Themostresponsiblepersonatthefirmshouldbepresent公司的主要負(fù)責(zé)人必須出席QA,Production,QCRepresentativesshouldbepresentQA,生產(chǎn)，QC代表必須出席8RFLAssociatesFlowofthepre-ApprovalInspectionInitialMeeting(1-1?hours)首次會(huì)議1-1.5小時(shí)Makesurethateverypersonisidentifiedbyname確保每一個(gè)人都通過(guò)名字來(lái)識(shí)別身份Nameandtitledisplayedatinitialmeeting名字和職務(wù)在首次會(huì)議上要說(shuō)明Nametagsonuniformduringinspection在檢查期間名字和簽名要一致Consideralsoahandoutwiththefollowinginformationforkeypeople:也要考慮為主要相關(guān)人員準(zhǔn)備下列資料FullChinesename(andEnglishsurnameifapplicable)中文名全名（如果需要，英文名）Title職務(wù)Thumbnailphotograph小照片9RFLAssociatesFlowofthepre-ApprovalInspectionInitialMeeting(1-1?hours)首次會(huì)議1-1.5小時(shí)CompanyPresentation公司介紹PowerPointwithhardcopiesprovided提供幻燈片和復(fù)印件FDAwillhaveinitialquestionsandwillrequestessentialdocumentsFDA會(huì)提出初步問(wèn)題，并要求一些必要的文件10RFLAssociatesFlowofthepre-ApprovalInspection/InitialMeeting

批準(zhǔn)前檢查的流程/首次會(huì)議TheCompanyPresentation(30-45minutes)公司介紹（30-45分鐘）ImportanceoftheInitialPresentation

首次介紹的重要性ItisFDA’sfirstimpressionofyourcompany這是FDA對(duì)你們公司的第一印象Itshouldbeveryprofessional(graphicsandpresentation)必須非常專業(yè)（圖表和介紹）ItshouldbeinEnglish必須是英文的Itshouldnotbetoolong(1houristoolong)

不能太長(zhǎng)（1個(gè)小時(shí)太長(zhǎng)）Youshouldrehearsegivingthepresentationtomakesureitisperfect你們應(yīng)該排練一下介紹，要確保做到完美11RFLAssociatesFlowofthepre-ApprovalInspection/InitialMeeting

批準(zhǔn)前檢查的流程/首次會(huì)議TheCompanyPresentation(30-45minutes)公司介紹（30-45分鐘）HistoryofBusiness歷史Whenwasitfounded?Bywhom?

什么時(shí)候創(chuàng)建？誰(shuí)創(chuàng)建？Importantmilestonesduringcompanydevelopment公司發(fā)展的重要里程碑Sitechanges

場(chǎng)地的變更Additionofbuildings,purchaseofmajorequipment

追加的建筑，關(guān)鍵設(shè)備的采購(gòu)Productintroductions

產(chǎn)品介紹TotalNumberofemployeesattheinspectionsite,andinthefollowingdepartments:在檢查工廠的員工總?cè)藬?shù)和下列部門(mén)的人數(shù)TopManagement高級(jí)管理層QualityAssuranceQAQualityControlQCProduction生產(chǎn)ResearchandDevelopment研發(fā)(Administrative)（行政）(FinancialandSales)（財(cái)務(wù)和銷售）12RFLAssociatesFlowofthepre-ApprovalInspectionTheCompanyPresentation(30-45minutes)公司介紹（30-45分鐘）AnnualSales(convertedtoUSDollars)年度銷售（轉(zhuǎn)化成美元）Certifications/AchievementsrelatingtoQuality(ISO,etc.)質(zhì)量體系相關(guān)證書(shū)（ISO等）Introductiontoproducts產(chǎn)品介紹AllAPIsandalldosageforms所有的API和制劑劑型USandnon-USmarkets美國(guó)和非美國(guó)市場(chǎng)InspectionalHistory檢查歷史USFDASFDA(CustomerAudits)客戶審計(jì)Other其他13RFLAssociatesFlowofthepre-ApprovalInspectionTheCompanyPresentation(30-45minutes)PlantLayout(PlanandPhotographs)

工廠布局圖（規(guī)劃圖和照片）IndicatetheproductionareasthatFDAwillaudit說(shuō)明FDA將要審計(jì)的生產(chǎn)區(qū)域Indicatewarehouseareas說(shuō)明倉(cāng)庫(kù)區(qū)域IndicateQCLaboratorylocation說(shuō)明QC實(shí)驗(yàn)室區(qū)域Givearea(squaremeters)ofeachworkshop,warehouse,QClaboratory給出每個(gè)車間，倉(cāng)庫(kù)，QC實(shí)驗(yàn)室的面積（平方米）14RFLAssociatesFlowofthepre-ApprovalInspectionTheCompanyPresentation(30-45minutes)OrganizationalChart組織機(jī)構(gòu)圖Companyasawhole整個(gè)公司的組織機(jī)構(gòu)圖QAOrganizationalChartQA組織機(jī)構(gòu)圖IntroductiontoQualitySystem介紹質(zhì)量體系OverviewofManufacturingProcess

生產(chǎn)工藝過(guò)程概述15RFLAssociatesFlowofthepre-ApprovalInspection

WalkthroughofProductionandQCLaboratory(5-6hours)生產(chǎn)和QC實(shí)驗(yàn)室檢查Warehouses倉(cāng)庫(kù)ProductionAreas生產(chǎn)區(qū)域CleanFinishingArea潔凈區(qū)域PackagingandLabeling包裝和貼簽QCLaboratoryQC實(shí)驗(yàn)室Water,Air,Vacuum,PressureSystems水，空氣，真空，壓力系統(tǒng)16RFLAssociatesFlowofthepre-ApprovalInspectionDocumentsandRecordsReview(3-31/2days)文件和記錄審核（3-3.5天）Intheconferencerooms在會(huì)議室Itisessentialtoretrieverequesteddocumentsquickly必須快速找到和提供要求的文件Itisessentialtohavetherightpeopleintheconferenceroomsattherighttime必須是對(duì)的人在對(duì)的時(shí)間在會(huì)議室里Donotovercrowdtheconferencerooms會(huì)議室不要過(guò)度擁擠Dohavethepersonbestqualifiedtoexplaineachdocument要讓最好最有資歷的人來(lái)解釋每一個(gè)文件Domaintainasenseoforderandprofessionalism要維持有秩序和專業(yè)化，職業(yè)化的感覺(jué)17RFLAssociatesFlowofthepre-ApprovalInspectionFDAWillusuallygiveadailywrap-upFDA通常每天都會(huì)給出小結(jié)Endoftheday,15-30minutes在每天結(jié)束時(shí)，15-30分鐘Issuesandconcernsfoundduringthedayarediscussed

在一天當(dāng)中討論過(guò)的問(wèn)題和關(guān)注的事情L(zhǎng)astDay:最后一天Closeout(1-1?hours)結(jié)束總結(jié)（1-1.5小時(shí)）Presentationof483bytheFDAteamFDA小組給出483說(shuō)明Firm’sverbalresponsetothe483ispresented.公司對(duì)于483的口頭回復(fù)Awritten483responseshouldbegiventoFDAwithin30daysofcloseout.Youshould書(shū)面的483回復(fù)應(yīng)該在結(jié)束的30天之內(nèi)提交給FDASetout,correctiveactionplanto483observations(withdocumentation)針對(duì)483不符合項(xiàng)，要作出準(zhǔn)確的整改計(jì)劃（文件）Youcanobjecttoobservationsthatyoufeelareincorrect(withdocumentation)你們可以反對(duì)不符合項(xiàng)，如果你們覺(jué)得不正確（文件）18RFLAssociatesGeneralConsiderationsEstablishWorkHoursandLunchTimesatbeginningofaudit在審計(jì)開(kāi)始就要制定工作時(shí)間和午餐時(shí)間Lunchtimesgenerallyonehouratmost午餐時(shí)間一般最多為1小時(shí)Donothavelong,elaboratelunches不要太久，使午餐變復(fù)雜Bepreparedtoworkduringeveningsifneeded如果需要，準(zhǔn)備好晚上工作DeliverRequestedDocumentsPromptlyandEfficiently!傳遞文件要全面，有效19RFLAssociatesGeneralConsiderationsDonotusearecordertotapetheinspection審計(jì)中不要使用錄音機(jī)DonottakephotosduringtheinspectionwithoutFDA’spermission沒(méi)有FDA的允許，在檢查過(guò)程中不要拍照片Donotcarryoutloudside-discussionsduringtheinspection!在檢查過(guò)程中不要在旁邊大聲討論Duringthewalkthrough現(xiàn)場(chǎng)檢查過(guò)程中Duringdocumentreview文件審核過(guò)程中20RFLAssociatesGeneralConsiderationsLoudside-discussions(inChinese)

在旁邊大聲討論（用中文）AredistractingtotheFDA會(huì)讓FDA官員分心Appearextremelyunprofessional顯示極其不專業(yè)Givetheappearancethatthecompanyisnotprepared給人以公司沒(méi)有做好準(zhǔn)備的印象21RFLAssociatesGeneralConsiderationsAlwayskeepinMind:要時(shí)刻記著Thecompanyshouldalwaysappeartobeprofessional公司要表現(xiàn)出專業(yè)化Thecompanyshouldalwaysappeartobeprepared公司要表現(xiàn)出做好充分準(zhǔn)備Thecompanyshouldalwaysworktomaketheinspectionrunsmoothlyandefficiently公司要要確保檢查能夠順利有效第進(jìn)行Theinvestigatorswillbehappiestifyoucanmaketheirjobseasy如果你們可以讓他們的工作輕松，檢察官會(huì)非常高興22RFLAssociatesGeneralConsiderationsDecideyourcompany’spolicyonFDAtakingphotosbeforethePAI在檢查前，確定出你們公司對(duì)于FDA是否可以拍照相關(guān)政策Youarenotrequiredtopermitthemtophotographyourfacility你們沒(méi)有被要求你們必須允許FDA官員可以在你們公司拍照片However,youmaydecidetodothis但是你們可以做決定是不是允許Donotbringitup,butifitcomesup,makesurethatyouhaveaclearpolicy不要把這個(gè)事情單獨(dú)提出來(lái)，但是如果出現(xiàn)，那么確保你們有一個(gè)明確的政策23RFLAssociatesGeneralConsiderationsDecidebeforetheinspectionyourcompany’spolicyonprovidingdocuments

在檢查前，確定出你們公司對(duì)于是否提供文件的相關(guān)政策Ingeneral,youmustprovideallGMP-relateddocumentsrequested,butmarkthemas“Confidential”通常來(lái)說(shuō)，你們必須提供檢察官要求的全部與GMP相關(guān)的文件，但是要標(biāo)明他們是“保密的”YoudonothavetoprovideinternalauditandselfinspectionresultstoFDA,butyoumaywishtodosoinsomecases你們不必要提供內(nèi)審和自檢結(jié)果給FDA，但是有時(shí)你們可能自己希望這么做24RFLAssociatesGeneralConsiderationsUnderstandFDA’sPolicyonMeals,HotelAccommodations,andGifts了解FDA關(guān)于吃飯、賓館住宿和禮物的規(guī)定AtPresent,FDApaysformeals,hotelaccommodations目前，F(xiàn)DA支付吃飯和賓館住宿的費(fèi)用Askinspectorsabouttheirpreferencesforeveningmeals:詢問(wèn)檢察官關(guān)于晚餐安排的意見(jiàn)Theymaywishtodinewiththecompany他們可能希望和公司一起吃晚飯Theymaywishtodinealone他們可能希望單獨(dú)吃飯Askinspectorsabouttheirpreferencesonentertainmentafterhours詢問(wèn)檢察官關(guān)于休閑時(shí)間娛樂(lè)活動(dòng)意見(jiàn)Donotofferelaborategifts不要提供精心準(zhǔn)備的復(fù)雜的禮物25RFLAssociatesTheImportanceoftheInterpreter翻譯的重要性Interpretershouldbeveryprofessional翻譯應(yīng)該非常專業(yè)InterpretershouldrepresentFDAandbeneutral翻譯應(yīng)該代表FDA，必須中立Interpretershouldnotaddwordsorchangethemeaningofwords翻譯不能增加文字或是改變文字含義ChinesetoEnglish中文翻譯成英文EnglishtoChinese英文翻譯成中文26RFLAssociatesTheImportanceoftheInterpreterInterpretermustbefamiliarwith:

翻譯必須熟悉GMPterminologyGMP術(shù)語(yǔ)PharmaceuticalManufacturingterminology醫(yī)藥生產(chǎn)術(shù)語(yǔ)Chemicalnames(rawmaterials,intermediates,API,dosageforms)化學(xué)名詞（原料，中間體，API，制劑劑型）LaboratoryInstrumentnames實(shí)驗(yàn)室儀器名稱27RFLAssociatesPlanningandLogistics:計(jì)劃和后勤DocumentStagingArea文件存放區(qū)EstablishaDocumentStagingArea準(zhǔn)備一個(gè)文件存放區(qū)DocumentStagingAreaiswhereallplannedandanticipateddocumentsarestored文件存放區(qū)是指存放所有計(jì)劃和預(yù)計(jì)要提供的文件的地方DocumentStagingAreaisneartheConferenceRooms文件存放區(qū)要靠近會(huì)議室DocumentStagingAreaisstockedwithdocumentsbeforetheinspection在檢查之前文件存放區(qū)要放好文件28RFLAssociatesPlanningandLogistics:DocumentStagingAreaSeparateRoom,NearInvestigators要單獨(dú)的房間，靠近檢察官DocumentsArrangedandAvailable安排準(zhǔn)備好文件PeopleAssignedtoRetrieveDocuments指定人員檢索取文件Havedocumentsfiledsotheycanberetrievedinstantly文件要?dú)w檔好，這樣可以立即檢索取出文件Haveaphotocopiereasilyavailable(andaback-up)準(zhǔn)備好一個(gè)復(fù)印機(jī)（一個(gè)備用）29RFLAssociatesPlanningandLogistics:DocumentStagingAreaAllDocumentsrequestedbyFDAaretakenfromandreturnedtothisareaFDA要求的所有文件必須從這個(gè)房間取出，再放回到這個(gè)地方KeepalogofeachdocumentrequestedbyFDA

FDA要求的每一個(gè)文件都要有記錄Documentname文件名稱Requestdate/time要求的日期和時(shí)間Deliverydate/time提供的日期和時(shí)間IfFDArequestsacopyMake2copies:如果FDA要求復(fù)印件，那么就要準(zhǔn)備好2份復(fù)印件1.ForFDA1份提供給FDABriefreview(byQA)beforereleasingit在提供之前要（QA）簡(jiǎn)單審核Stampitas“Confidential”or“UncontrolledCopy”敲上”保密”或是“不控制”章2.FortheCompanyInspectionalFile1份作為公司檢查存檔30RFLAssociatesPlanningandLogistics:計(jì)劃和后勤CompanyInspectionalFile公司檢查記錄存檔ContainsaRecordofnotestakenbythescribe包括記錄員的記錄ContainsaRecordofallemployeesinterviewedbyFDAInspectorsandthesubjectmatter包括FDA檢察官面談所有員工的記錄和主題ContainsCopiesofalldocumentsgiventoFDAInspectors包括提供給FDA檢察官的所有文件的復(fù)印件ContainsaRecordofanydiscussionswithFDAInspectors包括和FDA檢察官討論的所有內(nèi)容記錄Duringinspection檢察過(guò)程中討論內(nèi)容Dailycloseouts每天總結(jié)討論內(nèi)容483closeout483總結(jié)時(shí)討論內(nèi)容ContainsaRecordofanycorrectionsmadeduringtheinspection包括在檢查過(guò)程中做的所有整改工作的記錄31RFLAssociatesPlanningandLogistics:TheScribe(s)計(jì)劃和后勤：記錄員Scribe(s):Takeswrittennotesduringthewalkthrough(andintheconferenceroom)記錄員：在現(xiàn)場(chǎng)審計(jì)和文件審核過(guò)程中做書(shū)面記錄TheScribeshouldtakeallnotesoftheinspection記錄員應(yīng)該記錄所有檢查的事項(xiàng)TheScriberecordsallFDArequestsfordocuments記錄員應(yīng)該記錄FDA要求的所有文件32RFLAssociatesTheRunnersBeijing200833RFLAssociatesPlanningandLogistics:TheRunners計(jì)劃和后勤：文件傳送者Runners:Retrievedocumentsrequestedduringthewalkthrough(andduringdocumentreview)

文件傳送者：在檢查過(guò)程中取出要求的文件TheRunnersretrievetheDocumentsrequestedduringPlantTour,anddeliverthemtotheConferenceRoom在工廠參觀期間，文件傳送者要取出官員要求的文件，把文件送到會(huì)議室Documentsrequestedshouldbeavailableinconferenceroomwhenplanttouriscompleted當(dāng)工廠參觀結(jié)束時(shí)，F(xiàn)DA官員要求的文件必須已經(jīng)在會(huì)議室QAshouldpresentthedocumentsrequestedassoonasFDAreturnstotheconferenceroom當(dāng)FDA回到會(huì)議室時(shí)，QA應(yīng)該馬上提供要求的文件ShowFDAthedocumentsthatwererequested向FDA展示是他們要求的文件Thisgivesanexcellentimpressionofefficiencyandprofessionalism這會(huì)留下非常好的印象：有效率，專業(yè)化34RFLAssociatesFactoryTour工廠參觀Warehouses倉(cāng)庫(kù)RawMaterial原料Solvents溶劑Intermediates中間體FinalProduct成品PackagingandLabeling包裝和貼簽Samplingroomsorareas取樣室或區(qū)域Rejectedproductareas拒收產(chǎn)品區(qū)域35RFLAssociatesFactoryTourProductionAreas生產(chǎn)區(qū)域Frombeginningtoend從開(kāi)始到結(jié)束Followingthemanufacturingprocess根據(jù)生產(chǎn)工藝Describethematerialflowandthepeopleflow

描述物流和人流Ifintermediatesaretransferred,explainhow(openorclosed):如果中間體轉(zhuǎn)移，解釋如何轉(zhuǎn)移（開(kāi)放系統(tǒng)還是密閉系統(tǒng)）Dischargethroughreactoroutlet(liquids)

通過(guò)反應(yīng)釜出口排出（液體）Transferredtobins(wetcake,powders)

轉(zhuǎn)移到容器中（濕的塊狀物，粉末）Pumpedthroughpiping(liquids)通過(guò)管道來(lái)泵壓（液體）36RFLAssociatesFactoryTour/ProductionAreas

工廠參觀/生產(chǎn)區(qū)域FDAmay,duringtheWarehouseandFactoryTourFDA可能在倉(cāng)庫(kù)和工廠參觀中做以下事情：Askworkersquestions(jobknowledgeandGMPawareness)詢問(wèn)工人問(wèn)題（工作知識(shí)和GMP意識(shí)）RequestQCTestrecordsforselectedlotsofmaterials

要求選擇性批次物料的QC檢測(cè)記錄The‘runner’shouldretrievethesefromthestagingareaandhavethemreadyafterthetour文件傳送者應(yīng)該從文件存放區(qū)取出文件，在參觀結(jié)束后準(zhǔn)備好記錄Examinebatchrecordsforin-processproduction檢查生產(chǎn)記錄Makesurestepsaresignedandwitnessedatthetimetheyareperformed

確保每一步生產(chǎn)時(shí)有簽名，并有復(fù)核人RequestCleaningRecordsforequipment(forexamplelast6months)(Runner)要求設(shè)備的清潔記錄（例如過(guò)去6個(gè)月記錄）（文件傳送者）RequestcopiesofMasterLabels(Runner)要求空白標(biāo)簽的復(fù)印件（文件傳送者）MakesurethatSOPsarepresent確保SOP在現(xiàn)場(chǎng)37RFLAssociatesFactoryTour/QCLaboratory

工廠參觀/QC實(shí)驗(yàn)室QCLaboratory:Prepareto…QC實(shí)驗(yàn)室：準(zhǔn)備Explainpaperworkflowandrecords

解釋文書(shū)工作流程和記錄Requestsforsampling要求取樣Samplingandreceivinglogbook取樣和接收登記記錄Howsamplesareassigned樣品如何分配？Howtestdataisrecorded檢測(cè)結(jié)果如何記錄？Logbooks日志W(wǎng)orksheets工作表Reviewproceduresforcompletedwork

完成工作的審核程序IssuanceofCOACOA的發(fā)布38RFLAssociatesFactoryTour/QCLaboratory

工廠參觀/QC實(shí)驗(yàn)室QCLaboratoryExplainSampleflow解釋樣品流程Incomingsamplestorage新進(jìn)樣品的存放Samplelabeling樣品貼簽Samplestorageduringanalysis樣品在分析過(guò)程中的儲(chǔ)存Reservesamplesstorage留樣儲(chǔ)存Sampledisposal樣品處理39RFLAssociatesFactoryTour/QCLaboratory

工廠參觀/QC實(shí)驗(yàn)室Makesurepeoplearebusyandinstrumentsareoperational確保實(shí)驗(yàn)室人員忙于工作，儀器在運(yùn)行FDAmay,duringtheQCLaboratorytour:在QC實(shí)驗(yàn)室參觀期間，F(xiàn)DA可能AskanalyststechnicalandGMPquestions(everyanalystshoulddemonstratejobknowledge)詢問(wèn)分析人員技術(shù)和GMP問(wèn)題（每個(gè)熱分析人員應(yīng)該證明一定的工作知識(shí)技能）40RFLAssociatesFactoryTour:Peopletobepresent工廠參觀/出席人員Limitto8-9peopleifpossible如果可以，人員限定8-9人FDAInspectors(2)FDA檢查官（2個(gè)）Interpreter(1)翻譯（1個(gè)）EssentialCompanyPersonnelonly必要的公司人員QApersonnel(limitednumber)QA（限定人數(shù)）ResponsibleSupervisorforthatpartoftour

被參觀部門(mén)的負(fù)責(zé)主管Scribe(apersonwhorecordsnotes)記錄員（1個(gè)記錄）Twopeopletoretrieverequesteddocumentsforlater(Runners)2個(gè)稍后取文件的人（文件傳送者）41RFLAssociatesFactory/LabTour:Peopletobepresent工廠參觀/出席人員Warehouses倉(cāng)庫(kù)Warehousekeeperforthatwarehouse

倉(cāng)庫(kù)倉(cāng)管員Materialssamplingperson(QCLaboratory:toexplainsamplingifsamplingdonebyQC)物料取樣人員（QC實(shí)驗(yàn)室：如果取樣是QC進(jìn)行的，那么解釋取樣流程）QAperson,scribe,runnersQA人員，記錄員，文件傳送者42RFLAssociatesFactory/LabTour:Peopletobepresent工廠參觀/出席人員ProductionAreas生產(chǎn)區(qū)域ProductionManagerforthatworkshop車間的生產(chǎn)經(jīng)理Productionworkers(shouldbebusyandworking)

生產(chǎn)工人（必須忙于工作）IPCLaboratoryperson中控實(shí)驗(yàn)室人員QAperson,scribe,runnersQA人員，記錄員，文件傳送者43RFLAssociatesFactory/LabTour:Peopletobepresent工廠參觀/出席人員CleanProductionArea潔凈區(qū)LimitedAccess限制人員進(jìn)入Planwhowillgoin(limitednumber)

計(jì)劃誰(shuí)進(jìn)入潔凈區(qū)（人數(shù)限定）Makesuregowningproceduresareclearlyindicated確保著裝程序有清楚說(shuō)明Makesureshoecoversandgownsarelargeenough(XXXL)確保鞋子和衣服足夠大（XXXL）44RFLAssociatesFactory/LabTour:Peopletobepresent工廠參觀/出席人員QCLaboratoryQC實(shí)驗(yàn)室QCLaboratoryManagerQC實(shí)驗(yàn)室經(jīng)理QAPerson(s),Scribe,RunnersQA人員，記錄員，文件傳送者M(jìn)akesureshoecoversandlabcoatsarelargeenough確保鞋子和實(shí)驗(yàn)室工作服足夠大Analystsshouldbebusyandworking分析人員要忙于工作Instrumentsonandrunning儀器要開(kāi)著并運(yùn)行Showhowpaperworkishandledanddocumented顯示文書(shū)工作怎么處理和存檔Frombeginningtoend從開(kāi)始到結(jié)束45RFLAssociatesAnsweringQuestions回答問(wèn)題FDAwillinterviewproductionandQClabemployeesFDA將會(huì)面談生產(chǎn)和QC實(shí)驗(yàn)室人員IfFDAinterviewsemployees,managementmustnotanswerfortheemployee如果FDA面談職工，那么管理層不能替職工回答Employeesmustnotdiscussanswers(inChinese)withmanagementbeforeansweringquestions在回答問(wèn)題之前，職工不能和管理人員（用中文）討論怎么回答46RFLAssociatesAnsweringquestions(foremployees)回答問(wèn)題（給職工）Listentothequestioncarefully,thenanswerthatquestiondirectly

仔細(xì)聽(tīng)問(wèn)題，然后直接回答問(wèn)題Donotansweradifferentquestionthanwasasked(listencarefullyandthenanswer)不要答非所問(wèn)（先聽(tīng)清楚問(wèn)題，再回答）Donotansweronlywith:“IfollowtheSOP”不要只回答“我根據(jù)SOP來(lái)做的”Youmustdemonstratejobknowledge你必須證明你的工作知識(shí)Donotpre-discussanswerswithotheremployeesorsupervisors不要和其他員工或是主管預(yù)先討論答案AnswerdirectlytotheFDAperson:lookathim/her(nottheinterpreter,nottheboss)直接向FDA官員回答：看著官員（而不是看著翻譯或是老板）47RFLAssociatesAnsweringquestions(foremployees)回答問(wèn)題（給職工）IfFDAasksa“yesorno”question,answer“yes”or“no”first如果FDA詢問(wèn)的是一個(gè)“是或不是”的問(wèn)題，那么首先回答“是”或“不是”Thenexplainfurtherifneeded

如果需要，再解釋Ifyoudonotknowtheanswer如果你不知道答案(Forexample,ifthatisnotpartofyourjob)（例如，不是你的工作范圍部分）Suggestthatapersoninanotherdepartmentcouldanswerthequestionmoreclearly建議其他部門(mén)的另一個(gè)人可以更清楚地回答這個(gè)問(wèn)題Managementshouldthentakeover,andprovidetheanswerpromptly管理層應(yīng)該接過(guò)這個(gè)問(wèn)題，然后提供完整的回答48RFLAssociatesDocumentandRecordsReview

(3-3?Days)文件和記錄審核（3-3.5天）HaveFollowingProductionRecordsAvailable(Goingbackaboutthreeyears)下列生產(chǎn)記錄要能提供（追回到大概三年前）MasterandExecutedBatchRecords主生產(chǎn)記錄和已執(zhí)行的批生產(chǎn)記錄CleaningRecords清潔記錄QCLaboratoryTestRecordsQC實(shí)驗(yàn)室檢測(cè)記錄RawMaterialTesting原料檢測(cè)In-ProcessTesting中控檢測(cè)FinalReleaseTesting成品放行檢測(cè)ReprocessedSolventTesting返工的溶劑檢測(cè)MasterLabel(3copies)主標(biāo)簽（3份）49RFLAssociatesDocumentandRecordsReview

文件和記錄審核HavefollowingLists/Tablesavailable(inEnglish)下列清單/目錄要英文提供1.Tableofall

drugproducts,IntermediatesandAPI‘s

currentlymanufactured(regardlessof

intendedmarket)所有目前生產(chǎn)的藥品，中間體和API的目錄（不管市場(chǎng)）Product/APINameandCode產(chǎn)品/API名稱和編號(hào)ActiveIngredient活性組分Countrieswheremarketed(USA,etc.)市場(chǎng)所在國(guó)家（美國(guó)等）USApplicationNumber(NDA,ANDA)andApplicationHolderName美國(guó)申請(qǐng)?zhí)枺∟DA,ANDA）和申請(qǐng)持有者名稱ApplicationApprovalDate申請(qǐng)通過(guò)日期50RFLAssociatesDocumentandRecordsReview

文件和記錄審核HavefollowingList/TablesAvailable(InEnglish)下列清單/目錄要英文提供2.Listofalllots

manufactured

forthe

US

market

forthelast2yearstodateforallUSdrugproductsorAPIs過(guò)去兩年到日前為止，為美國(guó)市場(chǎng)的藥品或API生產(chǎn)的所有生產(chǎn)批次的清單DrugproductorAPInameandcode

藥品或API名稱和代號(hào)lotnumber批號(hào)Datemanufactured

生產(chǎn)日期Reworkedorreprocessed?(YorN)

重新加工或返工？（是或不是）lotstatusanddateoflaststatuschange批情況和最后狀態(tài)的變更日期Approved,rejected,onhold批準(zhǔn)，拒收，associateddeviationsorOOSinvestigations

相關(guān)的偏差或OOS調(diào)查51RFLAssociatesDocumentandRecordsReview

文件和記錄審核HavefollowingLists/Tablesavailable(inEnglish)下列清單/目錄要英文提供3.Listofalldrugproducts&APIsshippedtotheUSforthepast2yearstodate過(guò)去兩年到日前為止，所有發(fā)到美國(guó)的藥品和APIDrugProductorAPInameandcode

藥品或API名稱和編號(hào)lotnumber批號(hào)Datemanufactured生產(chǎn)日期Consignee&Location收貨人和地址lotstatus批狀態(tài)DateshippedtotheUS發(fā)貨到美國(guó)的日期VolumeShipped發(fā)貨量52RFLAssociatesDocumentandRecordsReview(List/Tables)文件和記錄審核（清單/目錄）4.Listofallcomplaintsforallproductsforthelastthreeyears過(guò)去3年全部產(chǎn)品的全部投訴清單Complaintnumber投訴編號(hào)APIorDrugproductAPI或藥品LotNumber批號(hào)ShippedtoUS?(Y/N)發(fā)貨到美國(guó)？（是或不是）ComplaintCloseoutdate投訴關(guān)閉日期HavecomplaintrecordsandalldocumentationavailableforreviewinDocumentStagingArea在文件存放區(qū)要確?？梢阅玫酵对V記錄和全部文件53RFLAssociatesDocumentandRecordsReview(List/Tables)文件和記錄審核（清單/目錄）5.List(inEnglish)ofallOutofSpecificationInvestigationsforthelastthreeyears過(guò)去3年全部OOS調(diào)查的清單（英文）OOSNumberOOS編號(hào)Material(RawMaterial,API,DrugProduct)物料（原料，API，藥品）LotNumber批號(hào)LabError?(Y/N)實(shí)驗(yàn)室錯(cuò)誤（是或不是）FinalDecisiononOOSOOS的最后決定OOSCloseoutDateOOS關(guān)閉日期HaveOOSrecordsandalldocumentationavailableforreviewinDocumentStagingArea在文件存放區(qū)要確保可以拿到OOS記錄和全部文件54RFLAssociatesDocumentandRecordsReview

文件和記錄審核HavefollowingLists/Tablesavailable(inEnglish)準(zhǔn)備下列清單/目錄（英文）MasterListofSOPsandSMPsSOP和SMP主清單SOPNumber,Title,VersionNumber,effectivedateSOP編號(hào)，名稱，版本號(hào)，有效日期ListofProductionEquipmentforProductInspected被檢查產(chǎn)品的生產(chǎn)設(shè)備清單EquipmentNumber,Name,Location設(shè)備號(hào)，名稱，位置ListofQCLaboratoryInstrumentsforProductInspected被檢查產(chǎn)品的QC儀器清單EquipmentName,Number設(shè)備號(hào)，名稱Manufacturer,ModelNumber生產(chǎn)商，型號(hào)ListofApprovedVendorsforRawMaterials,Intermediates原料，中間體的合格供方清單55RFLAssociatesDocumentandRecordsReview

文件和記錄審核HaveFollowingPlansandDrawingsAvailable下列設(shè)計(jì)圖和圖紙要準(zhǔn)備PlantLayout工廠布局圖IncludeAreas(SquareMeters)ofWorkshops包括車間的面積（平方米）IncludeArea(SquareMeters)ofQCLaboratory包括QC的面積（平方米）ShowMaterialFlowandPeopleFlow顯示物流和人流PurifiedWaterSystem純化水系統(tǒng)UpdatedPlans更新后的設(shè)計(jì)圖ModificationHistory修改歷史AirSystems(ProductionandCleanRooms)空氣系統(tǒng)（生產(chǎn)和潔凈室）UpdatedPlans更新后的設(shè)計(jì)圖ModificationHistory修改歷史OtherCriticalEngineeringDrawings(Vacuum,CompressedAir)

其他關(guān)鍵工程圖紙（真空，壓縮空氣）Critical=Contactwithproduct關(guān)鍵=與產(chǎn)品接觸56RFLAssociatesDocumentandRecordsReview

文件和記錄審核HaveFollowingChartsAvailable下列圖表要準(zhǔn)備CorporateOrganizationalChart公司組織機(jī)構(gòu)圖ShowingNamesandTitles顯示名字和職務(wù)Includethenameandtitleofthemostresponsiblepersonon-site包括現(xiàn)場(chǎng)主要責(zé)任人的名字和職務(wù)Shouldbepresentatbeginningandatthecloseout在首次和末次會(huì)議上要出席QualityUnitOrganizationalChart質(zhì)量部門(mén)組織機(jī)構(gòu)圖ShowingNamesandTitles顯示名字和職務(wù)ProcessFlowChart工藝流程圖Includeallsteps包括所有步驟IncludeallequipmentwithequipmentID