Effects of pyruvate on primary metabolism and product quality for a high-density perfusion process.

Autor: Caso S; Biotech Process Sciences, Merck KGaA, Corsier-sur-Vevey, Switzerland., Aeby M; Biotech Process Sciences, Merck KGaA, Corsier-sur-Vevey, Switzerland., Jordan M; Biotech Process Sciences, Merck KGaA, Corsier-sur-Vevey, Switzerland., Guillot R; Biotech Process Sciences, Merck KGaA, Corsier-sur-Vevey, Switzerland., Bielser JM; Biotech Process Sciences, Merck KGaA, Corsier-sur-Vevey, Switzerland.
Jazyk: angličtina
Zdroj: Biotechnology and bioengineering [Biotechnol Bioeng] 2022 Apr; Vol. 119 (4), pp. 1053-1061. Date of Electronic Publication: 2022 Jan 23.
DOI: 10.1002/bit.28033
Abstrakt: 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, cultures were operated at a constant biomass specific perfusion rate (BSPR) in this study. The cell density was monitored with a capacitance probe and a continuous bleed maintained the targeted viable cell volume. Despite our tightly controlled BSPR, a gradual accumulation of ammonium and changes in cell diameter were observed during the production phase for three different monoclonal antibodies. 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 study, we show that a continuous Na-pyruvate feed (2 g/L/day) strongly reduced ammonium production and stabilized fucosylation, sialylation and high mannose content for three different mAbs.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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