COVID-19 Test Development and Review: FAQs on Testing for SARS-CoV-2

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.

Questions and answers regarding other policies described in the Policy for Coronavirus Disease-2019 Tests are found in other pages in this section.

Q: What are FDA's priorities with respect to review of EUA requests for COVID-19 tests? (9/27/22)

A: The FDA prioritizes review of Emergency Use Authorization 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. 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's Policy for Coronavirus Disease-2019 Tests, reissued on September 27, 2022, describes FDA's intent to review only a small subset of new EUA requests for diagnostic tests and encourages developers of all test types interested in marketing authorization to pursue authorization through the de novo classification or 510(k) clearance premarket review pathways.

The FDA intends to prioritize its review of EUA requests and supplemental EUA requests from experienced developers (developers who have interacted with the FDA through a successful EUA request during the current public health emergency or have similar experience, as defined in footnote 5 of the guidance) for the following types of tests:

• Diagnostic tests that are likely to have a significant public health benefit (for example, employ innovative technology).
• Diagnostic tests that are likely to fulfill an unmet need (for example, diagnosing infection with a new variant or subvariant).

In addition to these priorities, the FDA also intends to focus its review on:

• EUA requests that are from or supported by a U.S. government stakeholder, such as tests funded by the Biomedical Advanced Research and Development Authority (BARDA) or the National Institutes of Health's Rapid Acceleration of Diagnostics (RADx); and
• Supplemental EUA requests that fulfill a condition of an EUA.

Tests for which EUA requests were submitted to the FDA prior to issuance of this updated guidance, where the EUA request remains under FDA review or in the FDA's queue for review at the time of issuance of this updated guidance, but which do not fall within one of the current review priorities, may continue to be reviewed.

The FDA intends to notify test developers of its intent by email if the FDA declines to review or otherwise decides not to authorize a test/modification in an EUA request or supplemental EUA request.

Q: I am developing a SARS-CoV-2 test and want to pursue an EUA. When should I contact the FDA? (9/27/22)

A: First please review the resources that will help with many potential questions:

• FAQs on Testing for SARS-CoV-2
• EUA Templates with recommendations to help facilitate EUA requests, as explained in the Policy for Coronavirus Disease-2019 Tests
• SARS-CoV-2 IVD EUAs (Letters of Authorization and Instructions for Use/EUA Summaries)

In addition, the FDA encourages test developers to make sure their SARS-CoV-2 test fits within priorities outlined in the Policy for Coronavirus Disease-2019 Tests. If you are unsure whether your test may be prioritized for review, we encourage you to reach out to CDRH-EUA-Templates@fda.hhs.gov; however, at this stage, the FDA strongly encourages developers of new tests and existing tests for which modifications are sought to pursue traditional premarket pathways.

If you have additional questions that are not addressed in the available FDA resources, the FDA can provide validation recommendations specific to a test developer's situation both for those seeking EUA and for those seeking marketing authorization through traditional review pathways. Developers can send simple inquiries to CDRH-EUA-Templates@fda.hhs.gov or submit a pre-EUA or pre-submission for more complex inquiries. For tests seeking marketing authorization through traditional premarket review pathways, the FDA may recommend validation studies or supportive evidence in addition to the recommendations in the EUA templates.

Q: I submitted a pre-EUA or EUA request for a COVID-19 test. How long will the review take? (9/27/22)

A: The FDA strives to communicate with sponsors about their pre-EUA or EUA request as quickly as possible. Review times are highly dependent on the quality and priority of the submission.

Given the need to address urgent public health priorities, the FDA has and continues to prioritize among the EUA requests it receives for COVID-19 tests, as discussed in Section IV. A of the FDA's Policy for Coronavirus Disease-2019 Tests. If your pre-EUA or EUA request is prioritized for review, the submission will be assigned a lead reviewer. The lead reviewer or another review team member will contact you when the review is complete or if there are questions.

The FDA intends to notify test developers of its intent by email if the FDA declines to review or otherwise decides not to authorize a test/modification in an EUA request or supplemental EUA request.

Q: What are the FDA's policies about distribution and offering of a test that is a modification of an EUA-authorized diagnostic COVID-19 test? (9/27/22)

A: The FDA's policies about 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 described in section IV.D of the FDA's Policy for Coronavirus Disease-2019 Tests, reissued on September 27, 2022.

The policies regarding offering a COVID-19 test 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.

For modifications made to an EUA authorized diagnostic test after issuance of this updated guidance, the FDA generally:

• Intends to review supplemental EUA requests that fulfill a condition of an EUA.
• Encourages test developers to consider including the modification in a submission through a traditional premarket review pathway if the modification is beyond the priorities outlined in the outside what is described in the priorities outlined in the Policy for Coronavirus Disease-2019 Tests.
• Expects such modified tests to be authorized under an EUA or pursuant to a traditional premarket review pathway before being distributed or offered.

For modifications made by a high-complexity CLIA-certified laboratory to an EUA authorized diagnostic test after issuance of this updated guidance, the FDA generally does not intend to object to implementation of the modification to the diagnostic test without notification to FDA or a new or amended EUA where:

• the modifications do not change the indication for use set forth in the EUA (e.g., including new/different extraction kits or instruments that would not be expected to change the indication for use),
• the modifications do not change the analyte specific reagents (e.g., the modifications do not change the PCR primers and/or probes),
• the laboratory has validated the modification and confirmed that the performance of the modified test is equivalent to the performance of the authorized test, and
• use of the test is limited to the high-complexity CLIA-certified laboratory in which the modification was made.

Modifications made before issuance of this updated guidance are discussed in section IV.D.2 of the Policy for Coronavirus Disease-2019 Tests, and reflect the policies described in previous versions of this guidance.

Transparency for Modified Tests

In order to provide transparency, when a test 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.C.2 and Section IV.D of the Policy for Coronavirus Disease-2019 Tests, the FDA provides recommendations regarding test reports and other information. Among other things, the FDA recommends that:

• The test developer post data about the modified test's performance characteristics on the test developer's website; and
• 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 the FDA and that the modified test has not been reviewed by the FDA.

Problems or Concerns with a Modified Test

If the 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, the FDA generally would expect the developer to cease distribution, marketing and offering the modified test and address the problem, which could include conducting a recall of the modified test and/or notification about corrected test reports indicating prior test results may not be accurate.

Q: I am seeking marketing authorization through the traditional premarket review pathways for a COVID-19 test. What do I need to know? (9/27/22)

A. The recommendations in the EUA templates may not be sufficient for developers seeking marketing authorization of their tests through traditional premarket review pathways. The FDA can provide validation recommendations specific to a test developer's situation both for those seeking EUA and for those seeking marketing authorization through traditional review pathways. Developers can send simple inquiries to CDRH-EUA-Templates@fda.hhs.gov or submit a pre-EUA or pre-submission for more complex inquiries.

On March 17, 2021, the FDA granted the first marketing authorization using the De Novo review pathway for the BioFire Respiratory Panel 2.1 (RP2.1). On November 1, 2021, the FDA cleared the first 510(k) for the BioFire COVID-19 Test 2. The FDA recommends that you review the authorization documentation for these tests to gain insight into the information FDA reviewed. These documents will also provide information you need to consider whether the tests are appropriate as a predicate for your test, such as whether they have the same intended use, to support submission through the 510(k) premarket clearance pathway.

Developers planning to submit a Pre-Submission (also known as a Q-Submission) for your COVID-19 test should:

• Send the Pre-Submission before you submit any premarket submission, including a 510(k), so that the FDA can provide feedback on your proposed approach.
• Review the guidance: Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.
• Send the Q-Submission through the eCopy Program for Medical Device Submissions process.

Q: What are the current validation study recommendations for a new COVID-19 assay? (9/27/22)

A: All clinical tests should be validated using clinical specimens and an appropriate comparator test prior to use. The FDA has many resources for test developers with questions about the FDA's COVID-19 test validation study recommendations. These resources include a series of EUA templates referenced in the Policy for Coronavirus Disease-2019 Tests and available on the FDA website.

• Reflect the FDA's current thinking on the validation recommendations for SARS-CoV-2 tests and the data and information that test developers should submit to facilitate the EUA process.
• Provide recommendations regarding testing that should be performed to ensure analytical and clinical validity to the level of evidence expected for an EUA, including descriptions of appropriate comparators for different types of tests. Depending on the characteristics of your test, additional validation studies may be recommended.
• Are tailored to different test types and attributes, which may involve different considerations, including:
  • Diagnostic tests - molecular and antigen tests with different attributes such as 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.
  • Serology tests, including fully quantitative antibody tests and tests that detect or correlate to neutralizing antibodies.

  Test developers can use alternative approaches. The FDA encourages test developers to discuss any alternative approaches with FDA through CDRH-EUA-Templates@fda.hhs.gov.

  Because the level of evidence required for authorization under traditional premarket review pathways is higher than that required for an EUA, the recommendations in the EUA templates may not be sufficient for developers seeking marketing authorization of their tests through traditional premarket review pathways. The FDA can provide recommendations specific to a test developer's situation through inquiries to CDRH-EUA-Templates@fda.hhs.gov or through pre-submission interactions.

  Q: I am developing a SARS-COV-2 diagnostic test. What should I consider about the potential impact of emerging and future viral mutations of SARS-CoV-2 on test performance? (1/21/22)

  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 web page, 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.

  Q: I am developing a COVID-19 diagnostic test. How can I obtain appropriate test materials for assay validation? (10/28/22)

  A: All COVID-19 clinical tests should be validated using clinical samples and an appropriate comparator test prior to use. At this time, prospective collection of clinical samples for validation is generally recommended, and clinical samples are typically readily available from clinical laboratories performing COVID-19 testing.

  For Limit of Detection (LoD) validation studies, the FDA recommends spiking quantified inactivated virus (for example, heat treated, chemically modified, or irradiated virus) into real clinical matrix (for example, nasal or nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid, sputum) confirmed negative for SARS-CoV-2.

  Commercially Available Quantified Inactivated Virus

  The list below provides resources for diagnostic assay validation test materials. The resources are for information purposes only and are not an FDA recommendation 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.

  • 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
    • Product # VR-1986HK: Heat-inactivated SARS-CoV-2 (strain 2019-nCoV/USA-WA1/2020)
    • 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.
      • This product contains approximately 1,000,000 copies/mL. The isolate is USA-WA1/2020, chemically inactivated.

      Q: Can I use or leverage validation data that has already been reviewed by the FDA for another COVID-19 test? (9/27/22)

      A: Yes, in many cases, test developers can use or leverage validation data that has already been reviewed by the FDA for another COVID-19 test EUA.

      A test developer or researcher may grant a right of reference to another test developer (called the "new" test developer here), or more than one new test developer, for validation data that was already reviewed by the FDA. A right of reference tells the FDA that the new developer(s) can reference the data without the new developer(s) having access to see the data. Since the FDA already has that data from the original developer or researcher, the FDA can consider it in the context of the new developer's submission without providing the data to the new developer directly. This allows the new developer to leverage the data without the original developer or researcher having to disclose proprietary information. See "Right of Reference" below. If the validation data is applicable to the new developer's test, the new developer would generally not have to repeat that validation for their submission to the FDA.

      Test developers seeking to leverage validation data in this way should include in their EUA request a letter from the original developer or researcher providing specific right of reference for the data, unless the granting test developer has already publicly announced a broad right of reference.

      Broad Right of Reference

      The CDC has granted a right of reference to the performance data contained in these EUA requests. If a new developer's test is similar to the CDC assay, they may be able to use the CDC's in silico and cross reactivity data, rather than performing their own in silico and cross-reactivity studies.

      • CDC 2019-nCoV Real-Time RT-PCR Diagnostic Panel (CDC): (FDA submission number EUA200001) Right of reference to any test developer seeking an EUA for a COVID-19 diagnostic device.
      • Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay: (FDA submission number EUA201781) Right of reference to any test developer seeking an EUA for a multi-analyte respiratory panel that includes SARS-CoV-2. The CDC has published the primer and probe sequences for the Influenza SARS-CoV-2 Multiplex Assay on the CDC website.

      Quantigen Biosciences has granted a right of reference, to any sponsor wishing to pursue an EUA, to leverage its COVID-19 swab stability data as part of that sponsor's EUA request.

      • The FDA 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 new test 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. For more information see the Molecular Diagnostic Home Specimen Collection Template.

      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.

      • The FDA 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 (MAF) submission to the FDA (FDA Master File number MAF3543) including a broad right of reference has been submitted to the FDA. The broad right of reference provides for 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) to leverage the data and protocols from the study, in conjunction with other data from the developer. See the next FAQ on this page for more information.

      Q: I want to offer my COVID-19 diagnostic test for pediatric self-swabbing. Is validation data available that I can use to support this indication? (3/29/22)

      A: Yes, there is FDA-reviewed data from a study on the adequacy of pediatric self-swabbing for COVID-19 diagnostic testing that you can use. The 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 Journal of American Medical Association article, and includes a description of the clear and age-appropriate instructional material used in the study. The instructional materials include a video and a handout to help children perform the self-swabbing correctly. The instructional materials note which steps should be 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 so that other test developers can use the performance data and specimen collection protocols from their study on pediatric self-swabbing for COVID-19, together with other data from the developer. The right of reference is granted to any test developer seeking an EUA 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). The data and the right of reference are contained in a Master File (MAF) submission to the FDA (FDA Master File number MAF3543) and developers should reference this MAF in their submission to FDA.

      Test developers using the Emory University and Children's Healthcare of Atlanta data to support a pediatric self-swabbing indication should note that the FDA may still have questions or request additional data from you. This is especially true if, for example, you use different instructional materials than those used in the Emory University and Children's Healthcare of Atlanta study.

      Q: I am developing a SARS-CoV-2 antibody test. What are the recommendations for traceability to an international standard material? (9/27/22)

      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.

      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.