一个通过N-1 perfusion启动的自动化高注射密度料批生物反应器,可以容纳克隆多样性和双重标位
Mikayla Olin1, Nicolas Wolnick1, Hunter Crittenden1
1Research and Development, Lonza Biologics, Bend, Oregon, USA.
Biotechnology progress
|November 28, 2023
概括
使用自动营养养的强化生物过程显著增加了单克隆抗体的产生. 这种高密度细胞培养方法提高了生物反应器的生产率,降低了制造成本.
科学领域:
- 生物制药制造业 生物制药制造业
- 生物技术是生物技术.
- 过程强化 过程强化
背景情况:
- 生物治疗制造中的高商品成本 (CoG) 需要提高生物反应器的生产率.
- 传统的低注射密度 (LID) 料批次工艺限制了整体制造效率.
研究的目的:
- 为了证明一个强化生物工艺,提高生物反应器的生产力.
- 评估强化过程在多种CHO细胞系和单克隆抗体中的通用性.
主要方法:
- 连接一个透的N-1种子反应堆与高注射密度 (HID) N阶段反应堆.
- 在线过程分析技术 (PAT) 用于在两个反应堆阶段自动营养料.
- 采用在线电容用于N-1阶段的养和拉曼光谱用于N阶段监测关键营养素.
主要成果:
- 实现了平均85%的标位增加和132%的时空收益率 (STY) 增加.
- 在六个CHO细胞系中证明了工艺通用性,具有不同的料要求.
- 成功地适应了克隆多样性,导致可复制的标位升高.
结论:
- 与LID控制过程相比,强化HID过程显著提高了生物反应器的生产率.
- 使用PAT的自动养策略对各种细胞系有效且可通用.
- 这种技术平台为进一步提高生物反应器生产率和减少COG提供了途径.
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