化学原料药生产起始物料的选择和论证要求思考.docx

Reflection paper on the requirements for selection and justification of starting materials for the manufacture of chemical active substances化学原料药生产起始物料的选择和论证要求思考Agreed by CHMP/CVMP Quality working party11 July 2014Adoption by CHMPSeptember 2014Adoption by CVMPSeptember 2014KeywordsStarting material, active substance.关键词起始物料、活性物质Introduction:?概述This reflection paper aims to clarify some of the expectations of EU competent authorities arising from the guidance found in ICH Q11 (Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities)1 regarding the information to be submitted in marketing authorisation dossiers to justify the selection of starting materials.Whilst ICH Q11 is not generally applicable to veterinary products, the principles outlined in this document should apply equally for active substances destined to treat both humans and animals. The document re-produces extracts from section 5 of ICH Q11?verbatim?in black text, and provides subsequent commentary on EU expectations in the form of explanatory notes within grey-shaded boxes.本思考文章目的是澄清由ICH Q11指南（原料药研发和生产（化学实体和生物技术/生物制品实体））引出的，关于上市许可文件提交的用于论述起始物料选择的资料中，欧盟药监机构的态度。尽管ICH Q11并没有普遍应用于兽药产品，在本文中列出的原则还是同样适用于人兽共用活性物质。文件中摘要的ICH Q11第5部分内容以黑体字表示，相应的欧盟态度的解说以注释形式放在灰色阴影方框中。It should be recognised that this document is not intended as a revision of ICH Q11, and rather as a reflection paper within the EU medicines regulatory network as prepared by the Quality Working Party (QWP).读者应知本文并无意作为ICH Q11的修订版本，而只是由质量工作组起草，反映了欧盟药监机构网络的思考的文章。Problem statement:?问题说明Disagreements between applicants and quality assessors on the suitability of proposed starting materials have become more frequent in recent times. This suggests that the current guidelines,1-3 intentionally high level to allow application to the wide range of chemical syntheses submitted to regulatory authorities, are open to interpretation. Furthermore, it is increasingly common for applicants to propose very short syn