Expanding Expression

Nearly 55 per cent of biomanufacturing facilities today are actively considering alternative expression systems for products in R&D (1). By the time these products leave the development pipeline, there may well be far greater numbers of biopharmaceutical expression systems in commercial manufacturing than we have seen over the past 30 years. While there have been substantial improvements in the classic three expression systems (E coli, CHO and yeast) over the years, until recently, there was a general lack of interest in the adoption of newer platform technologies. The result is that nearly all biotherapeutic products manufactured today use the same familiar technologies.

The underlying reason for this stagnation has been the industry’s inherent caution. “It is a conservative industry – nobody ever got fired for using E coli, yeast or CHO,” says Dr Tillman Gerngross, currently Professor of Engineering at Dartmouth College. One reason for the slow adoption of expression system technologies in biomanufacturing is the regulated nature of the industry. Dr Gerngross has found that “making things cheaper while increasing regulatory risk has not been a winning formula in this industry: consider transgenic animals and plants”.

Cost saving is a relatively small part of the equation. Gerngross believes that new expression system technologies must improve product quality and have a direct therapeutic impact. Simply reducing costs is not enough: “Production costs are a small fraction of the final cost of goods – it roughly breaks down into one third production, one third purification and one third formulation and QC”. Therefore, a protein cost-of-goods might be as low as four per cent, which means reducing production costs will not affect the overall cost structure.

THE NEED FOR NEW EXPRESSION SYSTEMS

Now, however, the need for innovation in the biopharmaceutical sector has taken on a greater urgency. In his recent book on expression systems, Ronald Rader notes that “High-tech industries adopt new technologies so they can produce better, cheaper and faster. Sticking with what you know may seem safe, but in biomanufacturing, this may have more to do with the lack of knowledge about emerging alternatives” (2). A range of promising technologies have been available for some years, but many companies continue to rely on outdated expression systems, which may compound the risks inherent to new drug development. This lack of forward-thinking is having a stifling effect on biopharmaceutical manufacturing. In this increasingly competitive environment, companies are recognising that they may not be able to afford to continue along this path.