Researchers working with Bilfinger Life Sciences are hoping to revolutionize downstream bioprocessing by replacing the capture chromatography step with precipitation. The team from the University of Natural Resources and Life Sciences (BOKU) in Vienna has added a filter to capture precipitated monoclonal antibodies in place of Protein A chromatography.
They believe that their technique, which removes the remaining impurities through later processing, could be applicable to a wide range of biopharma products and could allow a fully continuous bioprocess.
“If this works how we think, it could be a game changer because we’d move from chromatography to more simple unit operations,” explains Gabriele Recanati, a second year PhD student from BOKU.
According to Recanati, most of today’s downstream processing depends on chromatography. However, although chromatography columns can be integrated with upstream bioprocessing, they tend to run semi-continuously.
Also, with protein titers increasing in the last 10-20 years, he says precipitation and filtration have become feasible and are more readily scalable. Although manufacturers can overcome this problem by placing multiple columns in series, he notes, it still doesn’t allow for a truly continuous mass flow.
The team is working to overcome this problem by using precipitation for primary separation of proteins, followed by further removal of impurities later. “This makes the process simpler, easier to handle and–as another plus–it’s based on single-use technologies,” he explains, adding that single-use technologies avoid the need to spend time and effort cleaning chromatography columns and validating cleaning procedures and cycles.
The team has run a continuous process manually for six days in the lab so far, with the time limited by the availability of lab staff. Their process, produced products close to the purity of using Protein A (in the range of 1000-10000 ppm), says Recanati.
“I’d say that, already in the literature, there’s proof you don’t need high purity in the first stage of capture, and you can remove impurities later,” he tells GEN, pointing out that Protein A chromatography is expensive.
Recanati will be presenting on his technology at the Bioprocessing Summit Europe in March 2022. The team is currently preparing for longer runs and is planning a pilot-scale test of the technology–potentially as early as next month.