engleski

Purification of human immunoglobulins using ion- exchange monolithic columns

Intravenous immunoglobulin (IVIG) is a blood product prepared from human serum. Its use is indicated for treatment of various diseases with antibody deficiencies. IVIG has become a major plasma product of the global blood product market and in the last twenty years consumption of IVIG has increased about 7 % per year. For satisfying market needs it is necessary to collect larger quantities of human plasma and improve purification process. Selective ethanol precipitation is still the basis of human plasma processing to raw fractions, but chromatography is gaining increasing interest for IVIG fine purification. Goal of the improvement of the purification process is to obtain high yields and include virus removal/inactivation techniques resulting in high safety. Very important step of IVIG production is also stabilization during manufacturing and storage since aggregation tendency is common in protein based therapeutics. In addition to salt, various excipients such as sugars and amino acids are added to IVIGs to provide stabilization and result in formulation exhibiting high tolerability and low risk of adverse events. The aim of this work was to test a purification setup using two-step ion-exchange monolith chromatography including virus inactivation step using Tween/TnBP which was successfully removed in the cation-exchange step. Process was tested on small and medium scale with high efficiency and monitored regarding protein purity, osmolality, IgA removal, aggregation and anticomplementary activity. Several final formulation compositions were tested. Purification on monoliths exhibited very good recoveries, with substantial depletion of IgA and very low aggregation level in the final product.

immunoglobulin; monoliths; purification

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