High concentration subcutaneous biological drug products: challenges and advancements.

Subcutaneous (SC) administration is often a preferred approach for biologic therapeutics, offering enhanced convenience, improved patient adherence, and reduced healthcare costs compared to traditional intravenous (IV) infusion. The growing demand for high-dose subcutaneous formulations (HiSubQ), particularly for drugs requiring large doses, has driven advancements and innovations in formulation, manufacturing, device development, and analytical characterization. However, HiSubQ development faces challenges such as protein instability, high viscosity, and complex manufacturing processes. Addressing these hurdles requires innovative protein engineering, formulation strategies, advanced drug delivery devices, and high-resolution analytical tools to ensure stability, injectability, and bioperformance. A strong interdisciplinary collaboration across formulation, device, bioperformance, and analytics is required to drive such innovation. This review provides an overview of SC drug development, emphasizing key advancements in formulation design, biopharmaceutic considerations, device integration, and analytical characterization. We propose tactics and high-level roadmaps that can enable the development of patient-centric solutions to meet the rising demand for SC biologics.