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Review
. 2021 Nov 18;4(4):262-272.
doi: 10.1093/abt/tbab027. eCollection 2021 Oct.

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

Shawn Shouye Wang  1 , Yifei Susie Yan  2 , Kin Ho  1
Affiliations
Review

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

Shawn Shouye Wang et al. Antib Ther. .

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.

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Figures

Figure 1
Figure 1
Yearly US FDA approval numbers of therapeutic antibodies with high-concentration formulation during 1998–2021. The 2021 year’s data are as of October 2021. Only antibodies with ≥100 mg/mL protein concentration are counted in the data analysis. The first therapeutic antibody with high-concentration formulation (i.e., Synagis/Palivizumab, 100 mg/mL) was approved by US FDA in 1998. Thus, the data analysis in Fig. 1 was started from 1998.
Figure 2
Figure 2
Formulation excipient analysis of US FDA-approved therapeutic antibodies with high-concentration formulation. The formulation excipients of 34 therapeutic antibodies approved by US FDA with high-concentration formulation were analyzed. The frequency of each formulation composition in these 34 antibodies were calculated, and only formulation excipients with more than 5% frequency were presented in Fig. 2.
Figure 3
Figure 3
Dosage form analysis of US FDA-approved therapeutic antibodies with high-concentration formulation. Lyo: lyophilized powder; PFS: pre-filled syringe. Please note that liquid dosage form is liquid in a vial, and the formulation solution in PFS is also liquid.
Figure 4
Figure 4
Administration route analysis of US FDA-approved therapeutic antibodies with high-concentration formulation. IVI: Intravitreal injection; IV: intravenous; IM: intramuscular; SC: subcutaneous.
Figure 5
Figure 5
Sponsors vs. approval number analysis of US FDA-approved therapeutic antibodies with high-concentration formulation.
See this image and copyright information in PMC

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