Charge variant distribution is a critical protein quality attribute for monoclonal antibodies (MAbs). The study, demonstrated the effects of process parameters and medium components on charge variant distribution of a human IgG1 MAb. In several high-cell density fed-batch processes, culture duration was identified as the most significant factor for the formation of charge variants, especially acidic variants. Results have showed that the fraction of acidic charged variants increased by more than 30% when extending process time from 12 to 17 days. Using a design of experiments (DoE) approach, the effects of process parameters, IgG concentration, and cell culture medium components on the charge variant distribution were studied. The key process parameter affecting charge variant distribution was shown to be pH. A change in pH from 6 to 8 increased the relative amount of acidic variants almost 100%. In addition, concentrations of iron citrate, IgG, and sugar were also shown to have a significant impact on the charge variant distribution. With increasing iron citrate and sugar and decreasing IgG concentrations, a 10% to 20% relative increase in charge variants was observed.

Effects of process parameters and medium components on charge variant distribution of a human monoclonal antibody

251st National Meeting (2016)

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