title: Anion exchange membrane adsorbers for flow-through polishing steps: Part I. Clearance of minute virus of mice.
abstract: Membrane adsorbers may be a viable alternative to the packed-bed chromatography for clearance of virus, host cell proteins, DNA, and other trace impurities. However, incorporation of membrane adsorbers into manufacturing processes has been slow due to the significant cost associated with obtaining regulatory approval for changes to a manufacturing process. This study has investigated clearance of minute virus of mice (MVM), an 18-22 nm parvovirus recognized by the FDA as a model viral impurity. Virus clearance was obtained using three commercially available anion exchange membrane adsorbers: Sartobind Q®, Mustang Q®, and ChromaSorb®. Unlike earlier studies that have focused on a single or few operating conditions, the aim here was to determine the level of virus clearance under a range of operating conditions that could be encountered in industry. The effects of varying pH, NaCl concentration, flow rate, and other competing anionic species present in the feed were determined. The removal capacity of the Sartobind Q and Mustang Q products, which contain quaternary ammonium based ligands, is sensitive to feed conductivity and pH. At conductivities above about 20 mS/cm, a significant decrease in capacity is observed. The capacity of the ChromaSorb product, which contains primary amine based ligands, is much less affected by ionic strength. However the capacity for binding MVM is significantly reduced in the presence of phosphate ions. These differences may be explained in terms of secondary hydrogen bonding interactions that could occur with primary amine based ligands.
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Weaver
authors.forename: Scott M
authors.initials: SM
authors.lastname: Husson
authors.forename: Louise
authors.initials: L
authors.lastname: Murphy
authors.forename: S Ranil
authors.initials: SR
authors.lastname: Wickramasinghe
mesh_terms: D000327:Adsorption; D000837:Anion Exchange Resins / Q000737:chemistry*; D002852:Chromatography, Ion Exchange / Q000295:instrumentation* / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D008915:Minute Virus of Mice / Q000302:isolation & purification*; D012965:Sodium Chloride
chemical_list: D000837:Anion Exchange Resins; D008567:Membranes, Artificial; D012965:Sodium Chloride