通过"适合目的"建模,推进药物开发,采用知情的方法
Jennifer Sheng1, Tongli Zhang2
1College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
Journal of pharmacokinetics and pharmacodynamics
|September 15, 2025
概括
基于模型的药物开发 (MIDD) 提供了一个战略蓝图,将工具与药物开发问题保持一致. 该框架增强了目标识别,临床试验设计和生命周期管理,整合了像人工智能这样的新兴技术.
科学领域:
- 药理计量和药物开发研究
- 计算生物学和生物信息学
背景情况:
- 基于模型的药物开发 (MIDD) 对药物开发和监管决策至关重要.
- 现有的MIDD策略需要在所有开发阶段与关键利益问题 (QOI) 和使用内容 (COU) 进行战略调整.
研究的目的:
- 提出一个战略蓝图,将MIDD工具与QOI,COU以及整个药物开发生命周期的模型影响结合起来.
- 为了说明MIDD在目标识别,优化,临床前准确性,第一人 (FIH) 研究,临床试验设计和市场后支持方面的应用.
主要方法:
- 审查和综合当前的MIDD实践和工具.
- 强调常见的建模方法:QSAR,PBPK,PK/PD,PPK/ER和QSP.
- 探索MIDD与新兴技术 (AI,ML) 的整合及其在监管评估中的实用性 (例如,505b) 和仿制药).
主要成果:
- 从早期发现到批准后的标签更新,在各种开发阶段证明了MIDD的应用.
- 展示了MIDD在优化临床试验设计,剂量和理解人群药理动力学/暴露-反应 (PPK/ER) 中的作用.
- 讨论了MIDD在监管互动,资产收购方面的作用,以及其与AI/ML的不断演变的整合.
结论:
- 战略蓝图有效地使MIDD工具与发展需求保持一致,提高效率和监管支持.
- MIDD能够适应新兴技术和多样化的监管途径,为药物开发提供了巨大的潜力.
- 解决资源分配和组织调整等挑战是进一步扩大MIDD影响的关键.
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