Development, manufacturing and characterization of a highly purified, liquid immunoglobulin g preparation from human plasma.

Background: The use of plasma-derived immunoglobulin G (IgG) is increasing, and the number of diseases, including immunodeficiencies, neurological diseases and autoimmune conditions, treated with intravenous IgG (IVIG) is expanding. Consequently, there is a great need for high-yield production processes for plasma-derived IgG. The aim of this work was to develop a high-yield process leading to a highly purified, liquid, ready-to-use IgG for intravenous use. Methods: Plasma from healthy, voluntary, non-remunerated donors was fractionated by ethanol precipitation. IgG was extracted from fraction II + Ill using a phosphate/acetate buffer, pH 4, and purified by chromatography. Results: Precipitation with 6% polyethylene glycol at pH 7 removed high molecular-weight contaminating proteins, aggregates and contaminating viruses. Ion exchange chromatography at pH 5.7 on serially connected anion and cation exchange columns allowed for elution of IgG from the cation exchange column in good yield and high purity. Further safety was achieved by solvent/detergent treatment and repeated ion exchange chromatography. The product consisted of essentially only IgG monomers and dimers, and had a high purity with very low levels of IgM and IgA. Conclusion: A process providing highly purified IVIG in good yield was developed.