Emerging technology
Virus removal filters, due to the nature of their use, were originally designed as single use systems, and can be easily adapted to newer modular, disposable facility systems. One generally accepted drawback to current virus filter technologies, however, is the higher cost.
Here, we discuss potential technologies, pre-commercial or established, that have the potential to be eventually adapted as an orthogonal option to traditional virus filters.
Depth filters, as previously discussed, have been used as prefilters for viral filtration. However, due to the batch-to-batch variety in diatomaceous earth derived depth filters, they are rarely claimed for viral clearance. Recent advances in synthetically derived depth filtration media show increased process performance and batch-to-batch consistency. Due to these improvements, the newer depth filters have been posited as orthogonal viral clearance components to the traditional nanofilters used for viral filtration. In general, depth filters have already been adapted for high-density continuous culture systems (Oh, Choi et al. 1994) and for the higher load titers. The newer synthetic depth filters also show higher clearance levels of host-cell derived impurities (Khanal, Singh et al. 2018, Nguyen, Langland et al. 2019). Therefore, these newer single-use depth filters offer an orthogonal option to viral clearance especially in a continuous process with longer processing times and increased impurity and overall titer profiles. This could also provide longer lifetimes for viral filters and extend their ability to economically filter more products, a bonus for a continuous flow schematic. Studies are needed, however, to show viral clearance capabilities for these newer depth filter technologies. In addition, vendors are building data sets to more strongly establish viral clearance capabilities.
Beyond traditional filtration technologies, there are many exciting technologies in pre-commercial stages that could be developed and adapted to process scale. These include the use of electrospun nanofibers (Zeytuncu, Ürper et al. 2018), crystalline cellulose nanofibers (Metreveli, Wågberg et al. 2014), ceramic capillary membranes (Bartels, Batista et al. 2019), or isoporous self-assembled block copolymer films (Shethji, Dorin et al. 2019). The advent of adsorptive hybrid filters (Singh, Arunkumar et al. 2017) could allow for two-step purification schematics for biotechnology products. Issues, however, of orthogonality for viral clearance validation purposes, could arise with their use.
Another potential cost-saving emerging technology are “filter papers” derived from cellulose that can be applied at the point-of-use and are easily scalable both in filter size and pore-size distribution (Gustafsson, Lordat et al. 2016). Several groups have demonstrated the capability of these nanocellulose filter papers to remove bacteriophage, XMuLV, and MMV (Asper, Hanrieder et al. 2015, Gustafsson, Lordat et al. 2016, Gustafsson and Mihranyan 2016, Gustafsson and Mihranyan 2017, Gustafsson, Gustafsson et al. 2018) as well as the feasibility of use in typical bioprocess fluids e.g. cell culture media (Manukyan, Li et al. 2019, Manukyan, Padova et al. 2019).
While more work is needed until commercial use, many of these technologies offer potential orthogonal and possibly economical options to traditional viral filtration.