Validation of adventitious agent safety in Yimmugo®, a novel IVIG preparation for human use

• A novel process for IgG isolation from human plasma has been evaluated concerning safety. • Plasma samples were spiked with infectious agents and infectivity was evaluated. • Four individual preparation steps were found to provide robust elimination of infectivity. • The novel procedure provides a secure IgG preparation for human use. Intravenous infusion of human IgG (IVIG) is of vital importance for patients suffering from primary or secondary immunodeficiency syndromes, but also has been found to be clinically beneficial in other diseases with autoimmunogenic or inflammatory background. Its clinical application and therefore its demand have been continuously rising during the last decades. Besides IgG, other human antibody classes have also entered clinical applications, therefore a novel manufacturing procedure has been conceived which allows simultaneous isolation of two immunoglobulin preparations, Yimmugo™ (an IVIG) and trimodulin (an IgM concentrate). Since the only suitable source for these antibodies is human donor plasma, from which it is isolated using a series of dedicated purification steps, there is a risk of carrying over infectious human pathogens into the final preparations. We describe here validation of the measures taken to provide Yimmugo, an IVIG product, with robust margins of biological safety, free of pathogens of microbial, viral or prion origin. To this end, we spiked manufacturing process intermediates of Yimmugo with diverse pathogens and tested the capacity of the manufacturing steps to clear these from the preparation. We show that four different purification steps of the Yimmugo procedure efficiently confer clearance of viral and prion pathogens, thereby providing a safe product even in the hypothetical case that an infectious agent in the original material were present. Consequently, the novel preparation procedure yields a provably safe product and simultaneously allows production of an additional medicine from the same plasma pool.