A chromatographic method for the production of a human immunoglobulin G solution for intravenous use

ABSTRACT

Immunoglobulin G (IgG) of excellent quality for intravenous use was obtained from the cryosupernatant of human plasma by a chromatographic method based on a mixture of ion-exchange, DEAE-Sepharose FF and arginine Sepharose 4B affinity chromatography and a final purification step by Sephacryl S-300 HR gel filtration. The yield of 10 experimental batches produced was 3.5 g IgG per liter of plasma. A solvent/detergent combination of 1 per cent Tri (n-butyl) phosphate and 1 per cent Triton X-100 was used to inactivate lipid-coated viruses. Analysis of the final product (5 per cent liquid IgG) based on the mean for 10 batches showed 94 per cent monomers, 5.5 per cent dimers and 0.5 per cent polymers and aggregates. Anticomplementary activity was 0.3 CH50/mg IgG and prekallikrein activator levels were less than 5 IU/ml. Stability at 37oC for 30 days in the liquid state was satisfactory. IgG was stored in flasks (2.5 g/flask) at 4 to 8oC. All the characteristics of the product were consistent with the requirements of the 1997 Pharmacopée Européenne.