Monoclonal antibody formulations: a quantitative analysis of marketed products and patents

Since the approval of OKT3® in 1986, monoclonal antibodies (mAbs) have become a cornerstone of modern therapeutics. However, their complex physicochemical properties pose challenges, particularly for high-concentration formulation and subcutaneous administration. Excipient selection is crucial for maintaining mAb stability and efficacy, yet existing studies often lack systematic, cross-source analyses. This study integrates data from marketed products and patents to investigate formulation trends and excipient preferences. Data were retrieved from the Drugs@FDA databases, CAS Formulations Database and Derwent Innovation as of December 31, 2024. Extracted information included target, indication, dosage form, route of administration, and formulation composition. The associations between formulation-related factors (e.g., antibody concentration, route of administration) and excipient selection were evaluated using proportion tests. A total of 6,119 patent records and 108 marketed mAb products (covering 388 patented and 141 marketed formulations) were analyzed. Proportion tests revealed significant associations between antibody concentration and the use of histidine (marketed p = 0.0017) and citric acid (marketed p = 0.0047). The route of administration also influenced excipient choice, notably for hyaluronidase (marketed p = 0.0167; patent p = 0.0056). In addition, lyophilized formulations accounted for a relatively small fraction of both marketed (14.18%) and patented (14.69%) products, with sucrose emerging as the predominant lyoprotectant. This study analyzed excipient usage in marketed and patent formulations by time, concentration, and administration route. High-concentration products more frequently included histidine, arginine, and hyaluronidase, while low-concentration ones used citric/phosphoric acid, trehalose, and NaCl. Intravenous formulations commonly used phosphate/citric buffers, while histidine, arginine, hyaluronidase, and methionine buffers were favored for subcutaneous administration. Lyophilized formulations consistently contained sucrose as the main excipient to mitigate freeze-drying stresses. Additionally, surfactants were essential across formulations to prevent surface-induced aggregation. Patent data could provide early indications of emerging formulation strategies, though further validation is needed to confirm their predictive value.