EUAs And The FDAS Fight Against COVID-19: An Evolving Landscape – JD Supra

Christine Lentz, a Morrison & Foerster summer associate in our San Diego office,contributed to the writing of this article.

The outbreak of the COVID-19 pandemic in 2020 spurred rapid medical and technological innovation, leading to new medicines and devices designed in response to the virus. Under the traditional U.S. Food and Drug Administration (FDA) process, approval for these products could take months, if not yearstime many Americans did not have. Fortunately, the FDA had a secret weapon in the fight against COVID-19: emergency use authorizations (EUAs). In April 2020, we reported on the FDAs use of EUAs in the early months of the pandemic. Now, over one year later, we revisit the topic of EUAs to highlight the role they have played in pandemic responsiveness and explain what to expect going forward.

Congress first established the FDAs power to issue EUAs through the Project Bioshield Act of 2004. Generally speaking, EUAs enable the FDA to authorize unapproved products (or unapproved uses of approved products) for temporary use as emergency medical countermeasures against threats to public health and safety. From 2004 until recently, the FDA seldom issued EUAs; across the Zika, Ebola, MERS Coronavirus, H1N1/Swine flu, and Anthrax crises, the FDA issued EUAs for only a few dozen products combined.

The COVID-19 pandemic, however, led to the issuance of over 600 EUAs, including authorizations for three vaccines and ten drug and biological therapeutic products, as well as a wide range of personal protective equipment, in vitro diagnostics, ventilators, and more. Among these authorizations, the FDA responded to the testing and supply shortages prevalent at the start of the pandemic by issuing several umbrella EUAs for larger categories of devicese.g., Surgical Masks and Independently Validated Serology Tests for SARS-CoV-2which allowed those products on the market without individual review.

Several treatments for mild-to-moderate COVID-19 were authorized for emergency use, such as Gileads remdesivir, GlaxoSmithKlines Sotrovimab, Eli Lillys Bamlanivimab and Etesevimab, and Regenerons REGEN-COV (Casirivimab and Imdevimab). In addition, Fresenius Kabi received an EUA for its Propoven 2% Emulsion IV, which maintains sedation in patients requiring mechanical ventilation in an intensive care setting. Baxter Healthcare received authorization for its REGIOCIT replacement solutionfor adults treated with continuous renal replacement therapy in a critical care setting during the COVID-19 pandemic.

EUAs remain in effect until the circumstances justifying the authorization of emergency use during the pandemic end, the FDA revokes the EUA to protect public health or safety, or the FDA approves a marketing application for the product/use. To determine whether products temporarily authorized under EUAs remain necessary, the FDA periodically reviews the circumstances and appropriateness of existing authorizations, particularly the status of product approval. If the sponsor is not actively working toward approval, licensure, or clearance, the FDA may consider terminating the EUA. If an EUA remains in effect for more than one year, the FDA must provide the sponsor with a written explanation of obstacles to approval and specific actions to overcome them.[1]

During the current pandemic, the FDA has revoked, for a variety of reasons, three of its umbrella EUAs and several individual EUAs. One typical explanation for revocation is that when the FDA approves a product, it renders any prior EUA redundant. For example, the FDA revoked the corresponding EUA upon approving Gileads Veklury (remdesivir) for use in adults and certain pediatric patients.

Other times, however, the FDA revokes EUAs after learning that products are not completely effective or safe for use. Recent EUA revocations include reported adverse effects (Chloroquine phosphate and hydroxychloroquine sulfate); poor clinical performance (Chembios DPP COVID-19 IgM/IgG System); decreased effectiveness (Autobios Anti-SARS-CoV-2 Rapid Test; NovaSteriliss Nova2200 for Decontaminating Compatible N95 Respirators); increased viral variant resistance (Eli Lillys Bamlanivimab); and/or excessive risk-benefit ratio.

As the pandemic has evolved, so have public health needs and FDA priorities, which in turn have resulted in the discontinuation and de-prioritization of EUA application review for certain COVID-19 products.

For example, according to recent guidance (May 2021), the FDA may decline to review or process new EUA requests for COVID-19 vaccines, unless those developers have previously engaged with the Agency on the development of their manufacturing process and clinical trials program. If a developer has already received feedback from the FDA, its EUA request is more likely to contain comprehensive data and information that meet authorization issuance requirements, whereas quality and data in new applications may prove difficult to verify.

In addition to de-prioritizing new COVID-19 vaccine EUA submissions, the FDA no longer reviews requests nor adds new respirator models to the umbrella emergency use authorizations for Non-NIOSH-Approved Disposable Filtering Facepiece Respirators Manufactured in China (as of Oct. 15, 2020) orImported, Non-NIOSH-Approved Disposable Filtering Facepiece Respirators (as of Mar. 24, 2021). Respirator manufacturers who are not listed under the existing EUAs may submit a separate EUA request; however, the FDA does not encourage such submissions, as there is decreased demand for those devices.

Given the countrys continued recovery from the COVID-19 pandemic, we can likely expect additional classes of products to become deprioritized or ineligible for EUA. For example, as the proportion of vaccinated citizens increases and hospitalization rates decrease, many of the medical devices the country had scrambled to make available over a year ago will become less critical.

Companies with current EUAs or those considering applying for emergency use of their products should consult legal counsel to ensure continuity of product marketing and commercialization when the COVID-19 public health emergency is ended and/or EUAs are no longer effective.

Unless FDA announces a transitional policy for EUAs, manufacturers should assume they will need to receive full approval or clearance from the FDA to continue marketing their products after the public health emergency ends. For example, several Zika- and Ebola-related tests with emergency use authorizations received market clearance before the declared end of their respective emergencies. In October 2020, the FDA approved Inmazeb, the first treatment for Ebola Virus in the United States. To date, Pfizer-BioNTech and Moderna have submitted BLAs for their mRNA vaccines, along with requests for Priority Review to accelerate the approval process, while simultaneously expanding their EUAs.

The FDA encourages sponsors of EUA products to follow up EUA issuance with an appropriate approval, biologics license application (BLA), or device premarket submissionsuch as 510(k), De Novo Classification Request, or Premarket Approvalso that authorized products can remain on the market with minimal interruption once the EUA is no longer in effect. The FDA further expects sponsors to include a plan for safety follow-up in their EUA requests, which will inform benefit-risk determinations in support of EUA continuation.

The FDA also expects manufacturers who receive an EUA to continue their clinical trials to obtain additional safety and effectiveness information and pursue approval. Once enough data is available, EUA holders should consider submitting applications for FDA approval, as the process can take several months. Legal counsel can assist sponsors in navigating applications to accelerate the approval process, e.g., for Fast Track, Priority Review, or Material Threat Medical Countermeasure Priority Review Vouchers. Although the Secretary of Health and Human Services (HHS) must provide sufficient advance notice to allow for the disposition of an unapproved product, and of any other provided information/labeling related to an unapproved use before an EUA declaration terminates, this can unnecessarily disrupt the commercialization of your COVID-19 products.

[1] 21 U.S.C. 360bbb-3.

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EUAs And The FDAS Fight Against COVID-19: An Evolving Landscape - JD Supra