Characterization of the influence of cultivation parameters on extracellular modifications of antibodies during fermentation

Introduction The production of protein-based medical agents, like monoclonal antibodies (Mabs), by biotechnological processes requires a comprehensive quality control. The pharmaceutical industry and national health authorities support the complete characterization of therapeutic proteins to increase the quality and safety. During numerous and different production steps like fermentation, purification and storage, various protein modifications on therapeutic products can occur, like deamidation of asparagine and glutamine, oxidation of methionine tryptophan residues, clipping of terminal amino acids, glycation and others. During the development of fermentation processes, good growth conditions for the cell culture are of primary importance to obtain maximal productivity [1]. Until now only few efforts have been made to investigate the development of extracellular antibody modifications and their sources during fermentation as the first phase of the productions process. Already known is the fact that pH-value and temperature can induce modifications on monoclonal antibodies [2]. Aim of this work is to increase the knowledge about the development of extracellular modifications of monoclonal antibodies during the fermentation process. Therefore, parameters of fermentation were identified which influence modifications during cell-free incubation under common fermentation conditions (in shake flask and small scale bioreactor-systems).