欧盟GMP附录15：确认与验证(修订版英文+中文)

EUROPEANCOMMISSIONENTERPRISEDIRECTORATE-GENERALSinglemarket,regulatoryenvironment,industriesunderverticallegislationPharmaceuticalsandcosmeticsBrussels,30March2015EudraLex欧盟药品管理法Volume4EUGuidelinesforGoodManufacturingPracticeforMedicinalProductsforHumanandVeterinaryUse第四卷欧盟人用和兽用药品GMP指南Annex15:QualificationandValidation附录15:确认和验证Legalbasisforpublishingthedetailedguidelines:Article47ofDirective2001/83/EContheCommunitycoderelatingtomedicinalproductsforhumanuseandArticle51ofDirective2001/82/EContheCommunitycoderelatingtoveterinarymedicinalproducts.Thisdocumentprovidesguidancefortheinterpretationoftheprinciplesandguidelinesofgoodmanufacturingpractice(GMP)formedicinalproductsaslaiddowninDirective2003/94/ECformedicinalproductsforhumanuseandDirective91/412/EECforveterinaryuse.发布该细化指南的法律依据:人用药物欧共体法案指令2001/83/EC第47章和兽用药物欧共体法案指令2001/82/EC第51章。本文件为人药GMP指令2003/94/EC以及兽药GMP指令91/412/EEC的原则和指南提供诠释。第2页共32页Statusofthedocument:Revision文件状态：修订版Reasonsforchanges:SinceAnnex15waspublishedin2001themanufacturingandregulatoryenvironmenthaschangedsignificantlyandanupdateisrequiredtothisAnnextoreflectthischangedenvironment.ThisrevisiontoAnnex15takesintoaccountchangestoothersectionsoftheEudraLex,Volume4,PartI,relationshiptoPartII,Annex11,ICHQ8,Q9,Q10andQ11,QWPguidanceonprocessvalidation,andchangesinmanufacturingtechnology.变更原因：从2001年附录15发布以后，制药生产和法规环境都有了显著变化，需要相应的更新来反映变化的环境。本文对附录15所做的修订考虑了欧盟法规第四卷第一部分质量管理和第二部分活性物质作起始物料以及附录11计算机化系统的验证、ICHQ8药物研发、ICHQ9质量风向管理、ICHQ11药物研发和生产、质量工作组的工艺验证指南和生产技术的变化。Deadlineforcomingintooperation:1October2015最终实施日期：2015年10月1日第1页共33页目录原则..................................................................................................................2概述..................................................................................................................31.确认和验证的组织和计划...........................................................................32.文件，包括验证主计划...............................................................................53.设备、设施、公用工程和系统的确认阶段..................................................75.工艺验证..................................................................................................106.运输确认..................................................................................................197.包装验证..................................................................................................208.公用工程的确认.......................................................................................209.检验方法验证...........................................................................................2110.清洁验证...............................................................................................2111.变更控制...............................................................................................2512.词汇表...................................................................................................26第2页共32页PrincipleThisAnnexdescribestheprinciplesofqualificationandvalidationwhichareapplicabletothefacilities,equipment,utilitiesandprocessesusedforthemanufactureofmedicinalproductsandmayalsobeusedassupplementaryoptionalguidanceforactivesubstanceswithoutintroductionofadditionalrequirementstoEudraLex,Volume4,PartII.ItisaGMPrequirementthatmanufacturerscontrolthecriticalaspectsoftheirparticularoperationsthroughqualificationandvalidationoverthelifecycleoftheproductandprocess.Anyplannedchangestothefacilities,equipment,utilitiesandprocesses,whichmayaffectthequalityoftheproduct,shouldbeformallydocumentedandtheimpactonthevalidatedstatusorcontrolstrategyassessed.ComputerisedsystemsusedforthemanufactureofmedicinalproductsshouldalsobevalidatedaccordingtotherequirementsofAnnex11.TherelevantconceptsandguidancepresentedinICHQ8,Q9,Q10andQ11shouldalsobetakenintoaccount.原则本附录描述了确认与验证的基本原则，适用于药品生产中的设施、设备、公用系统及工艺,也可以用于第四卷第二部分《活性物质作起始物料》的附加要求中没有介绍部分的补充性、选择性指南。GMP要求生产商应通过确认和验证对整个生命周期内的产品和工艺涉及的关键操作中的关键因素来进行控制。所有影响产品质量的计划性变更（含设施、设备、工艺系统和工艺），都应当有正式文件或记录，并评估其对验证状态或是控制策略的影响。用于药品生产的计算机化系统也应根据附录11的要求进行验证。同时，应当考虑现行的ICHQ8、Q9、Q10、Q11中的相关理念和指南要求。GeneralAqualityriskmanagementapproachshouldbeappliedthroughoutthelifecycleofamedicinalproduct.Aspartofaqualityriskmanagementsystem,decisionsonthescopeandextentofqualificationandvalidationshouldbebasedonajustifiedanddocumentedriskassessmentofthefacilities,equipment,utilitiesandprocesses.Retrospectivevalidationisnolongerconsideredanacceptableapproach.Datasupportingqualificationand/or第3页共32页validationstudieswhichwereobtainedfromsourcesoutsideofthemanufacturersownprogrammesmaybeusedprovidedthatthisapproachhasbeenjustifiedandthatthereisadequateassurancethatcontrolswereinplacethroughouttheacquisitionofsuchdata.概述质量风险管理的方法应作为质量风险管理系统的一部分贯穿于药品的整个生命周期，应基于对设施、设备、公用系统和工艺的论证和书面风险评估决定确认和验证的范围和程度。回顾性验证不再被认为是可接受的方式。如果方法经过论证，并且获取数据的整个过程中有足够的保证性控制措施，也可以使用从生产商自身程序以外获得的用于支持确认和/或验证研究的数据。1.ORGANISINGANDPLANNINGFORQUALIFICATIONANDVALIDATION1.确认和验证的组织和计划1.1.Allqualificationandvalidationactivitiesshouldbeplannedandtakethelifecycleoffacilities,equipment,utilities,processandproductintoconsideration.1.1.所有的确认