On October 11, 2001 the Microbiology Devices Panel voted and made recommendations on a premarket approval application (PMA) from Sepsis, Inc., on their Endotoxin Activity Assay intended for the determination of endotoxin activity in whole blood samples to rule out gram negative infection. The Panel voted unanimously that the PMA was Not-Approvable. The Panel cited as reasons for their vote, the low confidence in the negative predictive value of the assay, the low number of gram negative patients evaluated, and that there were no compelling data to support the indications for use or utility of the test result in patient management.
On the same day, the Panel provided recommendations on a premarket notification submission [510(k)] from Osmetech, plc. for an in vitro diagnostic device for detecting and measuring urinary tract infection by semi-quantitative analysis of volatile compounds released from urine samples. The panel discussed the following topics: (1) populations at risk for urinary tract infections, such as diabetes, pregnant women, and children; (2) use of this screening test in asymptomatic patients; (3) the relevance of the performance values including sensitivity and negative predictive value and the significance in evaluating UTI patients.
On the second day, the Panel voted and made recommendations on a PMA from Cellestis Ltd., on their QuantiFERON- TB (QFT) assay, an in vitro diagnostic device for measuring the release of gamma-interferon from sensitized lymphocytes in PPD-stimulated whole blood. The device is intended as an aid in the diagnosis of tuberculosis infection. The Panel voted unanimously for Approvable with Conditions. The conditions were: (1) Statistical modeling of the data analyses to support use of an altered cutoff, as suggested by the FDA statistician. (2) Stratification of the data by risk groups, gender and age, with different cut-off values, (3) Additional inter-laboratory reproducibility studies to include a range of expected values and negative samples representative of risk groups who would be tested, (4) Interpretation of results and recommendations for use of the test provided in the labeling for the laboratory users along with separate recommendations for physician (physician education). CDC guidelines for testing to be incorporated in the package insert, (5) Risk groups data analysis presented in the package insert to show not only 2x2 tables for each risk group, but also overlap between tuberculin skin test (TST) and QFT, e.g. Venn diagrams. Data on agreement of low risk positives and negative in 2x2 tables, (6) The Labeling should be modified to include warnings or limitations for performing the QFT after administration of the (TST), and (7) Explicit directions for use of the QFT with groups should be based on data present; use with specific groups not evaluated should be focus of subsequent data .
During the Open Public Hearing Session the Medical Director of Cook County Jail, presented information on the practical limitations of using TST in their plan for eradication of TB infection in the correctional systems. He also described the logistical benefits the QFT assay would provide in this population. The Consumer Representative read a statement on behalf of the Director of the Pennsylvania State TB programs. He commented that problems with the PPD include ensuring trained staff placing and reading the test with accuracy and consistency, patients returning within 48-72 hours after the test is administered for reading, and difficulty in separating true LTBI from positive PPDs due to BCG or non-tuberculous mycobacteria (NTM).