Design Space Assessment of Virus Inactivation in Plasma-Derived Matrices Establishes a Single Detergent Alternative...

The detergent Triton X-100 (TX-100) is a typical component of solvent/detergent (S/D) mixes applied for virus inactivation steps of biomanufacturing processes, yet environmentally unfavorable properties have led to restrictions on its use. Deviron 13-S9 has recently been described as an eco-friendly TX-100 alternative, with powerful virus-inactivating properties determined in matrices representative of recombinant and some plasma-derived process intermediates such as cryo-poor plasma. The present study extends this knowledge via a side-by-side comparison of virus inactivation by Deviron 13-S9, applied as a single detergent, and a traditional TX-100-containing S/D mix, in four plasma-derived matrices, bracketing a broad range of protein concentrations and pH values. Across all conditions, three distinct model/target viruses were rapidly inactivated to below the respective assay detection limit, even at Deviron 13-S9 concentrations as low as 0.05% (v/v), that is, markedly below the lower limits of TX-100 concentrations in current GMP processes. In addition, Vaccinia virus, considered as the worst-case model with respect to detergent-mediated clearance, was inactivated by Deviron 13-S9 with similar kinetics as by a conventional, TX-100-containing S/D mix. Collectively, these results establish equivalent potency for virus inactivation, at a favorable use of only one detergent versus traditional S/D mixes from a biotechnological efficiency perspective.