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

Since 1986 when we first witnessed the approval of monoclonal antibody (mAb) Orthoclone OKT3 by the US FDA, FDA has approved 103 therapeutic antibody drugs in the past 35 years for marketing. Thirty four (34) of these 103 therapeutic antibody drugs (accounting for one third of the total FDA approved antibody therapeutics) are formulated with high protein concentration (100 mg/mL or above). These 34 high concentration antibodies are the focus of this article. The dosage forms of these 34 antibodies are analyzed and discussed in 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. The top players/sponsors of high concentration formulation are identified as Roche including its subsidiaries Genentech and Chugai, Novartis, Sanofi, Amgen, GSK, Johnson & Johnson including its subsidiary Janssen, and Regeneron. The FDA approval numbers are significantly increased since 2015 which account for 76% of the total approval number, 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.