Most of the biopharmaceuticals that have reached the market in the United States and the European Union are produced in just a few expression systems. A recent report in the September 2010 issue of Nature Biotechnology indicated that 32 of the 58 biopharmaceuticals approved between 2006–2010 were produced in mammalian expression systems (mostly Chinese hamster ovary [CHO] cells), and 17 were produced in Escherichia coli (E. coli). The remainder were produced in yeast (4 in Saccharomyces cerevisiae, 1 in Pichia pastoris), transgenic animals, insect cells, plants, or by direct synthesis (1).
Mammalian cells have become the system of choice for antibody production, which requires most of the posttranslational modifications that can't be achieved in E. coli. Mammalian cells—CHO cells being the most widely used— are best equipped to secrete glycosylated, multi-subunit proteins that will fold and assemble correctly. They are amenable to genetic manipulation, and lines exist that have been optimized for ease of transfection, increased protein expression, and high-density culture. The major drawback to mammalian cells is that compared with microorganisms, they are more difficult to culture, require expensive culture media and a low-shear environment, and they often produce lower yields. There are also biosafety concerns around the transmission of viruses that can be pathogenic in humans.Some more recent entrants on the market strive to address some of these drawbacks. Most notably, PerC.6, a transformed human cell line jointly developed by Crucell and DSM for use as a manufacturing-scale expression system, increased expression yields so dramatically, that it shifted manufacturers' concerns from producing adequate protein yields to having adequate capacity to efficiently purify the increased titers. PerC.6 can be grown in suspension cultures at relatively high densities in serum-free medium, and according to company literature, can achieve yields of up to 8 g/L in standard fed-batch cultures, and 20 g/L using DSM's proprietary culture system, which are levels comparable to those of microbial expression systems.