结合高吞吐量和建模方法,简化生物制剂的早期过程开发
John P Welsh1, Scott H Altern2,3, Jessica Y Lyall4
1Process Research and Development, Merck & Co., Inc., Rahway, New Jersey, USA.
Biotechnology progress
|January 23, 2025
概括
这项研究引入了单克隆抗体 (mAb) 过程开发的新工作流程,整合了高通量查和机械建模. 这种方法加快了开发速度,并提高了流程理解,而不需要传统的实验室规模列.
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
- 蛋白质净化 蛋白质净化
背景情况:
- 对单克隆抗体 (mAbs) 的下游过程开发传统上使用实验室规模的方法,导致漫长的时间表.
- 生物制剂的复杂性日益增加,需要简化和高效的开发策略.
- 自动化高通量选和机械模型正在成为生物处理中的强大工具.
研究的目的:
- 建议和验证一个精简的工作流程,用于早期下游流程开发.
- 整合高通量选和机械模型,以加速开发.
- 减少生物工艺开发中的时间表和材料要求.
主要方法:
- 使用自动化树脂板幕进行条件选和参数校准.
- 采用机械模型来定义制造过程中可靠的工艺条件.
- 使用小型化的RoboColumns确认了过程空间,避免了传统的实验室尺寸列.
- 将工作流应用于交换 (CEX) 和多式交换 (MMCEX) 过程.
主要成果:
- 集成的工作流成功地缩小了选条件,并校准了结合性异温参数.
- 机械模型准确地描述了早期制造业的一系列强大的条件.
- 微型RoboColumns证实了预测的过程空间.
- 对于CEX和MMCEX工艺的证明实用性,预测mAb产品和聚合物杂质.
- 模型预测的参数灵敏度与传统的实验设计 (DOE) 模型保持一致.
结论:
- 拟议的工作流提供了一个实用和有效的路线图,用于早期下游流程开发.
- 这种方法大大减少了开发时间表和材料消耗.
- 通过高通量选和机械建模的整合,可以实现更好的流程理解.
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