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.