SBIR Phase I: A high-efficiency filter for endotoxin removal

这个小型企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是开发一个系统，以改善药品生产和败血症治疗。被称为内毒素的有毒物质是许多类型的治疗剂中的常见污染物，并且它是药品制造中批次拒收的主要原因。由于污染导致的药品批次失效的经济影响很大，因为产品损失和设施关闭进行清洁。2018年，药物制造中的内毒素去除市场价值为3.15亿美元，预计将由于生物制药产品的增加而增长。此外，内毒素在进入患者血液时是危险的，并可导致各种医疗并发症，包括败血症。 该技术有可能比目前的解决方案更有效地清除患者血液中的内毒素。该项目将开发一种通用的高效内毒素清除过滤器，不仅有可能改善药物制造，而且还可以为败血症提供挽救生命的治疗。这个小型企业创新研究（SBIR）I期项目将开发一种高亲和力，通过使用特异性结合内毒素蛋白质去除内毒素的高特异性过滤器，已显示可从蛋白质制剂中去除99.9%的内毒素。传统上，使用蛋白质进行产物分离会导致耐久性和蛋白质密度、稳定性和活性方面的问题。这些问题可以通过独特的材料来克服，这些材料允许通过稳定融合100%掺入活性蛋白质，并大大提高蛋白质稳定性。材料与当前溶液（5，000，000 EU/mL）相似的内毒素结合能力被认为是成功的，尽管结合能力预计将大大超过当前标准。目前的解决方案仅与特定类型的治疗剂相容。将评价原型过滤器的内毒素分离和三种蛋白质治疗剂的蛋白质回收。预期每种治疗剂的回收率为80%，同时清除5，000，000 EU/mL内毒素。这些测试将证明原型过滤器的技术可行性，通过显示材料具有比当前方法更高的内毒素结合能力，并且它们与多种类型的治疗方法兼容。该奖项反映了NSF的法定使命，并被认为值得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来支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop a system to improve pharmaceutical manufacturing and sepsis treatment. A toxic substance known as endotoxin is a common contaminant in many types of therapeutics, and it is the primary cause of batch rejection in pharmaceutical manufacturing. The economic impact of pharmaceutical batch failure due to contamination is high due to loss of product and facility closure for cleaning. The endotoxin removal market within drug manufacturing was valued at $315 million in 2018 and is expected to grow due to the increase in biopharmaceutical products. Additionally, endotoxins are dangerous when they enter patients’ bloodstream and can cause various medical complications, including sepsis. The technology has the potential to remove endotoxins from patients’ bloodstream more effectively than current solutions This project will develop a universal high-efficiency endotoxin removal filter that has the potential to not only improve drug manufacturing but also provide a life-saving treatment for sepsis.This Small Business Innovation Research (SBIR) Phase I project will develop a high-affinity, high-specificity filter for endotoxin removal by using a protein that specifically binds endotoxin and has been shown to remove 99.9% of endotoxin from protein preparations. Traditionally, the use of proteins for product separations cause problems with durability and protein density, stability, and activity. These problems are overcome with unique materials that allow 100% incorporation of active proteins via a stable fusion with substantially increased protein stability. The binding capacity of the materials for endotoxin similar to current solutions (5,000,000 EU/mL) would be considered successful, although the binding capacity is expected to greatly exceed the current standard. Current solutions are compatible with only specific types of therapeutics. A prototype filter will be evaluated for endotoxin separation and protein recovery for three protein therapeutics. An 80% recovery of each therapeutic is expected, with simultaneous removal of 5,000,000 EU/mL of endotoxin. These tests will prove the technical feasibility of the prototype filter by showing the materials have a significantly higher binding capacity for endotoxin than current methods and that they are compatible with multiple types of therapeutics.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.