Biosimilars can be manufactured more cost effectively, depending on the risks that companies are willing to take. That’s the view of David Wood, PhD, professor of chemical and biomolecular engineering at Ohio State University.
According to Wood, who will be speaking at the BioProcess International Conference in Boston in September, many biosimilar manufacturers use legacy processes to simplify their regulatory submissions. But some manufacturers could adopt new technologies, such as continuous processing, cleavable tags or different expression systems, to reduce costs. This is especially important, he says, as biosimilar companies work to increase drug availability in the developing world.
“When these drugs were first developed, manufacturing was done using batch processes and chromatography,” says Wood. “New technologies for protein production can help biosimilar companies lower their capital investment and adopt a smaller manufacturing footprint.”
However, there are risks. If the company can’t demonstrate to the regulators their biosimilar is bioequivalent to the original product, they must perform expensive clinical trials, he says.
“If you’re the innovator company and patients get better, whatever comes out of the process is your drug,” Wood explains. “But, if you’re manufacturing a biosimilar, you now have to match a drug that exists–and in some cases, that’s more challenging than creating a new drug.”
Challenging to adopt novel technologies
Companies producing complex glycoproteins can find it more challenging to adopt new technologies, as they must match the glycosylation profile of the original product, he says.
But companies with simpler biosimilars can benefit from single-use disposables and continuous processing, enabled by new analytical sensors, as it reduces their upfront capital costs. Other useful technologies include self-removing affinity tags, such as those developed by Wood’s company, Protein Capture Science.
According to Wood, these amino acid sequences can be used to rapidly purify recombinant protein drugs, cutting costs by reducing the number of chromatography columns needed. When the mixture of proteins from the cells are passed through a chromatography column, he explains, the tag is immobilized on a solid support resin. The rest of the proteins can be washed through.
“The problem historically with affinity tags is a concern that they’re immunogenic,” he explains. “The worry is that the patient might develop antibodies against the tag, and then any other drugs using that tag would be off limits.”
To get around that problem, Protein Capture Science provides a cell-cleaving protein as the tag. When it becomes immobilized on the chromatography resin, a change in pH is used to trigger self-cleavage of the tag from the purified protein.
It’s among a couple of approaches for effective tag cleaving, notes Wood. These include a system using an engineered Caspase-2 protease developed by a team in Austria. Other potentially impactful technologies include alternative expression hosts, such as Thermothelomyces heterothallica C1, a filamentous fungus believed to be faster for manufacturing some proteins than traditional FDA-approved techniques.
