Removal of small parvoviruses from highly purified proteins can be performed using normal-flow filters. The entrapment of protein aggregates, denatured proteins and other impurities can cause plugging and a decrease in filter capacity. In the present study a variety of prefilters were investigated for their ability to remove the species that foul Viresolvetrade mark NFP (normal-flow parvovirus) filters. The Viresolvetrade mark Prefilter, which utilizes entrapped diatomaceous earth to hydrophobically bind fouling species, provided a dramatic increase in virus filter capacity for solutions containing human IgG or a variety of monoclonal antibodies. We found that the component of the human IgG stream that bound to the Prefilter, when analysed using SDS/PAGE, isoelectric-focusing, size-exclusion chromatography, CD and ANS (1-anilinonaphthalene-8-sulphonate) titration, consisted of monomeric IgG variants containing more exposed hydrophobic surfaces. The bound component may represent oxidized or otherwise degraded IgG species or a subset of IgG molecules with more hydrophobic antigen-binding surfaces. The results indicate that NFP membranes do not foul solely as a result of entrapment of protein aggregates in the pore structure. The Viresolvetrade mark Prefilter has a high permeability, did not diminish protein yield and provided consistent performance between different media lots, device lots and device scales.