title: Pathogen safety of intravenous Rh immunoglobulin liquid and other immune globulin products: enhanced nanofiltration and manufacturing process overview.
abstract: Plasma products for therapeutic use pose specific challenges in manufacturing to ensure products maintain biologic activity and are safe with respect to contamination and transmission of disease-causing agents. Various processes have demonstrated effectiveness in eliminating, reducing, or inactivating viral contaminants. Recently, the possibility of transmitting variant Creutzfeld-Jakob disease (vCJD) or transmissible spongiform encephalopathies (TSE) through blood-based products has become a concern. The present study involves the validation of a hyperimmune immunoglobulin manufacturing process incorporating a nanofiltration step with a nominal pore size of 20 nm for removal of viral contaminants and other adventitious agents. Processing intermediates during the manufacture of IV Rh IgG (WinRho SDF/WinRho SDF Liquid, Cangene Corporation, Manitoba, Canada) were spiked with model viruses and processed in scaled-down procedures to validate the viral reduction capacity of each step. Anion-exchange chromatography and solvent/detergent steps are known to contribute to virus removal and inactivation. The Planova 20 N nanofiltration step was effective in reducing model viruses representing a wide range of viral morphologies with varying degrees of resistance to physicochemical inactivation. All in-process and final batch testing met current standards for production of IV Rh IgG manufactured with the previously licensed filter, which had a larger nominal pore size of 35 nm. The manufacturing process, employing a Planova 35 N filtration step, has been proactively improved by the change to a smaller-pore 20 N filter. Replacement of the 35 N filter with the 20 N filter produces a similar product while enhancing the capability for removal of smaller viruses and prions.
authors.affiliation: Product Development, Cangene Corporation, Winnipeg, Manitoba, Canada.
authors.forename: Lori
authors.initials: L
authors.lastname: Soluk
authors.forename: Hugh
authors.initials: H
authors.lastname: Price
authors.forename: Chris
authors.initials: C
authors.lastname: Sinclair
authors.forename: Dina
authors.initials: D
authors.lastname: Atalla-Mikhail
authors.forename: Maurice
authors.initials: M
authors.lastname: Genereux
mesh_terms: D001782:Blood Donors; D002852:Chromatography, Ion Exchange; D007136:Immunoglobulins / Q000302:isolation & purification*; D036103:Nanotechnology; D011328:Prions / Q000302:isolation & purification; D018029:Rho(D) Immune Globulin / Q000302:isolation & purification; D013048:Specimen Handling; D014462:Ultrafiltration; D038301:Virus Inactivation; D014780:Viruses / Q000302:isolation & purification
chemical_list: D007136:Immunoglobulins; D011328:Prions; D018029:Rho(D) Immune Globulin