The U.S. FDA’s stated policy is that it will not review emergency use authorizations (EUAs) for lab-developed tests (LDTs) for the COVID-19 pandemic, but that doesn’t mean labs are completely shut out. The FDA’s Toby Lowe said that a lab that wants to pair an assay that already has an EUA with a new software installation on lab instrumentation can work with the assay developer to update that EUA, a development Lowe said would aid other labs that want to leverage the same assay.
Lowe, associate director of the FDA’s Office of In Vitro Diagnostics and Radiological Health, led the Nov. 4 COVID-19 testing town hall with the advisory that there will be no Nov. 11 town hall due to Veteran’s Day. She also made note of the agency’s Nov. 3 advisory to health care professionals regarding the not-unexpected rate of false positives associated with antigen tests conducted in areas with a low prevalence of COVID-19.
One of the callers on the Nov. 4 town hall, who is employed at “one of the smaller medical centers,” said the lab in his home institution is working with the manufacturer of an assay for use of which the agency has granted an EUA. The lab also has an EUA for the software used on their lab instrumentation, and lab personnel are working with the manufacturer to adapt the assay to develop a novel combination of software and instrumentation that he suggested would qualify as an LDT.
Assay maker liable for EUA update
Lowe confirmed the agency’s stance, stating, “we have indicated we are declining to review EUA requests for LDTs at this time.” but encouraged the caller to work with test kit maker on validation of the new configuration. The assay maker, rather than the lab, would have to file a supplemental request to update their EUA. “That would also help other labs that want to use the same combination,” Lowe said.
Lowe noted that the agency has granted no EUAs for over-the-counter (OTC) tests of any technological type, a statement that applies to tests that are conducted entirely at the user’s domicile. The agency is still quite interested in authorizing tests for both scenarios, and Lowe said the agency has demonstrated some flexibility as to how to validate any such tests.
Any research-use only (RUO) components used to develop a test should be re-labeled to reflect that component’s status in an EUA test, Lowe said. Lowe said also that the template for antigen tests calls for 20 asymptomatic positive samples when the developer wants to affix a claim for testing for asymptomatics, although one caller asked about the use of archived specimens when the EUA was granted with a post-grant requirement for additional studies. The agency has no formal policy on the use of archived specimens in this scenario, and Lowe suggested that developers approach the lead reviewer about whether this would be permissible.
Lowe said the template for molecular tests has recommendations for validation of the use of saliva, including the addition of saliva samples to an existing EUA that originated as a nasal swab sample. In the example of a lab that wants to add saliva sampling to a test that is run with a commercially distributed kit, the lab should contact the distributor about adding saliva to that kit’s EUA, but Lowe noted that the FDA would not expect to see an EUA amendment if the lab is adding saliva to an EUA originating solely from that lab.
Companies manufacturing viral transport media (VTM) are urged to perform a validation of sterility per guidelines published by the CDC, but one caller said that the CDC guidelines offer little guidance regarding the method for performing sterility checks. Lowe said the FDA’s expectation is that the company has internally validated the VTM as sterile, adding that a sterility check of the VTM constitutes validation of the method used. However, the FDA has not developed a fixed policy on how to establish sterility, a subject that can be handled with the lead reviewer for that EUA filing.
Distinguishing molecular from PCR tests
A caller affiliated with Hologic Inc., of Marlborough, Mass., noted that several U.S. states have begun promulgating recommendations for interstate travel to within those states, which may include a recommendation for diagnostic polymerase chain reaction (PCR) test. However, Hologic offers a non-PCR nucleic acid-amplified test, although some states are requiring travelers to quarantine even with a negative result from the Hologic test.
The caller said the term “PCR” is often used to describe other molecular tests that also use RNA amplification, which may be in use in return-to-work and return-to-school settings. The caller asked the FDA to update the templates to advise state and local policymakers that some of these molecular tests are non-PCR tests in an effort to avoid confusion.
Lowe acknowledged that the distinction is an important one, adding that the agency uses “molecular” as a general term when it may be more advisable to specify whether the test is a PCR test. She asked that industry communicate any such concerns to the FDA via e-mail.