The characteristics of a biological drug, e.g. charge variant profile, are determined to a large extent by the upstream expression system and conditions, and may be influenced by the purification process. Charge variant distribution is a critical protein quality attribute for monoclonal antibodies (MAbs) and is therefore of interest to monitor and control during the production process.<br/>In this study, we investigated the effects of cell-culture 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. 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 amount of acidic variants could be significantly reduced by process optimization and modification of the cell culture medium formulation.<br/>Furthermore, the MAb charge variant separation in the polishing steps of the downstream chromatography process was evaluated. Chromatography media screening, comparing traditional ion exchangers vs multi-modals, as well as a strategy for optimization of chromatographic conditions is presented. The effect of variation of the incoming cell culture material, on the charge variant separation, will also be discussed.

Modes of controlling charge variant distribution in mAb production by upstream and downstream process parameters

251st National Meeting (2016)

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