FDA Update: COVID-19 TEST

Policy for Coronavirus Disease-2019 Tests During Public Health Emergency

In the first week of May, the FDA released a new guidance document: “Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised).” This new policy supersedes the guidance document issued during the second week of March.

This new guidance document highlights policies for accelerating the development of certain laboratory-developed diagnostic tests for COVID-19. The first leading to an EUA submission to the FDA and the second not leading to an EUA submission when the test is developed under the authorities of the State in which the laboratory resides. The State takes responsibility for COVID-19 testing by laboratories in its State. Additionally, this guidance describes a policy for commercial manufacturers to more rapidly distribute their SARS-CoV-2 diagnostic tests to laboratories for specimen testing after validation, while an EUA is being prepared for submission to the FDA. This guidance also describes a policy regarding SARS-CoV-2 serological testing.

The policy leading to an EUA submission applies to laboratories certified under CLIA that meet the regulatory requirements to perform high-complexity testing and seek to develop and perform diagnostic tests to detect SARS-CoV-2 virus. This policy does not apply to home collection of specimens to be sent for testing at a laboratory certified under CLIA for high-complexity testing. The FDA does not intend to object to the use of SARS-CoV-2 tests for specimen testing for a reasonable period of time, where the test has been validated and while the laboratory is preparing their EUA request and where the laboratory gives notification of validation to the FDA. The FDA has also provided recommendations regarding testing that should be performed to ensure analytical and clinical validity in section V of this guidance document. Following validation completion, laboratories should notify FDA that their assays have been validated. FDA will acknowledge receipt of this notification and generally will add the laboratory name to the FDA’s website listing. The EUA request should be submitted within 15 business days of the notification of validation. If the EUA request is not submitted, the laboratory listing will be removed from the FDA website listing. The FDA has made a template available that laboratories may choose to use to help facilitate the preparation, submission and authorization of an EUA for a molecular diagnostic test. After receiving the request, a preliminary review is conducted to identify if there are any problems with the performance data. If a problem is found, the FDA intends to work with the laboratory to address the problem. If problems are significant and cannot be addressed in a timely manner, it is expected that testing comes to a halt, and issue corrected test reports indication prior results may not be accurate.

On March 13, 2020, the President issued a Memorandum which refers to the flexibility that FDA allowed New York State and states as follows:

“Should additional states request flexibility to authorize laboratories within the State to develop and perform tests used to detect COVID-19, the Secretary shall take appropriate action, consistent with law, to facilitate the request.”

The FDA policy, in accordance with the Memorandum, regards States and territories that authorize laboratories within their State or territory to develop their own COVID-19 tests and perform specimen testing, where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to the FDA. A State or territory choosing to authorize laboratories (within that State or territory) to develop and perform a test for COVID-19 would do so under its own State law, and under a process that it establishes. The FDA does not intend to object to the use of such tests for specimen testing where the notification of SARS-CoV-2 test validation is not submitted to FDA and the laboratory does not submit an EUA request to FDA, where the State or territory takes responsibility for COVID-19 testing by laboratories in its State during this outbreak. The FDA requests that they be notified by the State or territory if they choose to be flexible to expedite COVID-19 testing. The FDA expects that such states will require laboratories that develop and perform a test for COVID-19 under this policy to notify the FDA that they have started clinical testing by sending an email to that effect to [email protected].

The FDA policy regarding commercial manufacturer development and distribution and laboratory development and use of serology tests prior to or without an EUA applies to developers of serology tests that identify antibodies to SARS-CoV-2 from clinical responses. The FDA does not intend to object to a commercial manufacturers development and distribution of serology tests to identify antibodies to SARS-CoV-2 for a reasonable period of time, where the test has been validated and while the manufacturer is preparing an EUA request, where the manufacturer gives notification of validation to the FDA. Following the completion of assay validation, developers should notify the FDA, that their assays have been validated and they intend to begin distribution and testing, by emailing [email protected].

• For tests developed and used by laboratories certified under CLIA that meet the CLIA regulatory requirements to perform high-complexity testing, this notification should include the name of the laboratory, name of laboratory director, laboratory address, and contact person in this email. The receipt of this email will be acknowledged and generally will add laboratory name to FDA’s website listing.
• For tests developed and distributed by commercial manufacturers, this notification should include name of the manufacturer, address, contact person, and a comp of instructions for use that includes a summary of assay performance. FDA recommends that the manufacturer submit a completed EUA request within 10 business days of the notification to the FDA that assays have been successfully validated. In circumstances where manufacturers use distributor(s) for their test, the manufacturer should identify the names of all distributors in their notification. Distributors should not provide separate notification.

The FDA also recommends that instructions for use and patient test reports include information that helps users and patients understand the test results such as:

• This test has not been reviewed by the FDA
• Negative results do not preclude acute SARS-CoV-2 infection. If acute infection is suspected, direct testing for SARS-CoV-2 is necessary.
• Results from antibody testing should not be used to diagnose or exclude acute SARS-CoV-2 infection.
• Positive results may be due to past or present infection with non-SARS-CoV-2 coronavirus strains, such as coronavirus HKU1, NL63, OC43, 229E.

FDA encourages laboratories to discuss any alternative technological approaches to validating their test with FDA through [email protected]. FDA will communicate any questions or concerns regarding a pre-EUA or EUA submission to the developer.

The FDA has also issued validation study recommendations based on the technological principles of tests: molecular diagnostic tests, antigen detection tests, and serological tests.

1. Molecular Diagnostic Tests: Tests that detect SARS-CoV-2 nucleic acids from human specimens.
   1. Limit of Detection
   2. Clinical Evaluation
   3. Inclusivity
   4. Cross-reactivity
2. Antigen Detection Tests: Tests that detect proteins that are part of the SARS-CoV-2 virus directly from clinical specimens.
   1. Limit of Detection/Analytical Sensitivity
   2. Cross-reactivity/Analytical Specificity
   3. Microbial Interference
   4. Clinical Agreement Study
3. Serological Tests: Tests that identify antibodies to SARS-CoV-2 from clinical specimens.
   1. Cross-reactivity/Analytical Specificity
   2. Class Specificity
   3. Clinical Agreement Study

EUA templates are provided for manufacturers and laboratories in the appendices of the document as well as validation requirements to help facilitate pre-EUA/EUA submissions. The templates include additional information that should be provided to the FDA.

mdi is presently working with several companies in obtaining the EUA for their IVD tests and we are trying our best to keep on top of the FDA changes, which are very fluid. mdi is also assisting companies with the EUA for masks and ventilators as well as providing guidance on all PPE device.

If you want more information on our how we can provide you our assistance in dealing with the EUA submissions and to ensure compliance with the latest FDA guidelines contact us at:  [email protected] RE: COVID-19.