使用irAOP进行生物技术衍生药品和ATMP的非临床安全评估:转向系统和整体框架的范式转变
Armin Braun1,2,3,4, Susann Dehmel1,2,3
1Department for Preclinical Pharmacology and Toxicology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hanover, Germany.
Journal of immunotoxicology
|December 10, 2024
概括
新的生物疗法提供了令人兴奋的治疗可能性,但也带来了安全挑战. 免疫安全化身 (imSAVAR) 项目使用不良结果途径 (AOP) 来开发先进疗法的基于人体的安全测试.
科学领域:
- 生物技术和制药科学 生物技术和制药科学
- 免疫学和毒理学
- 监管科学 监管科学
背景情况:
- 现代生物学使得癌症和衰老等疾病的新疗法成为可能,但它们的复杂性挑战了传统的安全性评估.
- 现有的指导方针 (ICH S6 R1) 承认生物制药常规毒性测试的局限性,因为其具有独特的特性,如免疫性.
- 新方法方法 (NAM) 和非动物替代试验正在出现,正如经合组织试验指南和ICAPO所强调的那样.
研究的目的:
- 解决复杂生物制药和先进治疗药物 (ATMP) 的安全评估挑战.
- 为非临床安全性评估制定一个系统和整体的框架,重点是免疫调节疗法.
- 利用不良结果途径 (AOP) 实现以科学为基础的方法来理解和预测与免疫相关的不良结果 (irAO).
主要方法:
- 重新利用不良结果途径 (AOP) 概念来绘制与免疫相关的不良结果 (irAO).
- 专注于人类和替代体外模型的安全测试的开发和应用.
- 将对不良结果的机制性理解纳入安全评估框架.
主要成果:
- imSAVAR项目旨在建立一个框架,用于对免疫调节治疗药物的非临床安全性评估.
- 该方法强调通过AOP的机制理解,以指导相关测试系统的选择.
- 该联盟优先考虑使用和进一步开发人类和替代模型进行安全评估.
结论:
- 使用AOP的基于科学的,机械的方法对于确保新型免疫治疗药物的安全至关重要.
- imSAVAR倡议促进使用人体和替代模型来克服传统临床前安全测试的局限性.
- 这一框架支持生物制药安全的灵活,个案评估,与不断变化的监管期望保持一致.
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