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

BACKGROUND: 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. STUDY DESIGN AND METHODS: 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. RESULTS: Fast inactivation of vaccinia virus to the assay detection limit, that is, reduction of infectivity by greater than 4 log(10) 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. CONCLUSION: 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.