Study Models
As discussed previously in this review, validation and the development of viral filtration processes require scaled-down models studies. However, these studies can be laborious, costly, and time-consuming. Inadequate study design can translate into improperly sized filters. Under extreme circumstances, reprocessing may be triggered due to filtration failure or fouling at process scale. The advent of newer strategies to improve model design would reduce some of these hinderances to representative modeling at small scale. One such strategy is the use of high throughput process development (HTPD) proposed for resin screenings for viral filtration (Brown, Johnson et al. 2017, Brown, Burnham et al. 2018, Brown, Burnham et al. 2018). Filter plate technologies in combination with automated liquid and plate handling systems allow for high throughput analytics in filter process development. Screening of process conditions (e.g. load conditions) that may impact critical process parameters (e.g. flux decay ) can be performed rapidly. Initial work by Tang et al (Tang, Ramos et al. 2020) provided a framework for HTPD filter plate screening with recombinant proteins. These tools can rapidly screen out failure mode conditions early in process development.
Other new technologies that can aid in refining filter process development include particle tracking technologies. These particle tracking technologies use gold or fluorescent particles, as mentioned previously, but can only track aggregate particle movement. These technologies can be used to model flow and the impacts of flow interruptions. One drawback is that these studies tend to have high material costs. The advent of single-particle tracking technologies such as the nanoparticles presented by Wu et al 2020 have been used in PVDF membrane filters. n these technologies, nanoparticles are continuously imaged, such as with an optical microscope, and tracking algorithms implemented to localize particle positions and generate trajectories (Wu and Schwartz 2020) which theoretically could be adapted to viral filtration flow studies.