机械建模和模拟方法论对非口服药品产品特定产品指导制定的影响
Steven G Chopski1, Ross L Walenga1, Ming-Liang Tan1
1Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
CPT: pharmacometrics & systems pharmacology
|July 24, 2025
概括
机械模型帮助FDA制定非口服药物的生物等价性 (BE) 建议. 与生理学基础的药理动力学 (PBPK) 模型一样,in silico方法支持复杂的药物递送系统的产品特定指南 (PSG).
科学领域:
- 药理动力学和药物输送方法
- 计算机建模和模拟
- 监管科学 监管科学
背景情况:
- 美国食品和药物管理局 (FDA) 发布产品特定指南 (PSG),对仿制药提出生物等价性 (BE) 建议.
- 对于非口服产品 (如注射剂,吸入剂,局部,眼科,鼻腔) 确定BE是具有挑战性的,因为传统方法的局限性.
- 机械建模,包括基于生理学的药理动力学 (PBPK) 和计算流体动力学 (CFD) 模型,对于这些复杂的药物产品越来越重要.
研究的目的:
- 讨论在非口服药品的PSG开发中使用in silico方法的应用.
- 突出模型整合证据在支持仿制药开发监管决策中的作用.
- 展示各种非口服药物类别生物等价性评估的建模和模拟 (M&S) 方面的进展.
主要方法:
- 对FDA产品特定指南 (PSG) 的审查及其依赖机械模型.
- 分析涉及PBPK和CFD模型进行非口服药物产品BE评估的案例研究.
- 检查最近PSG中的建模和模拟 (M&S) 建议,特别是对于口服吸入产品.
主要成果:
- 机械建模方法是开发非口服药物的BE方法和标准在PSG中不可或缺的组成部分.
- 最近的一项Formoterol fumarate; glycopyrrolate inhalation metered aerosol的M&S使用例证了口服吸入产品的M&S使用,影响了其他16个PSG.
- PBPK模型成功地支持了对局部产品的修订PSG建议,减少了广泛的体外和人体研究的需要.
结论:
- 在 silico 方法,特别是 PBPK 和 M&S,对于推动 PSG 开发非口服药品至关重要.
- 这些先进的建模技术为药物输送提供了洞察力,并支持强大的BE评估,可能简化仿制药的批准.
- 预计M&S的持续开发和应用将进一步加强复杂药物配方的监管科学.
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