Understanding, Verifying, and Implementing Emergency Use Authorization Molecular Diagnostics for the Detection of SARS-CoV-2 RNA

Abstract

22The SARS-CoV-2 pandemic has brought a new wave of challenges to health care, particularly in 23 the area of rapid diagnostic test development and implementation. Acute diagnosis of infection is critically dependent on detection of SARS-CoV-2 RNA from clinical specimens (e.g. 25 nasopharyngeal swabs). While laboratory-developed testing for SARS-CoV-2 is an essential 26 component of diagnostic testing for this virus, the majority of clinical microbiology laboratories 27 are dependent on commercially available SARS-CoV-2 molecular assays. In contrast to assays 28 approved or cleared by the Food and Drug Administration for in vitro diagnostic use, assays for 29 the detection of SARS-CoV-2 nucleic acids have Emergency Use Authorization (EUA) from the 30 FDA. Outside of highly specialized academic and commercial laboratory settings, clinical 31 microbiology laboratories are likely unfamiliar with EUA classification and thus assay 32verification can be daunting. Further compounding anxiety for laboratories are major issues with 33 supply chain that are dramatically affecting the availability of test reagents and requiring 34 laboratories to implement multiple commercial EUA tests. Here, we describe guidance for the 35 verification of assays with EUA for the detection of SARS-CoV-2 nucleic acid from clinical 36 specimens. 37 38 on June 9, 2020 by guest http://jcm.asm.org/ Downloaded from The coronavirus disease (COVID-19) pandemic due to SARS-CoV-2-associated 39 respiratory tract illness has created unprecedented demand for diagnostic testing. Infection with 40 SARS-CoV-2 leads to a range of outcomes from asymptomatic infection to mild and moderate 41 symptoms including fever and cough to the requirement of intensive respiratory support and 42 death. According to the Johns Hopkins University COVID-19 Dashboard, as of May 6, 2020, 43 there are over 3.7 million confirmed cases of COVID-19 and more than 258,000 deaths 44 worldwide, with the U.S. representing the country with the largest number of reported cases and 45 deaths to date. Unfortunately, many cases are likely to have gone undocumented because testing 46resources have been limited such that testing has been predominantly restricted to the most at-47 risk individuals. As more resources are produced and more testing is implemented, less acute 48 cases of COVID-19 should be able to be tested and identified. 49The slow implementation of testing and the lack of testing capacity has repeatedly made 50 headlines. Initial problems with the CDC test led to delayed deployment to public health labs and 51 restricted testing to the CDC for several weeks. Further delaying implementation of testing was 52 the requirement for laboratory-developed tests (LDTs) to be submitted for U.S Federal Drug 53 Administration (FDA) Emergency Use Authorization (EUA) review (discussed below) and 54 shortages of collection devices, extraction kits, mastermix and other commercial reagents. 55Additionally, commercial manufacturers of diagnostic devices took several additional weeks to 56 devel...

Considerations for diagnostic COVID-19 tests

“…On 4 February 2020, the FDA issued an EUA for the COVID-19 rtPCR assay developed by the US Centers for Disease Control and Prevention (CDC), thereby enabling CDC-qualified laboratories to perform the test 57 . Unfortunately, and despite this EUA registration, as described in a news article , there were problems with one of the reagents described in the CDC protocol, partially blocking rapid implementation of the test or leading to retraction of test results.…”

Application, Verification, and Implementation of SARS-CoV-2 Serologic Assays with Emergency Use Authorization

“…The role that serologic assays play during this pandemic continues to be defined, and will likely evolve in the future. Recently, the American Society for Microbiology (ASM) provided recommendations for laboratory verification of SARS-CoV-2 molecular assays with Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) (1). In this matched but expanded document, we outline the current regulatory environment around serologic tests for SARS-CoV-2, review utilization guidelines, provide recommended verification strategies to employ once the choice of a serologic test has been made, and discuss assay limitations and reporting considerations for laboratories contemplating implementation of antibody tests for SARS-CoV-…”

Clinical Samples for SARS-CoV-2 Detection: Review of the Early Literature

“…Nucleic acid testing, most commonly reverse transcriptase polymerase chain reaction (RT-PCR), plays a significant role in the diagnosis of COVID-19 from respiratory samples from infected patients. However, despite the launch of commercially available diagnostic assays for the detection of SARS-CoV-2 nucleic acids, with emergency use authorization claims granted by the Food and Drug Administration (FDA) [ 4 ], diagnostic uncertainty remains. Pre-analytical factors, such as specimen selection, collection, and transport, are critical to optimal assay accuracy [ 5 ].…”