Viral filtration is an essential process step for ensuring the safety of a biological product by robustly clearing viral particles through a size-exclusion mechanism. Implementation of a cost effective viral filtration step, where the filtration area is optimized for maximum filtration volumetric throughput or mass loading while maintaining maximum viral clearance, is the ultimate goal of filtration step development. The filtration capacity is usually evaluated during viral validation at small scale, where pre-filters (e.g. Viresolve® Pro Shield) and also intermediate in-line sterile filtration can be utilized to improve filtration throughput upon introduction of virus (i.e. spiked pools) to the filtration stream. The viral filtration performance is highly dependent on the availability of its available pores to clear smaller, enveloped and non-enveloped viruses, sub-visible protein aggregates and foreign particles. These sub-visible particles can foul the filter, leading to decreased volumetric throughput. The intermediate sample handling, transfer method and load composition (e.g. pH, conductivity) were found to be critical in generation of the fouling particulates for monoclonal antibodies that were studied in this case. Biophysical tools such as FlowCam®, Dynamic Light Scattering, and Field Flow Fractionation were used to evaluate the particle generating effects of various transfer methods, load composition and filter setups. This data was used to optimize a small-scale methodology to minimize particle generation and resulted in a higher and robust consistent volumetric throughput and performance for the filtration process step.

Enhancement of viral filtration performance by characterization of the foulant particulates and controlling factors contributing to sub-visible particle formation

251st National Meeting (2016)

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