Effect of solution pH on protein transmission and membrane capacity during virus filtration

Abstract

Although virus filtration is now an integral part of the overall viral clearance strategy for the purification of many commercial therapeutic proteins, there is currently little understanding of the factors controlling the performance of the virus filters. The objective of this study was to examine the effects of solution pH on protein transmission and capacity during virus filtration. Data were obtained using bovine serum albumin as a model protein with Viresolve 180 membranes oriented with both the skin-side up and skin-side down. Membranes were also characterized using dextran sieving measurements both before and after protein filtration. Membrane capacity and protein yield were minimal at the protein isoelectric point, which was due to the greater degree of concentration polarization associated with the smaller protein diffusion coefficient at this pH. In contrast, the actual protein sieving coefficient was maximum at the protein isoelectric point due to the absence of any strong electrostatic exclusion under these conditions. The yield and capacity were both significantly greater when the membrane was oriented with the skin-side down. These results provide important insights into the effects of solution conditions on the performance of virus filtration membranes for protein purification.

The effects of buffer condition on the fouling behavior of MVM virus filtration of an Fc‐fusion protein

“…Previous studies (Bakhshayeshi & Zydney, 2008;G. R. Bolton, Spector, & LaCasse, 2006;Dishari et al, 2015;Hongo-Hirasaki, Komuro, & Ide, 2010;Rayfield et al, 2015;Wickramasinghe, Stump, Grzenia, Husson, & Pellegrino, 2010) show that buffer conditions, including pH, buffer type, and ionic strength could affect the filtration performance of the virus filters.…”

Role of electrostatic interactions during protein ultrafiltration

“…A few years later, Malone et al [11] demonstrated that the hindered diffusion coefficient of latex particles through synthetic track-etched mica membranes was significantly reduced at low salt concentrations, a phenomenon that they attributed to the stronger electrostatic interactions at low ionic strength. Subsequent studies extended these observations to pressure-driven filtration of charged proteins through a range of commercial ultrafiltration membranes with different surface charge characteristics and under different solution conditions [6,[12][13][14][15][16][17][18].…”

Viral clearance for biopharmaceutical downstream processes

“…Filtration through virus retentive filters is currently a key unit operation during the production of biopharmaceuticals [27][28][29][30]. Careful process design and appropriate validation are critical for the successful implementation and performance of virus retentive filters [13].…”