Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures

Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures

Biotechnology Journal

10.1002/biot.202400092

http://dx.doi.org/10.1002/biot.202400092

Jiayu Leong, Wen Qin Tang, Jake Chng, Wei Xuan Ler, Norhaizat Abdul Manan, Lyn Chiin Sim, Zi Ying Zheng, Wei Zhang, Ian Walsh, Gerben Zijlstra, Maarten Pennings, Say Kong Ng

11 July 2024

Leong, J., Tang, W. Q., Chng, J., Ler, W. X., Manan, N. A., Sim, L. C., Zheng, Z. Y., Zhang, W., Walsh, I., Zijlstra, G., Pennings, M., & Ng, S. K. (2024). Biomass specific perfusion rate as a control lever for the continuous manufacturing of biosimilar monoclonal antibodies from CHO cell cultures. Biotechnology Journal, 19(7). Portico. https://doi.org/10.1002/biot.202400092

Continuous manufacturing enables high volumetric productivities of biologics such as monoclonal antibodies. However, it is challenging to maintain both high viable cell densities and productivities at the same time for long culture durations. One of the key controls in a perfusion process is the perfusion rate which determines the nutrient availability and potentially controls the cell metabolism. Cell Specific Perfusion Rate (CSPR) is a feed rate proportional to the viable cell density while Biomass Specific Perfusion Rate (BSPR) is a feed rate proportional to the biomass (cell volume multiply by cell density). In this study, perfusion cultures were run at three BSPRs in the production phase. Low BSPR favored a growth arresting state that led to gradual increase in cell volume, which in turn led to an increase in net perfusion rate proportional to the increase in cell volume. Consequently, at low BSPR, while the cell viability and cell density decreased, high specific productivity of 55 pg per cell per day was achieved. In contrast, the specific productivity was lower in bioreactors operating at a high BSPR. The ability to modulate the cell metabolism by using BSPR was confirmed when the specific productivity increased after lowering the BSPR in one of the bioreactors that was initially operating at a high BSPR. This study demonstrated that BSPR significantly influenced cell growth, metabolism, and productivity in cultures with variable cell volumes.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the A*STAR - Industry Alignment Fund - Industry Collaboration Projects
Grant Reference no. : I1901E0047

https://oar.a-star.edu.sg/communities-collections/articles/20726

1860-6768
1860-7314

Bioprocessing Technology Institute

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/biot.202400092