This page is part of the FAQs on Testing for SARS-CoV-2 and provides answers to frequently asked questions related to COVID-19 test development and review.
A: The issuance of an EUA is discretionary. The FDA's decision to review and process an EUA request, and ultimately issue an EUA if the relevant statutory criteria are met, is based on a determination, on a case-by-case basis, that such action is necessary to protect the public health in an emergency. The FDA prioritizes review of EUA requests for tests taking into account a variety of factors, as discussed in the Emergency Use Authorization of Medical Products and Related Authorities Guidance, such as the public health need for the product and the availability of the product. We have, for example, prioritized review of EUA requests for tests where authorization would increase testing accessibility (e.g., point of care (POC) tests, home collection tests, and at-home tests) or would significantly increase testing capacity (e.g., tests that reduce reliance on test supplies and high-throughput, widely distributed tests). For at-home and home collection tests, we have prioritized review of EUA requests for diagnostic tests (molecular and antigen) in light of our current assessment of the public health needs.
As discussed in the FDA's Policy for Coronavirus Disease-2019 Tests, reissued on November 15, 2021, at this stage of the pandemic, the FDA generally intends to focus its review on EUA requests for the following types of tests (please see the guidance for additional details for each of these types of tests):
- At-home and point-of-care (POC) diagnostic tests for use with or without a prescription and that can be manufactured in high volumes;
- Certain high-volume, lab-based molecular diagnostic tests (and home collection kits for use with such tests) that expand testing capacity or accessibility such as through pooling of specimens to increase throughput, testing specimens collected at home and shipped to the lab, screening asymptomatic individuals, or detecting multiple different respiratory viruses at once;
- Certain lab-based and POC high volume antibody tests that can measure the amount of antibodies (fully quantitative antibody tests) or the amount of neutralizing antibodies; and
- Tests for which the request is from, or supported by, a U.S. government stakeholder, such as the Biomedical Advanced Research and Development Authority or the National Institutes of Health's Rapid Acceleration of Diagnostics.
A: FDA strives to review Pre-EUA and EUA requests as quickly as we can. FDA will communicate with each sponsor regarding its pre-EUA or EUA request as soon as possible. The review team will be in contact with you when its review is complete or if there are questions. If you have not yet been assigned a lead reviewer for your pre-EUA or EUA request, we recommend that you refer to the available resources to help you with your planning and submitting your EUA request:
- SARS-CoV-2 IVD EUAs (Letters of Authorization and Instructions for Use/EUA Summaries)
- EUA Templates with recommendations to help facilitate EUA requests, as explained in the Policy for Coronavirus Disease-2019 Tests
- FAQs on Testing for SARS-CoV-2
During this unprecedented public health emergency, the Agency has received an exceedingly high volume of EUA requests and is working as quickly as possible to review each request. There are hundreds of pre-EUA and EUA requests for COVID-19 tests under review and FDA continues to receive new submissions on a daily basis. To address this high volume of work, we have brought in additional scientific review staff to double the number of teams working on submissions; and we have implemented a triage program to prioritize submissions. As a result of these efforts, the FDA has authorized over 420 tests and sample collection devices that provide a wide array of test options. Since the start of the pandemic, the FDA has adapted to address the public's testing needs and has been working closely with test developers to adjust as those needs have changed. These efforts have helped increase testing capacity and broaden public access to tests, including rapid point-of-care and at-home tests.
With a large number of tests now authorized, the FDA's focus is on helping to increase the availability of specific types of tests that will have the biggest impact in addressing ongoing COVID-19 testing needs. By focusing our review on the types of tests discussed in Section IV. A of the FDA's Policy for Coronavirus Disease-2019 Tests, we can help our communities better respond to the pandemic as the nation's testing needs continue to evolve.
A:We encourage developers to first review the available resources, including the EUA templates, the FAQs on this webpage, and the Letters of Authorization and Instructions for Use/EUA Summaries from previously authorized tests (SARS-CoV-2 IVD EUAs). If you have additional questions or want to discuss novel approaches that are not addressed in the EUA templates and previous authorizations, please reach out to us at CDRH-EUA-Templates@fda.hhs.gov to begin pre-EUA discussions, even if you do not have your validation and/or documentation completed.
A: Yes. The FDA values collaboration between developers and researchers to reduce the burden for test validation. A developer or researcher that has provided data to the FDA may grant a right of reference to other developers, either broadly or to individual developers, to leverage that data. In these cases, if the data is applicable to the new developer's test, they would generally not have to repeat that validation for their submission to the FDA. For example, if a new developer's test is similar to the CDC assay, they may be able to leverage the CDC's in silico and cross reactivity data, rather than repeating it. Further, as discussed in the Molecular Diagnostic Home Specimen Collection Template, the FDA has reviewed analytical validation data from a swab stability study conducted by Quantigen Biosciences, with support from The Gates Foundation and UnitedHealth Group, that can be used, in conjunction with other data from the developer, to support sample stability of foam or polyester nasal swabs shipped dry or in saline for testing with authorized SARS-CoV-2 molecular diagnostic assays. Additionally, as discussed in the next FAQ on this page, the FDA has also reviewed data from a study on the adequacy of pediatric self-swabbing for COVID-19 testing, conducted by Emory University and Children's Healthcare of Atlanta, for which a Master File including a broad right of reference has been submitted to the FDA.
Any developer seeking to leverage data from an EUA-authorized assay must obtain a right of reference from the developer of that authorized test. A letter from the developer providing the right of reference should be included in any EUA request intending to leverage such data, unless a broad right of reference has been announced publicly.
The CDC has granted a right of reference to the performance data contained in the CDC's EUA request for the CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC) (FDA submission number EUA200001) to any entity seeking an FDA EUA for a COVID-19 diagnostic device.
The CDC has granted a right of reference to the performance data contained in the CDC's EUA request for their Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay (FDA submission number EUA201781) to any entity seeking an FDA EUA for a multi-analyte respiratory panel that includes SARS-CoV-2. CDC has published the primer and probe sequences for the Influenza SARS-CoV-2 Multiplex Assay on the CDC website.
A: Yes, the FDA has reviewed data from a study on the adequacy of pediatric self-swabbing for COVID-19 diagnostic testing. This study was conducted by Emory University and Children's Healthcare of Atlanta, with support from the National Institute of Biomedical Imaging and Bioengineering and the National Center for Advancing Translational Sciences at the National Institutes of Health. The study is discussed in the Adequacy of Nasal Self-Swabbing for SARS-CoV-2 Testing in Children preprint, and includes a description of the clear and age-appropriate instructional material used in the study, consisting of a video and a handout to help children perform the task correctly and noting which steps are performed by the adult supervisor (such as collecting and packaging the samples to be sent to the lab).
Emory University and Children's Healthcare of Atlanta have granted a broad right of reference to leverage the performance data and specimen collection protocols from their study on pediatric self-swabbing for COVID-19, contained in a Master File (MAF) submission to the FDA (FDA Master File number MAF3543), in conjunction with other data from the developer, to any entity seeking an FDA Emergency Use Authorization for a COVID-19 diagnostic device for use with self-sampling (under adult supervision) of anterior nares samples in pediatric populations (ages 4-14 years old).
Test developers seeking authorization for pediatric self-collection and seeking to leverage this data may be asked for additional data if, for example, different instructional material will be used than validated in the study.
A: The presence of viral mutations in the SARS-CoV-2 virus in a patient sample can potentially impact test performance. The impact of viral mutations on a test's performance is influenced by several factors, including the sequence of the variant, the design of the test, and the prevalence of the variant in the population.
In February 2021, the FDA issued the guidance Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests to provide a policy and recommendations on evaluating the potential impact of emerging and future viral mutations of SARS-CoV-2 on COVID-19 tests for the duration of the COVID-19 public health emergency, including considerations for test designs to minimize the impact of viral mutations and recommendations for ongoing monitoring. As noted in the guidance, designing redundancy into a test may prevent future variants from impacting test performance.
As discussed on the SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests webpage, tests with single targets are more susceptible to changes in performance due to viral mutations, meaning they are more likely to fail to detect new variants than tests with multiple targets. Multiple targets means that a molecular test is designed to detect more than one section of the SARS-CoV-2 genome or, for antigen tests, more than one section of the proteins that make up SARS-CoV-2. Test developers should consider including multiple targets as they develop new SARS-CoV-2 diagnostic tests.
A: FDA has provided recommendations regarding validation testing for SARS-CoV-2 tests in the EUA templates referenced in the Policy for Coronavirus Disease-2019 Tests and provided for download from the FDA website. These recommendations include the testing that should be performed to demonstrate that a SARS-CoV-2 test is validated based upon the underlying technological principles of the test, as well as generally expected performance metrics. Depending on the characteristics of your test, additional validation studies may be recommended.
The EUA Templates reflect FDA's current thinking on the data and information that developers should submit to facilitate the EUA process. The templates provide information and recommendations, and we plan to update them as appropriate throughout the public health emergency.
Developers can use alternative approaches. Developers who intend to use alternative approaches should consider seeking FDA's feedback or recommendations to help them through the EUA process. FDA encourages developers to discuss any alternative approaches with FDA through CDRH-EUA-Templates@fda.hhs.gov.
The EUA Templates include recommendations for diagnostic tests, including molecular and antigen tests with different attributes, which may involve different considerations, including multi-analyte respiratory panels that include SARS-CoV-2 and other respiratory pathogens, screening tests for asymptomatic individuals, tests for use with home collected specimens, and tests for use completely at home. There are also templates for serology tests, including fully quantitative antibody tests and tests that detect or correlate to neutralizing antibodies.
When determining whether to issue an EUA for a multi-analyte respiratory panel, FDA considers, among other things, the use of the test (multi-analyte pathogen detection as an aid in differential diagnosis), clearance/approval status of IVDs for the other panel members, whether the proposed intended use fits within the HHS emergency declaration and how the panel test would fit into current recommendations from public health authorities regarding patient testing.
The Molecular Diagnostic Home Specimen Collection Template addresses many issues specific to home collection, including recommendations on how to determine whether the lay user can safely and properly collect the specimen, whether the components of the specimen transport media are safe for use in the home environment (since some may be toxic), proper shipment, and adequate stability of the specimen given the time lapse between collection and testing and the potential impact of shipping conditions (such as, if the specimen sits in a hot truck). A healthcare provider watching the collection by way of telemedicine may address the issue of proper specimen collection (if the self-collection method does not raise safety concerns) but would generally not address other issues such as specimen stability and shipping conditions.
The Molecular Diagnostic Home Specimen Collection Template discusses a right of reference provided by Quantigen Biosciences to any sponsor wishing to pursue an EUA, which allows sponsors to leverage Quantigen's data to support specimen stability during shipping. The template also recommends that distributors of home collection systems contact the Pipeline and Hazardous Materials Safety Administration (PHMSA) within the Department of Transportation (DOT), at HMInfo@dot.gov, to confirm their packaging and shipping instructions will ensure users are in compliance with the hazardous materials regulations for shipping medical material.
The Molecular and Antigen Home Use Test Template includes recommendations about what testing should be performed to demonstrate that a COVID-19 test for home/non-lab use has been validated, recommendations for generally expected performance metrics, and recommendations for demonstrating the ability of lay users to collect their specimen, run the test, and interpret their results accurately. Additionally, this template provides recommendations about what safety considerations should be considered in such an EUA request, including safety from any exposure to toxic chemicals that may be used in the reaction. Due to the benefits of broader access to simple and fast testing options from tests that can be performed completely outside of a laboratory, a lower sensitivity of such tests, when compared to tests run in a laboratory, may be appropriate. The FDA is always open to alternative proposals, such as serial testing where the overall sensitivity can be considered cumulatively rather than based on one-time testing, and encourages developers to discuss such proposals with the FDA. Serial testing is further discussed in the Supplemental Template for Molecular and Antigen Diagnostic COVID-19 Tests for Screening with Serial Testing.
A: Below is information regarding various test materials for diagnostic assay validation. Links provided are for information purposes only and are not a recommendation by FDA to use that product. FDA encourages other suppliers of test materials to email COVID19DX@fda.hhs.gov to discuss whether materials they have available may also be appropriate for use.
As noted in the molecular diagnostic templates, FDA recommends using natural clinical specimens in the clinical evaluation for those tests. Please refer to those EUA templates for information regarding clinical study design for molecular diagnostic tests. If you do not have access to positive clinical samples from a clinical laboratory, these are available commercially:
- Boca Biolistics: Order by emailing COVID19support@BocaBio.com
- Product # C0040-0001: SARS-COV-2 Validation Panel
- This product includes 30 positive patient samples and 30 negative patient samples, as determined by CLIA-certified labs.
- Product # C0040-0001: SARS-COV-2 Validation Panel
- Discovery Life Sciences: Order by emailing firstname.lastname@example.org OR following the instructions on their COVID-19 website links below:
- Product: Discovery COVID-19 Remnant Biospecimen Sets
- Discovery Life Sciences has positive and negative patient specimens, as determined by CLIA-certified labs, for several remnant biospecimen types. Contact them to discuss options.
- Product: Fully Consented Matched Biospecimen Sets
- Matched sets can include Plasma, Serum, PBMCs and Saliva with comprehensive patient data available.
- Product: Discovery COVID-19 Remnant Biospecimen Sets
As also noted in the molecular diagnostic templates, in the absence of known positive samples, Limit of Detection (LoD) validation studies may also be performed with contrived clinical specimens. We recommend spiking quantified inactivated virus (e.g., heat treated, chemically modified, or irradiated virus) into real clinical matrix (e.g., nasal or nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid, sputum, etc.). You may request inactivated virus directly from:
- BEI Resources: Order through BEI Resources website
- Product # NR-52286: SARS-Related Coronavirus 2, Isolate USA-WA1/2020, Heat inactivated
- Product # NR-52287: SARS-Related Coronavirus 2, Isolate USA-WA1/2020, Gamma-Irradiated
- ATCC: Order through their Coronavirus Resources website
- Product # VR-1986HK: Heat-inactivated SARS-CoV-2 (strain 2019-nCoV/USA-WA1/2020)
- ZeptoMetrix: Order by emailing email@example.com OR calling customer service at 1-800-274-5487 OR through their website
- Product # NATSARS(COV2)-ERC: NATtrol SARS-Related Coronavirus 2 (SARS-CoV-2) External Run Control (6 X 0.5mL)
- This product contains approximately 50,000 copies/mL. The isolate is USA-WA1/2020, chemically inactivated.
- Product # NATSARS(COV2)-ST: NATtrol SARS-Related Coronavirus 2 (SARS-CoV-2) Stock (1mL)
- This product contains approximately 1,000,000 copies/mL. The isolate is USA-WA1/2020, chemically inactivated.
- Product # NATSARS(COV2)-ERC: NATtrol SARS-Related Coronavirus 2 (SARS-CoV-2) External Run Control (6 X 0.5mL)
A: The FDA's policies regarding the distribution or offering of a test that is a modification of an EUA-authorized diagnostic test prior to or without authorization of the modified test are discussed in section IV.D of the FDA's Policy for Coronavirus Disease-2019 Tests, reissued on November 15, 2021. These policies address modifications made before and after the issuance of this updated guidance, including modifications made by a commercial manufacturer to its own EUA-authorized test, and modifications made by a high-complexity CLIA-certified laboratory to an authorized COVID-19 molecular diagnostic test, including one for which such laboratory is not the developer of the original, EUA-authorized test.
The policies regarding offering a COVID-19 tests prior to or without an EUA, including the policies for modifications to EUA-authorized diagnostic tests, have never applied to at-home tests or tests with home specimen collection, or any testing outside of a high-complexity CLIA-certified laboratory.
Unless and until an EUA is issued that authorizes additional testing environments for a specific test, under the Clinical Laboratory Improvement Amendments (CLIA), section 353 of the Public Health Service Act (42 USC 263a), use of that test is limited to laboratories that are certified under CLIA, and meet the requirements to perform tests of high-complexity, and at the point-of-care (POC) when covered by such a laboratory's CLIA certificate.
In order to provide transparency, when a developer is distributing or offering a test that is a modification of an EUA-authorized diagnostic test prior to or without authorization of the modified test, as discussed in Section IV.D of the Policy for Coronavirus Disease-2019 Tests, the FDA provides recommendations regarding test reports and other information. Specifically, the FDA recommends that the developer post data about the modified test's performance characteristics on the developer's website, and that the instructions for use or test protocol and the test reports accurately reflect the modification and prominently disclose that the test has been modified since authorization by FDA and that the modified test has not been reviewed by FDA.
If FDA identifies a significant problem or concern with a modified test, based either on the provided information or external reports, that cannot be addressed in a timely manner, FDA generally would expect the developer to cease distribution, marketing and offering the modified test and address such problem, which could include conducting a recall of the modified test and/or notification concerning corrected test reports indicating prior test results may not be accurate.
A. There is a World Health Organization (WHO) anti-SARS-CoV-2 antibody international standard material, also called a Certified Reference Material (CRM). Currently, not all SARS-CoV-2 antibody tests are traceable to a CRM. Without traceability to the same CRM, test results cannot be compared between different SARS-CoV-2 antibody tests since each test uses its own calibration units.
The Policy for Coronavirus Disease-2019 Tests discusses the FDA's general intention to prioritize the review of EUA requests for laboratory-based and point-of-care (POC) antibody tests that promote an increased understanding of immune responses to SARS-CoV-2, including:
- Tests that are high throughput (if laboratory-based), can be manufactured in high volume, and that are intended for the quantitative measurement of antibody titers, and
- Tests that can be manufactured in high volume and are intended for the quantitative detection of neutralizing antibodies.
Additionally, the EUA Templates include additional details about the FDA's recommendations for antibody tests, including fully quantitative antibody tests and tests that detect or correlate to neutralizing antibodies.