Effect of manufacturing process parameters on virus inactivation by dry heat treatment at 80 degrees C in factor VIII.

BACKGROUND AND OBJECTIVES: Dry heat treatment at 80 degrees C for 72 h is used as a virus inactivation step for some coagulation factor concentrates such as Bio Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of this process has been tested on a range of viruses. In addition the effect of various manufacturing process parameters on virus inactivation has been investigated. MATERIALS AND METHODS: Samples of product intermediate were obtained from manufacturing, spiked with virus and subjected to freeze drying and dry heat treatment. Virus inactivation was determined by infectivity assay. RESULTS: Freeze drying followed by dry heat treatment was effective for inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or protein concentration had no effect on virus inactivation. Product presentation or the interruption of heat treatment also had no effect. The inactivation of some of the viruses was greater at higher residual water content but under such conditions the stability of the product was reduced. CONCLUSION: This virus inactivation step was effective for a wide range of viruses and over the range of process conditions encountered in manufacturing. This demonstrates the robustness of this process step.

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

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.