Continuous cold ethanol precipitation of immunoglobulin G from human plasma

Abstract

Currently intravenous immunoglobulin G (IVIG) is manufactured by cold ethanol precipitation in batch, which results in a slow process with a high footprint due to the use of large tanks. A batch precipitation method using ethanol for the production of IVIG from “cryo-poor plasma”, a starting material obtained after removal of cryoprecipitate from thawed fresh frozen plasma was rendered into a continuous method using a tubular reactor. This reactor consisted of double jacketed stainless-steel tubes filled with static mixers for efficient cooling, because the heat transfer in stainless steel is very high. The pH adjusted, precooled plasma and ethanol were fed into a tubular reactor and cooled down to − 7 °C and precipitation was induced and completed after having left the reactor. The precipitate at the reactor effluent was harvested by tandem precoat filtration or pseudo continuous batch centrifugation. Yield and purity were in the same range as the batch precipitation method, with 95% yield. Even with a residence time of one minute, complete precipitation with same yield and purity could be achieved. A tubular reactor with a length of 3.5 m and 3.7 cm internal diameter would be suited to process 4000 L of plasma per day. This concept will be the basis to substantially shrink the plant footprint of new plants or be a way to intensify existing manufacturing plants.