结合描述性和预测性建模,系统地设计基于深度过的生物产品收获过程
Peter Liu1, Michael Hartmann2, Ajay Shankaran1
1Biologics Process Research and Development, Merck & Co., Inc., Kenilworth, New Jersey, USA.
Biotechnology and bioengineering
|June 5, 2024
概括
生物制品生产的进步压力深度过. 混合建模方法预测过器的性能,加速开发和减少实验负载,以实现稳健的收获过程.
科学领域:
- 生物工艺工程 生物工艺工程
- 分离科学 分离科学
- 计算机建模 计算建模
背景情况:
- 强化上游生物处理导致细胞碎片增加,在生物制造中挑战深度过.
- 目前深度过的发展依赖于资源密集的选,受限于料流的变化和缺乏预测工具.
- 现有的半经验性污染模型是描述性的,阻碍了它们在指导过程开发中的应用.
研究的目的:
- 开发一种预测建模方法,用于生物收获的深度过性能.
- 将机械污染见解与计算预测能力相结合.
- 为深度过开发建立一个强大的平台战略.
主要方法:
- 开发了一种混合建模方法,将机械化污染模型和计算模型结合起来.
- 利用历史的基板尺度过数据来构建一个部分最小平方回归模型.
- 基于过器和料流属性的预测颗粒突破率,以预测过器性能.
主要成果:
- 使用混合模型先验成功预测了深度过器的性能.
- 证明了模型能够解释污染机制并提供物理意义的能力.
- 建立了一个强大的平台策略,用于深度过中国仓鼠卵巢细胞培养.
结论:
- 混合建模方法有效预测深度过性能.
- 通过连续数据获取信息的in silico工具将是加速收获过程发展的关键.
- 这种方法使得前性的实验设计成为可能,并减少了整体的实验负担.
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