2024年关于美国FDA实施部分区域在生物可用性和生物等价性评估曲线下的更新
Robert Hopefl1, Yuqing Gong1, Elizabeth Bielski1
1Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clinical pharmacology and therapeutics
|January 18, 2025
概括
度与时间曲线下的部分面积 (pAUC) 越来越多地用于评估药物的生物可用性 (BA) 和生物等价性 (BE),当传统措施不足时. 本更新详细介绍了最近的美国监管申请和全球协调 pAUC 建议的努力.
科学领域:
- 药理动力学和药物新陈代谢
- 监管科学 监管科学
- 制药发展 制药发展
背景情况:
- 使用最大药物度 (Cmax) 和曲线下的总面积 (AUC) 的传统生物可用性 (BA) 和生物等价性 (BE) 评估可能无法完全捕捉所有药物配置文件的临床性能.
- 药物的药理动力学 (PK) 概况的形状可以显著影响其临床疗效和安全性,需要更细致的评估方法.
研究的目的:
- 为度与时间曲线 (pAUC) 建议下的部分面积提供一个更新的框架,基于Fang等先前的工作. 在美国食品和药物管理局.
- 讨论最近在美国对pAUC的监管应用,支持对特定药物产品的BA/BE评估.
- 突出pAUC建议的关键例子,并探索全球协调这些评估的机会.
主要方法:
- 使用pAUC框架对监管指南和产品特定指南 (PSG) 的审查和分析.
- 对特定药物产品的pAUC应用的案例研究讨论,包括洛克萨吸入粉和长效注射剂 (LAI),如乐普罗利德和戈塞林.
- 检查最近在pAUC实施和全球监管调整方面的趋势和挑战.
主要成果:
- 自2020年8月以来,使用一般的pAUC框架发布或修订了18个PSG,确保一致,科学和基于风险的建议.
- 对于各种配方,包括吸入粉末和LAI,已经证明了pAUC的成功监管应用.
- 该论文确定了需要全球协调pAUC建议的领域,以简化药物开发和监管审查.
结论:
- 曲线下的部分面积 (pAUC) 是BA/BE评估的一个有价值的工具,特别是当药物动力学形状对临床性能至关重要时.
- 更新的框架和最近的美国监管应用表明了PAUC的实际实用性和日益接受.
- 进一步的全球协调工作对于标准化pAUC建议和促进国际药物批准至关重要.
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