Virus reduction in an intravenous immunoglobulin by solvent/detergent treatment, ion-exchange chromatography and terminal low pH incubation.

ABSTRACT

Virus reduction by several steps in the manufacturing process for the intravenous immunoglobulin Vigam(®), has been investigated. The solvent/detergent step based on treatment with 0.3% tri-n-butyl phosphate and 1% polysorbate 80 at 37 °C, was confirmed to be effective for a range of enveloped viruses. Virus infectivity was undetectable i.e. >6 log inactivation within 30 min of the standard 6 h process. This was consistent over the range of conditions tested i.e. solvent/detergent and protein concentration, temperature and pH. The ion-exchange chromatography step in the process was also able to remove some viruses. Virus spiked followed by blank column runs confirmed the effectiveness of the sanitisation step for ensuring there was no virus cross contamination between column runs. The terminal low pH incubation step was also able to inactivate enveloped viruses, as well as some non-enveloped viruses. The combination of these three steps ensures a high margin of virus safety for this product.