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

这个小企业创新研究（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来改善制药和败血症治疗。一种被称为内毒素的有毒物质是许多类型的治疗中常见的污染物，它是制药生产中批次排斥的主要原因。由于污染导致的药品批次失效的经济影响很大，因为产品损失和设备关闭以进行清洗。2018年，药品制造领域的内毒素去除市场价值3.15亿美元，由于生物制药产品的增加，预计还将增长。此外，当内毒素进入患者的血液时是危险的，并可能导致各种医疗并发症，包括败血症。这项技术有可能比目前的解决方案更有效地去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去除过滤器，不仅有可能改善药物生产，而且还可能为败血症提供挽救生命的治疗方法。这个小企业创新研究（SBIR）第一阶段项目将开发一种高亲和力、高特异性的过滤器，通过使用一种特异性结合内毒素的蛋白质来去除内毒素，该过滤器已被证明可以从蛋白质制剂中去除99.9%的内毒素。传统上，使用蛋白质进行产品分离会导致耐久性和蛋白质密度、稳定性和活性的问题。这些问题可以通过独特的材料来克服，这种材料可以通过稳定的融合使活性蛋白质100%结合，从而大大提高蛋白质的稳定性。材料对内毒素的结合能力与现有溶液（5,000,000 EU/mL）相似，即被认为是成功的，尽管结合能力有望大大超过现行标准。目前的解决方案仅与特定类型的疗法兼容。原型过滤器将评估内毒素分离和蛋白质回收的三种蛋白质治疗。预计每种疗法的回收率为80%，同时去除5,000,000 EU/mL的内毒素。这些测试将证明原型过滤器的技术可行性，表明这些材料对内毒素的结合能力比目前的方法要高得多，而且它们与多种治疗方法兼容。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。

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.