Enveloped Virus Inactivation by Caprylate: a Robust Alternative to Solvent-detergent Treatment in Plasma Derived Intermediates

Solvent-detergent treatment, although used routinely in plasma product processing to inactivate enveloped viruses, substantially reduces product yield from the human plasma resource. To improve yields in plasma product manufacturing, a new viral reduction process has been developed using the fatty acid caprylate. As licensure of plasma products warrants thorough evaluation of pathogen reduction capabilities, the present study examined susceptibility of enveloped viruses to inactivation by caprylate in protein solutions with varied pH and temperature. In the immunoglobin-rich solutions from Cohn Fraction II+III, human immunodeficiency virus, Type-1, bovine viral diarrhea virus (BVDV), and pseudorabies virus were inactivated by caprylate concentrations of >/=9 mM, >/=12 mM, and >/=9 mM, respectively. Compared to solvent-detergent treatment, BVDV inactivation in Fraction II+III solution was significantly faster (20-60 fold) using 16 mM caprylate. Caprylate-mediated inactivation of BVDV was not noticeably affected by temperature within the range chosen manufacturing the immunoglobulin product. In Fraction II+III solutions, IgG solubility was unaffected by </=19 mM caprylate. In albumin solution from Cohn supernatant IV-1, 40 mM caprylate rapidly inactivated BVDV, demonstrating versatility in inactivating enveloped viruses potentially present in other protein solutions. Our data show that caprylate is a robust enveloped virus inactivating agent for immunoglobulins and albumin which may potentially be utilized for other proteins; viral inactivation was not adversely affected by protein content and the buffer composition conditions evaluated. Within the parameters examined, caprylate inactivation of enveloped viruses provided comparable activity or advantages relative to the current, standard solvent-detergent treatment.