Performance Validation of a Multiplexed IVD System for Gastrointestinal Pathogens

Several NIAID Category B select agents are pathogens capable of causing infectious gastroenteritis. In addition to their potential use in a bioterrorism attack, naturally occurring gastrointestinal illness is a major health concern. An estimated 3-4 million children below the age of five years die worldwide each year as a result of complications related to diarrhea. Every year in the United States, there are an estimated 211 to 375 million episodes of acute diarrhea resulting in 5,000 deaths. The number and diversity of diarrhea causing pathogens, including viruses, bacteria, and protozoa along with the similarities in clinical presentation pose significant problems for diagnosis and subsequent treatment. Current microbiological methods used to identify the responsible pathogen are often slow and laborious, requiring several days to obtain each result. Meanwhile, the patient remains undiagnosed, untreated, and possibly spreading infection. This results in individual patient suffering and a public health threat if an outbreak spreads undetected. Idaho Technology Inc. has developed the FilmArray Gastrointestinal (GI) Panel, an innovative molecular diagnostics device that streamlines gastrointestinal pathogen identification in individual human stool specimens. The FilmArray GI Panel simultaneously identifies 26 different analytes in ~1 hour (18 of which are NIAID Category B agents), and requires only a minimally trained operator to perform the test. The FilmArray GI Panel system comprises a uniquely designed 'lab-in-a-pouch', which together with the FilmArray instrument, automatically performs all steps needed for detection and identification of pathogens (from nucleic acid extraction to multiplex real time PCR and data analysis). The goal of this project is to determine the performance of the FilmArray GI Panel when testing clinical specimens, and to use this data (as well as data collected under a previous award) to create regulatory documents for the United States (FDA) and Europe (CE Mark). Regulatory clearance of the FilmArray GI Panel will allow the device to be used as an in vitro diagnostic (IVD) test for GI illness in these regions. Establishing clinica performance of the FilmArray GI Panel will require testing of both prospectively collected, freshly tested specimens as well as preselected, known-positive archived specimens. The analyte status of the specimens (positive or negative for a given pathogen) must be determined by standard laboratory reference methods in order to calculate sensitivity and specificity for the FilmArray GI Panel. PCR reference methods will be required for testing of many analytes, and these PCR assays must be designed and validated. Thus, the main tasks will be to (1) design and characterize PCR reference methods for assessment of clinical specimens, (2) establish FilmArray GI system performance using prospective and archived clinical specimens, and (3) develop and submit regulatory applications.