US FDA-approved therapeutic antibodies with high-concentration formulation: summaries and perspectives

Abstract

Thirty four (34) of the total US FDA approved 103 therapeutic antibody drugs, accounts for one third of the total approved mAbs, are formulated with high protein concentration (100 mg/mL or above) which are the focus of this article. The highest protein concentration of these approved mAbs is 200 mg/mL. The dominant administration route is subcutaneous (76%). Our analysis indicates that it may be rational to implement a platform formulation containing polysorbate, histidine and sucrose to accelerate high concentration formulation development for antibody drugs. Since 2015, the FDA approval numbers are significantly increased which account for 76% of the total approval numbers, i.e., 26 out of 34 highly concentrated antibodies. Thus, we believe that the high concentration formulations of antibody drugs will be the future trend of therapeutic antibody formulation development, regardless of the challenges of highly concentrated protein formulations.

Keywords: US FDA; administration route; approval; dosage; excipient; formulation; formulation composition; high concentration; lyophilization; pre-filled syringe; subcutaneous; therapeutic antibodies.