title: A step-wise approach to define binding mechanisms of surrogate viral particles to multi-modal anion exchange resin in a single solute system.
abstract: Multi-modal anion exchange resins combine properties of both anion exchange and hydrophobic interaction chromatography for commercial protein polishing and may provide some viral clearance as well. From a regulatory viral clearance claim standpoint, it is unclear if multi-modal resins are truly orthogonal to either single-mode anion exchange or hydrophobic interaction columns. To answer this, a strategy of solute surface assays and High Throughput Screening of resin in concert with a scale-down model of large scale chromatography purification was employed to determine the predominant binding mechanisms of a panel of bacteriophage (i.e., PR772, PP7, and ϕX174) to multi-modal and single mode resins under various buffer conditions. The buffer conditions were restricted to buffer environments suggested by the manufacturer for the multi-modal resin. Each phage was examined for estimated net charge expression and relative hydrophobicity using chromatographic based methods. Overall, PP7 and PR772 bound to the multimodal resin via both anionic and hydrophobic moieties, while ϕX174 bound predominantly by the anionic moiety. Biotechnol. Bioeng. 2017;114: 1487-1494. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Division of Biotechnology Research and Review II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Matthew R
authors.identifier: 0000-0003-2556-2539
authors.initials: MR
authors.lastname: Brown
authors.affiliation: Division of Biotechnology Research and Review II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: Division of Biotechnology Research and Review II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Brorson
authors.affiliation: Division of Biotechnology Research and Review II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Lute
authors.affiliation: Merck, Sharp, and Dohme, MRL, BioProcess Development, Biologics and Vaccines, Kenilworth, New Jersey.
authors.forename: David J
authors.initials: DJ
authors.lastname: Roush
mesh_terms: D000327:Adsorption; D000837:Anion Exchange Resins / Q000737:chemistry*; D000838:Anions; D001435:Bacteriophages / Q000737:chemistry*; D001665:Binding Sites; D002852:Chromatography, Ion Exchange / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D055672:Static Electricity; D014771:Virion / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D000837:Anion Exchange Resins; D000838:Anions
keywords: binding mechanism; chromatography; high throughput screening; hydrophobicity; multi-modal; viral clearance