"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," says Ronald Rader, author of the BioPlan Associates report, Biopharmaceutical Expression Systems: Current and Future Manufacturing Platforms. 1
Of course, one reason for the limited adoption of expression system technologies in biomanufacturing is the conservative, regulated nature of the industry. Tillman Gerngross, PhD, professor of engineering at Dartmouth College, co-founder and CEO of Adimab Inc. (Lebanon, NH) and co-founder, and ex-CSO at GlycoFi, which was recently sold to Merck & Co. (Whitehouse Station, NJ), says that, "Making things cheaper while increasing regulatory risk has not been a winning formula in this industry; consider transgenic animals and plants."Rather, Gerngross believes adopting technologies that improve product quality in ways that have a direct therapeutic impact is where the greatest value is added. Improved expression systems must do more than simply reduce costs. "Production costs are a small fraction of the final cost of goods—it roughly breaks down into a 1/3 production, 1/3 purification, and 1/3 formulation and QC." Therefore, cost-of-goods for a protein might be as low as 4%, which means reducing production costs will not significantly affect the overall cost structure, and that doesn't leave much room for royalties to the supplier of such technologies.
ADOPTION OF NEW EXPRESSION SYSTEM TECHNOLOGIES
We also found that royalty payments for new expression system technologies were seen as much more acceptable to many biomanufacturers than we had expected. The acceptance of new technologies seems to be dictated by how a new system would improve manufacturing. For example, nearly 46% would pay royalties if the system offered greater yield, and 36% would pay royalties if they were able to commercialize their failed projects.
STICKING WITH OLD METHODS
The historical reasons that biopharmaceutical organizations are now primarily using the tried-and-true, common protein production expression systems stem from the industry's conservatism. Today, there is a need for increasing titers. Many believe that as long as the large numbers of current manufacturing projects using conventional expression systems continue to improve, the demand for novel systems will stagnate. "It is a conservative industry—nobody ever got fired for using E. coli, yeast, or CHO," says Gerngross. Many in the industry expect alternative expression systems to make strong headway, but only when they go beyond simply reducing costs, and provide such advantages as improved therapeutic properties.