药物杂质遗传毒性评价策略与监管研究

伴随大量创新及仿制药面世而来的是对遗传毒性杂质加强监管的迫切需求。一系列与国际接轨的指南性文件的出台,弥补了我国杂质监管的空白,但难点尚存。传统评价方法具有局限性,新方法与传统方法间缺乏一致性比较,药物特定合成路线实际产生的大量含警示结构杂质缺乏毒理学评价数据支持,毒性预测软件的预测效力不足等。本文就国内外杂质遗传毒性杂质监管科学现状、遗传毒性杂质控制策略、杂质遗传毒性评价方法进行论述,并提出充分结合计算机毒理学、毒性评价方法和符合我国国情的监管限度制定三个维度开展杂质监管工作。

Strategy and Regulatory Research for Genotoxicity Evaluation of Impurities

Along with the emergence of a large number of innovations and generic drugs, there is an urgent need to strengthen the regulation of genotoxic impurities. The introduction of a series of guide documents that are in line with international standards has made up for the gap in the regulation of impurities in China, while the difficulties still exist. For instance, the limitations of traditional evaluation methods, the lack of consistency comparison between the new method and the traditional method, the lack of non-toxicological data of a large number of synthetic structure-containing impurities generated during the synthetic routes, and the insufficient predictive effectiveness of the toxicity prediction softwares. This article discussed the current regulation status of genotoxic impurities domestic and abroad, the control strategies of genotoxic impurities, and the genotoxicity evaluation methods for impurities. In addition, in silico toxicology, toxicity evaluation methods and regulatory limits in line with China''s national conditions should be combined in three dimensions was proposed for the supervision of impurities.