美国FDA原料药生产质量管理规范(中英文)

DIRECTIONOFGMP(GOODMANUFACTURINGPRACTICE)OFRAWMATERIALSBYFDA美国FDA原料药生产质量管理规范（中英文）TableofContents目录1.INTRODUCTION简介1.1Objective目的1.2RegulatoryApplicability法规的适用性1.3Scope范围2.QUALITYMANAGEMENT.质量管理2.1Principles总则2.2ResponsibilitiesoftheQualityUnit(s)质量部门的责任2.3ResponsibilityforProductionActivities生产作业的职责2.4InternalAudits(SelfInspection)内部审计（自检）2.5ProductQualityReview产品质量审核3.PERSONNEL人员3.1PersonnelQualifications人员的资质3.2PersonnelHygiene人员卫生3.3Consultants顾问4.BUILDINGSANDFACILITIES建筑和设施4.1DesignandConstruction设计和结构4.2Utilities公用设施4.3Water水4.4Containment限制4.5Lighting照明4.6SewageandRefuse排污和垃圾4.7SanitationandMaintenance卫生和保养5.PROCESSEQUIPMENT工艺设备5.1DesignandConstruction设计和结构5.2EquipmentMaintenanceandCleaning设备保养和清洁5.3Calibration.校验5.4ComputerizedSystems计算机控制系统6.DOCUMENTATIONANDRECORDS文件和记录6.1DocumentationSystemandSpecifications文件系统和质量标准6.2EquipmentcleaningandUseRecord设备的清洁和使用记录6.3RecordsofRawMaterials,Intermediates,APILabelingandPackagingMaterials原料、中间体、原料药的标签和包装材料的记录6.4MasterProductionInstructions(MasterProductionandControlRecords)生产工艺规程（主生产和控制记录）6.5BatchProductionRecords(BatchProductionandControlRecords)批生产记录（批生产和控制记录）6.6LaboratoryControlRecords实验室控制记录6.7BatchProductionRecordReview批生产记录审核7.MATERIALSMANAGEMENT物料管理7.1GeneralControls控制通则7.2ReceiptandQuarantine接收和待验7.3SamplingandTestingofIncomingProductionMaterials进厂物料的取样与测试7.4Storage储存7.5Re-evaluation复验8.PRODUCTIONANDIN-PROCESSCONTROLS生产和过程控制8.1ProductionOperations生产操作8.2TimeLimits时限8.3In-processSamplingandControls工序取样和控制8.4BlendingBatchesofIntermediatesorAPIs中间体或原料药的混批8.5ContaminationControl污染控制9.PACKAGINGANDIDENTIFICATIONLABELINGOFAPIsANDINTERMEDIATES原料药和中间体的包装和贴签9.1General总则9.2PackagingMaterials包装材料9.3LabelIssuanceandControl标签发放与控制9.4PackagingandLabelingOperations包装和贴签操作10.STORAGEANDDISTRIBUTION.储存和分发10.1WarehousingProcedures入库程序10.2DistributionProcedures分发程序11.LABORATORYCONTROLS实验室控制11.1GeneralControls控制通则11.2TestingofIntermediatesandAPIs中间体和原料药的测试11.3ValidationofAnalyticalProcedures分析方法的验证11.4CertificatesofAnalysis分析报告单11.5StabilityMonitoringofAPIs原料药的稳定性监测11.6ExpiryandRetestDating有效期和复验期11.7Reserve/RetentionSamples留样12.VALIDATION.验证12.1ValidationPolicy验证方针12.2ValidationDocumentation验证文件12.3Qualification确认12.4ApproachestoProcessValidation工艺验证的方法12.5ProcessValidationProgram工艺验证的程序12.6PeriodicReviewofValidatedSystems验证系统的定期审核12.7CleaningValidation清洗验证12.8ValidationofAnalyticalMethods分析方法的验证13.CHANGECONTROL变更的控制14.REJECTIONANDRE-USEOFMATERIALS.拒收和物料的再利用14.1Rejection拒收14.2Reprocessing返工14.3Reworking重新加工14.4RecoveryofMaterialsandSolvents物料与溶剂的回收14.5Returns退货15.COMPLAINTSANDRECALLS投诉与召回16.CONTRACTMANUFACTURERS(INCLUDINGLABORATORIES)协议生产商（包括实验室）17.AGENTS,BROKERS,TRADERS,DISTRIBUTORS,REPACKERS,ANDRELABELLERS代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1Applicability适用性17.2TraceabilityofDistributedAPIsandIntermediates已分发的原料药和中间体的可追溯性17.3QualityManagement质量管理17.4Repackaging,Relabeling,andHoldingofAPIsandIntermediates原料药和中间体的重新包装、重新贴签和待检17.5Stability稳定性17.6TransferofInformation信息的传达17.7HandlingofComplaintsandRecalls投诉和召回的处理17.8HandlingofReturns退货的处理18.SpecificGuidanceforAPIsManufacturedbyCellCulture/Fermentation用细胞繁殖/发酵生产的原料药的特殊指南18.1General总则18.2CellBankMaintenanceandRecordKeeping细胞库的维护和记录的保存18.3CellCulture/Fermentation细胞繁殖/发酵18.4Harvesting,IsolationandPurification收取、分离和精制18.5ViralRemoval/Inactivationsteps病毒的去除/灭活步骤19.APIsforUseinClinicalTrials用于临床研究的原料药19.1General总则19.2Quality质量19.3EquipmentandFacilities设备和设施19.4ControlofRawMaterials原料的控制19.5Production生产19.6Validation验证19.7Changes变更19.8LaboratoryControls实验室控制19.9Documentation文件20.Glossary术语1.INTRODUCTION1.简介1.1Objective1.1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规范（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/orfilingrequirementsormodifypharmacopoeialrequirem