Conclusions
Viral filtration is commonly utilized in a well-designed recombinant
therapeutic protein purification process and is a robust and effective
component in an overall strategy to minimize the risks of adventitious
and endogenous viral particles during the manufacturing of biotechnology
products. .
Key takeaways include:
- There is a consensus based on decades of data that parvovirus filters
robustly remove both small and large viral species in various
processes and product types providing a strong rationale for
performing viral filtration validation studies with small viruses as
worst-case to establish retention claims for larger viruses in
regulatory submissions.
- Worst-case conditions for virus retention include low transmembrane
pressure, pressure transitions, pauses in pressure or flow, and low
flux based on recent data.
- For scale-down models of viral filtration, key considerations include:
- Filter load/feed material, virus spiking strategies, prefilter use,
and the potential impacts of process parameters such as the target
operating pressure, low pressure, a flow pause, and a buffer chase
should be included.
- The viral validation study should be performed under challenging, or
worst case, conditions using representative feed materials.
- High purity and high titer virus stocks are desirable to evaluate
virus removal while maintaining product filtration capacity.
- Virus filters often require prefilters to achieve the desired virus
filter throughput. Prefilters may remove virus when used in-line
with the viral filter, necessitating novel spiking strategies.
- Emerging viral filtration technologies to consider include:
- Viral filtration of media for various manufacturing processing,
including facilities that implement single-use, disposable
manufacturing or newer products like cell and gene therapy.
- New viral filter development strategies include HTPD and filter
plate technologies in combination with automated liquid and plate
handling systems. Particle tracking technologies can be used to
model flow and the impacts of flow interruptions.
- Viral filtration in continuous manufacturing requires new spiking
models such as switch-in and switch-out filtration, filter trains,
and bracketed or daily spiking.
- Depth filters, electrospun nanofibers, crystalline cellulose
nanofibers, ceramic capillary membranes, filter papers derived from
cellulose, or isoporous self-assembled block copolymer films are
potentially new viral filtration modalities that require further
development for commercial application.
Viral filtration will continue to be relied upon to provide robust and
effective viral clearance as the technologies and industry-wide process
knowledge continue to improve.