THE USE OF TRI(N-BUTYL)PHOSPHATE DETERGENT MIXTURES TO INACTIVATE HEPATITIS VIRUSES AND HUMAN-IMMUNODEFICIENCY-VIRUS IN PLASMA AND PLASMAS SUBSEQUENT FRACTIONATION

The treatment of plasma with organic solvent/detergent mixtures at the time of plasma collection or pooling could reduce the exposure of technical staff to infectious viruses and enhance the viral safety of the final product. Treatment of plasma for 4 hours with 2‐percent tri(n‐ butyl)phosphate (TNBP) at 37°C, with 1‐percent TNBP and 1‐ percent polyoxyethylensorbitan monooleate (Tween 80) at 30°C, or with 1‐percent TNBP and 1‐percent polyoxyethylene ethers, (Triton X‐ 45) at 30°C resulted in the rapid and complete inactivation of ≥ 104 tissue culture‐infectious doses (TCID50) of vesicular stomatitis and Sindbis viruses, which are used as surrogates. Treatment of plasma with TNBP and TNBP and Tween‐80 was shown to inactivate ≥ 104 TCID50 of human immunodeficiency virus. TNBP treatment of plasma contaminated with 106 chimpanzee‐infectious doses (CID50) of hepatitis B virus and 105 CID50 of non‐A, non‐B hepatitis virus prevented the transmission of hepatitis to chimpanzees. Immediately after treatment of plasma with 2‐percent TNBP, the recovery of factors VIII, IX, and V and antithrombin III was 80, 90, 40, and 100 percent, respectively. Recovery of all factors was ≥ 90 percent after treatment with TNBP and detergent mixtures. Treated plasma was fractionated by standard techniques into antihemophilic factor and prothrombin complex concentrates, immune globulin, and albumin. Prior treatment with TNBP or TNBP and detergent did not affect the separations of desired proteins. Therefore, it appears possible to inactivate viruses in plasma before the execution of standard fractionation procedures. 1990 AABB