Load conditions
Another parameter known to potentially affect viral filter performance are the conditions at which material is loaded onto the filter. A large number of studies have examined filter performance under wide ranges of loading conditions (such as product type, product concentration, pH, conductivity, and temperature) that are typical for the purification of therapeutic proteins (Marques, Roush et al. 2009, Hongo-Hirasaki, Komuro et al. 2010, Gefroh, Dehghani et al. 2014, Stuckey, Strauss et al. 2014, Strauss, Goldstein et al. 2017). Large virus (e.g., retrovirus, pseudorabies virus, reovirus 3) removal by small virus filters is robust regardless of the load conditions tested. This was consistent with the size exclusion mechanism and was corroborated by clearance results from more than 2000 validation studies spanning over two decades (Stanley, Holmes et al. 2021), as well as the experience from the plasma industry (Roth, Dichtelmüller et al. 2020). When small virus filters were used for parvovirus clearance, virus breakthrough has been reported. Significantly virus breakthrough and lower LRVs can occur as a result of a combination of low operating pressure and certain solution conditions (Strauss, Goldstein et al. 2017). However, at recommended operating pressure, no apparent correlation can be established between virus breakthrough and an individual feedstream condition (Stuckey, Strauss et al. 2014). This points to the importance of operating within the defined robust ranges to ensure effective parvovirus removal. In many cases, feedstream conditions can affect flux or cause filter fouling by modulating interactions of product, virus, and filter membranes (Marques, Roush et al. 2009, Hongo-Hirasaki, Komuro et al. 2010). Therefore, loading conditions can be optimized to improve filter flux and volumetric throughput.