(188dp) Media Supplementation Strategies for Improving Stability and Glycan Quality in Mabs

Monoclonal antibodies (mAbs) have become the largest growing class of therapeutics because of how effectively they treat cancers, chronic illnesses, and inflammation. More and more of these therapeutics are approved each year, and patent-expiring innovators are seeing competition from biosimilars with an expected global market value of 1.4 trillion dollars by 2020. Intensive development and production processes drive up the price of these therapeutics, which limits accessibility in both the US and abroad. To ensure safety and efficacy, product quality must remain high from all steps of production through patient delivery. Antibody aggregate formation can appear in any step of the production process and increases the risk of immunogenic side effects. Also, structural changes associated with antibody glycosylation greatly contributes to effector functions (ADCC, CDC) and serum half-life, and thus glycosylation is considered a significant product quality attribute. While cell engineering for improving antibody stability and glycosylation characteristics has never been easier, the processes for controlling gene and protein expression are still time and labor intensive. Implementing changes to process conditions or media components can more rapidly manipulate the quality of an expressed antibody and can be utilized dynamically during a process run. Here, we examine effects of various media supplementation regimes on glycan distribution and subsequent protein stability to better understand the relationship between process conditions and product quality for CHO-expressed mAbs.