In response to the COVID-19 pandemic and the need for more diagnostic testing, the U.S. Food and Drug Administration (FDA) has developed several pathways for manufacturers and developers of COVID-19 diagnostic tests to lawfully market their products – even without FDA clearance or approval.
Under current law, during a public health emergency, the FDA can use its Emergency Use Authorization (EUA) authority to allow the use of unapproved medical products when certain criteria are met, including that there are no adequate, approved and available alternatives. The FDA has used this authority to increase the number of COVID-19 tests on the market. By granting an EUA to a manufacturer, the FDA specifically authorizes the marketing of the particular test.
On May 4, 2020, FDA issued a revised version of its Policy for Diagnostic Tests for Coronavirus Disease-2019, outlining the agency's approach for EUAs and its applicability to COVID-19 diagnostics (See Holland & Knight's Healthcare Blog, "FDA's COVID-19 Guidance and Policy Update: March 23, 2020," March 24, 2020.) The policy applies to both antibody tests (also known as serology tests) that determine the amount of antibodies present in the blood when the body is responding to a specific infection, such as COVID-19, as well as molecular tests (such as nasal swab tests) that are designed to determine whether a patient has COVID-19.
Under the revised policy, all COVID-19 test manufacturers must submit an EUA. This is a policy change since the March 2020 policy. We provide more details on each tests' pathways below. The FDA also has outlined pathways for laboratories to develop their own tests, but these pathways are outside the scope of this article.
SARS-CoV-2 Antibody Tests
EUA Pathway for Antibody Tests that have Notified FDA of Test Validation
The FDA's Policy identifies a pathway to market for developers of antibody tests applicable to SARS-CoV-2. Antibody tests measure the amount of antibodies present in the blood. While these types of tests are not designed to be used as a diagnostic tool for COVID-19, the FDA has said antibody tests "can play a critical role in the fight against COVID-19 by helping healthcare professionals identify individuals who have been exposed to SARS-CoV-2 virus and have developed an immune response."
As of the May 4, 2020, policy, manufacturers who have validated their test and notified the FDA that the test has been validated have 10 business days (from the date of the notification or the date of this policy, whichever is later) to prepare and submit an EUA. During this 10-day period and EUA review period, the test may stay on the market as long as the following information related to the intended use of the test is included on product packaging, labeling and the manufacturer's website:
- This test has not been reviewed by the FDA.
- Negative results do not rule out SARS-CoV-2 infection, particularly in those who have been in contact with the virus. Follow-up testing with a molecular diagnostic should be considered to rule out infection in these individuals.
- Results from antibody testing should not be used as the sole basis to diagnose or exclude SARS-CoV-2 infection or to inform infection status.
- Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43 or 229E.
To date, the FDA has received notification from 170 test manufacturers, all of whom will need to submit an EUA within 10 business days.
The FDA has provided EUA templates in its May 4, 2020, policy for manufacturers to use. In the event the FDA is unable to issue an EUA, the FDA will notify the manufacturer, and the manufacturer will be expected to suspend distribution of the test and remove the manufacturer from the FDA's website.
SARS-CoV-2 Antibody Test "Umbrella EUA"
The FDA released on April 28, 2020, an EUA pathway for serology tests, known as an "Umbrella EUA." This EUA does not replace the above pathway, rather it provides another route to market for certain antibody tests under specific conditions.
The Umbrella EUA is specific for SARS-CoV-2 antibody tests. It requires the test to have been evaluated in an independent validation study performed at the National Institutes of Health's (NIH) National Cancer Institute (NCI), or another government agency designated by the FDA. The validation and labeling requirements applicable to other serology tests apply: these tests still must be validated by the manufacturer and have the appropriate labeling. To take advantage of the Umbrella EUA, manufacturers must ensure that these tests are for use in Clinical Laboratory Improvement Amendment (CLIA)-certified labs to perform moderate or high complexity tests, and that the Indication for Use includes "human plasma and/or serum." To date, Holland & Knight is aware of only one test receiving an Umbrella EUA.
In Vitro Diagnostics and Test Kit EUAs
The FDA's Policy also describes a pathway for developers of diagnostic test kits to detect the SARS-CoV-2 virus. These tests are molecular tests that detect the virus's genetic material in a sample that typically comes from a patient's respiratory system. Manufacturers of an in vitro diagnostic test that plan to submit an EUA may begin marketing and distributing the test once they notify the FDA that the test has been validated or may wait to begin distributing the device until the EUA is issued. If the former, the manufacturer must submit its EUA within 15 days of marketing. If the EUA is denied, the FDA will expect the manufacturer to remove its product from the market.
Manufacturers should use the FDA's EUA template to submit their applications. In particular, the FDA will review the performance evaluation of the test, including results of an inclusivity study that demonstrates the strains of SAR-CoV-2 that can be detected by the proposed molecular assay and cross-reactivity studies that demonstrate that the test does not react with related pathogens, high prevalence disease agents and normal or pathogenic flora that are reasonably likely to be encountered in the clinical specimen. The FDA collaborates with test developers throughout the EUA process to address any potential concerns or safety considerations raised in the request and will contact the manufacturer when it makes a final determination. While there are no timeframes established in law or regulation, the FDA is working to respond to requests as expeditiously as possible.
Once an EUA is issued, the FDA will provide the authorized setting and documentation that is required to accompany marketing of the product, including instructions for use, the applicable care setting and healthcare provider that must administer the test, and patient information. The FDA said it has worked with more than 380 test developers that either have or will be submitting EUA requests and issued over 50 individual EUAs for test kit manufacturers.
The FDA continues to provide additional guidance and pathways for test manufacturers, especially noteworthy is that none of its current pathways apply to home tests.
It is important to note that products that are lawfully marketed during the pandemic under any of these pathways are not FDA approved. The FDA has made clear that when the emergency is over, the EUA declaration will be terminated, and all EUAs issued based on that declaration will no longer remain in effect. Thus, manufacturers will have to seek clearance and approval under the 510(k) or other traditional market pathways. It is currently not clear whether the FDA will allow the products to remain on the market during this interim period. Therefore, manufactures of tests should develop their long-term regulatory marketing strategy now to ensure their products can stay on the market after the emergency.