Cell culture performance
The current industry standards for the production of stable mAbs is a fed-batch process in stirred tank bioreactors. Perfusion methods offer not only process advantages but also possibly low HCPs released into the condition media due to high viability and less apoptosis in the culture. Three culture processes, FB, SS perfusion and NSS perfusion, have been compared from same host cell line, producing the same recombinant product, mAb1. FB culture was harvested 11 days after the production bioreactor was inoculated and perfusion supernatants were sampled daily.
Figure 1 shows the profiles of cell growth, viability and mAb1 production in culture supernatants during FB, SS and NSS perfusion cultures. In FB cultures, a maximum viable cell concentration (MVCC) of 15.6 X 106 cells/ml was achieved on day 7 (Fig1a). In NSS perfusion, the trend for MVCC was very similar to fed-batch but reached around 221.7 X 106 cells/ml on day 7, which was 14 times more cell density than FB culture. In SS perfusion, the viable cell density was maintained at 40 X 106cells/ml throughout the culture days with ~95% viability (Fig1b). Fed-batch viability was reduced to ~25% and NSS perfusion viability was also reduced to ~37% on day 11. Perfusion cultures were intended to have high productivity therefore average productivity is 5.7 times greater in SS and 18.5 times greater in NSS compared from FB (Fig1c).