Impact of virus filter pore size/morphology on virus retention behavior

Virus filters provide size-based removal of >99.9% of viruses and virus-like particles during biopharmaceutical processing. Here, we quantitatively evaluate the 3D pore space and virus capture behavior in two commercial virus removal filters with very different morphologies: the highly asymmetric Viresolve (R) Pro and the relatively homogeneous PegasusTM SV4 virus filters. Focused ion beam (FIB) - SEM was used to reconstruct the 3D pore morphology of both virus filters. The PegasusTM SV4 filter had pores that were, on average, significantly larger than 20 nm, which is the size of small parvovirus (as well as the average size of the pore throats near the exit of the Viresolve (R) Pro filter). Virus retention within each membrane was simulated using GeoDict (R), which evaluates the detailed particle trajectories and capture locations through the filter. The PegasusTM SV4 filter showed virus capture throughout a significant fraction of the filter depth, in contrast to virus capture in the Viresolve (R) Pro filter that occurred only in the very small pores in the 2 mu m region near the filter exit. In both cases, viruses were captured in highly restrictive regions within the pore space. These results provide new insights into the impact of pore morphology on virus capture during virus removal filtration.