title: Anion exchange chromatography provides a robust, predictable process to ensure viral safety of biotechnology products.
abstract: The mammalian cell-lines used to produce biopharmaceutical products are known to produce endogenous retrovirus-like particles and have the potential to foster adventitious viruses as well. To ensure product safety and regulatory compliance, recovery processes must be capable of removing or inactivating any viral impurities or contaminants which may be present. Anion exchange chromatography (AEX) is a common process in the recovery of monoclonal antibody products and has been shown to be effective for viral removal. To further characterize the robustness of viral clearance by AEX with respect to process variations, we have investigated the ability of an AEX process to remove three model viruses using various combinations of mAb products, feedstock conductivities and compositions, equilibration buffers, and pooling criteria. Our data indicate that AEX provides complete or near-complete removal of all three model viruses over a wide range of process conditions, including those typically used in manufacturing processes. Furthermore, this process provides effective viral clearance for different mAb products, using a variety of feedstocks, equilibration buffers, and different pooling criteria. Viral clearance is observed to decrease when feedstocks with sufficiently high conductivities are used, and the limit at which the decrease occurs is dependent on the salt composition of the feedstock. These data illustrate the robust nature of the AEX recovery process for removal of viruses, and they indicate that proper design of AEX processes can ensure viral safety of mAb products.
authors.affiliation: Process Research and Development, Genentech, Inc., One DNA Way, South San Francisco, California 94080, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Strauss
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gorrell
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plancarte
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Blank
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
mesh_terms: D000911:Antibodies, Monoclonal / Q000302:isolation & purification*; D001709:Biotechnology / Q000379:methods*; D002852:Chromatography, Ion Exchange; D004203:Disinfection / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D014780:Viruses
chemical_list: D000911:Antibodies, Monoclonal; D004364:Pharmaceutical Preparations