A Device for Measuring Blood Concentrations of Unbound Bilirubin in Neonates

Project Summary/AbstractThe overall goal of this project is to complete development of the unbound bilirubin (Bf) assay system for assessing the risk of neonatal bilirubin encephalopathy (kernicterus). This includes establishing a manufacturing process for the components of the assay (reagents, disposable test cartridge, reader), transferring the manufacturing process to a contract manufacturer, instituting FDA quality systems and obtaining FDA 510(k) clearance. This test, the UBCheck assay, was developed with the assistance of a grant from NICHD (5R44HD080412).The reason for developing a test for Bf is that it is clear from numerous studies over the past 40 years that Bf is a much more reliable indicator of the risk of bilirubin encephalopathy (kernicterus) than total bilirubin (TSB)- the current standard of care. Almost all studies that have demonstrated the superiority of Bf to TSB have used an assay based upon peroxidase oxidation of bilirubin. The FDA cleared the Arrows UB Analyzer (Japan) test for Bf in 1987 which is based on the peroxidase assay. However, the Arrows device has not been adopted for use, except in Japan, for a variety of technical issues.The assay we developed (UBCheck) solves the technical/scientific issues that prevented widespread adoption of the Arrows method. The assay, is complete within~ 1 minute and requires 5 µL of plasma or whole blood (CVs ≤ 8%). There is confidence that our assay will be commercialized because we have executed a license agreement with Masimo, a publicly traded medical device company with a large sales force focused on hospital intensive care units, including neonatal units. The license requires that Fluoresprobe complete development, obtain FDA approval and initiate manufacturing through a contract manufacturer. If those milestones are achieved Masimo will be obligated to market and distribute the test worldwide. Aim 1: We will develop the scaled-up manufacturing processes and transfer this to the contract manufacturerAim 2: With the CRO DOCRO we will perform the analytical studies required for FDA submission and seek 510(k) FDA clearance for the UBCheck assayProject Narrative High bilirubin levels are currently determined by measuring the total bilirubin however only a small fraction, the unbound bilirubin (Bf), is neurotoxic, but until now there has been no simple reliable test for Bf. We have developed such a test with support from the NIH and in this project, we will investigate, validate and implement the necessary components of the manufacturing process. This will include selection of a contract manufacturer for the disposable test cartridges, completing the necessary analytical studies needed to obtain FDA approval and finally seeking FDA approval to market the test.