Human plasma is our most valuable source of therapeutic proteins, and intravenous gamma globulin (IVIg) is the most widely used plasma derivative. Traditional yields of the product from alcohol fractionation are not optimal; added to this, viral contamination and other well known side effects, including fever and aseptic meningitis, continue to be of concern. A method of precipitating very high yields of cryoprecipitable proteins with sodium citrate (“Supercryoprecipitation”) has been previously described. A by-product of “Supercryoprecipitation” is a very clean cryoprecipitate-free plasma supernatant, with a citrate concentration of 5% to 6% (w/v). When up to 10% (w/v) additional citrate is introduced into the supernatant, there is a preferential precipitation of nearly 100% of the remaining gamma globulin. Immunoglobulin G (IgG) yield was measured by radial immunodiffusion (86.3% ± 12.5%). IgG, being the largest fraction of gamma globulin, is most often used as a measure of product quality. Protein electrophoresis of the citrate precipitation product showed very little contamination by other plasma fractions (albumin: 9.8% ± 3.3%, alpha globulin: 1.6% ± 0.6%, beta globulin: 3.9% ± 1.2%, gamma globulin 84.3% ± 13.8%). Unlike present protein precipitation methods, citrate precipitation does not rely on denaturation, thereby better preserving the native structure of immunoglobulin. This may lead to improved tolerance during infusion, and may allow for more rapid infusion rates, or improved subcutaneous infusion. Stability and safety studies are currently underway. Considering the current unsettled climate in the world, the potential for improved gamma globulin therapies and supply should not be overlooked.

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