Abstract
High volumetric productivities can be achieved when perfusion processes
are operated at high cell densities. Yet it is fairly challenging to
keep high cell density cultures in a steady state over an extended
period. Aiming for robust processes, in this study cultures were
operated at a constant biomass specific perfusion rate (BSPR). The cell
density was monitored with a capacitance probe and a continuous bleed
maintained the cell density at the targeted viable cell volume (VCV).
Despite our tightly controlled BSPR, a gradual accumulation of ammonium
and changes in cell diameter were observed during the production phase
for the three different monoclonal antibodies (mAbs). Although a lot of
efforts in media optimization have been made to reduce ammonium in
fed-batch process, less examples are known about how media components
impact the cellular metabolism and thus the quality of monoclonal
antibodies in continuous processes. In this work, we show that a
continuous Na-pyruvate fed at 2 g/L/day strongly reduced ammonium
production and stabilized fucosylation, sialylation and high mannose
content for three different mAbs.