AN INTEGRATED PROCESS FOR THE PRODUCTION OF THERAPEUTICS (HUMAN ALBUMIN, INTRAVENOUS IMMUNOGLOBULINS, CLOTTING FACTOR VIII AND CLOTTING FACTOR IX) FROM HUMAN PLASMA

摘要

The invention relates to an integrated scheme for fractionation and purification of plasma products (human albumin, intravenous immunoglobulin (IVIG), clotting factor VIII and clotting factor IX) by sequential chromatography and virus reduction steps. The therapeutically administrable protein IVIG has purity levels exceeding 98%, aggregates and dimers at less than 0.2%, Fc function of > 90% and anti-complementary activity of less than 0.5 CH50 per mg of Ig. The distribution of IgG isomers is comparable to the ranges seen in normal plasma. Human albumin for therapeutic use, purified by this integrated scheme has an electrophoretic purity of close to 100%, with monomers exceeding 98%. The levels of aluminium and pre-kallikrein activator are below the detection limit for the respective tests. The Factor IX preparations have a specific activity of ? 200 IU/ mg. The impurity levels of Factor-II, Factor VII, Factor X are at least 10-fold lesser (? 0.5% instead of 5%) and the heparin impurity of ? 0.01 IU (against 0.5 IU limit for this impurity) is 50-fold lesser the specified pharmacopoeial limits. The purification carried out by an all-chromatography scheme, avoids the use of ethanol precipitation in the entire manufacturing process of the said four plasma products. The invention describes an integrated process for purifying four different proteins from human plasma to high therapeutic grade purity levels, with a potential to purify more therapeutic proteins from a given plasma sample by incorporating additional chromatography steps in the sequence.