Impact of Change in Fermentation Process pH and Dissolved Carbon Dioxide Concentration on Secreted Antibody Structure and Cell Physiology of a GS-NS0 Cell Line Expressing a Human Antibody

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Increased production of recombinant proteins from mammalian cells is a key focus of process development. Process pH is one factor well known to dramatically affect growth and productivity of some mammalian cells (1-3). Most mammalian cell culture systems use a bicarbonate based pH buffer system, in which pH setpoint is maintained by addition of carbon dioxide or bicarbonate. When pH set-point is lowered, more carbon dioxide is required to maintain pH, which may elevate the dissolved carbon dioxide (pCO2) to growth inhibitory levels (4). To counteract this, the bicarbonate concentration in the medium can also be reduced. Changes to pH and pCO2 have also been shown to affect protein glycosylation (5), which may affect protein function (6). This study describes the impact of changing process pH and pCO2 on a GS-NS0 cell line expressing a human monoclonal antibody.