Metabolic Flux Balances of Mammalian Cho Cells for Investigation of Trace Element Effects On Productivity and Product Quality

Biopharmaceuticals (defined as recombinant proteins, monoclonal antibody and nucleic acid-based products) is the fastest growing sector within the pharmaceutical industry. About 900 to 1,200 clinical candidate proteins and/or peptides are currently being investigated. Approximately one in every four drugs introduced to the market is a biopharmaceutical.  The global biopharmaceutical market was estimated at $80 billion in 2007 with antibodies representing around $28 billion sales and protein products generating almost $52 billion.  It is estimated that sales of biopharmaceutical products will exceed $150 billion by 2012. Despite all of the progress and commercial success, the development of production cell lines and fermentation processes with mammalian cells is, to a large extent, still based on empirical knowledge and historical experience. This is mainly because of missing qualitative and especially quantitative data and a lack of understanding of the intracellular mechanisms under bioprocess conditions. The challenges of selectivity, reproducibility and accurately quantitating these products, have seriously handicapped biopharmaceuticals from being commercialized.

Metabolic flux analysis of the mammalian CHO cells for explaining trace element effects for monoclonal antibody product in suspension cultured culture product and quality was assessed. Based on the metabolic flux analysis of the CHO cell culture samples, group of metabolites associated with the trace elements were identified. The Amino Acid metabolism were correspondingly analyzed. A group of amino acids were clustered. For the purpose of the resutlt confirmation, metabolomics was used.