The increasing demand for vaccines and gene therapies pushes the need to scale up manufacturing processes, such as producing virions from cell cultures. Gwendal Gränicher of the bioprocess engineering group at the Max Planck Institute for Dynamics of Complex Technical Systems in Magdeburg, Germany, keeps looking for better ways to make more virions.

To reach high cell densities from a culture using a perfusion mode, bioprocessors often rely on membrane-based alternating tangential flow filtration (ATF) or an acoustic settler. In a recent study, Gränicher says, “We could observe up to a three-fold increase regarding virus production yields and less large-sized aggregates when continuously harvesting with an acoustic settler, compared to an ATF system, which was not allowing continuous harvesting.

“This finding can be applicable for other viruses, which would be of large interest especially regarding the generation of viral vectors for gene therapies or vaccinations.”

Using an acoustic settler or ATF system, though, might make enough virus. Both systems “are suitable for large-scale virus manufacturing, as they allow at least a perfusion rate equal to 1,000 liters per day,” according to Gränicher.

Still, systems could be optimized to make even more virions. Gränicher wants to learn more about ATF technologies.

“Knowing the virus product sieving effect for ATF perfusion systems when using different membrane materials with different characteristics—such as the membrane pore size distribution, static charge or hydrophobicity—in order to allow continuous virus harvesting through the membrane would be highly beneficial,” he says. “For example, using polypropylene for hollow-fiber membranes seems to be a promising material, as cell-culture clarification using a depth filter with polypropylene material is well adapted for vaccine production.”

Gränicher and his colleagues can already collect high numbers of virions—up to 7 x 1013 influenza A virions in a 1-liter bioreactor, with up to 70 million cells in a milliliter. Still, manufacturing viral particles in even more efficient ways will improve the bioprocessing of many medicines.

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