高吞吐量在工作流,用于优化和表征多模式色谱过程
Scott H Altern1,2, Jessica Y Lyall3, John P Welsh4,5
1Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA.
Biotechnology progress
|June 10, 2024
概括
这项研究引入了一种高吞吐量在 (HT-IS) 工作流,将实验和建模结合起来,以更快地开发染色学过程. 在HT-IS工作流程中,有效地开发了mAb聚合物去除的抛光步骤,证明了它对于快速过程优化有多有用.
科学领域:
- 生物制药工艺开发 生物制药过程开发
- 染色学分离 染色学分离
- 计算机建模 计算建模
背景情况:
- 高通量 (HT) 实验和机械建模是染色学中的关键,但它们与工作流程的整合尚不清楚.
- 开发有效的单克隆抗体 (mAbs) 抛光步骤对于药物的纯度至关重要.
研究的目的:
- 构建和验证用于染色学过程开发的新型高吞吐量体 (HT-IS) 工作流.
- 应用HT-IS工作流来优化Capto MMC抛光步骤的mAb聚合物去除.
主要方法:
- 生成的HT批量异温数据和扩展体质量作用 (SMA) 异温的回归参数.
- 在CADET软件中使用扩展的SMA同热和一般速率模型验证了模型.
- 通过根据关键过程指标最小化目标函数来优化流程.
主要成果:
- 在HT-IS工作流程中,Capto MMC成功开发了一种mAb聚合物去除的抛光步骤.
- 实验室规模的评估证实了高单体产量 (>85%) 和有效的聚合物去除.
- 过程模拟确定了化缓冲器pH值和树脂离子容量作为关键参数.
结论:
- 集成的HT-IS工作流显著提高了染色学过程开发的效率和速度.
- 这种方法使生物过程的快速发展和表征成为可能.
- 该研究强调了化缓冲器pH值和树脂离子能力对工艺稳固性的重要性.
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