Three generations of immunoglobulin G preparations for clinical use

Abstract

The first purified human immunoglobulin G (IgG) preparation used clinically was immune serum globulin (ISG), which was prepared in the 1940s by E. J. Cohn's group. It was originally formulated in water with 0.3 M glycine at pH 6.8 and was 70%-80% monomeric. ISG was safe when given intramuscularly and efficacious for measles and hepatitis prophylaxis. The next generation of purified IgG began in the 1960s with chemically modified preparations suitable for intravenous administration. The first such IgG intravenous preparation (IGIV) in the United States was IGIV pH 6.8 (Gamimune, Cutter Biological), in which the anticomplement activity found in ISG was removed by reduction and alkylation of disulfide bridges. This product was originally formulated as a 5% IgG solution in water (pH 6.8) with 0.2 M glycine in 10% maltose for stabilization. It remained stable for at least 2.5 years at 5 degrees C, was 80%-90% monomeric, had virtually no anticomplement activity, was safe given intravenously, and was efficacious for prophylaxis in agammaglobulinemic patients. A third generation of purified IgG has since been developed; IGIV pH 4.25, (Gamimune N, Cutter Biological), which was isolated by the Cohn method from human plasma and is safe for intravenous use, is a 5% solution of IgG in water (pH 4.25) with 10% maltose. The product is greater than 99% IgG, greater than 95% monomeric, and has greater than 90% less anticomplement activity than ISG.