Many recombinant therapeutic proteins such as monoclonal antibodies are produced in eukaryotic cells to enable post-translational modifications such as glycosylation. Glycan profiles and charge variants are important quality attributes for the activity, efficacy, and safety of therapeutic proteins.
To meet these parameters highly efficient and targeted media development is crucial. Whereas systematic approaches such as QbD are increasingly applied, a deeper understanding of the interaction between metabolic alterations, protein production, and processing should significantly improve production processes (Figure 1).
Metabolomics is a valuable tool to study underlying mechanisms and involved biochemical pathways—especially for the widely used CHO cell line, for which little is known about its physiology.
In this tutorial we will show how we evaluated the potential of metabolomic tools to support cell-line characterization and subsequent process development, this information was also recently presented at the ESACT meeting in Vienna. As part of the study, we compared a CHO producer and its corresponding mock cell line (transfected with an empty plasmid) on a metabolic level in order to see whether the metabolite profile differences came from the increased protein production capacity. In addition, we were able to observe the complex glycosylation machinery.