On July 27, 2000, the Microbiology Devices Panel meet to discuss the appropriate types of, important, relevant, and reasonable data and information required to assess safety and effectiveness of diagnostic tests intended to identify the presence of biothreat agents, when used on different specimen types and under different conditions for evidence of exposure to biothreat agents. This was a General Issues meeting and not for a specific device application. Col. Eric Henchal, Ph.D. from USAMRID, Ft. Detrick and Richard Meyer, Ph.D., CDC, our Panel Discussants provided background information on the types of studies already being developed and the types of validation studies conducted by their agencies. The Panel provided recommendations on three questions asked by the FDA. As to the types of data and information considered appropriate to evaluate safety and effectiveness, the panel suggested that the sensitivity of the assays be close to100% when used for ‘rule-out’ type assays in A level laboratories in the civilian sector, because an effective response to unannounced events would be most dependent on accurate laboratory information. This position was qualified, after further panel discussions, to recognize the importance of specificity. For mass exposure and the announced event, specificity would be most important. The panel believed that spiked samples were valuable for analytical studies, but would have limited use for predicting performance with clinical specimens. When asked about the use of animal models, the panel suggested that animal models could be useful for estimating exposure variables and providing a source of infected specimens (vs. spiked samples) to study matrix effects; and that animal testing should not be expected to duplicate performance with human specimens. In general the panel recommended that animal testing should be limited to those types of studies that could give relevant performance information; specimens from infected animals could also be used for comparing different tests. For the question regarding other issues that would effect the reliability of the assays, the panel responded that specimen handling and storage conditions should be evaluated, and studies to assess test specificity could include testing a substantial number of specimens from normal individuals and also a broad range of potential conflicting agents. Additionally the rationale for why each study was conducted should be provided. During the Open Public Hearing session, Jack Sawicki of Geomet Technologies asked that FDA clarify the specific targets industry should have for development of these assays and who would be contacted in case of an unannounced attack.
On July 28, the committee discussed two premarket approval applications; The Roche Molecular Systems AmplicorÒ HCV Test v2.0 nucleic acid amplification (NAT)in vitro diagnostic qualitative device to detect hepatitis C virus (HCV) ribonucleic acid (RNA) and a semi-automated version Cobas AmplicorÔ HCV Test, v2.0 NAT device to detect HCV RNA. The committee provided recommendations on an appropriate Intended Use of the devices, proposed warnings and limitations of the assays, the range of HCV genotypes and subtypes evaluated, and the standard reference materials used. The Panel then voted on each device separately. The Panel unanimously recommended Approvable with Conditions, the same for both the AmplicorÔ HCV Test v2.0 NAT test and the Cobas AmplicorÔ HCV NAT Test, v2.0. The Conditions were: 1) the Intended Use statement should be revised to state that the assay is indicated "for patients who have liver disease and antibodies to HCV", removing references to the type of antibody test and the immunoblot assay. 2) The Warning Statement should be revised as follows: (a) remove part ii from first item; (b) revising the second item by adding "for monitoring progress of disease or response to treatment of HCV"; (c) revising third item to insert "all" to describe HCV genotypes and remove the last phrase concerning genotypes and false negative results. 3)Adding a Warning statement that HCV RNA should not be detected by diluting samples to remove inhibitory materials, instead, a new specimen should be collected. 4) Whenever quantity in international units is noted in the package insert it should be noted that the standard was based on the WHO Standard for genotype 1 HCV RNA.
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