Microbial Secretion via ESETEC(R) Technology

The success of biopharmaceuticals started about 30 years ago with the first production of recombinant human insulin (Humulin®) in Escherichia coli, followed by the first production of human tissue plasminogen activator (tPA) in mammalian host cells some years later. Due to the lack of glycosylation in E. coli, which is required for the biological activity of most monoclonal antibodies, the use of Chinese hamster ovary (CHO) cell lines soon became the industrial gold standard for the production of biopharmaceuticals. CHO cells possess the machinery for post-translational modifications and, in contrast to conventional E. coli systems, make it possible to purify correctly folded and secreted proteins directly from the culture broth. Consequently, the booming demand for antibodies led to the success of CHO cells in biomanufacturing. Nevertheless, CHO-based systems still suffer from slow cell growth and thus low productivity. Moreover, process development using mammalian cells is timeconsuming, due to tedious clone screening and selection, which can take up to five months. The demand for fast, safe, and cost-efficient manufacturing solutions is triggered by increasing pressure on clinical development timelines and public healthcare systems. Personalized medicine and biosimilars are just two examples underlining the need for innovative expression platforms that combine high productivity, protein secretion, and rapid process development.