Cultivation of the CHO Cell Line in Bioreactors of Various Volumes: Technological Optimization

Abstract Recombinant proteins for medical use obtained by genetic engineering technology have become an integral part of the pharmacopoeia of various countries. To obtain such proteins, the Chinese hamster ovary (CHO) cell culture is widely used in modern biotechnology due to its high proliferation rate and ease of cultivation. Here, the process of scaling up the production of Bevacizumab, a recombinant humanized monoclonal antibody (mAb) of the IgG1 subclass that selectively binds to and neutralizes the functional activity of the human vascular endothelial growth factor (VEGF), was studied. The process was scaled up in bioreactors with a volume of 10 to 2000 L. First, optimal conditions for culturing СНO cells in the 10-, 200-, 500-, and 2000-liter bioreactors were selected. After that, the production of Bevacizumab was analyzed. The developed process allowed us to obtain the target protein with a yield of 1.4‒2.3 mg/mL of the culture liquid. During scaling, an industrial technological process was developed, the qualitative and quantitative characteristics of which are not inferior to laboratory ones.