优化多列色谱的捕获和抛光在高蛋白负载的优化
Tiago Castanheira Silva1, Madelène Isaksson2, Bernt Nilsson2
1Department of Biotechnology, Delft University of Technology, Delft, The Netherlands.
Biotechnology progress
|June 9, 2025
概括
连续染色学,特别是3列周期反流染色学 (3C-PCC),通过优化列容量利用率和生产率来增强单克隆抗体 (mAb) 制造. 这种先进的生物制造方法可以降低成本,同时保持高质量的产品.
科学领域:
- 生物制药制造业 生物制药制造业
- 化学工程是化学工程的重要组成部分.
- 过程优化 过程优化
背景情况:
- 生物制药制造的高成本,特别是单克隆抗体 (mAbs) 的高成本,主要是由染色学过程驱动的.
- 传统的批量染色学常常导致列容量的不足利用,影响整体生产力和经济可行性.
- 连续色谱提供了一个有前途的解决方案,以增加容量利用率,而不会影响产量或生产力.
研究的目的:
- 为了在mAb生产中进行3列周期反流色谱 (3C-PCC) 系统的in-silico优化,用于捕获和抛光步骤.
- 通过优化各种mAb度下的流量和突破百分比来最大限度地提高生产率和列容量利用率 (CU).
- 通过实验验证模型预测,并提出一个优化的连续生物制造工艺.
主要方法:
- 使用连续模式和批量模式的帕雷托前线对3C-PCC系统进行建模和in-silico优化.
- 流量和突破率的系统变化,以确定不同mAb度的最佳运行条件.
- 使用三种不同的蛋白A配体和纯的mAb溶液进行实验验证,然后进行序列捕获和抛光过程.
主要成果:
- 该研究确定了3C-PCC的最佳参数,显示了与传统方法相比,生产力和CU的显著改善.
- 实验验证证证实了模型预测的偏差小于7%,展示了in-silico方法的可靠性.
- 使用MAbSelect SuRe pcc进行捕获和CaptoS ImpAct进行抛光的顺序3C-PCC工艺实现了大约100 mg/mL res/h的生产率.
结论:
- 在3C-PCC的in-silico优化是提高mAb生物制造效率和降低成本的有效策略.
- 连续染色学,特别是拟议的3C-PCC序列,为批量染色学提供了一种可行且高生产率的替代方案.
- 经过验证的模型为设计和优化单克隆抗体的连续生物制造过程提供了一个强大的工具.
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