Global pore blockage - cake filtration model including pressure effects on protein fouling in virus filtration

Abstract

Virus removal filtration is a key step in the manufacture of monoclonal antibodies and serum-derived products. There is significant interest in developing continuous biomanufacturing processes for these products, requiring operation at much lower operating pressures/fluxes than those used in batch operations. The objective of this study was to examine the effect of low operating transmembrane pressure (TMP between 0.2 and 5 psi) on the fouling rate and fouling mechanisms during filtration of human serum Immunoglobulin G (hIgG) through the Viresolve® Pro membrane. At equal throughput, the extent of flux decline increased with increasing pressure, with the greatest flux decline observed at TMP ≈ 5 psi, before decreasing at higher pressures. A flux decline model based on fouling by intermediate pore blockage followed by cake formation was developed and shown to be in good agreement with the experimental data. The data at low pressures were combined with previously published results at high TMP (10–60 psi) to develop a global fouling model that was valid at all TMP. The rate of pore blockage decreased with increasing TMP, whereas the cake filtration parameter increased with increasing TMP, with the latter likely reflecting the compressibility of the fouling deposit. The observed transition between intermediate and complete pore blocking occurred around a Péclet number equal to one, corresponding to TMP between 5 and 10 psi, suggesting the importance of protein diffusion on membrane fouling. These results provide important insights into the effects of pressure on both the rate and mechanisms controlling protein fouling during virus removal filtration.