title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Global Pathogen Safety and Molecular Biology, Baxter BioScience, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Berting
authors.forename: Jens
authors.initials: J
authors.lastname: Modrof
authors.forename: Ulrike
authors.initials: U
authors.lastname: Unger
authors.forename: Matthias
authors.initials: M
authors.lastname: Gessner
authors.forename: Andreas
authors.initials: A
authors.lastname: Klotz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Poelsler
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
mesh_terms: D001782:Blood Donors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000378:metabolism; D005374:Filtration; D005612:Freeze Drying; D005838:Genotype; D006358:Hot Temperature; D007700:Kinetics; D049329:Nanostructures; D016732:Parvovirus B19, Human / Q000502:physiology*; D038301:Virus Inactivation; D014835:Volatilization
chemical_list: D004791:Enzyme Inhibitors; D005169:Factor VIII