欧盟GMP中英文对照.docx

1、EuropeanUnion药品生产质量管理标准GUIDETOGOODMANUFACTURINGPRACTICEFORMEDICINALPRODUCTS目录第一章质量管理CHAPTER1:OUALITYMANAGEMENT原那么5PrinCiDle5质量保力正5QualityAssurance5药品生产质量管理标准(GMP)7GoodManufacturingPracticeforMedicinalProducts7质量控制(QC)9QualityControl9产品质量回忆10第二章人员CHAPTER2:PERSONNEL11原那么11Principle11通那么12General12关键人员

2、12KeyPersonnel12培训12Training15人员卫生16PersonnelHygiene16第三章厂篇和设备CHAPTER3:PREMISESANDEQUIPMENT18原那么18Principle18厂房18Premises18通刃口么18General18生产区19ProductionArea19贮存区21StorageArea21质量控制区22QualityControlArea22附助区22AncillaryAreas22设备23Equipment23第四章文件CHAPTER 4: DOCUMENTATION24原那么24Principle24通那么25General2

3、5文件要求27DocumentsRequired27Specifications27Specificationsforstartingandpackagingmaterials27SpecificationsforIntermediateandBulkProducts27SpecificationsforFinishedProducts28ManufacturingFormulaeandProcessingInstructions28PackagingInstructions30BatchProcessingRecords31BatchPackagingRecords32Proceduresa

4、ndRecords33Receipt34Sampling34Testing35Other35第五章生产CHAPTER 5: PRODUCTION36原那么36Principle36通那么36General36生产过程中对交叉污染的预防39PreventionofCross-contaminationinProduction39验证40Validation40原料41StartingMaterials41生产操作：中间产品和待包装产品42ProcessingOperations:IntermediateandBulkProducts42包装材料43PackagingMaterials43包装操作

5、44PackagingOperations44成品46FinishedProducts46不合格、回收料和退货物料46Rejected,RecoveredandReturnedMaterials46第六章质量控制CHAPTER 6: QUALITYCONTROL48原那么48Principle48通那么48General48质量控制实验室标准49GoodQualityControlLaboratoryPractice49Documentation49Sampling50Testing52销售产品的稳定性考察54第七章委托生产与委托检验CHAPTER 7: CONTRACTMANUFACTURE

6、ANDANALYSIS55原那么55Principle55通那么56General56委托方56TheContractGiver56受托方57TheContractAcceptor57合同58TheContract58第八章投诉与召回CHAPTER 8: COMPLAINTSANDPRODUCTRECALL59原刃卜么59Principle59I殳诉59Complaints59召回60Recalls60第九章自查CHAPTER 9: SELFINSPECTION61原那么61Principle61附件8原辅料和包装材料的取样ANNEX8SAMPLINGOFSTARTINGANDPACKAGIN

7、GMATERIALS63原那么63Principle63人员63Personnel63原辅料63Startingmaterials64包装材料65Packagingmaterial65第一章质量管理CHAPTER1QUALITYMANAGEMENTPrinciple原那么生产许可证持有厂家只能生产医药产品，以确保药品符合其预期的使用目的，符合销售许可证的要求，并不因药品平安性、质量或药效方面的问题而给患者带来风险。到达这一质量目标是高层管理者的责任，同时也需要公司各部门、各层次的职员以及公司的供给商和销售商的参与并承当义务。为了确保到达该质量目标，必须全面设计并正确贯彻实施包括GMP与质量控制

8、QC)在内的质量保证(QA)体系。该体系应用文件明文规定并对其有效性加以监控。质量保证体系的所有部门都必须充分配备胜任的人员，适宜足够的厂房、设备及设施。与此同时，生产许可证持有者及受权人员具有另外的法律责任。TheholderofaManufacturingAuthorisationmustmanufacturemedicinalproductssoastoensurethattheyarefitfortheirintendeduse,complywiththerequirementsoftheMarketingAuthorisationanddonotplacepatientsatris

9、kduetoinadequatesafety,qualityorefficacy.Theattainmentofthisqualityobjectiveistheresponsibilityofseniormanagementandrequirestheparticipationandcommitmentbystaffinmanydifferentdepartmentsandatalllevelswithinthecompany,bythecompanyssuppliersandbythedistributors.Toachievethequalityobjectivereliablyther

10、emustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQualityAssuranceincorporatingGoodManufacturingPracticeandthusQualityControl.Itshouldbefullydocumentedanditseffectivenessmonitored.AllpartsoftheQualityAssurancesystemshouldbeadequatelyresourcedwithcompetentpersonnel,andsuitableandsufficien

11、tpremises,equipmentandfacilities.ThereareadditionallegalresponsibilitiesfortheholderoftheManufacturingAuthorisationandfortheQualifiedPerson(s).质量保证、GMP和质量控制的根本概念是内在相互联系的。这里表达的主要目的是强调它们之间的关系以及药品生产和控制中的重要性。1.1. .ThebasicconceptsofQualityAssurance,GoodManufacturingPracticeandQualityControlareinter-rela

12、ted.Theyaredescribedhereinordertoemphasisetheirrelationshipsandtheirfundamentalimportancetotheproductionandcontrolofmedicinalproducts.QualityAssurance质量保证1.2. QualityAssuranceisawiderangingconceptwhichcoversallmatterswhichindividuallyOrcollectivelyinfluencethequalityofaproduct.ItisthesumtotaloftheOr

13、ganizedarrangementsmadewiththeobjectofensuringthatmedicinalproductsareofthequalityrequiredfortheirintendeduse.QualityAssurancethereforeincorporatesGoodManufacturingPracticeplusotherfactorsoutsidethescopeofthisGuide.1.3. 质量保证是一个宽泛的概念，它包括影响产品质量的所有问题，是确保药品质量符合预期使用目的而进行组织管理的总和。因此质量保证是由GMP本标准之外的其他因素所组成。T

14、hesystemofQualityAssuranceappropriateforthemanufactureofmedicinalproductsshouldensurethat:质量保证体系对于药品的生产而言，应保证：i.medicinalproductsaredesignedanddevelopedinawaythattakesaccountofIherequirementsofGoodManufacturingPracticeandGoodLaboratoryPractice;i.药品的设计与开发应按照GMP和GLP的要求进行；ii .productionandcontroloperat

15、ionsareclearlyspecifiedandGoodManufacturingPracticeadopted;iii 生产和控制操作应有明确规定，并采用GMP;iv i.managerialresponsibilitiesareclearlyspecified;iii .明确规定管理职责；iv .arrangementsaremadeforthemanufacture,supplyanduseofthecorrectStartingandpackagingmaterials;v v.安排生产、供给和使用正确的原、辅、包材料；vi allnecessarycontrolsoninterm

16、ediateproducts,andanyotherin-processcontrolsandvalidationsarecarriedout;vii 中间产品进行必要的控制、进行其他任何过程控制和验证；viii hefinishedproductiscorrectlyprocessedandchecked,accordingtothedefinedprocedures;vi. 按照规定的程序，正确地加工与核查成品；vii. medicinalproductsarenotsoldorsuppliedbeforeaQualifiedPersonhasCertifiedthateachproduc

17、tionbatchhasbeenproducedandcontrolledinaccordancewiththerequirementsoftheMarketingAuthorisationandanyotherregulationsrelevanttotheproduction,controlandreleaseofmedicinalproducts;vii.在受权人确认批产品按照销售许可证和其他与药品生产、检验和释放有关的法规要求进行生产和质量控制，并签发合格证之前，药品不得销售或供给；viii. satisfactoryarrangementsexisttoensure,asfarasp

18、ossible,thatthemedicinalproductsarestored,distributedandsubsequentlyhandledsothatqualityismaintainedthroughouttheirshelflife;viii.尽可能对药品贮存、销售及随后的处理做出满意的安排，以保证药品在货架寿命期内的质量；ix. thereisaprocedureforSelf-Inspectionand/orqualityauditwhichFegularlyappraisestheeffectivenessandapplicabilityoftheQualityAssur

19、ancesystem.ix.建立自检和/或质量审计程序，定期对质量保证体系的有效性和适用性进行评价。GoodManufacturingPracticeforMedicinalProducts(GMP)药品生产质量管理标准(GMP)1.3GoodManufacturingPracticeisthatpartofQualityAssurancewhichensuresthatproductsareconsistentlyproducedandcontrolledtothequalitystandardsappropriatetotheirintendeduseandasrequiredbytheM

20、arketingAuthorisationorproductspecification.1.3GMP是质量保证的一局部，它确保药品始终按照适合于其使用目的的质量标准进行生产和控制，并符合销售许可证的要求。GoodManufacturingPracticeisconcernedwithbothproductionandqualitycontrol.ThebasicrequirementsofGMParethat:GMP涉及生产和质量控制，其根本要求如下：i. allmanufacturingprocessesareclearlydefined,systematicallyreviewedinth

21、eIightofexperienceandshowntobecapableofconsistentlymanufacturingmedicinalproductsoftherequiredqualityandcomplyingwiththeirspecifications;i.所有生产工艺应有明确规定，根据经验进行系统的审核，并证明能够始终如一地生产出符合质量标准的药品。ii. criticalstepsofmanufacturingprocessesandsignificantchangestotheprocessarevalidated;ii.应对生产工艺的关键步骤和工艺的重要变更进行验证

22、iii. allnecessaryfacilitiesforGMPareprovidedincluding:iii.提供所有GMP必需的设施，包括：a. appropriatelyqualifiedandtrainedpersonnel;a.资历合格并经过培训的人员；b. adequatepremisesandspace;b.适宜的厂房和空间；c. suitableequipmentandservices;c.适宜的设备及配套设施；d. correctmaterials,containersandlabels;d.正确的物料、容器和标签；e. approvedproceduresandins

23、tructions;经批准的程序和指令；f. suitablestorageandtransport;f.适宜的贮存设施和运输设备。iv. instructionsandproceduresarewritteninaninstructionalforminclearandunambiguouslanguage,specificallyapplicabletothefacilitiesprovided;iv.指令和程序应使用清楚明了的语言，并适用于所提供的设施。V.operatorsaretrainedtoCarryoutprocedurescorrectly;v. 操作者应经过培训，以便按正确

24、地按照程序进行操作。vi. recordsaremade,manuallyand/orbyrecordinginstruments,duringmanufacturewhichdemonstratethatallthestepsrequiredbythedefinedproceduresandinstructionswereinfacttakenandthatthequantityandqualityoftheproductwasasexpected.Anysignificantdeviationsarefullyrecordedandinvestigated;vi.生产过程中采用手工和/或记

25、录仪填写记录，以证明已完成的所有生产步骤是按照确定的程序和指令要求进行的，产品到达预期的质量和数量。任何重要偏差都应详细记录和调查。vii. recordsofmanufactureincludingdistributionwhichenablethecompletehistoryofabatchtobetraced,areretainedinacomprehensibleandaccessibleform;Vii.采用适宜的方式保存生产记录包括销售记录，以便追溯各批产品的完整历史。viii. thedistribution(wholesaling)oftheproductsminimises

26、anyrisktotheirquality;viii.应将产品销售批发中影响质量的风险减至最低限度。ix. asystemisavailabletorecallanybatchofproduct,fromsaleorsupply;ix.建立从销售或供给渠道收回任何一批产品的系统。X.complaintsaboutmarketedproductsareexamined,thecausesofqualitydefecIsinvestigatedandappropriatemeasurestakeninrespectofthedefectiveproductsandtopreventreoccurr

27、ence.x. 了解上市产品的用户投拆，调查质量缺陷的原因，并采取的相应的整改措施，以防止再次发生。QualityControl质量控制(Qe)1.4QualityControlisthatpartofGoodManufacturingPracticewhichisconcernedWithsampling,specificationsandtesting,andwiththeorganisation,documentationandreleaseprocedureswhichensurethatthenecessaryandrelevanttestsareactuallycarriedout

28、andthatmaterialsarenotreleasedforuse,norproductsreleasedforsaleorsupply,untiltheirqualityhasbeenjudgedtobesatisfactory.1.4质量控制是GMP的一局部，它涉及取样、质量标准和质量检验、机构、文件和放行程序，以确保进行必要的相关检验，在判定质量符合要求之前，物料不得使用，产品不得销售或供给。ThebasicrequirementsofQualityControlarethat:质量控制的根本要求如下：i. adequatefacilities,trainedpersonnelan

29、dapprovedproceduresareavailableforsampling,inspectingandtestingstartingmaterials,packagingmaterials,!ntermediate,bulk,andfinishedproducts,andwhereappropriateformonitoringenvironmentalconditionsforGMPpurposes;i.有适宜的设施、经过培训的人员和批准的程序，以便对原辅料、包装材料、中间产品、待包装品和成品进行取样、检查、测试以及必要时按照GMP要求对环境进行监测。ii. samplesofst

30、artingmaterials,packagingmaterials,intermediateproducts,bulkproductsandfinishedproductsaretakenbypersonnelandbymethodsapprovedbyQualityControl;ii.由质量部门批准的人员并使用已批准的方法对原辅料、包装材料、中间产品、待包装品和成品进行取样。iii. testmethodsarevalidated;iii.对检验方法进行验证。iv. recordsaremade,manuallyand/orbyrecordinginstruments,whichdemo

31、nstratethatalltherequiredsampling,inspectingandtestingprocedureswereactuallycarriedout.Anydeviationsarefullyrecordedandinvestigated;iv.采用手工和/或记录仪进行记录，以证明规定的取样、检查和测试程序均已完成。详细记录出现的任何偏差，并进行调查。V.thefinishedproductscontainactiveingredientscomplyingwiththequalitativeandquantitativecompositionoftheMarketin

32、gAuthorisation,areofthepurityrequired,andareenclosedwithintheirpropercontainersandcorrectlylabelled;成品应含有符合销售许可证规定的定性、定量要求的活性成分，应具有规定的纯度，包装在适宜容器中，并正确加贴标签。vi. recordsaremadeoftheresultsofinspectionandthattestingofmaterials,intermediate,bulk,andfinishedproductsisformallyassessedagainstSpecification.Pr

33、oductassessmentincludesareviewandevaluationofrelevantproductiondocumentationandanassessmentofdeviationsfromspecifiedprocedures;vi.记录应包括检查结果以及物料、中间产品、待包装品和成品依照质量标准进行检验的评价结果。产品评价包括对有关生产文件的审核与评价以及对偏离规定程序的偏差的评价。vii. nobatchofproductisreleasedforsaleorsupplypriortocertificationbyaQualifiedPersonthatitisi

34、naccordancewiththerequirementsoftheMarketingAuthorisation;vii.任何一批产品在未经受权人按照销售许可证的要求审核并签发合格证之前，不得放行销售或供给。viii. sufficientreferencesamplesofstartingmaterialsandproductsareretainedtopermitfutureexaminationoftheproductifnecessaryandthattheproductisretainedinitsfinalpackunlessexceptionallylargepacksarep

35、roduced.viii.原料有充足的对照品，产品应保存以便用于将来必须的产品检验，除产品的大包装外，产品保存最终包装形式。1.5. 产品质量回忆应对药品定期进行质量回忆以证明所用工艺的始终一致性，并重点反映出变化趋势。产品质量回忆一般情况下每年进行一次，并形成文件。内容至少应包括：(1)对产品中所使用的原辅料进行质量回忆，特别是那些由新供给商提供的原辅料。(2)对关键的过程控制和成品的检验结果进行质量回忆。(3)对所有不符合质量标准的批次进行回忆。(4)对所有关键性的偏差或不符合项以及与之相关的调查进行回忆。(5)对所有工艺或检验方法的变更进行回忆。(6)对销售许可证变更内容的申报/批准/拒

36、绝批准的情况进行回忆，包括第三国申报的资料。(7)对稳定性监测结果进行回忆。(8)对所有与质量相关的退货、投诉、召回进行回忆，包括那些只出口的药品。(9)对以前整改措施的适合性进行回忆。(10)对于新的销售许可证，那么对其执行情况进行回忆。(11)已进行验证的设备清单和再验证的日期。生产厂家和销售许可证的持有者应对产品质量回忆的结果进行评价，对于差异，应评价其是否采取整改措施或是否应进行再验证。进行整改的原因应形成文件。对于已同意的整改措施应通过有效的方法适时完成。产品质量回忆可根据产品类型进行相应的分类，例如：固体制剂、液体制剂、无菌产品等。当工艺发生重大变更和/或对工艺进行了再验证时，应将

37、一个批次或多个批次的产品列入稳定性考察方案。无论如何，每年应对每一产品的一个批次进行稳定性考察；如果某产品每年的生产批次缺乏一批，那么所生产的每一批产品都应列入稳定性考察方案。当生产厂家与销售许可证的持有者不是同一单位时，应签订技术协议详细说明双方在生产和产品质量回忆方面各自相应的职责。受权人应确保产品质量回忆适时进行，并且确保其结果的准确性。第二章人员CHAPTER2PERSONNELPrinciple原那么Theestablishmentandmaintenanceofasatisfactorysystemofqualityassuranceandthecorrectmanufacture

38、ofmedicinalproductsreliesuponpeople.Forthisreasontheremustbesufficientqualifiedpersonneltocarryoutallthetaskswhicharetheresponsibilityofthemanufacturer.Individualresponsibilitiesshouldbeclearlyunderstoodbytheindividualsandrecorded.AllpersonnelshouldbeawareoftheprinciplesofGoodManufacturingPracticeth

39、ataffectthemandreceiveinitialandcontinuingtraining,includinghygieneinstructions,relevanttotheirneeds.良好的质量保证体系的建立和保持以及药品的正确生产都需要依靠人来完成，因此必须有足够的高素质人员来承当企业的全部工作和责任。应清楚地了解并记录各自的职责。所有人员均应了解与其有关的GMP的原那么，并接受其工作所需要的初步培训和继续培训，其中包括卫生学知识的培训。General通那么2.1 Themanufacturershouldhaveanadequatenumberofpersonnelwit

40、hthenecessaryqualificationsandpracticalexperience.Theresponsibilitiesplacedonanyoneindividualshouldnotbesoextensiveastopresentanyrisktoquality.2.1. 生产厂应有足够数量的具有资格和实践经验的人员，任何一个人所担负的责任不应太多，以免出现质量隐患。2.2 Themanufacturermusthaveanorganisationchart.PeopleinresponsiblepositionsShouldhavespecificdutiesrecor

41、dedinwrittenjobdescriptionsandadequateauthoritytocarryouttheirresponsibilities.TheirdutiesmaybedelegatedtodesignateddeputiesofaSatisfactoryqualificationlevel.ThereshouldbenogapsorunexplainedoverlapsintheFesponsibilitiesofthosepersonnelconcernedwiththeapplicationofGoodManufacturingPractice.2.2.生产厂应有组

42、织机图，重要岗位的负责人应有明确的书面岗位职责，并有权履行其职责。他们职责可以委派给具有满意资历水平的副职人员代理。执行GMP的有关人员的职责，不应有空缺或重叠。KeyPersonnel关键人员2.3KeyPersonnelincludetheheadofProduction,theheadofQualityControl,andifatIeastoneofthesepersonsisnotresponsibleforthedutiesdescribedinArticle22ofDirective75319EEC,theQualifiedPerson(s)designatedforthepur

43、pose.Nonnallykeypostsshouldbeoccupiedbyfull-timepersonnel.TheheadsofProductionandQualityControlmustbeindependentfromeachother.Inlargeorganisations,itmaybenecessarytodelegatesomeofthefunctionslistedin2.5,2.6and2.7.2.3.关键人员包括生产部门负责人和质量控制部门负责人，如果其中至少一人不负责75/319/EEC指南第22条款中所描述的职责，那么应指定受权人QP负责。通常，关键岗位人员应

44、为全职人员。生产部门和质量控制部门的负责人不能兼任。在较大的生产厂里，有必要将2.5、2.6、2.7条所列的一些职能委派给代理人。2.4ThedutiesoftheQualifiedPerson(s)arefullydescribedinArticle22ofDirective75319EEC,andcanbesummarisedasfollows:2.4. 受权人QP的职责在75/319/EEC指南第22条款中有详细描述，概括如下：a)formedicinalproductsmanufacturedwithintheEuropeanCommunity,aQualifiedPersonmust

45、ensurethateachbatchhasbeenproducedandtested/checkedinaccordancewiththedirectivesandthemarketingauthorisation(1);(1)AccordingtoDirective75/319/EECandtheRuling(Case247/81)oftheCourtofJusticeoftheEuropeanCommununities,medicinalproductswhichhavebeenproperlycontrolledintheEUbyaQualifiedPersondonothavetob

46、erecontrolledorrecheckedinanyotherMemberStateoftheCommunity.(a)对于在欧共体内生产的药品，受权人必须确保每批药品的生产和检验符合指导的条款和销售许可证。(b)formedicinalproductsmanufacturedoutsidetheEuropeanCommunity,aQualifiedPersonmustensurethateachimportedbatchhasundergone,intheimportingcountry,thetestingspecifiedinparagraph1(b)ofArticle22;对于

47、在欧共体之外生产的药品，受权人必须确保每批进口药品在进口国均经过第22条款1(b)中规定的检查。(c)aQualifiedPersonmustcertifyinaregisterorequivalentdocument,asOperationsarecarriedoutandbeforeanyrelease,thateachproductionbatchsatisfiestheprovisionsofArticle22.(C)受权人在产品放行前必须在记录或相应文件中证明每批产品符合第22条款的规定。ThepersonsresponsibleforthesedutiesmustmeetthequalificationrequirementsIaiddowninArticle23ofthesameDirective,theyshallbepermanentlyandcontinuouslyatIhedisposaloftheholderoftheManufacturingAuthorisationtocarryouttheirresponsibilities.Theirresponsibilitiesmaybedelegated,but