SBIR Phase II: Novel Formulation for the Delivery of High Concentration Protein Therapeutics

This SBIR Phase II project aims to transform intravenous (IV) infusions of biologic medicines into simple subcutaneous (SC) injections. Biologics have improved the treatment of human disease. Unfortunately, their delivery is burdensome. The standard of administration of these biologics is often by IV infusion at low concentrations, which can take multiple hours to deliver, cause patient discomfort, and increase the risk of infection. Although SC injection is preferred, constraints on SC volume (1.5-2.0 mL) would necessitate concentrations much greater than 100 mg/mL, which are often unfeasible. Solutions at concentrations exceeding 100 mg/mL are highly viscous (honey-like), making them difficult to inject and leading to unstable products. This project's microparticle suspension technology can deliver high concentrations while fully preserving the protein structure, function, and efficacy. Transforming the delivery of biologics offers advantages to patients, healthcare providers, payers, and biopharmaceutical companies. Patients will experience less pain and discomfort, save time, have fewer infections, and have better access to biologics. Healthcare providers will be able to process more patients, decrease the chance of complications, and use fewer human resources. Payers will have decreased reimbursement costs. Biopharmaceutical companies will have patented product differentiation and the ability to develop otherwise intractable biologics. This SBIR Phase II project aims to develop a soft atomization manufacturing platform for the production of microparticle suspensions capable of transforming intravenous (IV) infusions of biologics into simple subcutaneous (SC) injections. The standard of administration of biologics is intravenous infusion at low concentrations, which can take hours to deliver, cause patient discomfort, and increase the risk of infection. Although SC injection is preferred, constraints on SC volume (1.5-2.0 mL) necessitate concentrations greater than 100 mg/mL, which are often unfeasible. Solutions at concentrations exceeding 100 mg/mL are highly viscous (honey-like), making them difficult to inject and leading to unstable products. This project's gently processed microparticle suspensions can deliver high concentrations while preserving protein structure and bioactivity, an accomplishment not well-demonstrated with other microparticle technologies. This project aims to advance the readiness level of the innovation by performing process calibration of a bench-scale system, followed by developing and characterizing the resulting particles and suspensions produced on that system. With well-formulated suspensions, in vivo pharmacokinetic and efficacy studies will commence. The project will support the development of manufacturing capabilities towards a goal of transitioning to pilot-scale production. This project aims to offer advantages to patients, healthcare providers, payers, and biopharmaceutical companies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.