A large number of monoclonal antibodies under pharmaceutical development are low potency molecules and require several mg/kg body weight doses. For patient convenience and in-home administration to reduce cost, self-injections via subcutaneous route are preferred. The Subcutaneous route of administration poses a volume restriction (< 1.5 mL), which necessitates the use of formulations containing high concentration of the drug. The high concentration protein solutions lead to many challenges to processing and manufacture of the drug because of high viscosity, and increased aggregation propensity. This talk will focus on protein-protein interactions contributing to solution viscosity and possible steps required to reduce solution viscosity. The rheological behavior of high concentration antibody solutions under various pH and ionic strength conditions is analyzed by high frequency ultrasonic rheometry. The viscosity of a number of molecules of similar amino acid framework show remarkable difference. The viscosity behavior is systematically investigated to understand the contribution of protein-protein interactions. The role of intrinsic viscosity and net protein charge fails to explain the overall viscosity behavior. Finally, the measurement of dipole moment and its role in overall protein-protein interactions is discussed.

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