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

该SBIR二期项目旨在将生物药物的静脉（IV）输注转变为简单的皮下（SC）注射。生物制剂改善了人类疾病的治疗。不幸的是，他们的交付是繁重的。这些生物制剂的标准给药方式通常是低浓度静脉输注，这可能需要数小时才能输送，引起患者不适，并增加感染风险。虽然SC注射是首选，但SC体积（1.5-2.0 mL）的限制将需要远高于100 mg/mL的浓度，这通常是不可行的。浓度超过100 mg/mL的溶液是高度粘稠的（像蜂蜜一样），很难注射，导致产品不稳定。本项目的微粒悬浮技术可以在提供高浓度的同时，充分保留蛋白质的结构、功能和功效。改变生物制剂的交付方式对患者、医疗保健提供者、支付方和生物制药公司都有好处。患者将经历更少的痛苦和不适，节省时间，减少感染，并有更好的途径获得生物制剂。医疗保健提供者将能够处理更多的患者，减少并发症的机会，并使用更少的人力资源。支付方将减少报销费用。生物制药公司将获得产品差异化的专利，并有能力开发其他棘手的生物制剂。该SBIR二期项目旨在开发一种软雾化制造平台，用于生产能够将生物制剂静脉（IV）输注转化为简单的皮下（SC）注射的微粒悬浮液。生物制剂的给药标准是低浓度静脉输注，这可能需要数小时才能输送，引起患者不适，并增加感染的风险。虽然SC注射是首选，但SC体积限制（1.5-2.0 mL）需要大于100 mg/mL的浓度，这通常是不可行的。浓度超过100 mg/mL的溶液是高度粘稠的（像蜂蜜一样），很难注射，导致产品不稳定。该项目的微颗粒悬浮液可以在保持蛋白质结构和生物活性的同时提供高浓度，这一成就在其他微颗粒技术中没有得到很好的证明。该项目旨在通过对实验规模系统进行过程校准，然后开发和表征在该系统上产生的最终颗粒和悬浮液，从而提高创新的准备水平。有了配方良好的混悬液，体内药代动力学和疗效研究将开始。该项目将支持制造能力的发展，以实现向中试规模生产过渡的目标。该项目旨在为患者、医疗保健提供者、付款人和生物制药公司提供优势。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.