(30d) Controlling Glycation Levels In Antibodies Produced In Fed-Batch Cell Culture Processes

This poster will focus on a case study of cell culture process development for the synthesis of a monoclonal antibody that experienced glycation levels exceeding 25%, when produced in a standard platform cell culture process. Glycation is the non-enzymatic addition of reducing sugars such as glucose to specific lysine resides.   Glycation levels observed in recombinant monoclonal antibodies can vary depending on the presence or absence of a "glycation hot spot".  In this specific study, such a hot spot was apparently caused by the spacial proximity of lysine 49 and aspartate 31 in the light chain. Cell culture process development efforts were focused on reducing the fraction of glycated antibody without making major modifications to the process platform.  To aid this effort, a dynamic mathematical model was developed to simulate the relationship between certain process parameters and observed glycation levels.  The model simulated the growth of cells, substrate consumption, protein synthesis and glycation.  After it was confirmed that previously collected experimental data were in general agreement with the results of these simulations, the simulation was used to guide the design of subsequent experiments.  Using this approach, glycation levels as low as 15% were achieved by lowering the glucose concentration in the nutrient feeds as well as the overall glucose feeding strategy.