药物杂质的毒理学评价要求及进展.pdfVIP

C h in e se Jo u rna l o f N ew D rug s 20 10, 19 (24 ) , , , (山东省药品检验所, 济南 2 0101) [] 药物原料或制剂中的杂质可能引起临床不良反应杂质毒 学评价是药物研究的重要内容 ICH 关于药物及制剂杂质方面指导原则规定了杂质的报告鉴定和质控限度, 含量超过质控限度的杂质应进 行毒 学评价但指导原则对于研发阶段的药物杂质和遗传毒性杂质的限度未作明确要求EMEA 对于遗 传毒性杂质制定了专门的指导原则, 引入了毒 学担忧阈值(TTC) 的概念对遗传毒性杂质限度进行控制, 遗 传毒性杂质每日接触量应小于 1. gFDA 也推荐采用 TTC 原则控制遗传毒性和致癌性杂质本文结合 ICH, EMEA 及美国FDA 等指导原则, 对药物杂质毒 学评价的要求及其进展进行了综述 [] 杂质; 毒 学评价; 遗传毒性; 毒 学担忧阈值 [] R96 . 3 [] A [] 1003- 3734( 2010) 24- 2271- 06 Gu idelin es and recen t developm en ts of toxicological assessm en t of im purities in pharm aceu tical products ZHU Q ingfen, LIT ao, GUO M ing, LI Jun (Shandong Institutef or Drug Control, Jinan 2 0101, China) [ Abstract] Impurities in pharmaceutical drug substances and drug products may be harm ful to humans. It is mi portant to establish the safety of the mi purities. ICH haspublished general gu idelines on the quality and safety assessment of mi purities in pharmaceutical drug substances and drug products. The threshold of mi purities for re porting, identifying and qualifying w ere listed in these gu idelines. The safety of the mi purity must be established w hen its content reaches the qualification threshold. How ever, a number of mi portant issues are not addressed in the gu idelines, for example, the acceptable levels of mi purities in drugs under development and that of genotoxic mi purities. Based on the concept ofThreshold ofToxicological Concern (TTC), EMEA has published a gu ideline focusing on the lmi its for genotoxic mi purities. The TTC conceptw as also recommended in the recent gu idance for genotoxic and carcinogenic mi puritiespu lishd byU. S. FDA. In th is article, w e review ed the guidelines and recent developm