Cell Engineering and Analytical Strategies for Control of Recombinant Biopharmaceutical Aggregate Levels in Cell Culture Media

For recombinant protein biopharmaceuticals produced by mammalian cells in culture, formation of protein aggregates or oligomers can be severe problem with respect to product quality, efficacy, immunogenicity and therefore safety. Very recent studies (1,2) show that alteration of culture environment can be an effective strategy to reduce the formation of bispecific antibody aggregates. An underlying mechanism, elucidated by AZ at Gaithersburg (2), was shown to be associated with impaired metabolism (oxidation) of the tripeptide glutathione (GSH) mediated by mitochondrial dysfunction, accumulation of reactive oxygen species (ROS) and ER stress during fed-batch culture.