男性生殖系统用药生殖毒性评价的监管要求和关注要点  

The regulatory requirements and points to consider for the developmental and reproductive toxicity assessment for male reproductive system medicines

作　　者：周植星 陈美灵 张晓东 崔岚 黄芳华 ZHOU Zhi-xing;CHEN Mei-ling;ZHANG Xiao-dong;CUI Lan;HUANG Fang-hua(Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国临床药理学杂志》2023年第21期3183-3192,共10页The Chinese Journal of Clinical Pharmacology

摘　　要：男性生殖系统用药的生殖毒性评价具有特殊性,需要关注雄性生殖毒性风险,还需关注雄性介导的发育毒性风险。对于男性生殖系统用药,需基于其特殊性,具体问题具体分析,综合受试物的药理/毒理作用机制、同类药物信息、组织分布(精液分布)、适应证特点等因素来开展合适的生殖毒性试验。不同适应证对于生殖毒性风险的接受程度不同,需根据相关试验结果进行获益-风险综合评价,制定相应的风险管控措施,以降低临床试验中受试者和临床应用中患者的生殖毒性风险。本文阐述了国际人用药品注册技术要求协调会和监管机构相关指导原则的相关要求,梳理分析已批准上市男性生殖系统用药的生殖毒性研究情况,并在此基础上提出了男性生殖系统用药生殖毒性评价需要关注的要点。The developmental and reproductive toxicity assessments of male reproductive system medicines have their particularities,which should be paid attention to the risk of male reproductive toxicity and the risk of male-mediated developmental toxicity.For these kinds of medicines,based on their particularities and case-by-case,it is necessary to comprehensive analysis of pharmacological/toxicological mechanism of action,the information of similar class drugs,tissue distribution(semen distribution),indication characteristics etc,and carry out appropriate developmental and reproductive toxicity studies.Considering that different indications have diferent acceptance degrees for developmental and reproductive toxicity risks,it is necessary to conduct a comprehensive benefit-risk assessment based on results of relevant studies,and formulate corresponding risk management and control measures to reduce the risk of reproductive toxicity of subjects in clinical trials and patients in clinical uses.This article described requirements of relevant guidelines of ICH and various regulatory agencies,summaried and analyzed the developmental and reproductive toxicity studies of male reproductive system medicines approved,and on these basis,proposed some points to consider for the developmental and reproductive toxicity assessment for male reproductive system medicines.

关 键 词：男性生殖系统用药 生殖毒性 风险评价 获益-风险评估 

分 类 号：R97[医药卫生—药品]