在连续流通模式下进行疏水性相互作用色谱,以消除与产品相关的变异
Yiran Wang1, Ujjwal Bhaskar1, Naresh Chennamsetty1
1Biologics Development, Bristol Myers Squibb, 38 Jackson Road, Devens, MA, USA.
Journal of chromatography. A
|September 14, 2024
概括
这项研究引入了用于单克隆抗体净化的连续染色学方法,提高了10%的产量,同时保持高纯度. 这种创新过程有效地去除了具有挑战性的产品相关杂质.
科学领域:
- 生物制药制造业 生物制药制造业
- 染色学分离科学 染色学分离科学
背景情况:
- 与产品相关的杂质在单克隆抗体 (mAb) 净化过程中存在重大挑战,原因是它们与目标产品的分子相似性.
- 传统的批量染色学通常涉及到实现高纯度和最大限度地减少产量损失之间的权衡.
研究的目的:
- 开发和验证使用连续染色学来改善单克隆抗体的净化过程.
- 为了有效地去除具有挑战性的产品相关杂质,同时最大限度地提高产品产量.
主要方法:
- 实施一套两列多列连续色谱 (MCC) 系统,使用正面分析和疏水相互作用树脂.
- 开发和验证一种机械模型,以预测多组件突破并管理非稳定状态回收.
- 优化操作参数,使用验证的模型来处理料原料质量的变化.
主要成果:
- 在抛光MCC操作中,在保持99%的纯度的同时,产品产量增加了10%.
- 成功地从含有高达20%杂质的料中去除了与产品相关的杂质.
- 通过模拟,证明了与传统批次染色学相比,生产率的潜在翻倍.
结论:
- 提出的多列连续色谱 (MCC) 工艺为mAb净化提供了强大而高效的解决方案,克服了产量损失的权衡.
- 经过验证的机械模型允许稳健的工艺运行和优化,考虑到杂质积累和料变化.
- 这种方法显著提高生物制药制造效率和产品回收.
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