Production of humanized monoclonal antibodies using CHO cells is a major area of interest in the biotechnology industry. Some product heterogeneity is introduced in the cell culture unit operation that cannot be removed in downstream processing. Of interest is the charge variant level and controlling it within an acceptable range. There are many sources of charge variants including sialylation, deamidation, C-terminal lysine cleavage and adduct formation as in glycation. Glycation is a non-enzymatic process where glucose binds to a lysine residue, blocking a positive change and increasing the level of acidic variants. Using data from multiple pilot scale runs we showed a positive correlation between the level of glycation and acidic variant level. Taking glucose concentration and product titer time courses from the runs as input to a kinetic model, we showed that glucose concentration was a primary cause of glycation. In scale down runs we confirmed the relation between glucose and glycation. The close control of glucose concentration in cell culture through simple approaches can reduce variations in glycation and acidic variant levels, resulting in more consistent product quality profiles.

Achieving consistent and improved product quality profile by addressing glucose control in a fed batch reactor producing a recombinant monoclonal antibody

243rd National Meeting (2012)

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