Probing effects of additives on the filterability of oncolytic viruses via a microfiltration process

One major part of therapeutic oncolytic viruses (OV) manufacturing is a membrane-based process with a major challenge of membrane fouling and consequent product loss. A small-scale microfiltration setup was developed, allowing online transmembrane pressure (TMP) measurement through a constant flux filtration using a low volume of a representative OV solution (< 3 mL). Using this setup, the effects of different additives including various proteins (bovine serum albumin and alpha-lactalbumin) and organic polymers (polyethylene glycol and polyvinylpyrrolidone) on microfiltration of the OV solution were screened. Results demonstrated that examined proteins significantly decreased membrane fouling rates and increased the virus recoveries. An addition of 5% bovine serum albumin (BSA) to the virus solution increased the virus recovery about 6-times compared to microfiltration of the virus solution without any additive. In contrast, none of the organic polymers could imitate effects of the protein additives. In a separate set of experiment, to study effect of protein on the membrane surface, the membrane surface was pre-blocked using a BSA protein solution and then subsequently utilized to filter the virus solution. This result also demonstrated a significant increase in virus recovery through the blocked membrane, about 4-times higher virus recovery compared to a non-blocked membrane.