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.