UNIVERSITY PARK, Pa. – Antibody injections are a highly desirable treatment for people with chronic conditions such as cancer, psoriasis, Crohn’s disease, and arthritis. And recently, antibodies have made headlines as a promising treatment for severe cases of COVID-19.
But the expensive and time-consuming manufacturing process to produce antibodies prevents these treatments from being available to most patients.
Andrew Zydney, President Bayard D. Kunkle and professor of chemical engineering at Penn State, has identified a new method of manufacturing antibodies, which could reduce production costs. His research results were recently published in Biotechnology Progress.
“If you look at the top 10 selling drugs, in terms of annual sales, eight fall into the monoclonal antibody category,” Zydney said. “And each year, individuals and insurance companies spend more than $ 100 billion on antibodies, with the costs of treating a single patient often exceeding $ 50,000. There remains a huge unmet need for these products in the treatment of a growing range of diseases. ”
Known as precipitation, Zydney’s new protein purification process involves adding zinc chloride and polyethylene glycol, a water-soluble polymer, to a solution containing the antibody. This causes the antibody to precipitate so that the impurities can be removed.
Although the precipitation process has been used for 70 years in the treatment of blood plasma, it has never been used for the commercial production of antibodies, according to Zydney.
“To precipitate means to ‘come out’ of a solution in a solid form,” he said. “For example, when you put salt in lukewarm water, it dissolves. But if you put a lot of salt in cold water, some of that salt will remain as solid crystals. Likewise, proteins would normally dissolve in solution, but you may find certain conditions where they come out as a solid.
Zydney explained that the zinc chloride used in precipitation is a simple salt, which makes it much cheaper than other purification methods. It also saves time, as it is possible to produce large amounts of protein in a short time.
Currently, antibodies are produced using a process called protein A affinity chromatography, where the antibody binds to protein A, which is immobilized in a chromatography column. Impurities can be removed by washing the bound antibody, after which the pH level is adjusted to recover the purified antibody product. A single protein A chromatography column can cost over $ 10 million.
“This is just one step in the current manufacturing process, and that’s what makes making antibodies so expensive,” Zydney said. “All the big biotech companies are big players in this space. ”
The precipitation process eliminates the need for the expensive chromatography process, as the antibodies are purified directly from solution by filtration through hollow fiber membranes.
“What we’re doing in our research group is on a relatively small scale,” he said. “But the precipitation process has the potential to be easily scaled up, potentially allowing biopharmaceutical companies to produce antibodies more cheaply for patients who need them.”
Todd Przybycien, professor of chemical and biological engineering at Rensselaer Polytechnic Institute, contributed to this research.
The National Science Foundation’s Grant Opportunities for Academic Liaison with Industry (GOALI) program supported this work. As part of the grant, Zydney’s research group collaborated with Boehringer Ingelheim, a leading biopharmaceutical company that produces antibodies.