《EDMF培训资料》PPT课件VIP

,TechnicalRequirementsfortheRegistrationDossierofEDMF/COS/CTDandFilingstrategiesinEUcountries,EDMF/COS/CTD注册文件的技术要求及在欧盟国家的文件编撰策略,TechnicalRequirements,EDMFcompilationinCTDformat:a)Module3.2.S.DrugSubstanceb)Module2.3QualityOverallSummaryCEPProcedureversustheDMFProcedureFilingstrategiesinEUcountriesCertificationofsuitabilitytothemonographsoftheEuropeanPharmacopoeiaProcedure,SubmissionoftheDossier,ContentoftheDossier/ExpertReport,Assessment,Timetable,Follow-up,技术要求,CTD格式的EDMF的编撰:a)模块3.2.S.药物物质b)模块2.3质量概述CEP程序对DMF程序在欧盟国家的文件编撰策略针对欧洲药典专论的适应性证书程序，文件递交，文件内容/专家报告，评估，时间表，后续工作,HowtogettheguidelinefromtheInternet?,HumanmedicineorvetmedicineGuidancedocumentsICHQWPApprovedguidelinesGuidelinesunderdiscussion,如何从互联网得到指南?,人用药或兽药指南文件ICHQWP批准的指南讨论中的指南,Filingstrategies,CEPASMF/EDMFprocedure?,文件编撰策略,CEPASMF/EDMF程序?,CEPProcedureversustheDMFProcedure,GuidelineonSummaryofrequirementsforactivesubstancesinthequalitypartofthedossierClassificationofactivesubstances:NewactivesubstancesusedforthefirsttimeinamedicinalproductExistingactivesubstancesnotdescribedintheEuropeanPharmacopoeiaExistingactivesubstancesdescribedintheEuropeanPharmacopoeia,CEP程序对DMF程序,针对文件质量部分中活性物质要求的概述的指南活性物质的分类:在药品中第一次使用的新的活性成分在欧洲药典中没有描述的现有的活性物质在欧洲药典中有描述的现有的活性物质,ApplicationforamarketingauthorisationofaMedicinalProduct,requiresinformationontheActiveSubstance(AS):CertificateofsuitabilitytotheMonographoftheEuropeanMonographActiveSubstanceMasterFile(ASMF)procedureFulldetailsofmanufacture,药品市场许可申请,活性物质(AS)的要求信息:针对欧洲药典专论的适应性证书活性物质主文件(ASMF)程序完整的制造细节,Feasiblewaystosubmit,DependingontheclassificationoftheASFornewactivesubstancesandsubstancesnotdescribedinthePh.Eur.:ASMF/EDMFForexistingsubstances,descrribedinthePh.Eur.:CEPorASMF/EDMFTheASmanufacturerprovideseither:No1)CEPorNo2theASMF/EDMF(ApplicantspartbeincludedintheMA),可行的递交方式,取决于活性物质的分类对于在欧洲药典中没有描述的物质和新的活性物质:ASMF/EDMF对于在欧洲药典中描述的现有的活性物质:CEP或ASMF/EDMFAS制造商提供下列两者中的一个:第1，CEP或第2，ASMF/EDMF(MA包括此申请部分),SubmissionoftheCEP,GenerallyavoidinganysubsequentreassessmentASmanufacturersubmits:copyofthemostcurentCEPWrittenasurancethatnosignificantchangesinthemanufacturingmethodhavetakenplaceApplicantsubmits:ResultsofbatchanalysisdemonstratingcompliancewiththePh.Eur.Monograph,CEP的递交,通常应避免下列任何的重新评估作为制造商递交:最新的CEP的复印件书面保证：在采用的制造方法中没有发生重大变更申请人递交:批分析结果要证明符合欧洲药典专论的要求,ASMF/EDMFprocedure,GuidelineonActiveSubstanceMasterFileprocedure:CPMP/QWP/227/02TermsEuropeanDrugMasterFile(EDMF)andActiveSubstanceMasterFile(ASMF)areinterchangableOverviewEDMFcontentTemplateletterofaccessandcoveringletter,ASMF/EDMF程序,活性物质主文件程序的指南:CPMP/QWP/227/02欧洲药物主文件(EDMF)和活性物质主文件(ASMF)的条款可以通用EDMF内容概览准阅信和封面信的模板,ASMF/EDMFprocedure,OverallcontentoftheASMF/EDMFasindicatedinNTA/CTDformatModule3APcontainsinformationnon-condidentalRPcontainsremaininginformationsuchas:Detailedinformationonthemanufacturingsteps(reactionconditions,temperatureetc.)EvaluationofcriticalstepsQualitycontrolduringmanufactureValidation,ASMF/EDMF程序,按照NTA/CTD格式模块3的指示做ASMF/EDMF的全部内容AP包含非保密的信息RP包含剩余的如下信息:制造步骤的详细信息(反应条件，温度，等等)关键步骤的评估制造中的质量控制验证,ASMF/EDMFSubmission,EDMFcanonlybesubmittedinsupportofanMAAEDMFHoldershouldsubmittotheMAholder:CopyofthelatestversionoftheAPCopyoftheQOSLetterofaccessAPcontainsinformationnon-condidentalEDMFHoldershouldsubmittotheauthoritiesCompleteEDMFwithcoveringletterLetterofaccess,ASMF/EDMF递交,EDMF只能在MAA的支持下递交EDMF的持有者递交到MA的持有者:AP的最近版本的复印件QOS的复印件EDMF持有者应当把AP包含的非保密内容的准阅信递交到官方部门有封面信的完整EDMF准阅信,AREDE.TIEFENBACHER(GmbHe.gBenzeneinToluolStartingmaterial:justification,characterisation,specification,includingpotentialimpuritiesDiscussionofpossiblecarryingthroughofimpuritiesAnalyticaltestmethodsdescriptionIncasethesynthesisofAPIconsitsofonlyoneorafewsteps,manufactureofthestaringmaterialshouldbegivenIfmorethanonesupplierofthestartingmaterialisused,batchanalysisresultsfromtheAPImanufacturedfromthedifferentsupplierstobegiven,3.2.S.2.3物料控制,原料和溶剂的规格，适当的如果在溶剂中可能有一类溶剂应注明其规格和检测方法；如：甲苯中的苯起始物料:评定，性状，规格，包括潜在杂质讨论运行中可能的杂质分析检测方法的描述如果原料药的合成仅有一步或几步构成，起始物料的制造应详细描述如果所使用的起始物料的供应商不只一个，从不同的供应商生产而来的原料药的批分析结果应被提供。,3.2.S2.4ControlofCriticalstepsandintermediates:,Criticalstepsdefinition:whereprocessconditions,testrequirementsorotherrelevantparametersmustbecontrolledwithinthepredeterminedlimitstoensurethatASmeetsspecificationDescriptionofInProcesscontrolsIntermediates:Informationonthequalityandcontrolofintermediates,3.2.S2.4关键步骤和中间体的控制：,关键步骤的定义：工艺条件，检测要求或其他相关参数必须控制在预先确定的限度内的以确保AS符合标准过程控制的定义中间体:质量信息和中间体的控制,3.2.S.2.5Processvalidationand/orevaluation,ProcessValidationshouldbeprovidedasappropriate:Sterilisationprocess,includingfiltrationandasepticprocessingIncasethemonographindicatesspecificadditionalrequirementscomplianceshouldbedemonstraetedForbiologicalsubstances,specificmicrobialgrade,suitableinactivationshouldbedemonstrated3.2.S2.6ManufacturingprocessdevelopmentDescriptionanddiscussion,3.2.S.2.5工艺验证和/或评估,应提供适当的工艺验证：消毒工艺，包括过滤和无菌工艺如果药典专论中指出专门附加的要求，准则应该被证明对于生物物质，专门的微生物指标，适当的失活应当被证明3.2.S2.6制造工艺开发描述和讨论,3.2.S.3Characterisation,3.2.S3.1ElucidicationofStructureandotherCharacteristics:Evidenceofchemicalstructure:Elementalanalysis,IRspectra,NMR,MS,UVspectraEvidenceofstructureofkeyintermediates,X-Raychristallography,opticalrotationPhysico-chemicalCharacteristics:Polymorphism,Meltingpoint,DSCSolubilitypKaandpHvalues,3.2.S.3性状,3.2.S3.1结构分析和其他性状：化学结构的证据：元素分析，红外光谱，核磁共振，质谱，紫外光谱关键中间体的结构证据，X-射线晶型图，旋光度物理化学特性:多态性，熔点，DSC溶解度pKa和pH值,3.2.S.3Characterisation,3.2.S3.2Impurities:RequirementsconcerningrelatedsubstancesaccordingtothegeneralmonographSubstancesforPharmaceuticalUse(2034)andtheGuidelineControlofimpuritiesofpharmacopoeialsubstances(QWP1529/04)shouldbemetPossibleimpuritiesconsideredaspotentialimpuritiesarisingfromthesynthesisshouldbediscussed,indicatingorigin(staringmaterial,reagent,solvent,catalyst,intermediateordegradationproductDiscussionofpossibleroutesofdegradationAnalyticalmethods(LODandLOQ),3.2.S.3性状,3.2.S3.2杂质:关于相关物质的要求，根据总的专论药品使用的物质（2034）应符合药品物质的杂质控制指南(QWP1529/04)应该对可能的杂质进行讨论，对认为是在合成中出现的潜在杂质，指出杂质起源（起始物料，试剂，溶剂，催化剂，中间体或降解产物讨论降解可能的路线分析方法(LOD和LOQ),3.2.S.3Characterisation,3.2.S3.2Impurities:SuitabilityofthemethodsofthemonographtocontrolthequalityofthesubstancemustbediscussedanddemonstratedAdditionalimpuritiesabovethereportingthresholddemonstratingthatPh.EurMethodissuitableIfPh.Eur,methodnotsuitablealternativetestmethodincludingvalidationisrequiredChromatogramsforproductionbatches,withpeakarearesultsAdditionalrelatedsubstances,identificationandqualificationaccord.totheGuidanceImp.InnewDrugSubstances(ICH/2737/99),3.2.S.3性状,3.2.S3.2杂质:必须讨论和证明药典规定的原料药质量控制方法的适应性添加的杂质在报告的阈值之上，以此证明欧洲药典的方法是合适的如果欧洲药典的方法不适应，则需要替代的检测方法，并包括其相关的验证。生产批次有峰面积结果的图谱附加的相关物质，鉴别和验证符合在新原料药中的杂质的指南(ICH/2737/99),3.2.S.3Characterisation,3.2.S3.2Impurities:Otherimpurities:residualsoftoxicreagents,residuesofacidsorbasesshouldbediscussedConsiderrelevantguidelinesResidualcatalysts,possiblecarryover,justifiedcontrollimitsrequired,3.2.S.3性状,3.2.S3.2杂质:其它杂质：有毒试剂的残留，酸或碱的残留应被讨论考虑相关的指南催化剂残留，可能的运行产物，所要求的合理的控制限度,3.2.S.4ControloftheActivesubstance,3.2.S4.1Specification:DescriptionIdentificationImpuritiesAssayAdditionaltestsReferenceto:Impuritiestestingguideline(ICH/2737/99)NoteforGuidanceonSpecifications(ICH/367/96)Incasemonographunderrevision,newdraftwillbetakenintoconsideration,3.2.S.4活性物质的控制,3.2.S4.1规格：描述鉴别杂质含量附加的检测参考：杂质检测指南(ICH/2737/99)关于规格的指南的注解(ICH/367/96)如果专论在审核中，可以考虑新的草案,SpecificationoftheActiveSubstance,ICH/367/96NoteforGuidanceonSpecifications:GuidanceforsettingacceptancecriteriaJustificationofspecificationsSelectionoftestprocedures,pharmacopoeialtestsICH/2737/99ImpuritiestestingguidelineClassificationofimpurities;residualsolvents,startingmaterial,intermediates,by-products,degradationproductsReportingimpurities,quantitativeresultsnumericalterms!Reportingthreshold,identificationthreshold,qualificationthresholdNMT2g/dayIdent.0.1%,Qualif.0.15%MT2g/dayIdent.0.05%,Qualif.0.05%,活性物质的规格,ICH/367/96规格指南的注释：建立可接受的标准的指南规格的说明检测规程，药典检测方法的选择ICH/2737/99杂质检测指南杂质的分类；残留溶剂，起始物料，中间体，副产物，降解产物报告杂质，以数据定量的结果！报告阈值，鉴别阈值，验证阈值NMT2g/天，鉴别的0.1%,数量0.15%MT2g/天，鉴别的0.05%,数量0.05%,3.2.S.4ControloftheActivesubstance,3.2.S4.2AnalyticalProeceduresDetailsoftheanalyticalproceduresIncaseofTLCmethodsinthemonograph,suitabilitytodetectimp.atrelevantthreshold(0.05%or0.03%acc.Max.dailydose)TLCmethodonlyacceptedinrarecases,Requirementsofsuitability,detectionandquantificationlimithavetobeconsidered,3.2.S.4活性物质的控制,3.2.S4.2分析规程分析规程的详细内容如果是在专论中的TLC方法，在相关阈值内杂质检测的适应性(0.05%或0.03%根据日常最大计量)仅在很少的情况下，可接受TLC方法应考虑适应性，检测限和定量限的要求,3.2.S.4ControloftheActivesubstance,3.2.S4.3ValidationofAnalyticalProceduresReferencetovalidationofanalyticalmethods(ICH381/95andICH281/95);TypicalchromatogramsForadditionalmethodsacc.TothegeneralmethodsofthePh.Eur,likeforresidualsolventsapplicabilityissufficient,3.2.S.4活性物质的控制,3.2.S4.3分析规程的验证分析方法验证的参考(ICH381/95和ICH281/95);典型的图谱对于附加的方法，根据欧洲药典的一般方法，象残留溶剂，适应性就足够了,3.2.S.4ControloftheActivesubstance,3.2.S4.4BatchAnalysisDescriptionofbatchesandresultsofbatchesResultsbelow1%forrelatedsubstancesshouldbereportedwith2digitsPresentactualfigureswheneverpossibleinsteadofonlycompliesAnalyticalresultsfrommin.2batches,maximumbatchsizeResultsshouldinclude:Dateofmanufacture,batchsizeandbatchnumber,placeofmanufacture,resultsofanalyticaltest,useofbatches,3.2.S.4活性物质的控制,3.2.S4.4批分析批次描述和批次结果结果小于1的相关物质应用2位数报告现在的实际数据，每当可能时只是代替“遵守”分析结果从最少2批到最大批数量结果应当包括:制造日期,批大小和批号,制造地点,分析检测结果,批的使用,3.2.S.4ControloftheActivesubstance,3.2.S4.5JustificationofSpecificationSeeNoteforGuidanceonSpecification,impuritytestingguideline,residualsolvents3.2.S5ReferenceStandardsorMaterialsSpecifications,fullanalyticalandphysico-chemicalcharcterisation,impuritiesetc.Referencesubstances(primaryandsecondary)incl.fullanalyticalresultsorPh.Eur.CRS3.2.S6ContainerClosureSystemDescriptionofbulkstoragecontainerclosureSpecificationofprimarypackagingmaterial(e.g.Poleythylenebags)adsecondarypackaging(e.g.fibredrums,metaldrums),3.2.S.4活性物质的控制,3.2.S4.5规格的解释查看指南中有关规格，杂质检测指南，残留溶剂的注解3.2.S5对照品或对照物规格，完整的分析和物理化学特性，杂质等对照品（基准和二级）包括完整的分析结果或EP标准品3.2.S6容器密闭系统存放物料的密闭容器的说明第一层包装材料（例如聚乙烯袋）和第二层包装（例如纤维桶，金属桶）的规格,3.2.S7Stability,3.2.S7.2PostapprovalstabilityProtocolandcommitmentRetestperiodmaybeattributedbasedonextrapolation,seeNfGonstabilitytesting3.2.S7.3StabilityDataDetailedresultsintabularformat,StabilitytestingaccordingtoICHguidelineinformationontheanalyticalprocedures(validationifnecessary),3.2.S7稳定性,3.2.S7.2公布批准的稳定性方案和执行复测周期可以基于外推法来定性，参见NfG稳定性试验3.2.S7.3稳定性数据以表格形式的详细结果根据ICH指南进行稳定性试验基于分析规程（如果必要须验证）的信息,References,Noticetoapplicants(NTA)Volume2BCTDModule3SGuidelineonthechemistryofnewactivesubstancesValidationofanalyticalmethods,AnalyticalproceduresmethodologyICHStabilitytesting,photostabilitytestingICHImpuritiestestingguideline,residualsolventsICH.NoteforGuidanceonSpecifications,参考文献,通知申请者(NTA)第2册BCTD模块3S新活性物质化学部分指南ICH分析方法验证,分析规程方法学ICH稳定性试验,光稳定性试验ICH杂质试验指南，残留溶剂指南中关于规格的注意,ALFREDE.TIEFENBACHER(GmbHdefinedchemicalpropertiesandstructure!,1.介绍,1.2药政适应性当一种物料被一个地区或国家列为原料药，在该地区制造或在某种药物产品中使用，必须根据本指南遵循GMP要求。1.3范围本指南应用于由化学合成，提取，细胞培养/发酵，自然原料提取的原料药制造。原料药起始物料是原料，中间体，或一种原料药，它具有所要生产的原料药的有效结构部分；明确的化学属性和结构,ApplicationoftheGuidetoAPIManufacturing,Chemicalsynthesis:productionofAPIstartingmaterial-introductionofAPIstartingmaterialintoprocessproductionofintermediate(s)isolationandpurification-physicalprocessingandpackagingDerivedfromanimalsources:collectionoforgan,fluid,ortissuecutting,mixing,initialprocessingintroductionoftheAPIstartingmaterialintoprocessisolation.Extractedfromplantsources:collectionofplantscuttingandinitialextractionfurtherextractionphysicalprocessingAPIconsistingofcomminutedorpowderedherbs:collectioncutting/comminutingphysicalprocessingandpackagingBiotechnology-Fermentation/cellculture:establishmentofmasterandworkingcellbankmaintenanceofworkingcellbankcellculture/fermentationisolationandpurificationphysicalprocessingandpackagingClassical“fermentationtoproduceanAPI:Establishmentandmaintenanceofthecellbankintroductionofthecellsintofermentation,.,本指南在原料药制造的运用,化学合成：原料药起始物料的生产在工艺中加入原料药起始物料中间体生产分离和提纯物理加工和包装源于动物原料的：采集器官，液体，或组织切割，混和，初步加工在工艺中加入原料药起始物料分离从植物原料中提取的：采集植物切割和初步提取进一步提取物理加工原料药由粉末或粉末状草药组成：采集切割/粉末化物理加工和包装生物技术发酵/细胞培养：建立主细胞库和工作细胞库工作细胞库的维护细胞培养/发酵分离和提纯物理加工和包装生产一个原料药标准的发酵：细胞库的建立和维护在发酵中加入细胞,1.3Scope,ThecompanyshoulddesignateanddocumenttherationaleforthepointatwhichproiductionoftheAPIbegins.(available?,inspectorsaidememoire!(AM)Fromthispointon,appropriateGMPasdefinedintheGuideshouldbeappliedtotheseintermediateand/orAPImanufacturingsteps.ThisincludesvalidationofcriticalprocessstepsdeterminedtoimpactthequalityoftheAPI.(AMcriticalstepsidentified?)ThestringencyofGMPinAPImanufacturingshouldincreaseastheprocessproceedsfromearlyAPIstepstofinalsteps,purificationandpackaging.Physicalprocessingsuchasgranulating,coating,blendingwithexcipients/subbatches,millingrequirefullGMP!,1.3范围,工厂应确定并把原料药是从哪个点开始的制成文件（可能？检查官帮助备忘录！（AM)从这个确定的点起：本指南中相应的GMP规则应该被应用于这些中间体和/或原料药的制造步骤这包括对决定原料药质量的关键工艺步骤的验证（AM关键步骤的确认？）随着工艺从最初的原料药步骤到最终步骤，纯化和包装，原料药制造的GMP规则逐步严格。物理过程，例如造粒，包衣，和赋形剂/零头的混和，粉碎，满足GMP的要求,APIStartingMaterials(API-SM),ResponsibilityofcompaniestoproposetheAPIStartingMaterial(s);technical,quality,regulatorygroupshavetodefinethesignificantstructuralfragment!WithStartingMaterialGMPhastobeapplied!IfonlyoneortwosyntheticstepsexistbetweenanAPI-SMandtheAPIoriftheSMisanAPIitselfregulatoryauthoritieswillrequirefurtherinformationonAPI-SM!(manufactureraudited,qualitymanagementsystemestablished,documentation,changecontrol,etc.)Ingeneral,thesourceoftheAPI-SMisnotamajorfactor.EPcertificationsubmissionsrequireastatementtheproductismanufacturedaccordingtoGMP“(nottheAPI-SM!)Commerciallyavailablesubstances(latestageAPI-SM)like6-APAforsemi-syntheticpenicillinsacceptedbyFDAasAPI-SM!Authoritiesmayrequirefurtherdetails!,原料药起始物料(API-SM),工厂提出起始物料的责任：技术，质量，药政部门必须确定其重要的结构特征！必须应用起始物料的GMP规则。在原料药起始物料与原料药之间只存在一或两个合成步骤，或者如果这种起始物料本身便是一种原料药，药政官方部门将要求原料药的起始物料有更详细的资料！（受审计的制造商，已建立的质量管理系统，文件，变更控制，等）总之，原料药的起始物料的来源不是一个重要因素。EP证书的递交需要一个申明，说明产品是符合GMP的（不是原料药的起始物料）适用于商业的物质（原料药起始物料的后阶段），如用于半合成青霉素的6-APA是被FDA所接受的原料药起始物料。官方部门可能要求更详细的材料！,API-SM,WheretheproposedAPI-SMisclosetotheAPIensurethatdetailsonthesyntheticprocessandanalyticalcontrolsusedareavailableincasethesewouldberequiredbytheregulatoryauthorities!Includeinthecommercialcontractthataconfidentialparthastobeprovideddirectlytoauthoritiesifrequested!DefinealsoChangeControlRequirementsinthecontractforsupplyofAPI-SM!,Anychangeinsyntheticroute,analyticalcontrolsorspecification,needsnotificationtoandacceptancebytheAPImanufacturer,ManufacturersofIntermediates,API-SMs,APIsshouldhaveasystemforevaluatingthesuppliersofcriticalmaterials,API-SM,那些与原料药很接近的起始物料若能确定其详细的合成工艺并且有检验控制，这样做也是可以满足官方药监部门要求的！包括商业合同，如果需要，其中的保密部分必须直接提供给官方部门。对于起始物料的合同也要明确变更控制的要求,任何在合成路线，检验控制或规格中的变更，都需要告知并得到原料药制造商的接受,中间体，起始物料，原料药制造商应该对关键物料供应商进行评估。,API-SM,Syntheticorsemi-syntheticAPIsAPI-SMisanalyticallyfullycontrolledintermsofidentity,assayandimpurities!APIproducedbydirectfermentationDescribemicro-organismandmediacomponentsplustheirspecifications.Nospecificstartingmaterialtobedefined,unlessonecomponentisstructurallycloselyrelatedtotheAPI.APIextractedfromnaturalsourcesormanufacturedfromminedoreDescribethepurificationprocessand/ordefineAPI-SMbasedonascientificrationalewhichmayincluderiskassessment.,原料药起始物料,合成或半合成原料药起始物料按照鉴别，含量，杂质等全检控制由直接发酵产生的原料药在规格里加入微生物和培养基的描述如果一个要素的结构与原料药非常接近，则无须确定起始物料原料药从自然原料中提取或由矿石制造描述精制工艺并且/或根据科学原理，其中可能包括风险评估，来确定原料药的起始物料,2.QualityManagement,PrinciplesResponsibilitiesofQU(s)ResponsibilitiesofProductionInternalAuditsProductQualityReview,2.质量管理,原则质量部门职责生产部门职责内部审计产品质量审核,2.QualityManagement-Glossary,QualityAssurance(QA),QualityManagement(QM)ThesumtotaloftheorganisedarrangementsmadewiththeobjectofensuringthatallAPIsareofthequalityrequiredfortheirintendeduseandthatqualitysystemsaremaintained.QualityUnit(s)AnorganizationalunitindependentofproductionwhichfulfillsbothQAandQualityControl(QC)responsibilities.ThiscanbeintheformofseparateQAandQCunitsorasingleindividualorgroup,dependinguponthesizeandstructureoftheorganization.QualityControl(QC)Checkingortestingthatthespecificationsaremet.QualityAttribute:Anyproductcharacteristicwhichmayreflectquality,ormayaffectsafetyorpurityoftheproductduringitsexpectedshelflife.Quality:Totalityoffeaturesandcharacteristicsofaproductorserviceanditsabilitytosatisfystatedorimpliedneeds.Thisis,meetingagreedrequirementsinacosteffectivemanner.,2.质量管理词汇表,质量保证(QA),质量管理(QM)以确保所有原料药达到其应用所要求的质量，并以维持质量体系为目的的全部组织安排的总和。质量部门（QU）独立于生产部门的履行质量保证和质量控制职责的组织机构。按照组织机构的大小和结构，可以是单独的QA和QC部门,或个人,或小组。质量控制(QC)是否符合质量规格的检查或测试。质量属性:在预期的架上时间内任何可能影响产品质量，安全或纯度的产品特性。质量:产品或服务，满足规定或潜有需要的特征和特性的总和。即，采取有效的措施符合要求,Coordinatedactivitiestodirectandcontrolanorganizationthroughoutallareasandprocesseswithregardtoquality.,Glossary:QualityManagement,QualityManagementSystem-QMS,SystemneededtoimplementQualityManagementefficiently.,指导和控制一个组织的协调活动贯穿所有与质量有关的区域和工艺,词汇表：质量管理,质量管理系统QMS,需要有效的实施质量管理的系统.,TheQualityAssuranceSystem-QMSystem.recognizesanddescribesinterfaces,responsibilities,competences,Interactions.,.ensuresclearInputsfortasks,质量保证系统QM系统职责的识别和描述,管辖相互作用,确定明确的职责分配,InterfacesMilestonesInformationflow/InteractionsTasksCompetencesResponsibilities,QMSisthearrangementof,管辖分界信息流动/相互作用任务权限职责,质量管理系统,QMS,DocumentationSystem,GMP,Describessystemrelatedquality,Describesproductrelatedquality,QMS,文件系统,GMP,描述与质量相关的系统,描述与质量相关的产品,GMP+Processes=QMS,GMP,ProductrelatedQualityDocumentedevidence,Process,Asetofinterrelatedorinteractingactivitieswhichtransformsinputsintooutputs.,QMS,Includingtime-axisIncludinginterconnections,GMP+工艺=QMS,GMP,与质量相关的产品文件化的证据,工艺,一系列相关的或相互作用的，把输入转化为产出的活动,QMS,包括时间轴包括相互联络,GeneralConsiderations,PICGMPChapter1:QualityManagement“.ToachievethequalityobjectivereliablytheremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQualityAssuranceincorporatingGoodManufacturingPracticeandthusQualityControl.Itshouldbefullydocumentedanditseffectivenessmonitored.”,QMS,概论,PICGMP第1章:质量管理“要达到质量目标必须有广泛设计的和正确实施的质量保证系统，加之以GMP规范并如此质量控制。应该完全文件化并有效监督。”,QMS,GeneralConsiderations,IntroductionISO9001:“ItisemphasizedthatthequalitysystemrequirementsspecifiedinthisInternationalStandardarecomplementary-notal