Comprehensive cell culture monitoring: Leveraging in-line Raman spectroscopy for enhanced biopharmaceutical manufacturing insights

• Published in: Process biochemistry (1991) 2024-08, Vol.143, p.1-12
• Main Authors: Dong, Xiaoxiao, Shi, Yingting, Yan, Xu, Wan, Yuxiang, Gao, Dong, Chen, Zhenhua, He, Zhuohong, Wang, Haibin, Qu, Haibin
• Format: Article
• Language: English
• Subjects: Cell culture; Multiple components; Raman spectroscopy; Real-time monitoring
• ISSN: 1359-5113; 1873-3298
• DOI: 10.1016/j.procbio.2024.04.022

Many biopharmaceutical manufacturers and researchers seek a comprehensive understanding and real-time monitoring of cell growth and metabolism to enhance the cell culture process. However, the biological complexity of cells and the intricacies of cell culture process have impeded the development of analytical and monitoring techniques. This study aims to present a complete picture of cell culture processes using in-line Raman spectroscopy. Initially, we proposed an efficient method for discriminating and removing anomalous spectra. Subsequently, Raman-based models for 27 components including amino acid, organic acid, lipid, organic alkali, alkaloid, alcohol, saccharide, biomass, physicochemical parameter, ion, and protein titer were established. The Q2 obtained by these models was greater than 0.8, and the relative percent difference (RPD) from external validation was greater than 2.0 except for glucose. Additionally, the proposed control charts effectively monitored normal batches and abnormal conditions such as bacterial contamination and insufficient feeding. In cases of unexplained culture abnormalities, the proposed workflow offered explanations. [Display omitted] •Monitoring and analysis of CHO cell culture processes using Raman spectroscopy.•Raman-based models of 27 different components in bioreactors were established.•Process trajectory of normal cultivation was described.•Abnormal cultivation was identified and explained.