通过使用动态实验设计,高效优化食批量细胞培养过程中的时间变化的输入
Yu Luo1, Duane A Stanton2, Rachel C Sharp1
1GSK, Biopharm Drug Substance Development, King of Prussia, Pennsylvania, USA.
Biotechnology progress
|August 2, 2023
概括
动态实验设计 (DoDE) 通过高效建模时间变化的营养养策略,优化治疗单克隆抗体的产生. 这种方法显著增加了27%的标位,并保持了高细胞活力.
科学领域:
- 生物技术是生物技术.
- 化学工程是化学工程的重要组成部分.
- 过程开发 过程开发
背景情况:
- 传统的细胞培养过程的开发依赖于有限的,代的实验.
- 实验设计 (DoE) 提供系统分析,但在时间变化的输入方面存在困难.
- 在生物反应器中研究动态养配置通常需要过多的资源.
研究的目的:
- 应用动态实验设计 (DoDE) 来优化单克隆抗体生产中的时间变化的养概况.
- 为了有效地将动态养策略纳入后期生物工艺开发阶段.
- 通过动态优化来提高工艺效率和产品产量.
主要方法:
- 采用和应用动态实验设计 (DoDE) 方法.
- 将动态养配置文件纳入后期细胞培养过程的开发.
- 统计建模用于分析料率斜率和高阶动态的影响.
主要成果:
- 成功估计了营养料量的影响,并优化了时间趋势料速率的斜率.
- 证明料率的更高阶动态特征对测量反应没有显著影响.
- 与基线工艺相比,在200L批量中获得了27%的标位增加和92%以上的可行性.
结论:
- 在生物制药制造中,DoDE为优化动态工艺条件提供了一个有效的框架.
- 开发的统计模型能够显著提高生产率和产品质量.
- 这种方法作为更高效的生物工艺开发工作流程的基础.
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