A perspective on high-concentration spray-dried monoclonal antibody suspensions for subcutaneous delivery

Abstract There is a growing demand in the subcutaneous delivery of monoclonal antibodies (mAbs) to reduce treatment burden for both patients and healthcare systems when compared to intravenous administration. However, it poses significant challenges in formulation development primarily due to high viscosities in highly concentrated solutions of mAbs for subcutaneous injection, which impacts injectability and effective dosing. Advances in protein spray drying have enabled the production of solid protein powders with enhanced stability. When suspended in non-aqueous media, these spray-dried powders facilitate the achievement of protein concentrations far exceeding 200 mg/mL to overcome challenges associated with high-concentration formulations for biologics such as solubility, viscosity, and aggregation. This perspective aims to discuss recent studies showcasing the successful application of spray-dried proteins to achieve high protein concentrations; key formulation aspects of protein spray drying with respect to subvisible particles; formulation considerations for spray-dried protein suspensions in non-aqueous media; technical and regulatory challenges for subcutaneous delivery of non-aqueous suspensions for mAbs; their knowledge gaps in clinical translation; and the need for patient-centric studies to enhance patient experience, providing insights into how future research can better balance quality and compliance. Finally, with the growing exploration of drying technologies, this article discusses the future outlook for high-concentration suspensions of therapeutic proteins.