(146d) Understanding Fouling Mechanisms in Virus Filtration of Biotherapeutic Proteins

Virus filtration is an important step in the purification of monoclonal antibodies to ensure the safety of the product. Filters are designed to remove viruses down to approximately 20 nm in diameter from protein solutions, in which the product of interest is approximately 8 nm. Because of the small size difference between the product and the virus, virus filters can be prone to fouling by impurities in the process stream, such as protein aggregates. Understanding the mechanisms of fouling enables better design of both filters and filtration processes.

To better understand the mechanisms driving filtration performance, two feeds were identified: one dominated by size-based fouling and one with a significant pressure or velocity dependent fouling component. Fits of the filtration data to a combined blocking-adsorption fouling model confirmed a difference in the balance between pore blocking and inferred adsorptive fouling between the two feeds. The effects of both membrane characteristics (including structure and chemistry) and filtration process conditions were investigated to determine the impact on throughput performance and on the location and extent of fouling for the two feeds.

The fouling behaviors exhibited by each of the feeds are relevant for commercial therapeutic proteins, highlighting the importance of having a good understanding of process fluids in order to determine the best strategies to mitigate fouling.