准备FDA认证前检查中英文对照

RichardNeedham,RFLAssociates1PreparingforFDAPreapprovalInspections

准备FDA认证前检查RichardNeedham,RFLAssociates2Purposeofapre-ApprovalInspection(DMForANDA)

认证前检查的目的（DMF或ANDA）Ensurethatthefacilities,equipment,andinstrumentsaresuitableforproducingaqualityproduct确保设施，设备和仪器适合高质量产品的生产Ensurethatthequalitysystemisfunctioningcorrectly确保质量体系运行正常

EnsurethatproductismanufacturedundercGMPs

确保在cGMPs指导下进行产品生产RichardNeedham,RFLAssociates3Purposeofapre-ApprovalInspection

认证前检验的目的

RichardNeedham,RFLAssociates4ThePre-ApprovalInspection(PAI)认证前检查（PAI）WhenistheDMFreviewedbyFDA?DMF什么时候被FDA审查？

OnlyaftertheANDAholderfilestheANDAandreferstotheDMF只有在ANDA持有人将ANDA归档并提交到DMF后IfnoANDAisfiled,theDMFisfiledawaywithoutreview.如果ANDA没有归档，那么DMFjiang将其移开不进行审查。However,theDMFholdershouldstillupdatetheDMFthroughannualreportsandDMFamendmentstotheFDA然而，DMF持有人仍应通过年度报告和DMF修订将更新提交给FDAThisway,theDMFwillbeup-to-datewhenreviewed这样，DMF被审查时将是最新的

RichardNeedham,RFLAssociates5ThePre-ApprovalInspection(PAI)

认证前检查（PAI）WhenistheANDAreviewedbyFDA?FDA什么时候审查ANDAAftertheANDAholderfilestheANDA

ANDA持有人将ANDA归档后Becauseofbacklogs,expectatleast6monthdelaybeforereviewing由于积压，预计至少延迟6个月才能被审查WhenistheInspectionscheduled?什么时候进行预先审查

AftertheANDAissatisfactorilyreviewed

ANDA审查圆满后Deficiencylettermaybeissued信件缺乏可能成为问题Moreinformationmayberequested可能会要求更多的信息

RichardNeedham,RFLAssociates6Flowofthepre-ApprovalInspection

认证前检查流程FDAPersonnelInvolvedFDA涉及人员

Twopeopleareusuallyinvolved:通常涉及两个人FDAInvestigator(Productionissues)FDA调查人员（生产问题）FDAChemist(LaboratoryIssues)FDA化验师（实验室问题）Generally,theywillworkseparately一般来说，他们将分开工作Therefore,preparationfortwopeopleisneeded因此，需要配备两个人RichardNeedham,RFLAssociates7Flowofthepre-ApprovalInspection

认证前检查流程Preparationfortwopeoplegenerallymeans:配备两个人通常是指

TwoInterpreters(providedbythefirm,atpresent)两名翻译员（目前由公司提供的）Theinterpretersareextremelyimportanttothesmoothrunningoftheinspection翻译员对于检查顺利进行是非常重要的Twoadjacentconferencerooms两个相邻的会议室Investigator调查人员Chemist化验师RichardNeedham,RFLAssociates8Flowofthepre-ApprovalInspection

认证前检查Inspectionwillusuallytake4fulldays检查通常需要4天InitialMeeting(1-1½hours)首次会议（1-1个半小时）WalkthroughofWarehouses,Production,QCLaboratory(5-6hours)仓库，生产，QC实验室巡检（5-6小时）DocumentReview(2-2½days)文件审查（2-2天半）Closeout(1-2hours)总结（1-2小时）However,theFDAInspectorsmaychangethisschedule然而，FDA检查员可能会改变这个时间表

Bepreparedfortheunexpected做好出现意外的准备

RichardNeedham,RFLAssociates9Flowofthepre-ApprovalInspection

认证前检查流程InitialMeeting(1-11/2hours)首次会议（1-1个半小时）Introductionsandexchangeofbusinesscards介绍并交换名片Themostresponsiblepersonatthefirmshouldbepresent该公司负责人应该在场QA,Production,QCRepresentativesshouldbepresentQA，生产，QC代表应该在场RichardNeedham,RFLAssociates10Flowofthepre-ApprovalInspection

认证前检查流程InitialMeeting(1-1½hours)

首次会议（1-1个半小时）Makesurethateverypersonisidentifiedbyn101ame确保每个人标注姓名Nameandtitledisplayedatinitialmeeting姓名和标题呈现在首次会议上Nametagsonuniformduringinspection检查期间所有姓名标签格式应统一Consideralsoahandoutwiththefollowinginformationforkeypeople:还考虑分发含有以下信息的资料给关键人员：Fullname(andEnglishsurnameifapplicable)全名（如果适用加上英文姓氏）Title标题Thumbnailphotograph照片缩图RichardNeedham,RFLAssociates11Flowofthepre-ApprovalInspection认证前检查InitialMeeting(1-1½hours)首次会议（1-1个半小时）CompanyPresentation公司介绍PowerPointwithhardcopiesprovided提供可以拷贝的PPTFDAwillhaveinitialquestionsandwillrequestessentialdocumentsFDA会提出一些初始问题，并要求提供一些精炼的文档RichardNeedham,RFLAssociates12Flowofthepre-ApprovalInspection/InitialMeeting

认证前检查流程/首次会议TheCompanyPresentation(30-45minutes)公司介绍（30-45分钟）

ImportanceoftheInitialPresentation初始表现很重要ItisFDA’sfirstimpressionofyourcompany这是FDA对该公司的第一印象Itshouldbeveryprofessional(graphicsandpresentation)应该很专业（图形和文稿）ItshouldbeinEnglish应当是英文的Itshouldnotbetoolong(1houristoolong)不应该过长（不超过1小时）Youshouldrehearsegivingthepresentationtomakesureitisperfec您应该提前演练您的演讲，保证他的完美RichardNeedham,RFLAssociates13Flowofthepre-ApprovalInspection/InitialMeeting

认证前检查流程/首次会议TheCompanyPresentation(30-45minutes)公司介绍（30-45分钟）

HistoryofBusiness企业历史Whenwasitfounded?Bywhom?什么时候成立？由谁创建？Importantmilestonesduringcompanydevelopment公司发展中的重要里程碑Sitechanges

网站的变化Additionofbuildings,purchaseofmajorequipment

此外还有建筑物，主要设备的采购Productintroductions

产品介绍TotalNumberofemployeesattheinspectionsite,andinthefollowingdepartments:视察现场，以及以下部门的员工总数：

TopManagement高层管理人员QualityAssuranceQAQualityControlQCProduction生产ResearchandDevelopment研发(Administrative)（行政）(FinancialandSales)（财务和销售）RichardNeedham,RFLAssociates14Flowofthepre-ApprovalInspection

认证前检查TheCompanyPresentation(30-45minutes)公司介绍（30-45分钟）

AnnualSales(convertedtoUSDollars)年销售额（换算成美元）

Certifications/AchievementsrelatingtoQuality(ISO,etc.)

认证/质量成果（ISO，等）Introductiontoproducts产品简介

AllAPIsandalldosageformsproduceon-site所有API和所有剂型的生产现场

USandnon-USmarkets美国和非美国市场销路

InspectionalHistoryl查阅历史

USFDAUSFDASFDA食品药品监督管理局OtherRegulatoryAgencies其他管理机构(CustomerAudits)（消费者协会）Other其他RichardNeedham,RFLAssociates15Flowofthepre-ApprovalInspection

认证前检查流程TheCompanyPresentation(30-45minutes)公司介绍（30-45分钟）

PlantLayout(PlanandPhotographs)工厂布局（平面图和照片）

IndicatetheproductionareasthatFDAwillaudit说明FDA将审查的生产区域Indicatewarehouseareas请注明仓库区IndicateQCLaboratorylocation标明QC实验室位置Givearea(squaremeters)ofeachworkshop,warehouse,QClaboratory注明各车间，仓库，QC实验室面积（平方米）RichardNeedham,RFLAssociates16Flowofthepre-ApprovalInspection认证前检查RichardNeedham,RFLAssociates17Flowofthepre-ApprovalInspection

认证前检查

WalkthroughofProductionandQCLaboratory(5-6hours)

生产和QC实验室巡检（5-6小时）

Warehouses仓库ProductionAreas生产区CleanFinishingArea洁净完成区PackagingandLabeling包装和标签QCLaboratoryQC实验室Water,Air,Vacuum,PressureSystems水，通风，真空，压力系统RichardNeedham,RFLAssociates18Flowofthepre-ApprovalInspection

认证前检查流程RichardNeedham,RFLAssociates19Flowofthepre-ApprovalInspection

认证前检查FDAWillusuallygiveadailywrap-upFDA通常会做每日总结

Beproactiveandaskforoneduringtheinitialmeeting在首次会议上采取积极主动Endoftheday,15-30minutes总结一天的工作，15-30分钟Issuesandconcernsfoundduringthedayarediscussed讨论白天发现的问题和担忧Thisallowsthecompanytoassesshowtheinspectionisgoing这允许该公司评价检查进度Thisallowsthecompanytobeginpreparingcorrectionsorclearupmisunderstandings这允许该公司开始准备更正或澄清误解

RichardNeedham,RFLAssociates20Flowofthepre-ApprovalInspection

认证前检查流程Closeout(1-1½hours)总结（1-1个半小时）Presentationof483bytheFDAteam美国FDA团队提出483Firm’sverbalresponsetothe483ispresentedtothe483ispresented公司应口头答复提出的483Awritten483responseshouldbegiventoFDAwithin15daysofcloseout483书面答复应在工作结束后15天内上交给FDASetout,withdocumentation,correctiveactionplanto483observations列出更改483行动计划的意见，并列出依据Object,withdocumentation,toobservationsthatyoufeelareincorrect将你认为不正确的提出反对意见，并列出依据RichardNeedham,RFLAssociates21Whatisthe483(FDA483)?

什么是483（FDA的483）？Aformonwhichinspectionalobservationsarewritten检查意见的一种书面形式Theyareobservations,notnecessarilydeficiencies他们提出的只是意见并不是缺陷Theyaregroupedunderthesixystemsheadings:它们归入sixystems体系：QualitySystem质量体系FacilitiesandEquipmentSystem设施和设备系统MaterialsSystem原料系统ProductionSystem生产系统PackagingandLabelingSystem包装和标签制度LaboratoryControlSystem实验室控制系统RichardNeedham,RFLAssociates22TheFDAForm483

FDA的483表格Thecompanycandiscusstheobservationsverballyatcloseout在检查总结时该公司可以口头讨论检查Thecompanyshouldrespondinwritingwithin15daysofissuance该公司要在15日内发布书面答复The483,EstablishmentInspectionreport(EIR),andfirm’sdocumentedresponsearereviewedbyFDAComplianceBranchFDA下属分支将检查设立检查报告（EIR），和公司有证据的回复的483材料Adecisionismadewhethertheinspectionis:作出决定检查是否是NAI(NoActionIndicated)NAI（无行动可能性）VAI(VoluntaryActionIndicated)VAI（无随意行动的可能性）OAI(OfficialActionIndicated)OAI（无官方行动的可能性）RichardNeedham,RFLAssociates23GeneralConsiderations总则EstablishWorkHoursandLunchTimesatbeginningofaudit在审计工作开始时确定工作时间和午餐时间

Lunchtimesgenerallyonehouratmost午餐时间一般最多一小时Donothavelong,elaboratelunches午餐不要太长，太复杂Bepreparedtoworkduringeveningsifneeded如果有需要要在晚上做准备工作DeliverRequestedDocumentsPromptlyandEfficiently!迅速而高效地提供要求的文件！

RichardNeedham,RFLAssociates24GeneralConsiderations总则Donotusearecordertotapetheinspection不要使用磁带录音机在检查中录音

DonottakephotosduringtheinspectionwithoutFDA’spermission亦不得在未经FDA的许可的情况下在检查过程中拍照

Donotcarryoutloudside-discussionsduringtheinspection!不要在检查过程中大声进行多余的讨论

Duringthewalkthrough在巡检过程中Duringdocumentreview在文件审查过程中RichardNeedham,RFLAssociates25GeneralConsiderations一般考虑Loudside-discussions大声私下讨论AredistractingtotheFDA会分散FDA注意力Appearextremelyunprofessional出现极不专业情况Givetheappearancethatthecompanyisnotprepared给予公司没有事先准备的期望RichardNeedham,RFLAssociates26GeneralConsiderations一般考虑AlwayskeepinMind:始终牢记Thecompanyshouldalwaysappeartobeprofessional该公司应始终表现出专业性Thecompanyshouldalwaysappeartobeprepared该公司应始终表现出有所准备Thecompanyshouldalwaysworktomaketheinspectionrunsmoothlyandefficiently公司应该尽可能保证检查工作顺利高效的进行Theinvestigatorswillbehappiestifyoucanmaketheirjobseasy如果你们能让检查员工作顺利他们将非常高兴RichardNeedham,RFLAssociates27GeneralConsiderations一般考虑Decideyourcompany’spolicyonFDAtakingphotosbeforethePAI

在PAI之前在FDA发出的照片上决定公司的方针政策Youarenotrequiredtopermitthemtophotographyourfacility你不需要允许他们为设施设备拍照However,youmaydecidetodothis但是，您也可以决定这样做Donotbringitup,butifitcomesup,makesurethatyouhaveaclearpolicy不要提出，但是一旦提出，请确保你有一个明确的方针RichardNeedham,RFLAssociates28GeneralConsiderations一般考虑RichardNeedham,RFLAssociates29GeneralConsiderations一般考虑UnderstandFDA’sPolicyonMeals,HotelAccommodations,andGifts了解FDA关于餐饮，酒店住宿，及礼品的政策

AtPresent,FDApaysformeals,hotelaccommodations目前，FDA支付餐饮，酒店住宿费用Askinspectorsabouttheirpreferencesforeveningmeals:询问检查员对晚餐的需求；Theymaywishtodinewiththecompany他们可能希望与该公司吃饭Theymaywishtodinealone他们可能想单独用餐Askinspectorsabouttheirpreferencesonentertainmentafterhours询问他们业余时间的娱乐项目Donotofferelaborategifts不赠予贵重的礼物RichardNeedham,RFLAssociates30TheImportanceoftheInterpreter翻译员的重要性RichardNeedham,RFLAssociates31TheImportanceoftheInterpreter

翻译员的重要性Interpretermustbefamiliarwith:翻译员必须熟悉GMPterminologyGMP的术语PharmaceuticalManufacturingterminology制药业术语Chemicalnames(rawmaterials,intermediates,API,dosageforms)化学名称（原材料，中间体，空气污染指数，剂型）LaboratoryInstrumentnames实验室仪器名称RichardNeedham,RFLAssociates32PlanningandLogistics:DocumentStagingArea

规划和物流：文件临时存储区域

RichardNeedham,RFLAssociates33PlanningandLogistics:DocumentStagingArea

规划和物流：文件临时存储区域

SeparateRoom,NearInvestigators单独的房间，靠近调查员DocumentsArrangedandAvailable文件有规划并且容易找到PeopleAssignedtoRetrieveDocuments专人负责文件检索Havedocumentsfiledsotheycanberetrievedinstantly将文件归档，需要时就可以立刻被找到Haveaphotocopiereasilyavailable(andabackupmachine)有一台可用的复印机(和备份机)RichardNeedham,RFLAssociates34PlanningandLogistics:DocumentStagingArea

规划和物流：文件临时存储区域RichardNeedham,RFLAssociates35PlanningandLogistics:CompanyInspectionalFile

规划和物流：文件临时存储区域RichardNeedham,RFLAssociates36PlanningandLogistics:TheScribe(s)

规划和物流：记录员Scribe(s):TakesNotesduringthewalkthrough(andintheconferenceroom)记录员：在巡检过程中做记录（在会议室）TheScribe(s)shouldtakenotesoftheinspection记录员应在检查过程中做笔记TheScriberecordsallFDArequestsfordocuments记录员记录FDA对文件的要求RichardNeedham,RFLAssociates37TheRunnersBeijing2008RichardNeedham,RFLAssociates38PlanningandLogistics:TheRunners

规划和物流：联络员Runners:Retrievedocumentsrequestedduringthewalkthrough(andduringdocumentreview)联络员：检索在巡检过程中要求的文件（文件审查期间）TheRunnersretrievetheDocumentsrequestedduringPlantTour,anddeliverthemtotheConferenceRoom联络员检索在车间检查时要求的文件，并送到指定的会议室Documentsrequestedshouldbeavailableinconferenceroomwhenplanttouriscompleted在车间检查结束后在会议室应该可以找到要求的文件QAshouldpresentthedocumentsrequestedassoonasFDAreturnstotheconferenceroomQA应在FDA回到会议室前尽快提供要求的文件ShowFDAthedocumentsthatwererequested出示FDA要求的文件Thisgivesanexcellentimpressionofefficiencyandprofessionalism这将给人一种高效专业的印象RichardNeedham,RFLAssociates39FactoryTour工厂检查Warehouses仓库RawMaterial原料Solvents溶剂Intermediates中间体FinalProduct最终产品PackagingandLabeling包装和标签Samplingroomsorareas采样室或采样区Rejectedproductareas不合格产品区RichardNeedham,RFLAssociates40FactoryTour工厂检查ProductionAreas生产区Frombeginningtoend从开始到结束Followingthemanufacturingprocess按照制造流程Describethematerialflowandthepeopleflow标示出人流和物流Ifintermediatesaretransferred,explainhow(openorclosed):如果中间体转移，描画出具体的程序（打开或关闭）Dischargethroughreactoroutlet(liquids)出口释放（液体）Transferredtobins(wetcake,powders)转至储藏箱（湿滤饼，粉末）Pumpedthroughpiping(liquids)泵压管道（液体）RichardNeedham,RFLAssociates41FactoryTour/ProductionAreas

工厂检查/生产区RichardNeedham,RFLAssociates42FactoryTour/QCLaboratory

工厂检查/QC实验室RichardNeedham,RFLAssociates43FactoryTour/QCLaboratory

工厂检查/QC实验室RichardNeedham,RFLAssociates44FactoryTour/QCLaboratory

工厂检查/QC实验室RichardNeedham,RFLAssociates45FactoryTour:Peopletobepresent

工厂检查：在场人员RichardNeedham,RFLAssociates46Factory/LabTour:Peopletobepresent

工厂/实验室检查：在场人员Warehouses仓库Warehousekeeperforthatwarehouse该仓库的仓库管理员Materialssamplingperson(QCLaboratory:toexplainsamplingifsamplingdonebyQC)材料取样人（QC实验室：解释抽样如果质控完成采样）QAperson,scribe,runnersQA人员，记录员，联络员RichardNeedham,RFLAssociates47Factory/LabTour:Peopletobepresent

工厂/实验室检查：在场人员ProductionAreas生产区ProductionManagerforthatworkshop该车间的生产经理Productionworkers(shouldbebusyandworking)生产工人（应正在工作）IPCLaboratorypersonIPC实验室人员QAperson,scribe,runnersQA人员，记录员，联络员RichardNeedham,RFLAssociates48Factory/LabTour:Peopletobepresent

工厂/实验室检查：在场人员RichardNeedham,RFLAssociates49Factory/LabTour:Peopletobepresent工厂/实验室检查：在场人员QCLaboratoryQC实验室QCLaboratoryManagerQC实验室管理者QAPerson(s),Scribe,RunnersQA人员，记录员，联络员Makesureshoecoversandlabcoatsarelargeenough确保鞋套和实验服足够大Analystsshouldbebusyandworking分析师应忙于工作Instrumentsonandrunning仪器正在运行Showhowpaperworkishandledanddocumented显示如何记录和处理文件Frombeginningtoend从开始到结束RichardNeedham,RFLAssociates50AnsweringQuestions回答问题FDAwillinterviewproductionandQClabemployeesFDA将面试生产和QC实验室员工IfFDAinterviewsemployees,managementmustnotanswerfortheemployee如果FDA面试员工，管理层不能替员工回答

Employeesmustnotdiscussanswers(inChinese)withmanagementbeforeansweringquestions

员工不得在回答前用中文与管理层讨论答案

RichardNeedham,RFLAssociates51Answeringquestions(foremployees)回答问题（员工）RichardNeedham,RFLAssociates52Answeringquestions(foremployees)

回答问题（员工）IfFDAasksa“yesorno”question,answer“yes”or“no”first

如果FDA提出了一个要求回答“是或否”的问题，首先回答回答“是”或“不是”Thenexplainfurtherifneeded然后，如果需要，进一步解释Ifyoudonotknowtheanswer如果你不知道答案

(Forexample,ifthatisnotpartofyourjob)（例如，如果这不是你的工作的一部分）Suggestthatapersoninanotherdepartmentcouldanswerthequestionmoreclearly建议一个其他部门能够更清楚回答这个问题的人Managementshouldthentakeover,andprovidetheanswerpromptly管理人员应接管，并迅速给出答复RichardNeedham,RFLAssociates53DocumentandRecordsReview

(2-2½Days)

文件和记录的审查（2-2天半）RichardNeedham,RFLAssociates54DocumentandRecordsReview

文件和记录的审查HavefollowingLists/Tablesavailable(inEnglish)有以下可用的列表/表格（英文）Tableofall

drugproductsandAPI's

currentlymanufactured(regardlessof

intendedmarket)所有的药品和API的目前生产品（不论目标市场）Product/APINameandCode产品/API的名称和代码ActiveIngredient活性成分Countrieswheremarketed(USA,China,etc.)上市国家（美国，中国等）USApplicationNumber(NDA,ANDA)andApplicationHolderName美国申请编号（NDA，ANDA）持有人姓名ApplicationApprovalDate申请批准日期RichardNeedham,RFLAssociates55DocumentandRecordsReview

文件和记录检查HavefollowingList/TablesAvailable(InEnglish)

有以下列表/表格（英文）

2.Listofalllots

manufactured

forthe

US

market

forthelast2yearstodateforallUSdrugproductsorAPIs迄今为止过去两年为美国市场生产的的所有药品、批次的列表

DrugproductorAPInameandcode药物产品或API的名称和代码lotnumber批号Datemanufactured生产日期Dateshipped(orifnotshipped,currentstatus)发货日期（如果没有发运，现状）Amountshipped发货额Nameandaddressofconsignee收货人名称地址Reworkedorreprocessed?(YorN)

返工或再加工（是或否）Currentlotstatus当前很多现状Approved,rejected,expired,onhold合格，不合格，国企，待验associateddeviationsorOOSinvestigations相关偏差或OOS调查RichardNeedham,RFLAssociates56DocumentandRecordsReview(List/Tables)

文件和记录检查（列表/表格）3.Listofallcomplaintsforallproductsforthelastthreeyears过去3年的所有产品的所有投诉的列表

Complaintnumber投诉电话APIorDrugproductAPI或药品LotNumber批号ShippedtoUS?(Y/N)是否运送到美国？（是/否）ComplaintCloseoutdate投诉解决日期HavecomplaintrecordsandalldocumentationavailableforreviewinDocumentStagingArea有投诉记录和所有文件，在文件的临时区域可供审查

RichardNeedham,RFLAssociates57DocumentandRecordsReview(List/Tables)

文件和记录审查（列表/表格）4.ListofallOutofSpecificationInvestigationsforthelastthreeyears过去三年的说明书之外的调查的列表OOSNumber缺货数Material(RawMaterial,API,DrugProduct)物料（原材料，空气污染，药品）LotNumber批号LabError?(Y/N)实验室失误？（是/否）FinalDecisiononOOS缺货最终结果OOSCloseoutDate缺货结束日期HaveOOSrecordsandalldocumentationavailableforreviewinDocumentStagingArea缺货记录和所有可用文件在文件临时存存储区备查RichardNeedham,RFLAssociates58DocumentandRecordsReview(List/Tables)

文件和记录审查（列表/表格）5.ListofallDeviationInvestigationsforthelastthreeyears过去三年的所有偏差研究的列表

DeviationNumberandDate

偏差号码及日期SubjectofDeviation偏差项目MaterialAffected(RawMaterial,API,DrugProduct)受影响内容（原材料，空气污染，药品）LotNumber批号CAPARecords记录FinalDecisiononDeviation偏差导致的最终结果DeviationCloseoutDate偏差解决日期HaveDeviationrecordsandalldocumentationavailableforreviewinDocumentStagingArea偏差记录和所有可用文件在文件临时存放区备查RichardNeedham,RFLAssociates59DocumentandRecordsReview

文件和记录的审查HavefollowingLists/Tablesavailable(inEnglish有以下列表/表格（英文）MasterListofSOPsandSMPsSOPS和SMPS主要程序列表SOPNumber,Title,VersionNumber,effectivedateSOP号，标题，版本号，生效日期ListofProductionEquipmentforProductInspected

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