High-Dose Subcutaneous Administration of Biologics: Overcoming Barriers Through Formulation and Device Innovation.

The therapeutic landscape for biologics is rapidly transitioning from intravenous (IV) to subcutaneous (SC) administration, offering significant benefits in cost reduction and patient convenience through enabling treatment in flexible care settings. This shift necessitates patient-centric SC administration solutions. To address this, two primary innovative strategies are emerging: higher concentration formulations and large-volume SC (LVSC) injection/infusion. Ultra-high concentration biologic (UHCB) formulations, defined here as ≥250 g/L, are actively being pursued as suspensions. These UHCB suspension approaches rely on processing methods to entrap biologics within microparticles of a defined particle size (e.g., spray drying, electrospraying, solvent evaporation and dehydration, alginate, crystals). These UHCB suspension formulations are shear-thinning injectable drug product solutions. For LVSC administration, delivery is aided by co-formulating with hyaluronidase and/or utilizing on-body injectors (OBIs), high-volume autoinjectors (HVAI), or other administration equipment that reduces the treatment burden for healthcare professionals, caregivers, and patients. Despite promising preclinical data, the commercial translation of these platforms faces substantial hurdles, including establishing robust aseptic manufacturing processes for suspensions, developing specialized analytical control strategies, ensuring device compatibility (e.g., avoiding needle clogging), and navigating complex regulatory pathways requiring clinical bridging and comparability assessments. Continued collaborative efforts among industry and regulators will be essential to streamline development and realize patient-centric high-dose SC options.