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

SBIR II 期：用于提供高浓度蛋白质治疗药物的新配方

• 批准号: 1831212
• 负责人: Paul Brown
• 金额: $ 75万
• 依托单位: Elektrofi Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1831212&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Novel; Formulation

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.

SBIR二期项目旨在将生物药物的静脉（IV）输注转化为简单的皮下（SC）注射。生物制剂改善了人类疾病的治疗。不幸的是，它们的交付是繁重的。这些生物制剂的给药标准通常是通过低浓度的IV输注，这可能需要数小时才能输送，导致患者不适，并增加感染风险。尽管SC注射是优选的，但对SC体积（1.5-2.0 mL）的限制将需要远大于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（蜂蜜状），使其难以注射并导致不稳定的产品。该项目的微粒悬浮技术可以提供高浓度，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为患者、医疗保健提供者、付款人和生物制药公司带来了优势。患者将经历更少的疼痛和不适，节省时间，减少感染，并更好地获得生物制剂。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。付款人将减少报销费用。生物制药公司将拥有专利产品的差异化和开发其他棘手的生物制剂的能力。SBIR第二阶段项目旨在开发一种用于生产微粒悬浮液的软雾化制造平台，该平台能够将生物制剂的静脉（IV）输注转化为简单的皮下（SC）注射。生物制剂的给药标准是低浓度的静脉输注，这可能需要数小时才能输送，导致患者不适，并增加感染风险。尽管SC注射是优选的，但SC体积（1.5-2.0 mL）的限制要求浓度必须大于100 mg/mL，这通常是不可行的。浓度超过100 mg/mL的溶液是高度粘稠的（蜂蜜状），使其难以注射并导致不稳定的产品。该项目的温和处理的微粒悬浮液可以提供高浓度，同时保留蛋白质结构和生物活性，这一成就在其他微粒技术中没有得到很好的证明。该项目旨在通过对实验室规模的系统进行过程校准，然后开发和表征该系统产生的颗粒和悬浮液，来提高创新的准备水平。对于配制良好的混悬液，将开始体内药代动力学和疗效研究。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NSF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。