Overview of the biochemistry and safety of a new native intravenous gamma globulin, IGIV, pH 4.25.

Immune serum globulin has been available for approximately 40 years. Although this substance represented a major advance in the treatment of patients with agammaglobulinemia and hypogammaglobulinemia, it has a number of major limitations that restrict its clinical utility. These include the need for intramuscular administration, pain at the site of injection, loss of immunoglobulin G (IgG) extravascularly, limitations on the degree to which serum IgG can be increased, incomplete and delayed onset of absorption, and limitations on the volume of material administered. Intravenous forms of gamma globulin do not have these limitations and, therefore, have been preferred for therapeutic use. While studying the physical chemistry of IgG in solution, it was observed that lowering the pH to the range of 4.0 to 4.5 markedly enhanced its monomer content and stability, obviating the need for any chemical modification, enzymatic treatment, or lyophilization. A new IgG preparation suitable for intravenous administration, IGIV, pH 4.25, has been developed and subjected to extensive clinical testing. It is licensed in the United States (Gamimune N) for replacement therapy of IgG in immunodeficiency syndromes and for the treatment of idiopathic thrombocytopenic purpura. The biochemistry and safety of IGIV, pH 4.25, are reviewed.