Ultrasonic rheology of a monoclonal antibody (IgG2) solution: implications for physical stability of proteins in high concentration formulations.

The purpose of this work was to investigate if physical stability of a model monoclonal antibody (IgG(2)), as determined by extent of aggregation, was related to rheology of its solutions. Storage stability of the model protein was assessed at 25 degrees C and 37 degrees C for three months in solutions ranging from pH 4.0 to 9.0 and ionic strengths of 4 mM and 300 mM. The rheology of IgG(2) solutions has been characterized at 25 degrees C in our previous work and correlation of solution storage modulus (G') with protein-protein interactions established. The extent of aggregation was consistent with solution rheology as understood in terms of changes in G' with protein concentration. Thermodynamic stability of native IgG(2) conformation increased with increasing pH. The correlation between rheology and aggregation was also assessed at increased ionic strengths. The decrease in aggregation was consistent with change in solution rheology profile at pH 7.4 and 9.0. The results provide evidence of a relationship between solution rheology and extent of aggregation for the model protein studied. The implications of this relationship for formulation and physical stability assessment in high concentration protein solutions are discussed.