This page provides answers to frequently asked questions related to serology/antibody tests for SARS-CoV-2.
This section includes questions and answers regarding the policies outlined in the Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug Administration Staff: Policy for Coronavirus Disease-2019 Tests during the Public Health Emergency (Revised). In this section, this guidance is referred to as the Policy for Coronavirus Disease-2019 Tests.
For a directory of FAQs related to SARS-CoV-2 testing, see FAQs on Testing for SARS-CoV-2.
A: The terms "serology" or "antibody" tests are generally used to refer to tests that detect antibodies to the SARS-CoV-2 virus. Because these tests identify antibodies that are part of the body's immune response to infection with the virus and do not detect the virus itself, such testing cannot be used for diagnosis of infection. Based on the underlying scientific principles of antibody tests, we do not expect that an antibody test can be shown to definitively diagnose or exclude COVID-19 infection. SARS-CoV-2 antibody tests are intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection, by detecting antibodies to SARS-CoV-2 in human blood specimens.
As stated in the EUA Templates, antibody tests should, among other things, include in the proposed intended use in the EUA request (which would then be included in any authorized labeling), a statement that negative results do not preclude acute SARS-CoV-2 infection and that, if acute infection is suspected, direct testing for SARS-CoV-2 is necessary. SARS-CoV-2 serology tests should be ordered only by clinicians who are familiar with the use and limitations of the test.
A: Serology (antibody) tests may detect different types of antibodies. The most common are IgM and IgG. High quality serological tests can help us understand whether a person or population of people have developed antibodies indicative of an adaptive immune response to COVID-19.
Because a serology test can yield a negative test result even in infected patients (e.g., if has antibodies have not yet developed in response to the virus) or may generate false positive results (e.g., if antibody to a coronavirus type other than the current pandemic novel strain is present), antibody tests should not be used in the immediate (or acute) diagnosis of a patient where COVID-19 infection is suspected. That is, these tests should not be used to diagnose acute COVID-19 infection. Using this type of test on many patients may help the medical community better understand how the adaptive immune response against the SARS-CoV-2 virus develops in patients over time and how many people may have been infected. While there is a lot of uncertainty with this new virus, it is also possible that, over time, broad use of antibody tests and clinical follow-up will provide the medical community with more information on whether or not, and how long, a person who has recovered from the virus is at lower risk of infection if they are exposed to the virus again.
Positive results from appropriately validated serology tests that are designed to be very specific to the SARS-CoV-2 virus can indicate whether a patient has had recent or prior COVID-19 infection. In addition, although not everyone who is infected will develop an antibody response, appropriately validated serology tests, when used broadly, can be useful in understanding how many people have developed an adaptive immune response to the virus and how far the pandemic has progressed.
Serology tests can play a critical role in the fight against COVID-19 by helping healthcare professionals identify individuals who have antibodies to SARS-CoV-2 virus and have developed an adaptive immune response. In the future, this may potentially be used to help determine, together with other clinical data, whether these individuals may be less susceptible to infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity.
A: All clinical tests should be validated prior to use. Tests, including serology tests, being offered prior to or without an EUA under a policy outlined in the Policy for Coronavirus Disease-2019 Tests, have not been reviewed or authorized by the FDA. As stated in the guidance, all such tests should be validated by the developer prior to being offered for clinical use. The FDA has issued policies explaining regulatory flexibility regarding the timing of the independent check by the FDA for certain tests used during the public health emergency, but still expects all developers to validate their tests prior to offering them for limited clinical uses.
The FDA is working with the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Biomedical Advanced Research and Development Authority (BARDA) to assess the performance of certain serological tests for detection of SARS-CoV-2 antibodies. This project is intended to complement and inform FDA review of certain tests. As part of this project, the FDA, and partnering agencies, designed and are using a performance assessment protocol that offers a mechanism for an independent evaluation of certain lateral flow and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests in a laboratory environment. Under this protocol, tests are evaluated at the National Cancer Institute (NCI)/NIH with a well-characterized sample panel consisting of positive and negative plasma and/or serum samples. The NIH/NCI validation project is an important resource to independently validate certain SARS-CoV-2 serology tests. FDA has requested that certain serology tests, including lateral flow serology assays (IgM, IgG, etc.) and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests, be independently evaluated by the NIH/NCI prior to authorization. FDA may leverage data from testing at the NCI/NIH, or at another federal government laboratory designated by FDA, to inform decisions on EUA requests and other actions.
If you are interested in participating in this independent evaluation, please send an email to CDRH-OIR-POPS@fda.hhs.gov. Include the following information in your email:
- Manufacturer and test name as provided in your notification to FDA,
- Volume of tests currently available to distribute in the United States,
- Weekly production volume available to distribute in the United States,
- Test technology,
- Sample type, and
- Pre-EUA (PEUA) or EUA number if you have been assigned one.
Please be advised that a request for NCI evaluation is not a request for an EUA. To submit an EUA request, we recommend that you consider the EUA Templates available to help facilitate the preparation, submission, and authorization of an EUA. Your EUA request can be sent to CDRH-EUA-Templates@fda.hhs.gov.
Evaluation of tests submitted to NCI are prioritized for testing based on several factors. For example, if the developer has submitted clinical performance data in its EUA request that demonstrates poor performance, evaluation of that test at NCI may not be a priority.
A. FDA will continue to decide whether to authorize a test based on the totality of scientific evidence available. The capability to evaluate SARS-CoV-2 serology (antibody) tests at NCI was established to enhance the U.S. Government's ability to conduct an independent evaluation of certain serology tests and inform FDA recommendations and decision making. Since the program began, we have seen some inconsistent performance between the clinical validation performed by the sponsor and the independent evaluation performed at NCI for various serology tests evaluated to date, particularly lateral flow tests. We have also received reports of under-performing serology tests in clinical use and there have been several reports published in the scientific literature suggesting that some lateral flow tests, in particular, have clinically unacceptable performance. In light of these findings, FDA has requested that certain serology tests from commercial manufacturers, including lateral flow serology assays (IgM, IgG, etc.) and certain enzyme-linked immunosorbent assay (ELISA) or similar technology-based SARS-CoV-2 antibody tests, be evaluated by NIH/NCI prior to authorization. As the pandemic progresses and FDA continues to learn through real world experience with SARS-CoV-2 antibody tests, FDA will continue to adapt to the rapidly evolving circumstances as public health needs warrant.
A. Developers may seek authorization of serology tests through an individual EUA request. For developers who already submitted a request to be added to the serology umbrella EUA, their request will automatically be considered as an individual EUA request.
This is an administrative change and FDA's general performance expectations for serology tests remain unchanged.
The Department of Health and Human Services' independent evaluation of serology tests will continue to be used to inform our decision making on certain EUA requests and other actions. If acceptable clinical performance is demonstrated when a test is evaluated at NCI (or by another government agency designated by the FDA), additional clinical performance data may not be necessary to support authorization of the test for the same use and sample types evaluated through the independent evaluation program.
We encourage developers to consider the EUA templates provided for download from our website to help facilitate the preparation, submission, and authorization of an EUA request.