Title: Metabolomics in Industrial-Scale Cell Culture Engineering
Authors: Spyros Vernardis, Panagiotis Chrysanthopoulos, Chetan T. Goudar and Maria I. Klapa
Abstract:Mammalian cell cultures have been widely used for the production of therapeutic proteins, in which complex post-translational modifications are necessary to ensure efficacy. The primary objective of most current process development programs for therapeutic protein production is the rapid development of bioreactor processes characterized by high product yield and consistent product quality. In addition, due to the high manufacturing cost of these processes, the identification and use of accurate and sensitive controls for cell cultivation robustness is desirable. Today, both bioreactor monitoring and process improvements are based primarily on cell growth, metabolic activity and protein productivity data. While useful, the limitations of this cell specific rate-based approach have been recognized. There is thus a clear need for the development of methods that enable the comprehensive characterization of the physiological state of mammalian cell cultures, improving over the current set of monitoring measurements based also on a cost-efficient platform. The high-throughput molecular analysis platform of metabolomics could satisfy these requirements. Metabolomics, referring to the simultaneous quantification of the concentration of the free small metabolite pools, enables the monitoring of a metabolic fingerprint of a biological system. In this poster, we will present the results of the first reported application of metabolomics on industrial-scale cell culture samples. It was shown that metabolomics could detect subtle differences in metabolic physiology due to cell age, bioreactor size and cell bank vial in a consistent with respect to protein quality fermentation campaign. This is a very encouraging result, indicating that molecular phenotyping could be used to provide early warnings of problems in the culture physiology and protein productivity and/or final quality before the end of the cultivation. Ongoing research is carried out to further validate these findings.
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