Optimization of Hydrolysate-Free Media Composition and Feeding Strategy for Antibody Production through Nutrient Monitoring

The production of antibodies using mammalian cells involves a complex balance of nutrients contained in basal media and feeds, which provide cells with metabolic energy for growth and protein production. While the addition of hydrolysates to chemically-defined media has typically improved product titer, its use is undesirable due to various risks of using undefined raw materials. These include sole-sourced raw material risk, variability among lots, and the risk of adventitious agents presented by the use of biologically-derived hydrolysates. Therefore, it is advantageous to develop hydrolysate-free media and feeds to meet antibody production needs.

A case study will be presented demonstrating the optimization of chemically-defined medium and feeds for a CHO cell line producing a monoclonal antibody. Nutrient profiles for a given cell line were optimized by modification of media and feed composition, feed timing, and feed volumes. Fed-batch experiments were conducted using 2-L bioreactor and shake flask models. Various techniques used to monitor and optimize nutrient composition to prevent depletion of important components, minimize accumulation of toxic by-products, and maximize antibody production will be discussed.