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).