ICHQ中英文对照

集团化办公室：[VV986T-J682P28-JP266L8-68PNN]ICHQ中英文对照Q7a（中英文对照）FDA原料药GMP指南TableofContents目录1.INTRODUCTION1.简介Objective目的RegulatoryApplicability法规的适用性Scope范围2.QUALITYMANAGEMENT2.质量管理Principles总则ResponsibilitiesoftheQualityUnit(s)质量部门的责任ResponsibilityforProductionActivities生产作业的职责InternalAudits(SelfInspection)内部审计（自检）ProductQualityReview产品质量审核3.PERSONNEL3.人员PersonnelQualifications3.人员的资质PersonnelHygiene人员卫生Consultants顾问4.BUILDINGSANDFACILITIES4.建筑和设施DesignandConstruction设计和结构Utilities公用设施Water水Containment限制Lighting照明SewageandRefuse排污和垃圾SanitationandMaintenance卫生和保养5.PROCESSEQUIPMENT5.工艺设备DesignandConstruction设计和结构EquipmentMaintenanceandCleaning设备保养和清洁Calibration校验ComputerizedSystems计算机控制系统6.DOCUMENTATIONANDRECORDS6.文件和记录DocumentationSystemandSpecifications文件系统和质量标准EquipmentcleaningandUseRecord设备的清洁和使用记录RecordsofRawMaterials,Intermediates,APILabelingandPackagingMaterials原料、中间体、原料药的标签和包装材料的记录MasterProductionInstructions(MasterProductionandControlRecords)生产工艺规程（主生产和控制记录）BatchProductionRecords(BatchProductionandControlRecords)批生产记录（批生产和控制记录）LaboratoryControlRecords实验室控制记录BatchProductionRecordReview批生产记录审核7.MATERIALSMANAGEMENT7.物料管理GeneralControls控制通则ReceiptandQuarantine接收和待验SamplingandTestingofIncomingProductionMaterials进厂物料的取样与测试Storage储存Re-evaluation复验8.PRODUCTIONANDIN-PROCESSCONTROLS8.生产和过程控制ProductionOperations生产操作TimeLimits时限8.3In-processSamplingandControls工序取样和控制BlendingBatchesofIntermediatesorAPIs中间体或原料药的混批ContaminationControl污染控制9.PACKAGINGANDIDENTIFICATIONLABELINGOFAPIsANDINTERMEDIATES9.原料药和中间体的包装和贴签General总则PackagingMaterials包装材料LabelIssuanceandControl标签发放与控制PackagingandLabelingOperations包装和贴签操作10.STORAGEANDDISTRIBUTION10.储存和分发WarehousingProcedures入库程序DistributionProcedures分发程序11.LABORATORYCONTROLS11.实验室控制GeneralControls控制通则TestingofIntermediatesandAPIs中间体和原料药的测试ValidationofAnalyticalProcedures分析方法的验证CertificatesofAnalysis分析报告单StabilityMonitoringofAPIs原料药的稳定性监测ExpiryandRetestDating有效期和复验期Reserve/RetentionSamples留样12.VALIDATION12.验证ValidationPolicy验证方针ValidationDocumentation验证文件Qualification确认ApproachestoProcessValidation工艺验证的方法ProcessValidationProgram工艺验证的程序PeriodicReviewofValidatedSystems验证系统的定期审核CleaningValidation清洗验证ValidationofAnalyticalMethods分析方法的验证13.CHANGECONTROL13.变更的控制14.REJECTIONANDRE-USEOFMATERIALS14.拒收和物料的再利用Rejection拒收Reprocessing返工Reworking重新加工RecoveryofMaterialsandSolvents物料与溶剂的回收Returns退货15.COMPLAINTSANDRECALLS15.投诉与召回16.CONTRACTMANUFACTURERS(INCLUDINGLABORATORIES)16.协议生产商（包括实验室）17.AGENTS,BROKERS,TRADERS,DISTRIBUTORS,REPACKERS,ANDRELABELLERS17.代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者Applicability适用性TraceabilityofDistributedAPIsandIntermediates已分发的原料药和中间体的可追溯性QualityManagement质量管理Repackaging,Relabeling,andHoldingofAPIsandIntermediates原料药和中间体的重新包装、重新贴签和待检Stability稳定性TransferofInformation信息的传达HandlingofComplaintsandRecalls投诉和召回的处理HandlingofReturns退货的处理18.SpecificGuidanceforAPIsManufacturedbyCellCulture/Fermentation18.用细胞繁殖/发酵生产的原料药的特殊指南General总则CellBankMaintenanceandRecordKeeping细胞库的维护和记录的保存CellCulture/Fermentation细胞繁殖/发酵Harvesting,IsolationandPurification收取、分离和精制ViralRemoval/Inactivationsteps病毒的去除/灭活步骤19.APIsforUseinClinicalTrials19.用于临床研究的原料药General总则Quality质量EquipmentandFacilities设备和设施ControlofRawMaterials原料的控制Production生产Validation验证Changes变更LaboratoryControls实验室控制Documentation文件20.Glossary20.术语Q7aGMPGuidanceforAPIsQ7a原料药的GMP指南1.INTRODUCTION1.简介Objective目的Thisdocumentisintendedtoprovideguidanceregardinggoodmanufacturingpractice(GMP)forthemanufacturingofactivepharmaceuticalingredients(APIs)underanappropriatesystemformanagingquality.ItisalsointendedtohelpensurethatAPIsmeetthequalityandpuritycharacteristicsthattheypurport,orarerepresented,topossess.本文件旨在为在合适的质量管理体系下制造活性药用成分（以下称原料药）提供有关优良药品生产管理（GMP）提供指南。它也着眼于帮助确保原料药符合其旨在达到或表明拥有的质量与纯度要求。Inthisguidance,thetermmanufacturingisdefinedtoincludealloperationsofreceiptofmaterials,production,packaging,repackaging,labeling,relabeling,qualitycontrol,release,storageanddistributionofAPIsandtherelatedcontrols.Inthisguidance,thetermshouldidentifiesrecommendationsthat,whenfollowed,willensurecompliancewithCGMPs.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatues.Forthepurposesofthisguidance,thetermscurrentgoodmanufacturingpracticesandgoodmanufacturingpracticesareequivalent.本指南中所指的“制造”包括物料接收、生产、包装、重新包装、贴签、重新贴签、质量控制、放行、原料药的储存和分发及其相关控制的所有操作。本指南中，“应当”一词表示希望采用的建议，除非证明其不适用或者可用一种已证明有同等或更高质量保证水平的供选物来替代。本指南中的“现行优良生产管理规范（cGMP）”和“优良生产管理规范（GMP）”是等同的。Theguidanceasawholedoesnotcoversafetyaspectsforthepersonnelengagedinmanufacturing,noraspectsrelatedtoprotectingtheenvironment.Thesecontrolsareinherentresponsibilitiesofthemanufacturerandaregovernedbynationallaws.本指南在总体上未涉及生产人员的安全问题，亦不包括环保方面的内容。这方面的管理是生产者固有的责任，也是国家法律规定的。Thisguidanceisnotintendedtodefineregistrationand/orfilingrequirementsormodifypharmacopoeialrequirements.Thisguidancedoesnotaffecttheabilityoftheresponsibleregulatoryagencytoestablishspecificregistration/filingrequirementsregardingAPIswithinthecontextofmarketing/manufacturingauthorizationsordrugapplications.Allcommitmentsinregistration/filingdocumentsshouldbemet.本指南未规定注册/归档的要求、或修改药典的要求。本指南不影响负责药政审理部门在原料药上市/制造授权或药品申请方面建立特定注册/归档要求的能力。注册/归档的所有承诺必须做到。RegulatoryApplicability法规的适用性Withintheworldcommunity,materialsmayvaryastotheirlegalclassificationasanAPI.WhenamaterialisclassifiedasanAPIintheregionorcountryinwhichitismanufacturedorusedinadrugproduct,itshouldbemanufacturedaccordingtothisguidance.在世界范围内对原料药的法定定义是各不相同的。当某种物料在其制造或用于药品的地区或国家被称为原料药，就应该按照本指南进行生产。Scope范围ThisguidanceappliestothemanufactureofAPIsforuseinhumandrug(medicinal)products.ItappliestothemanufactureofsterileAPIsonlyuptothepointimmediatelypriortotheAPIsbeingrenderedsterile.ThesterilizationandasepticprocessingofsterileAPIsarenotcoveredbythisguidance,butshouldbeperformedinaccordancewithGMPguidancesfordrug(medicinal)productsasdefinedbylocalauthorities.本文件适用于人用药品（医疗用品）所含原料药的生产。它适用于无菌原料药在灭菌前的步骤。本指南不包括无菌原料药的消毒和灭菌工艺，但是，应当符合地方当局所规定的药品（医疗用品）生产的GMP指南。ThisguidancecoversAPIsthataremanufacturedbychemicalsynthesis,extraction,cellculture/fermentation,recoveryfromnaturalsources,oranycombinationoftheseprocesses.SpecificguidanceforAPIsmanufacturedbycellculture/fermentationisdescribedinSection18.本文件适用于通过化学合成、提取、细胞培养/发酵，通过从自然资源回收，或通过这些工艺的结合而得到的原料药。通过细胞培养/发酵生产的原料药的特殊指南则在第18章论述。Thisguidanceexcludesallvaccines,wholecells,wholebloodandplasma,bloodandplasmaderivatives(plasmafractionation),andgenetherapyAPIs.However,itdoesincludeAPIsthatareproducedusingbloodorplasmaasrawmaterials.Notethatcellsubstrates(mammalian,plant,insectormicrobialcells,tissueoranimalsourcesincludingtransgenicanimals)andearlyprocessstepsmaybesubjecttoGMPbutarenotcoveredbythisguidance.Inaddition,theguidancedoesnotapplytomedicalgases,bulk-packageddrug(medicinal)products.,tabletsorcapsulesinbulkcontainers),orradiopharmaceuticals.本指南不包括所有疫苗、完整细胞、全血和血浆、全血和血浆的衍生物（血浆成分）和基因治疗的原料药。但是却包括以血或血浆为原材料生产的原料药。值得注意的是细胞培养基（哺乳动物、植物、昆虫或微生物的细胞、组织或动物源包括转基因动物）和前期生产可能应遵循GMP规范，但不包括在本指南之内。另外，本指南不适用于医用气体、散装的制剂药（例如，散装的片剂和胶囊）和放射性药物的生产。Section19containsguidancethatonlyappliestothemanufactureofAPIsusedintheproductionofdrug(medicinal)productsspecificallyforclinicaltrials(investigationalmedicinalproducts).第19章的指南只适用于用在药品（医疗用品）生产中的原料药制造，特别是临床实验用药（研究用医疗产品）的原料药制造。AnAPIstartingmaterialisarawmaterial,anintermediate,oranAPIthatisusedintheproductionofanAPIandthatisincorporatedasasignificantstructuralfragmentintothestructureoftheAPI.AnAPIstartingmaterialcanbeanarticleofcommerce,amaterialpurchasedfromoneormoresuppliersundercontractorcommercialagreement,orproducedin-house.APIstartingmaterialsnormallyhavedefinedchemicalpropertiesandstructure.“原料药的起始物料”是指一种原料、中间体或原料药，用来生产一种原料药，或者以主要结构的形式被结合进原料药结构中。原料药的起始物料可能是在市场上有售、能够通过或商业协议从一个或多个供应商处购得，或由生产厂家自制。原料药的起始物料一般来说有特定的化学特性和结构。ThecompanyshoulddesignateanddocumenttherationaleforthepointatwhichproductionoftheAPIbegins.Forsyntheticprocesses,thisisknownasthepointatwhichAPIstartingmaterialsareenteredintotheprocess.Forotherprocesses.,fermentation,extraction,purification),thisrationaleshouldbeestablishedonacase-by-casebasis.Table1givesguidanceonthepointatwhichtheAPIstartingmaterialisnormallyintroducedintotheprocess.生产厂商要指定并用书面文件说明原料药的生产从何处开始的理论依据。对于合成工艺而言，就是“原料药的起始物料”进入工艺的那一点。对其他工艺（如：发酵，提取，纯化等）可能需要具体问题具体对待。表1给出了原料药的起始物料从哪一点引入工艺过程的指导原则。Fromthispointon,appropriateGMPasdefinedinthisguidanceshouldbeappliedtotheseintermediateand/orAPImanufacturingsteps.ThiswouldincludethevalidationofcriticalprocessstepsdeterminedtoimpactthequalityoftheAPI.However,itshouldbenotedthatthefactthatacompanychoosestovalidateaprocessstepdoesnotnecessarilydefinethatstepsascritical.从这步开始，本指南中的有关GMP规范应当应用在这些中间体和/或原料药的制造中。这包括对原料药质量有影响的关键工艺步骤的验证。但是，值得注意的是厂商选择某一步骤进行验证，并不一定将该步骤定为关键步骤。TheguidanceinthisdocumentwouldnormallybeappliedtothestepsshowningrayinTable1.However,allstepsshownmaynotbecompleted.ThestringencyofGMPinAPImanufacturingshouldincreaseastheprocessproceedsfromearlyAPIstepstofinalsteps,purification,andpackaging.PhysicalprocessingofAPIs,suchasgranulation,coatingorphysicalmanipulationofparticlesize.,milling,micronizing)shouldbeconductedaccordingtothisguidance.本文件的指南通常适用于表1中的灰色步骤。但在表中体现的所有步骤并不是将应用GMP管理的所有步骤全部体现出来了。原料药生产中的GMP要求应当随着工艺的进行，从原料药的前几步到最后几步，精制和包装，越来越严格。原料药的物理加工，如制粒、包衣或颗粒度的物理处理（例如制粉、微粉化）应当按本指南的标准进行。ThisGMPguidancedoesnotapplytostepspriortotheintroductionofthedefinedAPIstartingmaterial.本GMP指南不适用于引入定义了的“原料药的起始物料”以前的步骤。Table1:ApplicationofthisGuidancetoAPIManufacturingTypeofManufacturingApplicationofthisguidancetosteps(showningray)usedinthistypeofmanufacturingChemicalmanufacturingProductionoftheAPIStartingmaterialIntroductionoftheAPIstartingmaterialintoprocessProductionofIntermediate(s)IsolationandpurificationPhysicalprocessing,andpackagingAPIderivedfromanimalsourcesCollectionoforgan,fluid,ortissueCutting,mixing,and/orinitialprocessingIntroductionoftheAPIstartingmaterialintoprocessIsolationandpurificationPhysicalprocessing,andpackagingAPIextractedfromplantsourcesCollectionofplantCuttingandinitialextraction(s)IntroductionoftheAPIstartingmaterialintoprocessIsolationandpurificationPhysicalprocessing,andpackagingHerbalextractsusedasAPICollectionofplantsCuttingandinitialextractionFurtherextractionPhysicalprocessing,andpackagingAPIconsistingofcomminutedorpowderedherbsCollectionofplantsand/orcultivationandharvestingCutting/comminutingPhysicalprocessing,andpackagingBiotechnology:fermentation/cellcultureEstablishmentofmastercellbankandworkingcellbankMaintenanceofworkingcellbankCellcultureand/orfermentationIsolationandpurificationPhysicalprocessing,andpackaging“Classical”fermentationtoproduceanAPIEstablishmentofcellbankMaintenanceofthecellbankIntroductionofthecellsintofermentationIsolationandpurificationPhysicalprocessing,andpackagingIncreasingGMPrequirements表1:本指南在原料药生产中的应用生产类型本指南在用于各类生产的工艺步骤（灰色背景）中的应用化学品的生产原料药起始物料的生产原料药起始物料引入工艺过程中间体的生产分离和纯化物理加工和包装动物源原料药器官、分泌物或组织的收集切割、混合和/或初步加工原料药起始物料引入工艺过程分离和纯化物理加工和包装从植物源提取的原料药植物的收集切割和初步提取原料药起始物料引入工艺过程分离和纯化物理加工和包装草药提取物用作原料药植物的收集切割和初步提取进一步提取物理加工和包装由粉碎的或粉末状草药组成的原料药植物的收集和/或培养和收获切割/粉碎物理加工和包装生物技术：发酵/细胞培养主细胞库和工作细胞库的建立工作细胞库的维护细胞培养和/或发酵分离和纯化物理加工和包装“经典”发酵生产原料药细胞库的建立细胞库的维护细胞引入发酵分离和纯化物理加工和包装GMP的要求增加2.QUALITYMANAGEMENT2．质量管理Principles总则Qualityshouldbetheresponsibilitiesofallpersonsinvolvedinmanufacturing.参与原料药生产的每一个人都应当对质量负责。Eachmanufacturershouldestablish,document,andimplementaneffectivesystemformanagingqualitythatinvolvestheactiveparticipationofmanagementandappropriatemanufacturingpersonnel.每一个生产商都应当建立并执行一套有管理人员和有关员工积极参与的有效的质量管理体系，并使其文件化。Thesystemformanagingqualityshouldencompasstheorganizationalstructure,procedures,processandresources,aswellasactivitiestoensureconfidencethattheAPIwillmeetitsintendedspecificationsforqualityandpurity.Allquality-relatedactivitiesshouldbedefinedanddocumented.质量管理体系应当包括组织机构、规程、工艺和资源，以及确保原料药会符合其预期的质量与纯度要求所必需的活动。所有涉及质量管理的活动都应当明确规定，并使其文件化。Thereshouldbeaqualityunit(s)thatisindependentofproductionandthatfulfillsbothqualityassurance(QA)andqualitycontrol(QC)responsibilities.ThequalityunitcanbeintheformofseparateQAandQCunitsorasingleindividualorgroup,dependinguponthesizeandstructureoftheorganization.应当设立一个独立于生产部门的质量部门，同时履行质量保证(QA)和质量控制(QC)的职责。依照组织机构的大小，可以是分开的QA和QC部门，或者只是一个人或小组。ThepersonsauthorizedtoreleaseintermediatesandAPIsshouldbespecified.应当指定授权发放中间体和原料药的人员。Allquality-relatedactivitiesshouldberecordedatthetimetheyareperformed.所有有关质量的活动应当在其执行时就记录。Anydeviationfromestablishedproceduresshouldbedocumentedandexplained.Criticaldeviationsshouldbeinvestigated,andtheinvestigationanditsconclusionsshouldbedocumented.任何偏离既定规程的情况都应当有文字记录并加以解释。对于关键性偏差应当进行调查，并记录调查经过及其结果。Nomaterialsshouldbereleasedorusedbeforethesatisfactorycompletionofevaluationbythequalityunit(s)unlessthereareappropriatesystemsinplacetoallowforsuchuse.,releaseunderquarantineasdescribedinSection10ortheuseofrawmaterialsorintermediatespendingcompletionofevaluation).在质量部门对物料完成满意的评价之前，任何物料都不应当发放或使用，除非有合适的系统允许此类使用（如条款所述的待检情况下的使用，或是原料或中间体在等待评价结束时的使用）。Proceduresshouldexistfornotifyingresponsiblemanagementinatimelymannerofregulatoryinspections,seriousGMPdeficiencies,productdefectsandrelatedactions.,quality-relatedcomplaints,recalls,andregulatoryactions).应当有规程能确保公司的责任管理部门能及时得到有关药政检查、严重的GMP缺陷、产品缺陷及其相关活动（如质量投诉，召回，药政活动等）的通知。ResponsibilitiesoftheQualityUnit(s)质量部门的责任Thequalityunit(s)shouldbeinvolvedinallquality-relatedmatters.质量部门应当参与所有与质量有关的事物。Thequalityunit(s)shouldreviewandapproveallappropriatequality-relateddocuments.所有与质量有关的文件应当由质量部门审核批准。Themainresponsibilitiesoftheindependentqualityunit(s)shouldnotbedelegated.Theseresponsibilitiesshouldbedescribedinwritingandshouldinclude,butnotnecessarilybelimitedto:ReleasingorrejectingallAPIs.ReleasingorrejectingintermediatesforuseoutsidethecontrolofthemanufacturingcompanyEstablishingasystemtoreleaseorrejectrawmaterials,intermediates,packaging,andlabelingmaterialsReviewingcompletedbatchproductionandlaboratorycontrolrecordsofcriticalprocessstepsbeforereleaseoftheAPIfordistributionMakingsurethatcriticaldeviationsareinvestigatedandresolvedApprovingallspecificationsandmasterproductioninstructionsApprovingallproceduresaffectingthequalityofintermediatesorAPIsMakingsurethatinternalaudits(self-inspections)areperformedApprovingintermediateandAPIcontractmanufacturersApprovingchangesthatpotentiallyaffectintermediateorAPIqualityReviewingandapprovingvalidationprotocolsandreportsMakingsurethatquality-relatedcomplaintsareinvestigatedandresolvedMakingsurethateffectivesystemsareusedformaintainingandcalibratingcriticalequipmentMakingsurethatmaterialsareappropriatelytestedandtheresultsarereportedMakingsurethatthereisstabilitydatatosupportretestorexpirydatesandstorageconditionsonAPIsand/orintermediates,whereappropriatePerformingproductqualityreviews(asdefinedinSection独立的质量部门的主要职责不应当委派给他人。这些责任应当以文字形式加以说明，而且应当包括，但不限于：所有原料药的放行与否。用于生产商控制范围以外的中间体的放行与否；建立一个放行与拒收原材料、中间体、包装材料和标签的系统；在供销售的原料药放行前，审核已完成的关键步骤的批生产记录和实验室检验记录；确保已对重大偏差进行了调查并已解决；批准所有的规格标准和主生产指令；批准所有可能影响原料药和中间体质量的规程；确保进行内部审计（自检）；批准中间体或原料药的委托生产商；批准可能影响到中间体或原料药质量的变更；审核并批准验证和报告；确保调查并解决质量问题的投诉；确保用有效的体系来维护和校验关键设备；确保物料都经过了适当的检验并报告结果；确保有稳定性数据支持中间体或原料药的复验期或有效期和储存条件；开展产品质量审核（详见节）。ResponsibilityforProductionActivities生产作业的职责Theresponsibilityforproductionactivitiesshouldbedescribedinwritingandshouldinclude,butnotnecessarilybelimitedto:Preparing,reviewing,approving,anddistributingtheinstructionsfortheproductionofintermediatesorAPIsaccordingtowrittenproceduresProducingAPIsand,whenappropriate,intermediatesaccordingtopre-approvedinstructionsReviewingallproductionbatchrecordsandensuringthatthesearecompletedandsignedMakingsurethatallproductiondeviationsarereportedandevaluatedandthatcriticaldeviationsareinvestigatedandtheconclusionsarerecordedMakingsurethatproductionfacilitiesarecleanand,whenappropriate,disinfectedMakingsurethatthenecessarycalibrationsareperformedandrecordskeptMakingsurethatthepremisesandequipmentaremaintainedandrecordskeptMakingsurethatvalidationprotocolsandreportsarereviewedandapprovedEvaluatingproposedchangesinproduct,processorequipmentMakingsurethatnewand,whenappropriate,modifiedfacilitiesandequipmentarequalified生产作业的职责应当以文字形式加以说明，并应当包括，但不限于以下内容：按书面程序起草、审核、批准和分发中间体或原料药的生产指令；按照已批准的指令生产原料药或者中间体；审核所有的批生产记录确保其完整并有签名；确保所有的生产偏差都已报告、评价，对关键的偏差已做了调查，并记录结论；确保生产设施的清洁，必要时要消毒；确保进行必要的校验，并有记录；确保对厂房和设备进行保养，并有记录；确保验证方案和报告的审核与批准；对产品、工艺或设备拟作的变更进行评估；确保新的或已改进的生产设施和设备经过了确认。InternalAudits(SelfInspection)内部审计（自检）ToverifycompliancewiththeprinciplesofGMPforAPIs,regularinternalauditsshouldbeperformedinaccordancewithanapprovedschedule.为确实符合原料药GMP原则，应当按照批准的计划进行定期的内部审计。Auditfindingsandcorrectiveactionsshouldbedocumentedandbroughttotheattentionofresponsiblemanagementofthefirm.Agreedcorrectiveactionsshouldbecompletedinatimelyandeffectivemanner.审计结果及整改措施应当形成文件，并引起公司责任管理人员的重视。获准的整改措施应当及时、有效地完成。ProductQualityReview产品质量审核Regularquality-reviewsofAPIsshouldbeconductedwiththeobjectiveofverifyingtheconsistencyoftheprocess.Suchreviewsshouldnormallybeconductedanddocumentedannuallyandshouldincludeatleast:Areviewofcriticalin-processcontrolandcriticalAPItestresultsAreviewofallbatchesthatfailedtomeetestablishedspecification(s)AreviewofallcriticaldeviationsornonconformancesandrelatedinvestigationsAreviewofanychangescarriedouttotheprocessesoranalyticalmethodsAreviewofresultsofthestabilitymonitoringprogramAreviewofallquality-relatedreturns,complaintsandrecallsAreviewofadequacyofcorrectiveactions原料药的定期质量审核应当以证实工艺的一致性为目的来进行。此种审核通常应当每年进行一次，并记录，内容至少应当包括：关键工艺控制以及原料药关键测试结果的审核；所有不符合既定质量标准的产品批号的审核；所有关键的偏差或违规行为及有关调查的审核；任何工艺或分析方法变动的审核；稳定性监测的审核；所有与质量有关的退货、投诉和召回的审核；整改措施的适当性的审核。Theresultsofthisreviewshouldbeevaluatedandanassessmentmadeofwhethercorrectiveactionoranyrevalidationshouldbeundertaken.Reasonsforsuchcorrectiveactionshouldbedocumented.Agreedcorrectiveactionsshouldbecompletedinatimelyandeffectivemanner.应当对质量审核结果进行评估，并做出是否需要整改或做任何再验证的评价。此类整改措施的理由应当文件化。获准的整改措施应当及时、有效地完成。3.PERSONNEL3.人员PersonnelQualifications员工的资质Thereshouldbeanadequatenumberofpersonnelqualifiedbyappropriateeducation,training,and/orexperiencetoperformandsupervisethemanufactureofintermediatesandAPIs.应当有足够数量的员工具备从事和监管原料药和中间体生产的教育、培训和/或经历等资格。TheresponsibilitiesofallpersonnelengagedinthemanufactureofintermediatesandAPIsshouldbespecifiedinwriting.参与原料药和中间体生产的所有人员的职责应当书面规定。Trainingshouldberegularlyconductedbyqualifiedindividualsandshouldcover,ataminimum,theparticularoperationsthattheemployeeperformsandGMPasitrelatestotheemployee’sfunctions.Recordsoftrainingshouldbemaintained.Trainingshouldbeperiodicallyassessed.应当由有资格的人员定期进行培训，内容至少应当包括员工所从事的特定操作和与其职能有关的GMP。培训记录应当保存，并应当定期对培训进行评估。PersonnelHygiene员工的卫生Personnelshouldpracticegoodsanitationandhealthhabits.员工应当养成良好的卫生和健康习惯。Personnelshouldwearcleanclothingsuitableforthemanufacturingactivitywithwhichtheyareinvolvedandthisclothingshouldbechanged,whenappropriate.Additionalprotectiveapparel,suchashead,face,hand,andarmcoverings,shouldbeworn,whennecessary,toprotectintermediatesandAPIsfromcontamination.员工应当穿着适合其所从事生产操作的干净服装，必要时应当更换。其它保护性用品如头、脸、手和臂等遮护用品必要时也应当佩带，以免原料药和中间体受到污染。PersonnelshouldavoiddirectcontactwithintermediatesandAPIs.员工应当避免与中间体或原料药的直接接触。Smoking,eating,drinking,chewingandthestorageoffoodshouldberestrictedtocertaindesignatedareasseparatefromthemanufacturingareas.吸烟、吃、喝、咀嚼及存放食品仅限于与生产区隔开的指定区域。PersonnelsufferingfromaninfectiousdiseaseorhavingopenlesionsontheexposedsurfaceofthebodyshouldnotengageinactivitiesthatcouldresultincompromisingthequalityofAPIs.Anypersonshownatanytime(eitherbymedicalexaminationorsupervisoryobservation)tohaveanapparentillnessoropenlesionsshouldbeexcludedfromactivitieswheretheconditioncouldadverselyaffecttheq