An industry perspective on clinical development and regulatory strategies for subcutaneously administered high-dose biologics

The Subcutaneous Drug Development and Delivery Consortium aims to advance the technical and regulatory understanding that can enable development of subcutaneous biotherapeutics towards improved outcomes. The Consortium's Clinical Development and Regulatory Strategy sub team conducted a cross-company survey to explore strategies, challenges, and best practices in developing subcutaneous products for high-dose biologics. With the growing prevalence of biologics, subcutaneous delivery is increasingly recognized for its potential to reduce healthcare burdens and enhance treatment convenience in treatment administered by healthcare providers, caregivers or individual users. The survey results indicate that industry participants view high-dose subcutaneous formulations as beneficial for customer-centered care, reducing clinical visits and enabling at-home administration. The primary drivers for subcutaneous development include improved experience with the parenteral dosing regimen, increased adherence, and continuous improvement towards emerging needs (lifecycle management). While companies are increasingly leveraging enabling technologies such as permeation enhancers, high concentration technologies, and wearable devices to resolve technical barriers with delivering high doses subcutaneously, challenges remain. These challenges can range from user acceptance to regulatory complexities with implementation of innovation and clinical strategies. One of the key opportunities identified is the advancement of bridging strategies to transition from intravenous to subcutaneous formulation, informed by pharmacokinetic/ pharmacodynamic modeling and simulation and pharmacokinetic clinical bridging studies. The survey highlights the need for continued collaboration and innovation to optimize subcutaneous high-dose biologic development, aligning industry practices with evolving regulatory and customer-centric demands.