Orthopox viruses and the safety margins of solvent-detergent treated plasma-derived medicinal products.

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The currently ongoing outbreak of monkeypox virus in many non-endemic countries around the world has also raised concerns about the safety of plasma-derived medicinal products. Based on what is known about the poxviridae, that is, that members are exceedingly large and carry a lipid envelope, effective removal and inactivation by plasma product manufacturing processes is expected. For the widely used solvent-detergent (S/D) treatments, however, poxviruses have been reported as potentially being a bit more resistant. Using a S/D mixture comprising tri-n-butyl-phosphate, polysorbate 80 and Triton X-100 (TX-100), inactivation of vaccinia virus (a model closely resembling monkeypox virus, both within the same genus, i.e., Orthopoxvirus) in a plasma-derived process intermediate was analyzed over 60 min. As use of Triton X-100 will, based on environmental concerns, be restricted, similar experiments were conducted with a physicochemically virtually identical alternative, Nereid. Fast inactivation of vaccinia virus to the assay detection limit, that is, reduction of infectivity by greater than 4 log10 within 10-20 min, was measured for the TX-100 S/D mixture. The alternative S/D mixture (Nereid instead of TX-100) was found fully equivalent. As for other lipid-enveloped viruses, treatment of process intermediates with S/D mixtures containing TX-100 or the closely related detergent Nereid are highly effective in inactivating poxviruses. Thus, the current spread of monkeypox virus does not compromise the viral safety margins of plasma-derived medicines.