EMA-药品、活性物质、辅料和内包材灭菌指南-2019(中英文)

16March2019EMA/CHMP/CVMP/QWP/850374/2015CommitteeforMedicinalProductsforHumanuse(CHMP)CommitteeforMedicinalProductsforVeterinaryuse(CVMP)Guidelineonthesterilisationofthemedicinalproduct,activesubstance,excipientandprimarycontainer药品、活性物质、辅料和内包材的灭菌指南DraftagreedbyQWPandBWPDecember2015AdoptedbyCHMPforreleaseforconsultationJanuary2016AdoptedbyCVMPforreleaseforconsultationFebruary2016Startofpublicconsultation13April2016Endofconsultation(deadlineforcomments)13October2016AgreedbyBWPJuly2018AgreedbyCATSeptember2018AgreedbyQWPandGMDPIWGOctober2018AdoptedbyCHMPforpublication15November2018AdoptedbyCVMPforpublication6December2018Dateforcomingintoeffect1October2019ThisguidelinereplacesthedocumentDecisiontreesfortheselectionofsterilisationmethods(CPMP/QWP/054/98),whichisanannextothenoteforguidanceondevelopmentpharmaceutics(CPMP/QWP/155/96);andthedocumentDecisiontreesfortheselectionofsterilisationmethods(EMEA/CVMP/065/99)whichisanannextothenoteforguidance:Developmentpharmaceuticsforveterinarymedicinalproducts(EMEA/CVMP/315/98).本指南取代了灭菌方法选择的决策树文件（CPMP/QWP/054/98），该文件是药品研发指南说明（CPMP/QWP/155/96）的附件；以及灭菌方法选择的决策树文件（EMEA/CVMP/065/99），该文件是指南说明的附件：兽药产品开发药剂学（EMEA/CVMP/315/98）。2Guidelineonsterilisationofthemedicinalproduct,activesubstance,excipientandprimarycontainer药品、活性物质、辅料和内包材的灭菌指南Tableofcontents目录1.Introduction(background)简介（背景）..............................................................................32.Scope范围..................................................................................................................................43.Legalbasis法规依据.................................................................................................................54.Generalrequirements一般要求..............................................................................................64.1.Requirementsforthemanufactureofsterilemedicinalproductsandsterilecomponents无菌药品和无菌部件的生产要求..................................................................................................64.1.1.Steamsterilisation蒸汽灭菌...............................................................................................84.1.2.Dryheatsterilisation干热灭菌.........................................................................................144.1.3.Ionizationradiationsterilisation电离辐射灭菌................................................................154.1.4.Gassterilisation气体灭菌.................................................................................................164.1.5.Sterilefiltration除菌过滤.................................................................................................184.1.6.Asepticprocessing无菌加工............................................................................................214.2.Goodmanufacturingpracticeforsterileactivesubstances,sterileexcipientsandsterilecontainers无菌活性物质、辅料和容器的良好生产规范..................................................224.2.1.Activesubstances活性物质..............................................................................................224.2.2.Excipients辅料..................................................................................................................234.2.3.Containers容器.................................................................................................................234.3.Selectionofsterilisationmethod灭菌方法的选择................................................................255.Decisiontrees决策树..............................................................................................................296.Definitions定义.......................................................................................................................327.References文献.......................................................................................................................37Keywords关键词Activesubstance,Asepticprocessing,Container,Decisiontrees,Excipients,Filtration,FinishedDosageform,Sterilisation,Sterilisationassurancelevel,Terminalsterilisation,Post-asepticprocessingterminalheattreatment.活性物质；无菌加工；容器；决策树；辅料；过滤；成品剂型；灭菌；无菌保证水平；终端灭菌；后无菌工艺的终端热处理3Executivesummary摘要Guidanceisprovidedontheselectionofappropriatemethodsofsterilisationforsterileproducts.Although,terminalsterilisationusingareferenceconditionoftheEuropeanPharmacopoeia(Ph.Eur.)isthemethodofchoicewheneverpossible,thisguidelineprovidesinformationonwhenotherterminalsterilisationprocesses,sterilisingfiltrationorasepticprocessing,(eitheraloneorwhencombinedwithanadditionalpost-asepticprocessingterminalheattreatment),couldbeacceptedasanalternative.本指南提出了无菌产品适当灭菌方法的选择。尽管使用欧洲药典（Ph.Eur）的参考条件进行终端灭菌是可能的选择方法，但本指南提供的有关其他终端灭菌工艺、除菌过滤或无菌工艺的信息（单独的或后无菌工艺终端热处理）也是可以接受的一种选择。Guidanceisprovidedonthedocumentationexpectedforsterilefinishedproducts,sterileactivesubstances,sterileexcipientsandsterileprimarycontainers(referredtoascontainerinthisguideline)inanewmarketingauthorisationapplicationoravariationapplicationforamedicinalproduct,(calledqualitydossierthroughouttheguideline).在新的上市许可申请或医药产品的变更申请（整个指南中称为质量档案）中，对无菌成品、无菌活性物质、无菌辅料和无菌内包材（本指南中称为容器）的