As it works to confront COVID-19, the FDA has been approving a record number of Emergency Use Authorization (EUA) requests for diagnostics, medical devices and drug products.
But as the FDA published a record number of authorizations, it will soon need to grapple with the exact opposite problem: How to remove record numbers of them from the market—a process required by law even as it is poorly defined by it.
By Aaron Badida, JD and Alexander Gaffney, RAC
The FDA’s Emergency Use Authorization program was established in 2004 by the Project Bioshield Act, which gave the FDA the authority to issue authorizations to allow for the use of otherwise unapproved products or unapproved uses of approved products. For the FDA to issue an Emergency Use Authorization (EUA), there must be a determination that a public health emergency exists and that there is need for a medical countermeasure to be put into effect.
Unlike an approval, and EUA is not intended to be on the market on a permanent basis, and the law (21 U.S.C. 360bbb-3(b)(2) et seq) has mechanisms for the termination of an EUA based on specific criteria and the disposal of those products.
There are several ways that an EUA may be terminated.
- The public health emergency may end.
- The product may be granted full approval.
- The FDA may determine that, based on new evidence, the product should no longer be authorized for use (e.g., if the product is no longer believed to be safe or effective).
- The FDA may determine that, based on new evidence, the product should no longer be authorized for some uses (e.g., if the product is still safe and effective for some uses, but not for others).
- The EUA for the product is not renewed (each EUA is only good for an initial one-year period, but may be extended).
- And finally, if another product for the same indication is approved, the FDA is required to terminate the authorizations of unapproved products. (One of the conditions for authorization is that there be “no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating such disease or condition.”)
Historically, most products (31 of the 33 EUAs granted between 2011 and 2019) authorized for use under an EUA have been diagnostics. EUAs for drug products are significantly less common. Only three drug authorizations have been made under the EUA pathway prior to 2020: two related to anthrax and one for nerve agents. In the case of nerve agents, the EUA was issued for the 2mg Atropine injector that was in process of gaining FDA approval. Upon approval, the EUA was terminated.
The FDA has already issued a record number of EUAs for COVID-19, indicating that it may soon have to deal with removing a record number of products from the market as well. To date, the FDA has issued COVID-related EUAs for more than 35 diagnostic products, 16 device products, and 1 pharmaceutical product.
Under federal law, once an EUA is terminated, those products must be “disposed of.” The exact nature of that disposal is somewhat unclear, according to both the statute and FDA guidance on the subject. If a product’s authorization ceases to be effective, “the Secretary shall consult with the manufacturer of such product with respect to the appropriate disposition of the product,” the law explains.
According to the FDA, the disposition of a product does not always happen immediately. For example, “an authorization shall continue to be effective to provide for continued use in any patient who began treatment before revocation or termination (to the extent found necessary by the patient’s attending physician).” In that case, any continuing study of the product would need to be authorized under an Investigation New Drug (IND) application (i.e., a clinical trial).
Product disposals are determined on a case by case basis and involve consultation between the Secretary and the manufacturer of the authorized product. The Secretary is required by law to provide advanced notice to manufacturers distributing products under an EUA.
The termination process for COVID-19 EUAs is likely to look different for different companies and different product types.
For example, a product with an EUA may go on to obtain approval. While this approval would permit the product to remain on the market beyond the termination of the public health emergency, it would also make other products marketed for the same indication no longer eligible for distribution. This is because the statutory criteria for receipt of an EUA explicitly requires no available alternative.
The longer the COVID-19 crisis continues, the more products are likely to be authorized for use. Eventually, some of these products are likely to be seen as highly effective and safe for use, while others may be found to be ineffective or unsafe for use. Based on the enormous number of separate products now authorized for use, it is likely that the FDA will begin to remove products based on their performance in patients.
Eventually, the COVID-19 public health emergency will end, at which time any unapproved product remaining on the market will need to be recalled and disposed of. It’s unclear as to whether the FDA would require an unapproved product to be disposed of or designate some other means of allowing them to be kept in reserve in case of a future public health emergency. For example, unused personal protective equipment, ventilators or other testing equipment might benefit from being kept in a stockpile in reserve rather than be destroyed.
Because EUAs have never been issued at this scale before, the disposal of those products may present a logistical challenge to both industry and the FDA, which may not have extensive data about the location of those products in the supply chain. Even the approval of a single product may have major implications for the continued market access for many other types of products, which may require planning on the part of FDA to assess the negative impacts of approving a product requiring other products to be removed from the market.
Companies that actively distributing medical products under a COVID-19 EUA should take stock of their product and its anticipated demand. While disposal of the product may be difficult, a bigger issue may be stock of leftover supplies used to make the products. Based on the scope of current demand, some companies could face financial difficulties if they have significant materials on hand to make the products but are then unable to do so.