FDA’s Emergency Use Process Under Scrutiny

Under pressure to expand public access to new medicines, diagnostic tests, and other medical products needed to detect and treat patients struck by COVID-19, FDA has issued more than 100 Emergency Use Authorizations (EUAs) since early February, compared to fewer than 75 during the 10 previous years. While this activity reflects the imperative for fast action by federal agencies and manufacturers to address the pandemic crisis, it also generates questions about the vetting of these requests and how well FDA can follow up with sufficient tracking of the safety and efficacy of these products. And some observers fear that political interference in the process may erode confidence in the scientific basis for FDA regulatory decisions.

FDA may issue an EUA to use an unapproved drug or medical product, or an approved drug for additional uses, in an emergency when there are no adequate, approved and available alternatives . Most of this year’s EUAs are for diagnostics and medical products needed to augment national resources for testing individuals for contamination. Some EUAs facilitate use of innovative technology, as seen in recent authorizations for a new saliva-based COVID-19 test that would permit wider at-home sample collection and for the first antigen test, which promises to be less costly and more rapid in detecting the virus. Some EUAs involve new respirator cleaning systems and innovative protective personal equipment.

Only two EUAs this year are for therapeutics. FDA issued an EUA May 1, 2020 to Gilead Sciences to permit limited use of the investigational drug remdesivir to treat very ill COVID-19 patients. Here the emergency authorization was approved after a clinical trial provided evidence of some effectiveness in highly critical situations. As expected, the EUA limits the drug’s use to hospitalized patients with severe COVID-19 disease, while clinical testing continues.

More controversial is FDA’s approval of an EUA to permit the use of certain widely available malaria drugs to treat COVID patients, despite concerns from medical authorities about no data supporting effectiveness against the coronavirus and the risk of serious adverse effects on individuals with certain heart conditions. Even so, FDA issued an EUA for chloroquine and hydroxychloroquine on March 28, 2020 to permit use of drugs in the Strategic National Stockpile (SNS) but only for distribution to health professionals treating hospitalized patients with confirmed COVID-19.

Despite such limitations, FDA continued to draw criticism for acceding to political pressure from the White House to enable broad use of these drugs. But in an interview posted on STAT on April 24, 2020, Center for Drug Evaluation and Research (CDER) Director Janet Woodcock explained that permitting access to some three million pills donated by Bayer and others augmented short supplies that undermined approved treatment for lupus and rheumatoid arthritis, and that FDA tested the donated drug, which came from uninspected manufacturing facilities in India, extensively for quality. Woodcock maintained that the EUA does not undermine FDA review standards and that the agency clearly stated such emergency use does not represent approval of the drug for a new use.

Woodcock is supported by subsequent revelations about the political infighting leading up to this EUA. The lengthy

filed May 5, 2020 by Rick Bright, director of Health and Human Services’ (HHS’) Biomedical Advanced Research and Development Authority (BARDA), details efforts by Bright and others to prevent widespread use of hydroxychloroquine as a supposed preventive and cure for COVID-19. Bright recounts how HHS officials initially pressured BARDA to establish a nationwide Expanded Access Investigational New Drug (IND) protocol for chloroquine, which would make the drug available outside the hospital setting and without close physician supervision, but that Woodcock provided support for an EUA from FDA with restricted uses.

In response to these developments, Sens. Elizabeth Warren (D-Mass) and Patty Murray (D-Wash) seek to examine more closely FDA’s role in enabling rapid emergency use of drugs, biologicals, and devices and the agency’s ability to track adverse events and other outcomes related to such authorizations. In a letter sent May 6, 2020, the legislators request information from FDA Commissioner Stephen Hahn on FDA arrangements with manufacturers and healthcare facilities to collect data on adverse events and outcomes, what actions FDA can take if these entities fail to provide such information, and whether FDA needs additional authorities to revoke EUAs and recall relevant products.

Meanwhile, FDA faces challenges in continuing to evaluate hundreds of EUA requests. The agency website on EUAs notes that some 385 diagnostic test developers plan to submit EUA requests for tests to detect the coronavirus. And, now with the emergence of evidence that Gilead’s remdesivir may offer greater benefits to very ill patients, demand for chloroquine has diminished, leaving hospitals and clinics with millions of unneeded pills.