生物制品非临床研究中的安全药理学考虑  

Safety Pharmacology Consideration in Non-Clinical Research of Biopharmaceuticals

作　　者：王庚莉 张冬霞 张引航 冯斐斐[1] 张巧[1] 姜德建[3] 张素才 Wang Gengli;Zhang Dongxia;Zhang Yinhang;Feng Feifei;Zhang Qiao;Jiang Dejian;Zhang Sucai(College of Public Health,Zhengzhou University,Zhengzhou 450066,China;JOINN Laboratories(China)Co.,Ltd.,Beijing 100176,China;Central South University Lotus Laboratories,Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Dru gs,Changsha 410331,China)

机构地区：[1]郑州大学公共卫生学院,郑州450066 [2]北京昭衍新药研究中心股份有限公司,北京100176 [3]中南大学芙蓉实验室,新药药效与安全性评价湖南省重点实验室,长沙410331

出　　处：《中国药事》2024年第11期1247-1262,共16页Chinese Pharmaceutical Affairs

基　　金：国家重点研发计划资助项目(编号2021YFC2302505)。

摘　　要：目的:通过分析2013-2023年FDA批准上市的生物制品信息,结合实践经验,从生物制品的安全药理学研究的必要性、可行性及试验设计等方面提供一些建议,为其进入临床试验提供支持。方法:本文汇总了2013-2023年期间FDA批准的133个生物制品许可申请,包括非临床安全药理学、药理毒理信息以及临床研究中的不良反应等数据,通过分析单独开展、伴随开展和未开展安全药理学试验的原因来讨论安全药理学试验的必要性和可行性,以及分析是否存在相关动物种属、靶点相关风险以及核心组合试验要点等来探讨生物制品安全药理学研究的关注点。结果与结论:基于2013至2023年间FDA核准上市的生物制品信息以及生物制品安全药理学相关指导原则要求等,本文得出生物制品是依赖于药理学作用、是否有相关动物种属、靶点特征、适应证和相关药物上市信息等决定是否进行非临床安全药理学试验,包括单独开展、伴随开展还是豁免安全药理学研究,并且制定合理的安全药理学试验方案。生物制品的安全药理学评估通常与一般毒理学研究伴随进行,且此趋势日益显著。鉴于成本效益及动物福利3R原则,建议将生物制品的安全药理学研究整合至重复给药毒性研究中,但需注意研究设计的复杂性,包括动物数量、采样频率、毒代动力学采血干扰及动物驯化难度等挑战,确保关键指标如ECG和血压的精确测定,以保障研究的高效性。Objective:By analyzing the information of biopharmaceuticals approved by FDA for marketing in 2013-2023 and combining with practical experience,some suggestions are provided from the aspects of necessity,feasibility and trial design of safety pharmacology study of biopharmaceuticals,in order to provide supports for their entry into clinical trials.Methods:In this paper,133 applications for biopharmaceuticals licensing approved by FDA during 2013-2023 were summarized,including non-clinical safety pharmacology,pharmacological and toxicological information,adverse reactions in clinical studies and other data.The necessity and feasibility of safety pharmacology tests were discussed by analyzing the reasons for conducting safety pharmacology tests alone,concomitantly with and without conducting safety pharmacology tests,and discussed the concerns of safety pharmacology studies of biopharmaceuticals by analyzing whether there are relevant animal species,target-related risks and key points of core battery tests.Results and Conclusion:Based on the information of biopharmaceuticals approved by FDA for marketing between 2013 and 2023 and the requirements of relevant guidelines on safety pharmacology of biopharmaceuticals,this paper concludes that biopharmaceuticals rely on pharmacological effects,the presence of relevant animal species,target characteristics,indications,and relevant drug market information to determine whether to conduct non-clinical safety pharmacology trials,including conducting them separately,conducting them concurrently,or exempting safety pharmacology studies,and developing a reasonable safety pharmacology trial plan.Safety pharmacology assessments of biopharmaceuticals are often conducted concomitantly with general toxicology studies,and this trend is becoming increasingly apparent.In view of the cost-effectiveness and 3R principles of animal welfare,it is recommended to integrate the safety pharmacology study of biopharmaceuticals into the repeated-dose toxicity study,but attention should be paid t

关 键 词：生物制品 安全药理学试验 心血管系统 中枢神经系统 呼吸系统 

分 类 号：R96[医药卫生—药理学]