Effect of manufacturing process parameters on virus inactivation by solvent-detergent treatment in a high-purity factor IX concentrate

Abstract

Background and objectives: Treatment with solvent-detergent is widely used for ensuring the virus safety of plasma products. Laboratory studies have shown this procedure to be effective for inactivating enveloped viruses under manufacturing conditions. In the present study, the effect of different manufacturing process parameters on virus inactivation by treatment with polysorbate 80 and tri-n-butyl phosphate were investigated for a high-purity factor IX concentrate in order to evaluate the robustness of this step.

Materials and methods: Samples of factor IX intermediate were obtained, virus was added and the kinetics of virus inactivation followed during incubation. The effect of altering the conditions on virus inactivation was tested.

Results: Solvent-detergent treatment was confirmed to effectively inactivate, i.e. by > or = 5 log, a wide range of representative enveloped viruses under standard conditions. Virus inactivation was consistently effective in a number of different manufacturing batches. Of the parameters tested, only solvent-detergent concentration and temperature significantly effected virus inactivation.

Conclusions: The robustness of the solvent-detergent step for virus inactivation has been confirmed. Using the data generated, appropriate limits can be set for this manufacturing process step.