Characterizing Basal and Feed Media Effects on Mammalian Cell Cultures by Systems Engineering Approaches

Abstract

Choosing the right cell culture media to improve the culture performance is one of the major challenges in Biologics process development. In this regard, we investigated the effect of basal and feed media on cell growth, productivity, and cellular metabolism during CHO-K1 cell culture, which are the main workhorse in the biopharmaceutical industry. We elucidated how the cell performance changes under different combinations of basal and feed media (2 × 2) conditions. To do so, we exploited systems engineering approaches that four hierarchical steps which are data collections, multivariate statistical analysis, in-silico flux analysis with genome-scale metabolic model, and knowledge-based targeting media components. Our findings indicate that feed media have a much greater impact on cell growth and production than basal media. The framework characterized the major metabolic bottlenecks in central carbon metabolism and identified new manipulatable target components of the media reformulation in the feed that impeding improved growth.