复方中药国际化开发实例分析  

Case Study of Compound Traditional Chinese Medicine Globalization

作　　者：孙鹤 郭治昕 李凌艳 章顺楠 何毅 马晓慧 王根辈 王平 杨柳 

机构地区：[1]天士力控股集团/创新中药关键技术国家重点实验室,天津300410

出　　处：《世界科学技术-中医药现代化》2017年第6期914-923,共10页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：科学技术部国家"重大新药创制"科技重大专项(2008ZX09401-006):以现代中药为主;面向国际的创新药物研究与开发技术体系建设;负责人:闫希军

摘　　要：复方中药作为植物药向美国食品药品监督管理局(U.S.Food and Drug Administration,FDA)申报新药是一项开拓工程、系统工程和创新工程,复方丹参滴丸是中国中药产品进行国际化开发的标杆及典范,是中国自主研发的第一个完成FDA国际多中心Ⅲ期临床试验的创新药,是全球第一个顺利完成FDA国际多中心Ⅲ期临床试验的复方中药产品。二十年磨一剑的复方丹参滴丸国际化历程,跌宕起伏,探索了一条中国中药产品进行国际化开发的道路,从中积累了大量宝贵的中医药国际化经验。天士力在复方丹参滴丸FDA申报过程中,在符合FDA法规的同时也充分考虑到了复方中药的特点,明确了产品适应症,采用国际金标准科学、并创新的制定了临床试验方案,顺利完成了Ⅱ期探索性临床研究,成功获得了Ⅲ期临床试验SPA,并最终顺利完成了国际多中心Ⅲ期临床试验。申报过程中,天士力不断完善标准和路径,引入了多项创新,比如非线性多因素回归模型的应用、符合中药特点的临床试验设计、中药药物相互作用的鸡尾酒方法学研究、复方中药指纹图谱研究、复方中药质量一致性研究、生物效价研究以及数据统计方法的创新等。复方丹参滴丸的国际化历程,是天士力与美国FDA共同创新现代中药标准、完善天然药物产业链GMP体系、突破技术瓶颈、创新法规路径和提升产品价值的持续创新和共同创造历史的过程,是中国国家力量的展现,是人类医药历史的进步。Compound Traditional Chinese Medicine （CTCM） applying for FDA approval as botanical drug is a systemic and innovative work. Compound Danshen Dripping Pill （T89） is the first CTCM completed FDA global multi-center Phase III clinical trial, which has become a benchmark for TCM globalization. Extensive experiences have been accumulated through the 20 years＇ research and development. Tasly fully considered the characteristics of CTCM while complying with FDA regulations during the entire application process. In which, product indication was clearly defined and agreed, clinical trial protocol was scientifically and innovatively designed with gold standard, phase Ⅱ study was well completed, SPA for phase Ⅲ study was obtained, and eventually the global multi-center phaseⅢ study was successfully completed. In order to better support T89＇ s application, Tasly conducted series of additional studies and introduced many innovations, such as drug-drug interaction study for TCM, finger printing study for CTCM, quality consistency study, biological assay study and etc. Globalization of T89 is not only a product creating history, but also a process for Tasly and the US FDA working together to continuously innovate and create history in innovating modern TCM standards, improving industrial chain GMP system for botanical drugs, making technical breakthroughs, exploring regulatory pathways and increasing product value. It represents the national power and historical progress in medicine.

关 键 词：复方中药 复方丹参滴丸 T89 国际化 FDA申报 

分 类 号：R289[医药卫生—方剂学]