The Evolution of Commercial Antibody Formulations

• Published in: Journal of pharmaceutical sciences Vol. 112; no. 7; pp. 1801 - 1810
• Main Author: Mieczkowski, Carl A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023
• Subjects: Antibody; Biologic; Commercial; Formulation; Isoelectric point; ADC; FDA; PS; IgG; DLS; AC-SINS; SC; Formulation; pH; CMC; EMA; PFS; DTPA; Antibody; pKa; EDTA; IV; Tris; Commercial; PEG; Isoelectric point; MES; HC; PK; GRAS; Biologic
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2023.03.026

It has been nearly four decades since the first therapeutic monoclonal antibodies were approved and made available for widespread human use. Herein, US and EU approved antibody formulations are reviewed, and their nature and compositions are evaluated over time. From 1986 through Jan 2023, significant formulation trends have occurred and to represent this, 165 commercial antibody therapeutic formulations were binned into 5 different periods of time. Overall, we have observed the following: 1) The average formulation pH has decreased in recent years by over 0.5 units along with a decrease in variability that is largely driven by non-high concentration liquid in vial presentations for IV administration, 2) The use of certain excipients and buffers such as histidine, sucrose, metal chelators, arginine and methionine has become significantly more common, whereas formulations that contain phosphate, salt, no sugar or no surfactant have fallen out of favor, 3) Overall formulation space has increasingly become more homogenous and has converged in terms of formulation pH and excipient preferences regardless of formulation concentration, drug product presentation, and route of administration, 4) The average calculated isoelectric point (pI) has decreased 0.26 units, and 5) Overall, the average formulation pH and calculated pI for all commercial antibodies surveyed was 6.0 and 8.4, respectively. These trends and formulation convergence may be driven by multiple factors such as advancements in high-throughput computational and analytical technologies, the increased emphasis and understanding of certain developability attributes and formulation principles during lead selection and formulation development, and the adoption of low-risk development platform approaches.