在连续生物制造中,用拉曼控制的酸盐养来控制代谢活动和产品质量
Patrick Romann1,2, Sebastian Schneider1, Daniela Tobler1
1Institute for Pharma Technology, School of Life Science, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
Biotechnology journal
|October 28, 2023
概括
一种新的pyruvate养策略稳定了细胞培养代谢和输液过程中的产品质量. 这种方法减少了的积累,并改善了双特异抗体制造的糖化样本.
科学领域:
- 生物技术是生物技术.
- 生物工艺工程 生物工艺工程
- 细胞培养技术 细胞培养技术
背景情况:
- 在长期 perfusion 细胞培养中实现细胞稳定状态新陈代谢是具有挑战性的.
- 代谢活动的转变可能导致两种特异性抗体生产中的产品质量属性漂移.
研究的目的:
- 为了稳定双特异抗体生产的稳定状态 perfusion 过程.
- 为了解决由代谢转变引起的产品质量属性的漂移.
主要方法:
- 开发了一种按需的pyruvate养策略,使用乳酸作为三碳酸 (TCA) 循环和的指标.
- 实行实时乳酸监测与内线拉曼光谱用于精确的过程控制.
主要成果:
- 实现了三倍减少氨积累.
- 稳定产品质量概况,包括低标准偏差的甘化 (高曼诺,福克索化,银化,化).
- 通过调整乳酸设定点来微调甘氨酸形式的已被证明潜力.
结论:
- 拉曼控制的pyruvate养是稳定不断制造 perfusion 培养中的代谢活动的宝贵工具.
- 这一策略可以防止产品质量下降,并减少高曼糖形式.
- 该方法支持通过减轻延长培养时间和高细胞密度的挑战来加强过程.
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