Chemical, Clinical, and Immunological Studies on the Products of Human Plasma Fractionation. Xxxvi. Inactivation of the Virus of Homologous Serum Hepatitis in Solutions of Normal Human Serum Albumin by Means of Heat 12

Purification of human albumin by the combination of the method of Cohn with liquid chromatography

“…Viral inactivation was performed by pasteurization at 60 o C for 10 h (11,12). The final product was bottled in a vial containing 50 ml albumin at a concentration of 20%.…”

A Study of Eight Heated Plasma Protein Preparations

“…Three of the preparations, designated [1], [2] and [3], were in the first group and five, designated [E], were in the second. The methods of production will be described briefly and are summarized in Table I. 1953 Preparation [1] was iiia(le by heatinig for 10 hours at 600 C plasnma wlvich liad l)een irra(liated with ultraviolet light according to the requirements of the National Institutes of Health (5) and in which standard acid-citratedextrose (6) had been used as an anticoagulant.…”

“…Ultraviolet irradiation, which at one time seemed quite promising, proved incapable of inactivating the hepatitis virus at radiation doses which allowed preservation of the integrity of the plasma proteins. Another physical agent, heat, has demonstrated the ability to reduce markedly, if not completely eliminate, the hepatitis risk in human albumin (3). In this situation an albumin solution containing a stabilizer is heated for 10 hours at 600 C. This treatment does not modify the protein to an extent which makes it unsuitable for infusion.…”

“…On the basis of the work of Gellis and associates (3) and of Murray (1) on the heating of albumin, most of the investigators involved decided that a major effort should be devoted to developing a plasma derivative which could be heated without adversely affecting the constituent proteins. Murray and co-workers had shown previously (4) that the heating of whole plasma for 4 hours at 60°C produced gross changes in the proteins and did not eliminate hepatitis infectivity.…”

The Use of Chromatography to Manufacture Purer and Safer Plasma Products

“…Albumin, prior to the introduction of pasteurization in the 1940s, had been reported to transmit serum hepatitis (Gellis et al, 1948). Albumin prepared using cold ethanol fractionation and pasteurization of albumin in solution at 60 C for 10 hours has not been associated with viral transmission (Cuthbertson et al, 1991;Roberts, 1996a;Finlayson, 1979).…”