翻译完稿-GUIDE-TO-INSPECTIONS-OF-PHARMACEUTICAL-QUALIT

PharmaceuticalQualityControlLabs(7/93)药品质量控制实验室（7/93）GUIDETOINSPECTIONSOFPHARMACEUTICALQUALITYCONTROLLABORATORIES药品质量控制实验室检查指南Note:ThisdocumentisreferencematerialforinvestigatorsandotherFDApersonnel.ThedocumentdoesnotbindFDA,anddoesnoconferanyrights,privileges,benefits,orimmunitiesfororonanyperson(s).注：本文件是FDA调查员和其他人员的参考材料。该文件并没绑定FDA，也没授予任何人任何权利、特权或豁免权。1.INTRODUCTION1、简介Thepharmaceuticalqualitycontrollaboratoryservesoneofthemostimportantfunctionsinpharmaceuticalproductionandcontrol.药品质量控制实验室在药品生产与控制的过程当中，扮演着极其重要的角色。AsignificantportionoftheCGMPregulations(21CFR211)pertaintothequalitycontrollaboratoryandproducttesting.CGMP当中，有相当一部分规则是关于质量控制实验室及产品检测的。Similarconceptsapplytobulkdrugs.同样的概念也适用于原辅料。Thisinspectionguidesupplementsotherinspectionalinformationcontainedinotheragencyinspectionalguidancedocuments.该检查指南补充其他机构信息库中的指导文件。Forexample,ComplianceProgram7346.832requiringpre-approvalNDA/ANDAinspectionscontainsgeneralinstructionstoconductproductspecificNDA/ANDAinspectionauditstomeasurecompliancewiththeapplicationsandCGMPrequirements.例如，合则计划7346.832需要预先核准NDA/ANDA检查所包含的一般性指令，并以此来指导、衡量产品的具体NDA/ANDA检查程序是否符合CGMP的要求。Thisincludespharmaceuticallaboratoriesusedforin-processandfinishedproducttesting.这包括用于生产的制药实验室与终产品的测试。2.OBJECTIVE2、目的Thespecificobjectivewillbespelledoutpriortotheinspection.在检查之前，具体的目标就应该阐述清楚。Thelaboratoryinspectionmaybelimitedtospecificissues,ortheinspectionmayencompassacomprehensiveevaluationofthelaboratory'scompliancewithCGMP's.实验室检查可以仅限于具体问题或者围绕CGMP中实验室应符合的综合评价展开。Asaminimum,eachpharmaceuticalqualitycontrollaboratoryshouldreceiveacomprehensiveGMPevaluationeachtwoyearsaspartofthestatutoryinspectionobligation.作为最低要求，每个药品质量控制实验室都应执行自己的法定检验义务，即每两年都应该接受一次全面的GMP评估。Ingeneraltheseinspectionsmayinclude--thespecificmethodologywhichwillbeusedtotestanewproduct--acompleteassessmentoflaboratory'sconformancewithGMP's--aspecificaspectoflaboratoryoperations通常这个检查应该包括以下几点：--用于测试一个新产品的特定方法--实验室是否符合GMP的全面评估--一种特定的实验室操作--------------------------------------------------------陈淑贤3.INSPECTIONPREPARATIONFDAInspectionGuidesarebasedontheteaminspectionapproachandourinspectionofalaboratoryisconsistentwiththisconcept.Aspartofourefforttoachieveuniformityandconsistencyinlaboratoryinspections,weexpectthatcomplex,highlytechnicalandspecializedtestingequipment,proceduresanddatamanipulations,aswellasscientificlaboratoryoperationswillbeevaluatedbyanexperiencedlaboratoryanalystwithspecializedknowledgeinsuchmatters.Districtmanagementmakesthefinaldecisionregardingtheassignmentofpersonneltoinspections.Nevertheless,weexpectinvestigators,analystsandotherstoworkasteamsandtoadvisemanagementwhenadditionalexpertiseisrequiredtocompleteameaningfulinspection.检查人员的委派由地区主管部门确定，然而我们希望，调查人员、分析人员和其他人员能组成—个检查组，并在需要时为了完成—项有意义的检查，可建议主管部门增加有关方面的专家。Teammembersparticipatinginapre-approvalinspectionmustreadandbefamiliarwithComplianceProgram7346.832,Pre-ApprovalInspections/Investigations.RelevantsectionsoftheNDAorANDAshouldbereviewedpriortotheinspection;butiftheapplicationisnotavailablefromanyothersource,thisreviewwillhavetobeconductedusingthecompany'scopyoftheapplication.参加新药审批前检查的小组成员必须阅读并熟悉7346·832号文件即审批前检查或调查文件的内容。检查前应当审查新药申请或简略的新药申请的有关部分，如果该申请书不能从别的来源得到，可对由公司提供的副本进行审查。Teammembersshouldmeet,ifpossible,priortotheinspectiontodiscusstheapproachtotheinspection,todefinetherolesoftheteammembers,andtoestablishgoalsforcompletionoftheassignment.Responsibilitiesfordevelopmentofallreportsshouldalsobeestablishedpriortotheinspection.ThisincludesthepreparationoftheFDA483.如果可能的话，小组成员在检查之前就应当集中，以讨论检查方法，明确每位组员的角色，并确定目标以完成委派的任务。检查前还要确定负责起草各报告，包括准备FDA483文件的责任。TheCenterforDrugEvaluationandResearch(CDER)mayhaveissueddeficiencyletterslistingproblemsthatthesponsormustcorrectpriortotheapprovalofNDA/ANDA'sandsupplements.Theinspectionteamisexpectedtoreviewsuchlettersonfileatthedistrictoffice,andtheyareexpectedtoasktheplantforaccesstosuchletters.Theteamshouldevaluatetherepliestotheseletterstoassurethatthedataareaccurateandauthentic.Completetheinspectioneventhoughtherehasbeennoresponsetotheselettersorwhentheresponseisjudgedinadequate.药品评价和研究中心(CDER)可能已经发出有关缺陷信件，列举出存在的各种问题。要求受检企业必须在新药申请或简略的新药申请和补充文件被批准前予以改正。希望检查组审查这些已经在FDA地区办公室归档的信件，并向药厂要求了解这些信件的内容。检查组还要评价药厂对这些信件的答复，以确保数据的准确和真实。即使药厂没有对这些信件作出答复，或者认为药厂的答复不充分，也应当完成这项检查工作。4.INSPECTIONAPPROACH检查方法A.General总则InadditiontothegeneralapproachutilizedinadrugCGMPinspection,theinspectionofalaboratoryrequirestheuseofobservationsofthelaboratoryinoperationandoftherawlaboratorydatatoevaluatecompliancewithCGMP'sandtospecificallycarryoutthecommitmentsinanapplicationorDMF.Whenconductingacomprehensiveinspectionofalaboratory,allaspectsofthelaboratoryoperationswillbeevaluated.除了采用对药品进行现行药品生产质量管理规范的—般检查方法之外，对实验室的检查还要采用察实验操作和检查原始数据的方法，以评价其符合现行药品生产质量管理规范的情况，以及实现申请书中或者药品工艺档案中约定的义务。对实验室进行综合检查时，应评价实验室操作的各个方面。Laboratoryrecordsandlogsrepresentavitalsourceofinformationthatallowsacompleteoverviewofthetechnicalabilityofthestaffandofoverallqualitycontrolprocedures.SOPsshouldbecompleteandadequateandtheoperationsofthelaboratoriesshouldconformtothewrittenprocedures.Specifications