Nanocellulose-Based Nanoporous Filter Paper for Virus Removal Filtration of Human Intravenous Immunoglobulin

Human intravenous immunoglobulin (IVIG) is a highly valuable plasma-derived biotherapeutic with several important clinical indications in primary and acquired immunodeficiencies as well as autoimmune diseases, especially neuropathies. Ensuring the viral safety of plasma-derived products, such as human WIG, is mandatory. Viral filtration is commonly used to affect viral removal in the manufacture of plasma products. Viral filtration of large volumes of a IVIG feed solution can take significant time, the required filter area can be large, and the resultant total cost of filtration is considerable. Therefore, there is a need for a high-capacity filter, which can process large volumes of plasma-derived biotherapeutic products within a short time at reduced cost. Here, we describe for the first time the performance of a nanocellulose-based virus removal filter paper in the processing of human IVIG, which has the potential to address the above- stated issues. The filter exhibited 5-6 log virus clearance of Phi X174 (28 nm; pI 6.6) or MS2 (27 nm; pI 3.9) phages during the filtration of spiked IVIG solutions (11 mg/mL, pH 4.9). To simulate real-life production conditions, filtration at 288 L/m(2), corresponding to 3 kg of protein/m(2), at 3 bar was undertaken. No substantial filter fouling was evident, with the flux remaining stable throughout filtration at 20-30 L/m(2).h. The predicted volumetric capacity V-max was >= 1700 L/m(2), which corresponds to the processing of >= 19 kg/m(2) of immunoglobulins. A number of characterization tests encompassing size-exclusion high-pressure liquid chromatography, dynamic light scattering, and polyacrylamide gel electrophoresis confirmed immunoglobulin integrity before and after filtration. This study has shown that a mille-feuille filter paper manufacturing process offers the possibility of producing cost-efficient viral removal filters with the required performance capabilities suitable for the processing of plasma-derived immunoglobulins and recombinant monoclonal antibodies.