Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure.

Abstract

Human immunoglobulins are plasma derivatives with a low risk of transmitting viral infections. To the present, no proven case of human immunoglobulins transmitting human immunodeficiency viruses has been reported. However, there have been a few reports on the transmission of hepatitis C virus by these plasma proteins. To improve further the safety of both 5s iv human immunoglobulins and 7s im immunoglobulins, we introduced a 10-hour heat treatment of the aqueous solutions at 60 degrees C (i.e., pasteurization) into the manufacturing procedure. This treatment was not added to the manufacturing procedure of 7s iv immunoglobulin that already contained the S-sulfonation as a virus inactivating method. We now report on experimental data that show that the whole manufacturing procedures of the above immunoglobulins inactivate efficiently hepatitis C virus and that the specific virus inactivation methods alone, namely, pasteurization or S-sulfonation, also inactivate completely viruses of the flavivirus family, to which the hepatitis C virus belongs. The inactivation of the Flaviviridae bovine viral diarrhea virus, tick-borne encephalitis virus, and yellow fever virus by pasteurization or S-sulfonation was at least 10(5). The clearance of HCV achieved by the entire manufacturing process of each of these immunoglobulins was also at least 10(5). The experiments therefore show that pasteurization or S-sulfonation provides a high margin of safety to human immunoglobulins regarding the transmission of hepatitis C virus.