Controlled gamma-irradiation mediated pathogen inactivation of human urokinase preparations with significant recovery of enzymatic activity.
Human sources of urokinase have led to the contamination of in-process lots of commercially available material with human pathogens. Effective pathogen inactivation of urokinase preparations can be achieved through the use of gamma-irradiation. Additionally, the presence of a free radical scavenger (ascorbate) and the control of temperature have resulted in maintenance of the enzymatic activity of urokinase without a significant effect on the pathogen inactivation properties of gamma-irradiation. In this study we have optimized the conditions during gamma-irradiation to achieve inactivation of porcine parvovirus by 5 logs and vaccinia virus to levels below the limits of detection, while maintaining 92% of urokinase activity. Product specific optimization of gamma-irradiation has the potential to provide effective pathogen inactivation while maintaining substantial functional activity for many therapeutic proteins.
Amareld
Robert W
RW
Clearant, Inc., 401 Professional Drive, Gaithersburg, MD 20879, USA.
Wersocki
Melissa
M
Drohan
Maureen
M
Drohan
William N
WN
Burgess
Wilson H
WH
Mann
David M
DM
Forng
Ren-Yo
RY
D001688:Biological Products / Q000302:isolation & purification / Q000528:radiation effects; D004340:Drug Contamination / Q000517:prevention & control; D005720:Gamma Rays; D006801:Humans; D066298:In Vitro Techniques; D028323:Parvovirus, Porcine / Q000528:radiation effects; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification* / Q000378:metabolism / Q000528:radiation effects*; D014616:Vaccinia virus / Q000528:radiation effects
D001688:Biological Products; D014568:Urokinase-Type Plasminogen Activator