COVID-19 testing: FDA guidance update

As SARS-CoV2 continues to spread, resulting in Coronavirus Disease 2019 (COVID-19) in patients, we examine FDA guidance on in vitro diagnostic testing and respirator use in healthcare settings, and highlight current trials for treatment and vaccines.

The novel coronavirus, first detected in Wuhan City, Hubei Province, China, has now been detected in 50 locations worldwide, including the U.S., with more cases announced every day. The virus is called SARS-CoV2, and the disease it causes in patients is called Coronavirus Disease 2019 (COVID-19). Given the virus’s ability to spread rapidly, it could cause significant impact on the U.S. healthcare system and society as a whole, the FDA said.

The World Health Organization (WHO) reports that about 2% of people with the disease have died. Current efforts to address the spread of SARS-CoV2 include development of in vitro diagnostic testing, allowing use of certain respirators by healthcare personnel treating infected patients, and development of treatments and vaccines for COVID-19.


The need for rapid response testing in the U.S.

On February 29, 2020, the FDA announced a new policy for specific laboratories pursuing the opportunity to develop diagnostic tests for coronavirus. This policy comes in the form of immediately published guidance intended to help the U.S. achieve more rapid testing capacity. The agency stressed that it is not changing its standards for Emergency Use Authorization (EUA) issuance and that this action emphasizes the agency’s commitment to public health and addressing critical health needs. The most recent EUA the FDA issued for diagnostic and therapeutic medical devices to diagnose and respond to public health emergencies was in 2016 in response to the Zika virus.

In order to quickly respond to the COVID-19 outbreak, it is critical to rapidly detect instances of infection, identify those who were in contact with infected people and appropriately manage clinical care and infections. The FDA stated that testing capabilities need to be widely available in public healthcare settings, multiple types of laboratories and at the point of care.

Some laboratories now developing and using validated COVID-19 diagnostics are doing so before the agency has been able to complete reviews of their EUA requests. These EUAs are issued based on a review of scientific data for “certain medical products that may be effective in diagnosing, treating, or preventing a disease or condition when there is a determination” of a public health emergency or increased potential for a public health emergency by the U.S. Department of Health and Human Services (HHS).

This determination was made on February 4, 2020, by the Secretary of the HHS, to authorize emergency use of in vitro diagnostics (IVDs) to detect and/or diagnose the COVID-19 outbreak. The FDA has issued an EUA so far to the Centers for Disease Control and Prevention (CDC) and some public health labs across the U.S.


COVID-19 in vitro diagnostics testing guidance

On February 29, 2020, the FDA issued “Immediately in Effect Guidance for Clinical Laboratories and Food and Drug Administration Staff: Policy for Diagnostics Testing in Laboratories Certified to Perform High-Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Disease-2019 during the Public Health Emergency, 29-February-2020” without requesting public comment, due to the immediate need for testing. The FDA now welcomes comments on the guidance post-publication through electronic submission and via mail (Docket No. FDA-2020-D-0987).


“Such a step in expediency could reduce development costs and speed up the process at testing sites while also providing incentives for other private test development.”


The FDA said it would not object to the use of these tests for clinical testing while laboratories pursue an EUA with the agency. This policy only applies to laboratories certified to perform high-complexity testing consistent with Clinical Laboratory Improvement Amendments (CLIA) requirements [42 CFR 493]. Such a step in expediency could reduce development costs and speed up the process at testing sites while also providing incentives for other private test development.

In the guidance, the FDA recommends that laboratories do the following:

  • once test validation is complete, email the FDA to notify that the test has been validated;
  • confirm the first five positive and first five negative samples with an EUA-authorized test;
  • indicate in the test reports that the test has been validated but the FDA has not completed independent review; and
  • submit an EUA within 15 days of initiating testing.

It also outlines steps to take if any specimens fail confirmatory testing or if the FDA cannot authorize the EUA. Regarding test validation, recommendations for minimal testing to be performed for validation include limit of detection (LoD), clinical evaluation, inclusivity and cross-reactivity. Given the limited availability of viral materials, the FDA, the CDC and the Biomedical Advanced Research and Development Authority (BARDA) will prioritize and coordinate shipments to laboratories when they are ready for validation.


EUA test status

The CDC, the FDA and BARDA are working with IVD manufacturers and laboratories to issue EUA authorizations “as soon as possible” (updates can be found here). So far, two EUAs have been issued for IVDs to be used with individuals who meet CDC criteria for 2019-nCoV testing in accordance with section 564 of the Federal Food, Drug and Cosmetic Act (FD&C Act):

  1. On February 4, 2020, the CDC issued an EUA authorization for the 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel for the presumptive qualitative detection of nucleic acid from the 2019-nCoV in upper and lower respiratory specimens.
  2. On February 29, 2020, the FDA issued an EUA to Wadsworth Center, New York State Department of Public Health’s (CDC) New York SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Panel for the presumptive qualitative detection of nucleic acid from SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs and sputa.


FDA webinar on in vitro diagnostics testing guidance for COVID-19

On March 2, 2020, the FDA hosted a webinar to summarize the newly published guidance and to provide a question-and-answer (Q&A) session for manufacturers and sponsors. The following are additional recommendations made by the FDA during the Q&A session:

  • Since positive specimens can be limiting for testing, manufacturers can submit an email request to the FDA. They will then be added to the list of manufacturers in need of materials. Additional pathways for validation are also available.
  • In order to accelerate approval, the FDA suggested that once an IVD device manufacturer has a complete package, they can begin sending portions of the submission under the pre-EUA process so the agency can begin a rolling review [Guidance Bulletin, Updated 11-May-2017]. When the final portion of the application is submitted, the FDA will only assess that portion. This process was used for the 2 EUAs issued so far with final authorization within 24 hours of the final submission.


NIOSH-approved respirators for healthcare personnel

On March 2, 2020, the FDA issued an EUA for emergency use of respirators, including certain N95s, by healthcare personnel. These are typically reserved for industrial settings. The eligible respirators include:

  1. all disposable filtering facepiece respirators (FFRs) approved by the National Institute for Occupational Safety and Health (NIOSH), in accordance with 42 CFR Part 84 [21 CFR 880] as non-powered air-purifying particulate FFRs; and
  2. FFRs approved by NIOSH but have since passed the manufacturers’ recommended shelf-life for use in healthcare settings by healthcare personnel to prevent wearer exposure to pathogenic biological airborne particulates during FFR shortages resulting from the COVID-19 outbreak.

These devices are designed to provide efficient filtration of airborne particles and filter more than face masks, the FDA said. Because they are typically used in industrial settings, they are not required to meet FDA standards for testing. This action is a response to reports of an increase in the ordering of personal protective equipment that has resulted in shortages in healthcare institutions. The agency stated that the demand for these products will increase as the COVID-19 outbreak continues, and these devices can help alleviate the possible shortage in the supply chain; however, the public should not use certain NIOSH-approved respirators.


Treatment for COVID-19

The National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) is sponsoring a randomized, double-blind, placebo-controlled phase 2 study at the University of Nebraska Medical Center (UNMC) in Omaha to determine the safety and efficacy of novel therapeutic agents, including the investigational new drug (IND) remdesivir, in hospitalized adult patients diagnosed with COVID-19.

This study is recruiting 394 patients aged ≥18 years and will consist of a series of 2-arm comparisons between different investigational therapeutic agents and a placebo with interim monitoring to add new arms and to allow early discontinuation for futility, efficacy or safety. The primary outcome measure is the percentage of subjects reporting each severity rating on the 7-point ordinal scale by day 15.


“The National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring a randomized, double-blind, placebo-controlled phase 2 to determine the safety and efficacy of novel therapeutic agents, including the investigational new drug (IND) remdesivir, in hospitalized adult patients diagnosed with COVID-19.”



According to sponsor reports, Codagenix, Inc, in collaboration with the Serum Institute of India, is investigating a live-attenuated vaccine for the potential prevention of COVID-19 caused by the 2019-nCoV strain of SARS-CoV-2. By February 2020, numerous nCoV vaccine candidate genomes had been designed, and the sponsor planned to grow and evaluate the vaccine viruses in vivo prior to conducting clinical trials.

Novavax, Inc, is developing a novel vaccine to protect against COVID-19. The sponsor has produced and is currently evaluating multiple nanoparticle vaccine candidates in animal models before identifying an optimal candidate for human testing (expected to begin by the end of spring 2020). Novavax’s experience with Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) provides the ability for quick response against COVID-19, according to company reports. The sponsor’s COVID-19 vaccine candidates were created using its proprietary recombinant protein nanoparticle technology platform to produce antigens derived from the coronavirus spike protein. Novavax intends to use its proprietary Matrix-M adjuvant with its COVID-19 vaccine candidate to enhance immune response. The expected start date for phase 1 clinical testing is May or June 2020.


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