Inactivation of parvovirus B19 during STIM-4 vapor heat treatment of three coagulation factor concentrates

Abstract

Background: To enhance the viral safety margins, nanofiltration has been widely integrated into the manufacturing process of plasma-derived medicinal products. Removal of smaller agents such as parvovirus B19 (B19V) by filtration, however, is typically less efficient. Because recent investigations have demonstrated that B19V may be more heat sensitive than animal parvoviruses, the potential B19V inactivation by a proprietary vapor heating procedure (STIM-4) as incorporated into the manufacturing processes of several nanofiltered coagulation factor concentrates was investigated.

Study design and methods: An infectivity assay based on quantitative reverse transcription-polymerase chain reaction (TaqMan, Applied Biosystems) detection of B19V mRNA after inoculation of a permissive cell line (UT7 Epo S1 cells) was used to investigate the virus inactivation capacity of the STIM-4 vapor heat treatment as used during the manufacture of nanofiltered second-generation Factor VIII inhibitor-bypassing activity (FEIBA), F IX complex, and FVII products.

Results: In contrast to animal parvoviruses, both B19V genotypes investigated, that is, 1 and 2, were shown to be surprisingly effectively inactivated by the STIM-4 vapor heat treatment process, with mean log reduction factors of 3.5 to 4.8, irrespective of the product intermediate tested.

Conclusion: The newly demonstrated effective inactivation of B19V by vapor heating, in contrast to the earlier used animal parvoviruses, results in significant B19V safety margins for STIM-4-treated coagulation factor concentrates.