Researchers have discovered that intermediate pressures and flows can cause the worst cases of fouling-up of viral filters during mAb production. The team, from Pennsylvania State University, worked in collaboration with MilliporeSigma to understand how changing the flow through a filter affected how much mAb was accidentally caught in the pores.

The scientists hope their research can help companies better remove viral contamination without clogging the filter, a common challenge in mAb production.

“Viral filtration is an important step in downstream manufacturing, especially for mAbs because they can be contaminated by retroviruses upstream,” explained Joshua Peles, a PhD student at Penn State. “But [one of the challenges] is retention of the therapeutic protein and the transmission of viral particles.”

Tricky balance

According to Peles, the membrane pores need to be the right size to capture the virus while allowing the mAb through. However, this can be a tricky balance as the viruses and mAbs are similar in size. If the pores are too big, many viruses will get through and could endanger patients, he explained. While, if the pores are too small, large quantities of mAb block the pores.

The team investigated how changing the fluid pressure and flow rate through a Viresolve Pro membrane affected how much of a polyclonal antibody (human immunoglobulin G) was retained. The human immunoglobulin was used as a low-cost protein to model mAb behavior.

Peles noted that the researchers discovered that the worst fouling occurred at intermediate operating conditions. High or low flow rates or pressures led to less fouling.

The team is now investigating whether high or low flow is best for companies. They are also planning to create a model that other researchers—and companies—can use to find the best operating conditions to minimize filter fouling.

“Our objectives have always been to identify general trends in performance or in the rate of fouling under different operating conditions, to help [industry] work out which conditions best meet their needs,” said Peles. “It’s [currently] hard for us to say which flow conditions are best as we need to weigh whether they also affect the rate at which viral particles get held back. That’s a balance we need to define.”

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