对于在新药应用中溶解的连续制造和实时释放测试的监管经验
Maziar Kakhi1, Jing Li2, Angelica Dorantes2
1Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Journal of pharmaceutical sciences
|August 12, 2023
概括
对于连续制造 (CM) 和实时释放溶解测试 (RTRT-D) 的监管提交面临着共同的问题. 解决这些缺陷可以改善提交情况,并简化FDA对先进药物制造的审查.
科学领域:
- 制药科学 制药科学
- 药品制造技术 制造技术 制造技术
- 监管科学 监管科学
背景情况:
- 连续制造 (CM) 和实时释放溶解测试 (RTRT-D) 是制药生产中的先进方法.
- 美国食品和药物管理局 (FDA) 对使用这些技术的口服即时释放 (IR) 药片的监管提交日益增加.
- 从生物制药的角度对这些提交的审查对于确定挑战和机遇至关重要.
研究的目的:
- 识别CM和/或RTRT-D使用的监管提交中的常见缺陷.
- 为最佳实践提供建议,以提高提交的质量.
- 通过减少监管审查负担,促进更广泛地采用先进制造.
主要方法:
- 审查和分析关于红外线片的CM和RTRT-D对FDA的历史监管提交.
- 对确定提交的生物制药评估,以确定反复出现的问题.
- 在采样策略,实验设计,溶解建模,文档和体外方法中发现常见缺陷.
主要成果:
- 发现了一些常见的缺陷,包括药物产品单元的分层抽样计划不足.
- 经常观察到不适当的实验设计 (DoE) 和RTRT-D模型预测溶解变量的局限性.
- 不足够的文档和不合适的体外溶解方法也被认为是普遍存在的问题.
结论:
- 解决采样,DOE,RTRT-D建模,文档和溶解方法中发现的缺陷是必不可少的.
- 实施推的最佳实践可以提高CM和RTRT-D监管提交的质量.
- 推进这些制造方法需要共同努力,以克服监管障碍并充分发挥其潜力.
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