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

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.