摘要
致癌性试验是药物非临床安全性评价的重要内容之一。当前国内外普遍采用并认可基于ICH S1B指南建立的药物非临床致癌性试验替代方案。遗传修饰致癌性小鼠模型是替代方案中“卡脖子”的关键技术问题。从1997年ICH S1B指南发布至今,我国制药行业主要依赖进口获得小鼠模型,其价格高昂、进口周期长、条件严苛,且由于模型资源唯一,制药行业承受着成本高昂和供应链不稳的双重压力。本文概述了国内外致癌性试验相关指导原则,介绍了国内外主要的致癌性小鼠模型,包括Tg.rasH2、KI.C57-ras、p53^(+/-)小鼠等的构建、验证与应用历程,并展望了建立我国自主知识产权的致癌性小鼠模型以及标准化生产供应的途径。
The assessment of carcinogenicity is a pivotal element in the preclinical safety evaluation of pharmaceuticals.The alternative approach to non-clinical carcinogenicity assessment,as outlined in the ICH S1B guidelines,is widely endorsed both domestically and internationally.However,the development of genetically modified mouse models for carcinogenicity poses significant technical challenges within this alternative approach.Since the issued of the ICH S1B guidelines in 1997,China's pharmaceutical industry has heavily relied on costly and lengthy imports from overseas,which are subject to stringent conditions.Moreover,due to monopolied resources being controlled by Western countries,the pharmaceutical industry faces mounting pressure from high costs and unstable supply chains.This article outlines relevant guidelines for carcinogenicity evaluation at home and abroad,introduces the global development,validation,and application history of major carcinogenicity mouse models such as Tg.rasH2,KI.C57-ras V2.0,p53^(+/-) mice;it also looks ahead to establishing independent intellectual property rights for domestically produced carcinogenicity mouse models while standardizing their production and supply.
作者
刘甦苏
凌晨
耿兴超
王三龙
范昌发
LIU Su-su;LING Chen;GENG Xing-chao;WANG San-long;FAN Chang-fa(Institute for Laboratory Animal Resources,National Institutes for Food and Drug Control,National Rodent Laboratory Animal Resources Center;National Center for Drug Safety Evaluation and Monitoring,National Institutes for Food and Drug Control,Beijing Key Laboratory for Non-clinical Safety Evaluation of Drugs)
出处
《中国食品药品监管》
2024年第6期16-31,共16页
China Food & Drug Administration Magazine
基金
国家重点研发计划(2023YFC3402000-002)
药品监管科学全国重点实验室课题(2023SKLDRS0124)。
关键词
药物致癌性试验
致癌性小鼠模型
指导原则
遗传修饰动物模型
pharmaceutical carcinogenicity test
carcinogenicity mouse model
guidelines
genetically modified animal models
