First De Novo Clearance Signals that Premarket Pathway Is Open for COVID-19 Tests

Just over a year ago, the U.S. Food and Drug Administration (FDA) granted its first Emergency Use Authorization (EUA) for a coronavirus test. On March 17, 2021, the test review process moved to a new phase when the agency cleared a COVID-19 diagnostic via its traditional premarketing pathway for the very first time, thus allowing for marketing of the test beyond the public health emergency. The first test to make the transition from EUA to de novo clearance status is BioFire Diagnostics’ BioFire FilmArray Respiratory Panel (RP) 2.1, which detects 22 different viruses and bacteria associated with SARS-CoV-2 and other respiratory tract infections from a singly nasopharyngeal swab in 45 minutes. The FilmArray RP2.1, which was originally granted EUA clearance on May 1, 2020 (that EUA clearance has now been officially revoked as part of the transition to de novo status) runs on the firm’s FilmArray 2.0 and higher-throughput BioFire Torch systems. BioMérieux subsidiary BioFire has developed a suite of SARS-CoV-2 diagnostic products, including, among others, a singleplex assay for the FilmArray system and the RP 2.1-EZ Panel that detects the coronavirus and 18 other pathogens in point of care and near patient CLIA-waived settings. The FDA noted that it based its decision to grant de novo clearance, in part, on a review of analytical studies “which demonstrated a reasonable assurance that the BioFire RP2.1 was safe and effective at identification and differentiation of various respiratory viral and bacterial pathogens.” Data from a clinical study of more than 500 samples was apparently a major factor in the agency’s determination. A BioMeriéux statement described it as a multicenter prospective clinical study combining reference of three independent EUA molecular SARS-CoV-2 assays. According to the company, the panel demonstrated positive percent agreement of 98 percent and negative percent agreement of approximately 99 percent. Impact on Future COVID-19 Test Development The EUA pathway remains open. Thus, the FDA specifically noted that the FilmArray RP2.1 EUA revocation and de novo authorization do not affect the availability of other EUA tests. However, the move serves notice that COVID-19 test makers can also use the traditional premarket pathway if they are looking to develop products for the post-pandemic market. “While this is the first marketing authorization for a diagnostic test using a traditional premarket review process, we do not expect this to be the last and look forward to working with developers of medical products to move their products through our traditional review pathways,” noted FDA acting commissioner Janet Woodcock in a statement. The agency is also working on potential new pathways, including via the establishment of “special controls” for labeling and performance testing. “When met,” the FDA explained, “these controls, in combination with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type.” The FilmArray RP2.1 de novo clearance also creates a new regulatory classification, which, according to the agency, “means that subsequent devices of the same type with the same intended use may go through the FDA's 510(k) pathway, whereby devices can obtain clearance by demonstrating substantial equivalence to a predicate device.” Here are some of the other key new FDA EUAs and clearances announced in March: New FDA Emergency Use Authorizations (EUAs) & Approvals

Manufacturer(s)	Product
Abbott Laboratories	EUA for Alinity m Resp-4-Plex assay
Abbott Laboratories	EUA for AdviseDx SARS-CoV-2 IgG II test
Inivata	Breakthrough Device Designation for RaDaR liquid biopsy assay
Zymo Research	510(k) clearance for use of DNA/RNA Shield Collection Tube for SARS-CoV-2 testing
GetMyDNA (Gravity Diagnostics affiliate)	EUA for GetMyDNA COVID-19 Test Home Collection Kit
Gravity Diagnostics + Assurance Scientific Laboratories	EUA for Everlywell COVID-19 Test Home Collection Kit DTC
Broad Institute	EUA for CRSP SARS-CoV-2 Real-time Reverse Transcriptase-PCR Diagnostic Assay (Version 3)
Adaptive Technologies	EUA for T-Detect COVID-19 Test blood-based antibodies assay
Cue Health	EUA for Cue COVID-19 Test for home + over-the-counter use
Phosphorus Diagnostics LLC	EUA for Phosphorus COVID-19 RT-qPCR Test
Luminex	EUA for expanded version of multiplex NxTag Respiratory Pathogen Panel (RPP) that includes SARS-CoV-2 target
Fluidigm	EUA for Advanta Dx SARS-CoV-2 RT-PCR assay for use with Azova COVID-19 Test Collection Kit
Quidel	EUA for QuickVue At-Home COVID-19 rapid antigen test
Viracor Eurofins Clinical Diagnostics	EUA for Viracor SARS-CoV-2 assay
Clinical Enterprise, Inc.	EUA for EmpowerDX COVID-19 Home Collection Kit DTC
University of Illinois	EUA for CovidShield assay
Agilent Technologies	Clearance PD-L1 IHC 22C3 pharmDx as companion diagnostic for also newly approved Regeneron Pharmaceuticals and Sanofi’s PD-1 inhibitor cemiplimab-rwlc (Libtayo) as a front-line treatment for advanced non-small cell lung cancer patients with high PD-L1 expression in their tumors
Inova Diagnostics	510(k) clearance for Nova Lite DAPI dsDNA Crithidia luciliae Kit