Insights from a Survey of Drug Formulation Experts: Challenges and Preferences in High-Concentration Subcutaneous Biologic Drug Development.

Increasing the concentration of intravenous (IV) biologic formulations to render them appropriate for subcutaneous (SC) delivery is challenging because it impacts many interrelated variables, including volume, viscosity, and stability. This study gathered drug formulation expert insights regarding these challenges as well as development approach preferences and perceptions concerning formulation volume. Biotechnology and pharmaceutical industry experts familiar with creating high-concentration (≥ 100 mg/mL) biologic drug formulations for SC delivery completed an online survey between 26 April and 7 May 2024. In total, there were 100 respondents included. When asked to rank seven approaches to transitioning a formulation from IV to SC administration, responses showed that increasing drug concentrations to reduce injection volume and/or changing the primary container were considered riskier, more time-consuming, and more costly than maintaining the concentration and using an on-body delivery system (OBDS). The greatest challenges mentioned were solubility issues (75%), viscosity-related challenges (72%), and aggregation issues (68%). Most respondents (69%) reported delays in clinical trials or product launches due to high-concentration SC formulation challenges. Of these, 33.3% experienced delays of 6-9 months (weighted mean: 11.3 months), while 4.3% indicated that trials or launches were canceled entirely due to formulation difficulties. In conclusion, making minimal drug formulation concentration changes to an IV biologic formulation may reduce the risk, time commitment, and cost associated with developing a SC biologic formulation. Further education is needed around the transition of traditional IV formulations to low-concentration, large-volume SC formulations utilizing delivery formats such as an SC infusion pump or OBDS.