FDA Zika virus reference panel for molecular-based diagnostic devices supports product testing for Emergency Use Authorization and 510(k) submissions
In response to the urgent need for performance assessment of diagnostic devices that detect Zika virus (ZIKV), scientists at the U.S. Food and Drug Administration (FDA) developed a reference panel composed of vials containing different concentrations of the virus’s genetic material that manufacturers can use to evaluate the performance of their ZIKV virus nucleic acid test (NAT). NAT tests detect the genetic material of microorganisms in samples such as blood, urine, or other fluids.
FDA’s Center for Devices and Radiological Health and the Center for Biologics Evaluation and Research collaborated on developing and producing the panel, which is now available to qualified companies on request.
ZIKV, which carries its genetic material in the form of RNA, triggered a public health crisis when it appeared in 2015, spreading from Brazil to other areas, such as Puerto Rico and the US Virgin Islands. While most people infected with the virus have no symptoms, fever, rash, joint pain, and red eyes can occur. In more serious cases, the disease can cause the neurologic disorder Guillain-Barré Syndrome or, if transmitted from mother to fetus, microcephaly, a disorder that can be fatal. Therefore, the availability of in vitro testing devices that provide early and specific diagnosis of ZIKV infection is critical to public health responses to the disease.
NAT is the most sensitive and specific diagnostic method during the early stage of ZIKV infection. Therefore, the development of the reference panel for Zika RNA (Zika FDA-RP) is important because the data generated using this panel enables FDA to directly compare the performance of different NATs under the same conditions. This is especially critical when FDA is comparing differently designed NAT tests while considering an emergency use authorization (EUA) for such a diagnostic device.
The panel comprises five vials of heat-inactivated ZIKV strains, two in concentrated stocks (S1 and S2) and three diluted concentrations prepared from those two strains (S3, S4, S5).
FDA researchers grew ZIKV in animal cells and prepared a series of five concentrations of material from these cell culture supernatant stocks, which they designated S1-S5. Manufacturers use the Zika reference panel to test the performance of their devices. FDA discloses to companies requesting the vials the concentrations of ZIKV in S1 and S2, so the manufacturers can determine the limit of detection of their devices (lowest quantity of a ZIKV genome distinguishable from a blank value); but the concentrations in S3-S5 are not disclosed, enabling “blind” testing of NAT assays by each company to corroborate both the reported limit of detection as well as the proficiency in handling the reference panel. In this way, FDA is able to directly compare the sensitivity of different diagnostic assays using the same reference vials.
FDA has issued EUAs to 15 NAT-based assays for ZIKV, 13 of which are still on the market.
TITLE
A Zika Reference Panel for Molecular-Based Diagnostic Devices as a US Food and Drug Administration Response Tool to a Public Health Emergency
J Mol Diagn 2019, 21: 1025e1033; https://doi.org/10.1016/j.jmoldx.2019.06.004
AUTHORS
Mayra García,* Rafaelle Fares-GusmaoϮ Kim Sapsford,* Caren Chancey,Ϯ Andriyan Grinev,Ϯ Stephen Lovell,* Uwe Scherf,* and Maria RiosϮ
*Office of in Vitro Diagnostics and Radiological Devices, Center for Devices and Radiological Health and
ϮOffice of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland