Optimization of Perfusion Rate Acceleration is a Key Stage in Development of Highly Productive Perfusion Cultivation of CHO Cells

Abstract

The influence of perfusion rate at the early phase of continuous cultivation on growth characteristics of CHO cells produ cing the therapeutic IgG1 and on the glycan profile of the produced MAb has been examined. It was established that non-optimal perfusion acceleration values caused some deviations from the normal transition of the cell culture to a steady-state phase of the process. For example, an excessive acceleration rate resulted in exceeding the maximum cell concentration that can be supported by cell culture medium. The cell growth was therefore limited and their viability dramatically decreased. The further recovery of growth and viability took a few days and reduced the economic efficiency of the process. Too low perfusion acceleration rate caused metabolic modifications in cell culture that affected its specific productivity and the quality of the synthesized protein. In particular, we observed the decrease in the target MAb fucosylation that could have a negative effect on the protein safety profile. In addition, the proliferation rate slowed down and cell volume increased by 2-2.5 times