Expression System Royalties Battle

With all of the new expressions systems being developed, companies must decide what improved production and yield are really worth.
Apr 01, 2009
Volume 22, Issue 4

Eric S. Langer
Biopharmaceutical companies generally try to avoid the idea of paying royalties on novel technologies, including novel expression systems, in part because of the inability to predict revenue flow after a product is commercialized. But even when a new expression system could sugnificantly reduce cost, many remain hesitant. Despite this, adopting new technologies continues to be fundamental to improving product quality and cost.

"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.


Figure 1
As part of our Sixth Annual Report and Survey of Biopharmaceutical Manufacturing, we explored the potential for adoption of new expression systems (Figure 1).2 We were not surprised to find that 55% of respondents at biomanufacturing facilities indicated they would consider an alternative expression system in early R&D. However, we did find that 43% of respondents in process development stages would consider alternative expression systems. This suggests that for new drug products, manufacturing technologies are not written in stone.

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.


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.

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