Implementing viral clearance in the manufacturing process of plasma-derived therapeutics and biopharmaceutical products ensures that potential viral contaminants and infectious agents are removed from the final product. The virus filtration step, considered to be the most robust and effective viral clearance method, is validated in scale down studies. These studies are typically performed at a contract research organization (CRO) where selected viruses are used in spiking studies and overall achieved viral clearance can be determined. For such studies, a targeted virus spiking approach helps to achieve logarithmic reduction values (LRV) above 4 log10. The goals of this study are to achieve complete viral clearance using both the regenerated cellulose membrane nanofilter (Planova 20N) and hydrophilic modified polyvinylidene fluoride (PVDF) membrane nanofilter (Planova BioEX) and to generate virus LRV data for difficult filtration conditions such as low filtration pressure and filtration with a process pause. In collaboration with a CRO active in viral clearance studies, we evaluated the use of Ultrapure minute virus of mice (MVM) and xenotropic murine leukemia virus (XMuLV) spikes on the two types of Planova filters. Filtrations were performed using a polyclonal h-IgG product and the targeted spike approach in which the product was spiked with either virus to a total virus challenge of 10.5 log10 PFU/m<sup>2</sup>. With large volume testing, complete clearance with a virus LRV above 4 log10 was achieved while having minimal impact on filtration flux. The targeted virus spiking approach avoids unnecessarily high challenges on the virus removal filter during viral clearance studies.

Robust viral clearance on virus removal filters using a targeted virus spiking approach

2019 Spring National Meeting

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