FDA’s Revocation of the Hydroxychloroquine and Chloroquine EUA May Test the Limits of PREP Act Immunity

On June 15, 2020, the U.S. Food & Drug Administration (FDA) revoked the Emergency Use Authorization (EUA) that permitted emergency distribution of chloroquine phosphate (CQ) and hydroxychloroquine sulfate (HCQ) from the Strategic National Stockpile. (https://www.fda.gov/media/138945/download) The FDA concluded, based on clinical trial data and the continuing failure of treatment guidelines to support use of CQ or HCQ to treat patients with COVID-19, that “it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks.”

Implications for CQ

The revocation of the EUA has significant implications for liability exposure for the continued use of CQ to treat patients with COVID-19. The Public Readiness and Emergency Preparedness (PREP) Act, 42 U.S.C. § 242d-6d, offers broad liability immunity to “Covered Persons” against suits arising out of the administration or use of “Covered Countermeasures” pursuant to “Recommended Activities” within the scope of a March 10, 2020, declaration by the Secretary of Health and Human Services invoking the Act. All three prongs must be satisfied for PREP Act coverage.

Pharmaceuticals must be approved by the FDA or be the subject of an EUA in order to qualify as “Covered Countermeasures,” and, as the revocation notes, CQ has not been approved by the FDA for any indication apart from the EUA. Now that the EUA has been revoked, CQ no longer qualifies as a “Covered Countermeasure” within the meaning of the PREP Act and the Secretary’s COVID-19 PREP Act Declaration. [See 42 U.S.C. § 242d-6d(i)(1); 85 FR 15198 at § VI; 85 FR 21012 at § VI.] Therefore, the PREP Act does not provide liability immunity for the continued “manufacture, testing, development, distribution, administration, [or] use” of CQ to treat patients with COVID-19. [See 42 U.S.C. § 242d-6d(a)(1) (extending liability immunity only to suits involving administration or use of a Covered Countermeasure)].

Implications for HCQ

The question is far more nuanced as to HCQ, which raises the novel issue of whether off-label use of pharmaceuticals and medical devices can be protected by the PREP Act. Unlike CQ, HCQ has been FDA-approved since 1955 and remains approved for several indications including, among other things, the treatment and prevention of malaria under certain conditions. [See https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=009768; see also, e.g., Plaquenil® Hydroxychloroquine Sulfate Tablets Package Insert, available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/009768Orig1s051lbl.pdf (approved on 1/5/19).]

An FDA-approved product that is designed to treat or prevent “a pandemic or epidemic” meets the PREP Act’s definition of a Qualified Pandemic or Epidemic Product and, therefore, is a Covered Countermeasure. See 42 U.S.C. § 242d-6d(i)(1, 7). The terms “pandemic” and “epidemic” are not defined in the PREP Act, which instead uses the phrase “disease or other health condition or other threat to health” when discussing the HHS Secretary’s authority to invoke the PREP Act. 42 U.S.C. § 242d-6d(b)(1).

Moreover, the use of the article “a pandemic or epidemic” rather than “the pandemic or epidemic” does not seem to require any connection to the specific public health emergency that causes the Secretary to invoke the PREP Act. Notably, malaria has been described as an “epidemic,” if not a pandemic, by health authorities. [See, e.g., World Health Organization, Malaria – Epidemics and Emergencies, Dec. 6, 2018, available at https://www.who.int/malaria/areas/epidemics_emergencies/en/.] Arguably, then, HCQ is a Covered Countermeasure because it has been approved by the FDA to treat and prevent an epidemic.

The PREP Act provides immunity “from suit or liability … caused by, arising out of, relating to, or resulting from the administration to or the use by an individual of a covered countermeasure.” 42 U.S.C. § 242d-6d(a)(1). Notably absent from this grant of immunity is any express requirement that the “administration or use” occur within a product’s intended and approved indications. The immunity is limited to administration or use “for the category or categories of diseases, health conditions, or threats to health specified in the [Secretary’s] declaration” invoking the PREP Act. Id. at § 242d-6d(a)(3).

However, nothing in the PREP Act expressly requires that the administration or use be consistent with the indications for which the product has been approved or cleared by the FDA. The Secretary is free to narrow the grant of immunity when issuing a PREP Act declaration, but the Secretary’s COVID-19 Declaration broadly extends immunity for “the manufacture, testing, development, distribution, administration, and use of the Covered Countermeasures.” 85 FR 15198 at §§ III, IV. Although the term “Covered Countermeasures” is defined more narrowly in the Declaration than in the PREP Act, as is expected because the Declaration is specific to the COVID-19 pandemic, it still includes any drug that is “used to treat, diagnose, cure, prevent, or mitigate COVID-19” and is a Qualified Pandemic or Epidemic Product as defined by the PREP Act. Id at §VI.

While this definition does not expressly require that the “use” of the product to treat, diagnose, cure, prevent, or mitigate COVID-19 fall within an FDA-approved indication for the product, it must be considered more broadly in the context of the definitions for “Covered Person” and “Recommended Activity” included in the Declaration and the April 14 Advisory Opinion. The Declaration limits immunity to Covered Persons’ use of a “Covered Countermeasure” in furtherance of a “Recommended Activity,” which is one that is related to (a) federal contracts, grants, agreements, and the like, or (b) “activities authorized in accordance with the public health and medical response of the Authority Having Jurisdiction (AHJ) to prescribe, administer, deliver, distribute or dispense the Covered Countermeasures following a Declaration of an emergency.” Id at § VII.

The introductory notes to the Declaration make clear that “federal, state, local, and tribal authorities and institutions or organizations acting on behalf of those governmental entities” can all be AHJs. Assuming that HCQ is indeed still a Covered Countermeasure, a state governor, state department of health, mayor, or other entity or individual qualified as an AHJ could authorize the use of HCQ to treat COVID-19, thereby extending PREP Act immunity to Covered Persons.

The PREP Act in Play

Lawsuits are historically filed by patients who experience adverse events. If that occurs here, the situation appears likely to test whether off-label use of a pharmaceutical is protected by the PREP Act.