Development of a dynamic model of monoclonal antibody production and glycosylation for product quality monitoring

A comprehensive dynamic model to describe monoclonal antibody (MAb)-producing mammalian cell cultures is presented featuring: (i) cell growth kinetics, (ii) cell metabolism, (iii) MAb synthesis and secretion and (iv) MAb glycosylation. Its simulation results are in good agreement with experimental data for macroscopic culture variables and qualitative observations for glycosylation. The combined model allows us to examine in silico and a priori the impact of feeding schedules on the extent of MAb glycosylation and productivity. Optimisation results for different feeding strategies and their effect on glycosylation patterns are also presented, based on which product quality monitoring strategies can be developed. [Copyright &y& Elsevier]