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

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 a t 60°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.