FDA-连续制造的质量考量-2019(中英文)

QualityConsiderationsforContinuousManufacturing连续生产的质量考量GuidanceforIndustry行业指南DRAFTGUIDANCE草案指南Thisguidancedocumentisbeingdistributedforcommentpurposesonly.本指南仅供征求意见用。Commentsandsuggestionsregardingthisdraftdocumentshouldbesubmittedwithin90daysofpublicationintheFederalRegisterofthenoticeannouncingtheavailabilityofthedraftguidance.Submitelectroniccommentsto(HFA-305),FoodandDrugAdministration,5630FishersLane,Rm.1061,Rockville,MD20852.AllcommentsshouldbeidentifiedwiththedocketnumberlistedinthenoticeofavailabilitywhenpublishedintheFederalRegister.有关该草案文件的意见和建议应在公布指南草案通知后90天内提交。将电子意见提交至。将书面意见提交给FDA文件管理人员（HFA-305），地址为5630FishersLane,Rm.1061,Rockville,MD20852.所有意见都应在联邦公报通知所列出的案卷号中标明。Forquestionsregardingthisdraftdocument,contact(CDER)SauL.Leeat301-796-2905.有关本草案文件的问题，请联系（CDER）SauL.Lee，电话：301-796-2905。U.S.DepartmentofHealthandHumanServicesFoodandDrugAdministrationCenterforDrugEvaluationandResearch(CDER)February2019PharmaceuticalQuality/CMCPharmaceuticalQuality/ManufacturingStandards(CGMP)TABLEOFCONTENTS目录I.INTRODUCTION介绍....................................................................................................1II.BACKGROUND背景.......................................................................................................2III.QUALITYCONSIDERATIONS质量考虑因素............................................................3A.KeyConceptsofContinuousManufacturing连续生产的关键概念...........................31.ProcessDynamics工艺动力学..........................................................................................42.DefiningBatchesforContinuousManufacturingProcesses规定连续生产工艺的批次.5B.ControlStrategy控制策略...............................................................................................61.InputMaterialControl投入物料控制...............................................................................72.ProcessMonitoringandControl过程监控与控制...........................................................83.MaterialDiversion物料转移...........................................................................................104.RealTimeReleaseTesting实时放行检测.......................................................................125.Specification质量标准.....................................................................................................156.Equipment设备................................................................................................................157.SystemIntegration,DataProcessing,andManagement系统集成、数据处理和管理.17C.ProcessValidation工艺验证.........................................................................................191.Stage1–ProcessDesign第1阶段-工艺设计...............................................................202.Stage2–ProcessQualification第2阶段-工艺确认.....................................................203.Stage3–ContinuedProcessVerification第3阶段-持续工艺确证..............................22D.AdditionalPharmaceuticalQualitySystemConsiderations药品质量体系的其他考量......................................................................................................................................23E.Scale-Up工艺放大..........................................................................................................24F.Stability稳定性...............................................................................................................27G.BridgingExistingBatchtoContinuousManufacturing现有批次生产过渡到连续生产......................................................................................................................................27IV.LOCATIONOFINFORMATIONINANAPPLICATION申请文件中连续生产信息的位置..........................................................................................................................29V.DEFINITIONS定义........................................................................................................33VI.REFERENCES参考文献...............................................................................................361QualityConsiderationsforContinuousManufacturing连续生产的质量考量GuidanceforIndustry1行业指南I.INTRODUCTION介绍ThisguidanceprovidesinformationregardingFDA’scurrentthinkingonthequalityconsiderationsforcontinuousmanufacturingofsmallmolecule,solidoraldrugproductsthatareregulatedbytheCenterforDrugEvaluationandResearch(CDER).Theguidancedescribesseveralkeyqualityconsiderationsandprovidesrecommendationsforhowapplicantsshouldaddresstheseconsiderationsinnewdrugapplications(NDAs),abbreviatednewdrugapplications(ANDAs),andsupplementalNDAsandANDAs,forsmallmolecule,solidoraldrugproductsthatareproducedviaacontinuousmanufacturingprocess.FDAsupportsthedevelopmentandimplementationofcontinuousmanufacturingfordrugsubstancesandallfinisheddosageformswhereappropriate,includingthosesubmittedinNDAs,ANDAs,drugmasterfiles(DMFs),biologicslicenseapplications(BLAs),andnonapplicationover-the-counter(OTC)products.Scientificprinciplesdescribedinthisguidancemayalsobeapplicabletocontinuousmanufacturingtechnologiesusedforthesedrugs.However,this