制造过程转移到30公斤/小时的连续直压线,实时监控组合
Adam Waněk1, Lorenzo Menarini2, Federica Giatti2
1Zentiva, k.s., U Kabelovny 130, Prague 10, Czech Republic; Department of Chemical Engineering, University of Chemistry and Technology, Prague, Technická 5, Prague 6, Czech Republic.
International journal of pharmaceutics
|April 12, 2024
概括
将制药生产转变为连续制造 (CM) 是可以在没有监管变更的情况下实现的. 这项研究证明了批量向CM转移的成功,保持了产品质量,并使有效的药物生产能够进行实时监控.
科学领域:
- 制药制造业 制药制造业 制药制造业
- 化学工程是化学工程的重要组成部分.
- 过程分析技术 过程分析技术
背景情况:
- 将现有制药产品从批量制造转移到连续制造 (CM) 提出了重大监管和技术挑战.
- 在保持关键质量属性的同时,CM提供了潜在的好处,如提高生产率和提高设备利用率.
- 使用过程分析技术 (PAT) 实时监测关键质量属性,例如近红外 (NIR) 探测器,对于CM至关重要.
研究的目的:
- 报告现有市场化药品从批量转移到连续制造的成功转移,而不改变配方或监管注册.
- 调查和优化连续粉末混合的设计和操作参数,以实现过程的重复性.
- 开发和验证基于NIR的多变量数据模型,用于在线成分监测,并评估其性能与传统质量控制方法相比.
主要方法:
- 系统地调查连续粉末混合参数 (型,率,动态保留,停留时间) 以确保过程的重复性.
- 基于近红外 (NIR) 的多变量数据模型的开发和验证,用于实时在线组合监测.
- 进行长期连续制造试验 (每小时30公斤的吞吐量320分钟),以验证工艺传输和数据模型.
主要成果:
- 已有的药物产品成功地从批量转移到连续制造,而没有改变配方.
- 连续粉末混合参数被系统地优化为过程重复性.
- 一个经过验证的基于NIR的多变量模型准确地实时监测了平板电脑含量的一致性.
- 与批量生产的药片相比,通过连续制造生产的药片表现出相当的分解和溶解特性.
结论:
- 成功地将批量制造转换为连续制造,证明了在不经监管重新注册的情况下,为现有药品采用CM的可行性.
- 连续粉末混合和基于NIR的实时监测是强大和高效的连续制药生产的关键技术.
- 这种方法确保了产品质量的等价性,在生产效率和设备利用方面提供了显著的优势.
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