By Sugato De, Vice President - Technical
In a direct and timely action to address the acute shortage of diagnostic tests currently available to test for COVID-19 disease, the FDA has issued a new policy that enables both commercial manufacturers and CLIA-certified laboratories to manufacture and distribute validated tests immediately with the expectation that they follow up with an Emergency Use Authorization within 15 days. While this action is critical to increase availability of tests, sufficient validation of these tests must be prioritized by developers to ensure that erroneous information does not exacerbate the crisis. FDA has also taken concrete steps to expand the use of medical devices to monitor vital signs remotely and increase the availability of ventilators and other critical care devices. Parexel’s Regulatory & Access team is directly engaged in supporting manufacturers in bringing needed diagnostics and therapeutic products to the market quickly to address the COVID-19 pandemic.
On February 29, 2020, the U.S Food and Drug Administration (FDA) published an “immediately in effect guidance” that is designed to directly address the acute shortage of diagnostic tests currently available to test for SARS-CoV-2, the causative virus for COVID-19 disease. The policy allows for the immediate availability of validated diagnostic tests developed in laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) that meet applicable requirements for high-complexity testing. Importantly, the new policy circumvents existing requirements to obtain an emergency use authorization (EAU) prior to deploying tests of this nature in the field. Instead, FDA recommends that laboratories submit a completed EUA within 15 days of notifying the agency of a successful validation. On March 16, FDA expanded the policy to indicate that it “does not intend to object” to commercial manufactures distributing and labs using commercially developed tests as long as accurate instructions for use are provided to end users and data about the test’s performance characteristics are available on the manufacturer’s website. These steps are intended to swiftly expand the development and availability of validated SARS-CoV-2 tests to address the ongoing public health crisis.
FDA’s expedience in taking decisive action during the crisis is admirable, and it is clear that the policy is garnering immediate results. According to FDA Commissioner Stephen M. Hahn’s statement on March 16, 2020, at least 90 test developers have approached FDA for tests that they plan to bring through the EUA process. In addition, more than 40 laboratories have notified FDA that they plan to leverage the new policy to bring new diagnostic tests to the market as soon as validation studies have been completed. To date, FDA has approved EUAs for at least 13 different tests for SARS-CoV-2, including those developed by the U.S. Centers for Disease Control and Prevention (CDC), the New York State Department of Health (NYSDOH), Integrated DNA Technologies, Roche Molecular Systems, Thermo Fisher, Hologic, and the Laboratory Corporation of America (LabCorp). The latter four tests were formally approved by FDA within 24 hours of receiving the EUA applications, demonstrating a strong commitment by FDA officials to ensure the availability of validated tests without delay. Just this past Saturday, FDA issued an EUA for a point-of-care COVID-19 diagnostic for the Cepheid Xpert Xpress SARS-CoV-2 test. This test can deliver results in less than an hour and may prove to be a critical tool for patient screening at the frontlines in particularly affected locations.
The necessity of bringing validated tests to the market quickly cannot be underestimated. To date, there have been 46,332 confirmed diagnoses in the United States (U.S.) with at least 610 deaths attributable to the virus. The majority of people who are infected most likely have not been tested, are not showing symptoms, and have been newly infected. In order to slow the exponential growth of infections and allow a strained healthcare system to adequately address the oncoming flood of patients, the widespread availability of diagnostic tests is desperately needed. While officials from Roche indicate they have 400,000 tests ready to ship and the capacity to produce at least that number per week and ThermoFisher officials say that they have 1.5 million tests available with the production capability of five million tests per week, it is clear that several of the diagnostics currently in the pipeline must hit the market fast to meet demand.
While FDA has certainly taken the right steps to eliminate potential delays in bring these diagnostic tests to the market fast, sufficient validation of these tests must be prioritized by the developers and reviewed for adequacy by FDA experts on the back end. In the updated policy, FDA outlines a minimum level of expected validation studies for qualification of these laboratory developed tests, consisting of limit of detection, clinical evaluation in the absence of known positive samples, documentation of in silico analyses, and cross-reactivity. Already, the test developed by the CDC was demonstrated to be flawed and resulted in the recall of at least 120,000 tests distributed to various states. Inaccurate diagnostic tests could easily exacerbate an already unprecedented crisis by placing healthy individuals in harm’s way and potentially delaying treatment for patients who falsely test negative.
FDA is rapidly tackling several issues to combat the COVID-19 crisis. Just last Friday, FDA issued a new policy to allow for the expanded use of approved medical devices to monitor vital signs remotely. The agency has also expressed commitment to work with innovators to accelerate development and availability of medical countermeasures. Of note, FDA issued a new guidance on Saturday that takes several steps to help increase the availability of ventilators in the U.S. by (1) relaxing reporting requirements for certain modifications to cleared devices, (2) allowing for ventilators to be used outside of their intended and cleared environments for use (i.e., repurposing ventilators cleared for ambulatory settings to be used for long-term use), and (3) encouraging manufacturers without clearance to pursue of EUAs that would enable them to quickly bring new ventilators onto the market.
Outside of FDA, concrete measures must be taken to dramatically increase the production of critical life-saving devices including ventilators, respirators, personal protective equipment and much more. The Defense Production Act must be invoked to compel more manufacturers to quickly dedicate resources to manufacturing these products and to create an organized framework for distribution. To stem the tide of the pandemic and reach the downside of the curve as quickly as possible, we must leverage the innovative potential of the global community, eliminate obstacles to bringing validated diagnostics and therapies to the market quickly, and take the appropriate steps in our personal lives to reduce exposure.
Parexel’s 1000+ Regulatory & Access consulting team, including ~100 former regulators / inspectors / HTA assessors, are fully committed to supporting the development and marketing authorization for diagnostic tests, therapies and other medical countermeasures to address the COVID-19 crisis. For support in this area, please reach out to Sugato De (Sugato.De@parexel.com) for medical devices or Amy McKee (Amy.McKee@parexel.com) for drugs and biologics.