Developers of tests for the COVID-19 pandemic are deploying an increasingly wider range of test systems for molecular testing, but the FDA’s Toby Lowe said that despite the seeming interchangeability of real-time PCR (rt-PCR) systems, performance of a reference panel for a tweaked test must reflect the use of the rt-PCR system that is listed in the existing emergency use authorization (EUA).
Tim Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health (OIR), was not on the call due to other commitments, but Toby Lowe, associate director of OIR, handled the questions. Lowe noted at the outset of the session that the schedule for these town halls may change in 2021, but had no details to offer. Lowe also said the recommendations in EUA templates are recommendations and not compulsory, but said that for non-laboratory tests, inclusion of instructions for use in Spanish is highly recommended. This would carry a requirement for inclusion of Spanish-speaking subjects in usability tests, however.
Reference panel validation must reflect authorized test system
One caller indicated that his company was using rt-PCR equipment for reference panel validation for a client company located outside the U.S. The client is working to comply with a required reference panel, and the consultant company has two real-time PCR instruments, but the company’s EUA identifies a different rt-PCR system. The caller asked if the consulting company can perform a reference panel on an alternate system, and Lowe said performance of that reference panel has to be in line with instructions provided for the authorized tests. This stipulation, she said, is “so that [the reference panel validation] is reflective of the test that was authorized” by the FDA.
The FDA is interested in a home use antigen test with opt-in surveillance features that reports results to the federal government, but Lowe said that while this is recommended in templates for non-lab tests, there is no formal recommendation as to how to link the data. Lowe also said she is uncertain as to whether the FDA human factors testing team has a formal policy about the use of multiple-choice questionnaires for test usability studies, adding that sponsors should contact the agency about the use of any other approaches.
If a developer is anticipating a need for alternative swabs under a pending EUA, the developer might want to file the EUA with some anticipated flexibility. A caller noted that a change of swab might not require a regulatory filing under the traditional 510(k) program, but Lowe said the addition of alternate swab specimen types would likely require an amended EUA for the pandemic.
Lowe said that for the purposes of the pandemic, screening is defined by the FDA as “testing primarily asymptomatic individuals” without known exposure to identify those individuals who have been infected. Any sponsors who seek to file an EUA for a home-use configuration of a point-of-care platform can send a partially populated EUA template to the agency for feedback. Lowe said that if the sponsor cites specific questions in the partially filled-out template, it eases the task of providing the appropriate feedback.
The backlog of serology test validations at the National Cancer Institute is easing, but one caller asked whether the FDA is considering reviewing an EUA for a serology test without the NCI validation because of the continuing backlog. Lowe said the FDA prioritizes EUA filings based in part on the completeness of the submitted data, but that the FDA staff are still keying on the NCI validations. Part of the FDA’s reliance on NCI validations hinges on concerns revolving around the accuracy of some of these tests, including lateral flow devices, and Lowe said the FDA is unlikely to prioritize an EUA that lacks NCI validation data.
A developer that has an EUA for an antigen test and wants to add the ability to detect an additional antigen may have to file a new EUA. This depends to some extent on whether the sponsor intends to market two separate tests, which Lowe said would likely require two separate EUA filings.
One caller inquired as to whether changes to components used in an authorized molecular test process can be handled strictly via internal documentation – such as is the case with minor changes to 510(k) devices – rather than via amendments to an EUA. Lowe said it depends on how those components are specified in the EUA. If a test is authorized for use with a specific swab type, that change should be forwarded to FDA as an amendment. The addition of extraction kits to an existing EUA for a molecular test would have to be cited in a revised EUA. Whether a change to the buffer in the extraction kit would likewise require an amended EUA depends on how it was documented in the existing EUA, Lowe said.
FDA updates remote monitoring IIE
The FDA posted an enforcement policy for non-invasive remote monitoring devices for the COVID-19 pandemic, superseding similar policy documents from March and June. The immediately-in-effect (IIE) policy is restricted to non-invasive monitoring devices intended to measure common physiological parameters and covers more than 20 product codes. Some of the modifications to these devices that would ordinarily require a new 510(k), but for which the agency intends to exercise enforcement discretion, are inclusion of monitoring statements related to patients with COVID-19 or co-existing conditions.
Also subject to enforcement discretion are changes to site of use, such as devices that were previously indicated for facility use, but which can be re-labeled for home use. Changes to the hardware and/or software to increase monitoring capability are also in the scope of the policy.