(430d) Control of Deamidation of Monoclonal Antibodies in Mammalian Cell Culture Processes

Deamidation of asparagine residues represents one of the pathways for formation of product variants in therapeutic proteins such as monoclonal antibodies. Antibody deamidation may occur in any stage of a manufacturing process as well as during product storage, and may potentially affect both product efficacy and stability. Bioreactor process parameters such as pH and temperature have been observed to affect this particular product attribute. Studies were performed to evaluate the effects of cell culture process parameters such as pH, temperature, and culture duration on the level of deamidation in the product. Deamidation levels were measured using an analytical ion exchange chromatography (IEC) method. The IEC data demonstrated that lower temperature, lower pH, and shorter culture duration can be incorporated in control strategies to limit the deamidation of the product in the production bioreactor. The strategies developed in the laboratory-scale model were verified at various scales up to the production scale.