The U.S. Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) allowing distribution of two decades-old malaria drugs — Chloroquine Phosphate and Hydroxychloroquine Sulfate — to treat COVID-19. As required by the governing statute, this specific EUA was preceded by a more general declaration from the Secretary of Health and Human Services (HHS) “that circumstances exist justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic.” That declaration significantly expands the potential universe of treatments that may receive EUAs; the previous declarations were for in vitro diagnostics, personal protective equipment, and medical devices, including ventilators.
The underlying declaration creates a pathway for drugs and biologics to be authorized for use to prevent or treat COVID-19 if they meet threshold statutory criteria, including that it is “reasonable to believe” that the product “may be effective” and that its “known and potential” benefits exceed the risks, taking into account the threat posed by COVID-19. FDA found that the conditions for granting an EUA for Chloroquine Phosphate and Hydroxychloroquine Sulfate exist, subject to certain conditions, including:
- The drug products are:
- Supplied from the Strategic National Stockpile (SNS) to “public health authorities,” which are defined as public agencies with legal responsibility and authority for responding to public health emergencies;
- Distributed with certain labeling directed toward patients, caregivers and healthcare providers;
- Prescribed by a licensed practitioner to hospitalized COVID-19 patients who are adults or adolescents weighing 50 kg or more, and for whom a clinical trial is not available or participation is not feasible; and
- Administered by a healthcare provider.
- The chloroquine phosphate is not an FDA-approved drug product.
- The hydroxychloroquine sulfate product is FDA-approved (for other uses).
- Steps are taken to track distribution of the products, monitor and report adverse events and medication errors, and maintain patient information and data.
In some ways, this EUA resembles a very large-scale expanded access program, where the use of the drug is authorized only if the patient cannot participate in an ongoing clinical study. FDA’s desire not to undermine the development of clinical data is clear. The EUA states that the agency “encourages the conduct of and participation in randomized controlled clinical trials that may produce evidence concerning the effectiveness of these products in treating COVID-19.” FDA also notes that “[c]linical trial data results, and any information derived from clinical trials, as well as clinical trial results from studies of other investigational medical products to treat COVID-19, will continue to inform [the] risk benefit assessment” that supported issuance of the EUA.
The EUA also waives compliance with cGMP and provides for additional chloroquine phosphate and hydroxychloroquine sulfate products to be brought under the EUA.
It is noteworthy that the EUA was not granted to a drug manufacturer or application-holder for chloroquine phosphate or hydroxychloroquine sulfate. Instead, the applicant for, and recipient of, the EUA is an HHS component under the Assistant Secretary for Preparedness and Response. The unit that received the EUA is the Biomedical Advanced Research and Development Authority (BARDA). Only drugs obtained by the SNS are covered by this EUA, and such drugs can only be distributed to public health authorities and administered in accordance with the terms, scope, and conditions of the EUA. Therefore, the EUA does not authorize manufacturers of chloroquine phosphate or hydroxychloroquine sulfate to provide these drugs directly to public health authorities or healthcare providers. A related FDA announcement indicates that the products currently covered by the EUA were donated to the SNS.
In addition, the EUA imposes certain recordkeeping requirements on healthcare systems and healthcare provides who receive the drugs from the SNS under the EUA, and such records must be made available upon request for inspection by FDA, SNS, and BARDA. The recordkeeping requirements include: (1) tracking and reporting of adverse events; (2) maintaining inventory control records; (3) maintaining patient information and other relevant data, as feasible.
FDA’s determination that “it is reasonable to believe” the two products “may be effective” and their benefits outweigh any risks appears to rest in large part on the fact that, “[b]ased upon limited in-vitro and anecdotal clinical data in case series, chloroquine phosphate and hydroxychloroquine sulfate are currently recommended for treatment of hospitalized COVID-19 patients in several countries, and a number of national guidelines report incorporating recommendations regarding use of chloroquine phosphate or hydroxychloroquine sulfate in the setting of COVID-19.” It is not at all clear to what extent this finding with these drugs indicates how FDA will apply the standard with regard to other products.
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