EUGMPAnnex15QualificationandValidation

EUGMPannex15QualificationandValidation(draft)Page1/29Brussels,6February2014SANCO/TSE/Thereceivedcontributionstogetherwiththeidentityofcontributorswillbemadepubliclyavailable,unlessthecontributorobjectstopublicationofhisorherpersonaldataonthegroundsthatsuchpublicationwouldharmhisorherlegitimateinterests.Inthiscasethecontributionmaybepublishedinanonymousform.Otherwisethecontributionwillnotbepublishednorwill,inprinciple,itscontentbetakenintoaccount.Formoreinformationontheprocessingofyourpersonaldatainthecontextofthisconsultation,readthespecificPrivacyStatementavailableat:linktoPrivacyStatementEudraLexTheRulesGoverningMedicinalProductsintheEuropeanUnionVolume4EUGuidelinesforGoodManufacturingPracticeforMedicinalProductsforHumanandVeterinaryUseAnnex15:QualificationandValidation欧盟人用及兽用药品GMP指导原则附件15：确认和验证Legalbasisforpublishingthedetailedguidelines:Article47ofDirective2001/83/EContheCommunitycoderelatingtomedicinalproductsforhumanuseandArticle51ofDirective2001/82/EContheCommunitycoderelatingtoveterinarymedicinalproducts.Thisdocumentprovidesguidancefortheinterpretationoftheprinciplesandguidelinesofgoodmanufacturingpractice(GMP)formedicinalproductsaslaiddowninDirective2003/94/ECformedicinalproductsforhumanuseandDirective91/412/EECforveterinaryuse.Statusofthedocument:Revision1文件状态：修订EUGMPannex15QualificationandValidation(draft)Page2/29Proposeddocumenttimetable:DeadlineforcommentsonthedraftconceptpaperFebruary2013DraftguidelinediscussionintheGMDPIWGJune2013DraftguidelinediscussionwithothergroupsJune-September2013CommentsbyGMDPIWGandPIC/SOctober2013AdoptionofFinalDraftforpublicconsultation-DelayedduetoadditionalGMDPIWGcomments2014(November2013)-JanuaryStartofpublicconsultation-delayed(December2013)-February2014Endofpublicconsultation(deadlineforcomments)(March2014)-May2014Re-discussioninGMDPIWGSeptember2014ExpectedadoptionbyECOctober2014Reasonsforchanges:UpdateasperconceptpaperonrevisionofAnnex15.Summaryofchanges:Thischangetoannex15takesintoaccountchangestoothersectionsoftheEU-GMPGuidePartI,Annex11,ICHQ8,Q9,Q10andQ11,QWPguidanceonprocessvalidationandchangesinmanufacturingtechnology.变更概述：附件15的变更综合考虑了EUGMP第一部分附件11，ICHQ8,Q9,Q10andQ11,QWP指南中关于工艺验证的变更内容以及生产技术的变化。Deadlineforcomingintooperation:tobedetermined.生效时间：待定EUGMPannex15QualificationandValidation(draft)Page3/29重要的修订内容：本附件综合了ICHQ8制药研发，Q9质量风险管理，Q10制药质量体系，Q11原料药研发制造的内容。引入新的术语，例如进行中验证策略（ongoingvalidationstrategy）；回顾性验证和再验证的概念已经删除；在设备使用中，关于设备确认的信息几乎被忽略；增加运输确认的命名，包装验证；设施验证和分析方法验证有新的要求；工艺验证有2种不同的方法，一种是现代的“持续验证”方法，另一种是传统方法。但在任何情况下，应当证明工艺的耐用性；工艺验证的分组方法（Bracketingapproaches）；在工艺持续确认与传统工艺验证之间的混合方法仍然有些模糊（fuzzy）；关于清洁验证的“清洁”标准不再是唯一的标准；设备清洁验证的分组具有了明确的可能性，但需要创建；清洁验证的接受标准取绝于毒理数据PDE(permitteddailyexposure每天允许暴露量)；清洗验证的批次根据风险评估来决定，不在强求进行3个批次；生产批次很少的产品，对于清洁验证的理念也有了新的要求；要求研究和制定的清洁后的有效期；EUGMPannex15QualificationandValidation(draft)Page4/29Tableofcontent目录Principle原则......................................................................................................................................................5General通则........................................................................................................................................................51ORGANISINGANDPLANNINGFORQUALIFICATIONANDVALIDATION..................................6确认、验证的组织和计划....................................................................................................................................62DOCUMENTATIONINCLUDINGVMP文件，包括VMP.....................................................................73QUALIFICATIONSTAGESFOREQUIPMENT,FACILITIESANDUTILITIES................................8设备、设施和公用系统确认阶段........................................................................................................................84PROCESSVALIDATION工艺验证........................................................................................................125VERIFICATIONOFTRANSPORTATION运输确认............................................................................196VALIDATIONOFPACKAGING包装验证.............................................................................................197VALIDATIONOFUTILITIES公用系统验证..........................................................................................208VALIDATIONOFTESTMETHODS检验方法验证..............................................................................209CLEANINGVALIDATION清洁验证.......................................................................................................2010RE-QUALIFICATION再确认...............................................................................................................2311CHANGECONTROL变更控制...........................................................................................................24GLOSSARY术语..............................................................................................................................................25EUGMPannex15QualificationandValidation(draft)Page5/29QUALIFICATIONANDVALIDATION确认和变更Principle原则ThisAnnexdescribestheprinciplesofqualificationandvali