Biopharmaceutical companies generally try to avoid 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 significantly 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 (Hanover, NH, USA),
co-founder and CEO of Adimab Inc. (Lebanon, NH, USA) and co-founder, and exCSO at GlycoFi, which was recently sold to Merck
& Co. (Whitehouse Station, NJ, USA), 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 ⅓ production, ⅓ purification, and ⅓ 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 does not leave much room for royalties to the supplier of such technologies. Adoption of new expression system technologies
Figure 1: Adoption of new expression system: percent of biomanufacturers and contract manufacturing organizations who 'agree'
or 'strongly agree' with the statements below.
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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.
Sticking with old methods
The historical reasons that biopharmaceutical organizations are now primarily using the triedandtrue, 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.
