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

该SBIR第二阶段项目旨在将静脉注射(IV)生物药物转变为简单的皮下注射(SC)。生物制品改善了人类疾病的治疗方法。不幸的是，他们的交付是沉重的负担。这些生物制剂的给药标准通常是低浓度的静脉输液，这可能需要几个小时的时间才能输送，导致患者不适，并增加感染的风险。尽管SC注射剂是首选，但对SC体积的限制(1.5-2.0毫升)需要远高于100毫克/毫升的浓度，而这通常是不可行的。浓度超过100毫克/毫升的溶液粘度很高(类似蜂蜜)，难以注射，并导致产品不稳定。该项目的微粒悬浮技术可以提供高浓度的蛋白质，同时完全保留蛋白质的结构、功能和功效。转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提供了优势。患者将体验到更少的疼痛和不适，节省时间，更少的感染，并更容易获得生物制剂。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。付款人将降低报销成本。生物制药公司将拥有专利产品差异化和开发原本难以处理的生物制剂的能力。这个SBIR第二阶段项目旨在开发一种软雾化制造平台，用于生产能够将静脉注射(IV)生物制剂转变为简单的皮下注射(SC)的微粒悬浮液。生物制剂的给药标准是低浓度的静脉输液，这可能需要几个小时的时间才能输送，导致患者不适，并增加感染的风险。尽管SC注射剂是首选，但对SC体积(1.5-2.0毫升)的限制要求浓度超过100毫克/毫升，而这通常是不可行的。浓度超过100毫克/毫升的溶液粘度很高(类似蜂蜜)，难以注射，并导致产品不稳定。该项目的温和处理的微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，这一成就在其他微粒技术中没有得到很好的展示。该项目旨在通过对实验室规模的系统进行工艺校准，然后开发和表征在该系统上产生的颗粒和悬浮液，来提高创新的准备程度。有了配方良好的混悬剂，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智力优势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.