When a new virus like SARS-CoV-2 arises and causes widespread disease as COVID-19, part of the public health threat is that testing doesn’t yet exist. Emergency Use Authorization (EUA) from the FDA allows for testing to be developed and authorized very rapidly (weeks) compared with non-emergency pathways (months/years). With the prime directive of Public Health, the FDA’s program adjusts the data requirements to speed delivery of the test to clinicians. Once the emergency has passed, only those tests which have a non-EUA approval, with the usual data and clinical validation requirements, will be allowed to remain in use.
So how does it work?
Companies are advised to speed development by direct advisement from the FDA through use of a hotline 1-888-INFO-FDA, choose option*, or email to firstname.lastname@example.org. Information is updated regularly on their site, including EUAs granted.
Under the EUA for IVD development, normally exhaustive studies are abbreviated, fewer batches of materials are prepared and simulated clinical samples are allowed. Tests that can scale up rapidly and use existing, high throughput equipment are highly desirable. The testing bottleneck can be quickly relieved now that EUAs are granted to some of the biggest testing laboratories or companies and the list is growing to meet the extreme demand:
Thermo Fisher (3/13)
Quest Diagnostics (3/17)
DiaSorin Molecular (3/19)
GenMark Diagnostics (3/19)
How long is the process?
It depends on how your test performs. Considering the rapidly developing conditions in the COVID-19 global pandemic, the number of companies with tests to propose ballooned in response to the crisis. FDA staff, while working with the applicants in interactive Pre-EUA and EUA process, need to ensure the best testing outcomes for the clinical need. While it isn’t known how many EUAs will be authorized in this emergency, it is welcome news that testing is coming up to speed rapidly and that the overall process is faster for all applicants.
FDA encourages Pre-EUA submission to ensure good quality tests. The Agency selected molecular testing for the first focus to ensure the most sensitive tests were developed first. Early throughput issues for the semi-manual process are relieved now that tests for some of the largest automated testing platforms are available.
Serology testing for IgG and IgM are not used for screening tests but can be useful in following an individual’s disease progression, surveying the population exposure, and informing vaccine development. Antibody testing can be used in detecting people who had an immune response to SARS-CoV-2, whether they developed COIVD-19 infection or were asymptomatic.
The FDA templates were designed for use with molecular testing, products based on any other technology need a direct consultation with the FDA for development guidance. The CDC is acquiring samples from people with COVID-19 disease and developing testing parameters. For countries who have authorized IgG/IgM tests, they are also used to complement molecular testing.
Developers would be prudent to include the risk of rapid market changes when considering the EUA pathway for their SARS-CoV-2 or serological tests. Close communication with the FDA is crucial to managing that risk.
FDA’s Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency published March 16, 2020 outlines a switch in FDA’s approach to EUA’s and shows FDA’s flexibility and adaptability during times of public health emergencies. FDA describes policies for the following situations:
Tests developed under the authorities of the State in which the lab resides, and the State takes responsibility for COVID-19 testing by laboratories in its State will not need an EUA submission.
CLIA labs can now manufacture key components such as primers and probes and begin using on patient samples after the tests are validated but before the EUA is submitted.
Commercial manufacturers can now begin distributing validated tests before submitting an EUA.
The policy document states: “All clinical tests should be validated prior to use.” In the context of a public health emergency involving pandemic infectious disease, it is critically important that tests are validated as false results can have broad public health impact beyond that to the individual patient. The minimum validation requirements are outlined the policy document together with the appropriate template.
Our team of regulatory experts can help with multiple aspects of the process: communicating, registration and listing with the FDA, 3rd party review of validation and stability studies, labelling and instructions for use, submitting the EUA application, reporting adverse events and addressing safety or quality issues that may arise in clinical use. We can also act as the Official Correspondent to FDA for any company, the US Agent for non-US companies and assist with distribution connections.
Considerations for marketing diagnostic tests via EUA:
Contact FDA if clarification is needed on any point
Develop, manufacturer and validate tests
Conduct stability studies
Develop instructions for use (IFU)
Develop a procedure for complaint handling and adverse event reporting.
Day 1 activities:
Notify FDA that your diagnostic test has been validated and you intend to begin distribution
Register your company
List the device
Begin distributing devices
Activities that need to be completed within 15 days of distribution:
Submit EUA application using the most logical template published at the time (we expect additional templates to be published on FDA’s EUA web page)
Work collaboratively with FDA to address any concerns or safety considerations raised. (Note that this could include a recall of your product)
Update intended use statements based on EUA authorization
Continue real time stability studies
Report all events of false positive and false negative results to FD