Behavior of Monoclonal Antibodies: Relation between the Second Virial Coefficient (B ) at Low Concentrations and Aggregation Propensity and Viscosity at High Concentrations

Purpose: To investigate relationship between second virial coefficient B and viscosity and aggregation propensity of highly concentrated monoclonal antibody (MAbs) solutions. Methods: Intermolecular interactions of 3 MAbs solutions with varying pH were characterized according to B2 estimated by analytical ultracentrifugation sedimentation equilibrium with initial loading concentrations <10 mg/mL. Viscosity measurements and stability assessments of MAb solutions at concentrations higher than 100 mg/mL were conducted. Results: B of all MAb solutions depended on solution pH and have qualitative correlation with viscosity and aggregation propensity. The more negative the B values, the more viscous the solution, acquiring increased propensity to aggregate. Solutions with B values of ~2×10 mL·mol/g acquire similar viscosity and aggregation propensity regardless of amino acid sequences; for solutions with negative B values, viscosity and aggregation propensity differed depending on sequences. Results suggest attractive intermolecular interactions represented by negative B values are influenced by surface properties of individual MAbs. Conclusions B can be used, within certain limitations, as an effective indicator of viscosity and aggregation propensity of highly concentrated MAb solutions. © Springer Science+Business Media, LLC 2011.