FDA Needs Bold Reforms Instead of Kicking the Can Down the Road

When Dr. Robert Califf was selected by President Joe Biden for a second stint as Food and Drug Administration commissioner, we called it a safe but uninspired choice. Unfortunately, we have been proven right.

Califf is a distinguished academic cardiologist who specializes in clinical trial design, but the day-to-day regulatory decision-making happens at organizational levels below the commissioner, and he seems unwilling to engage with them. He has also made it clear that he’s not interested in criticism from the public, even though the FDA is required by law to consider public comments as part of the rulemaking process.

Dr. Califf did give some reason for hope last summer when he commissioned a review of the agency’s food and tobacco regulatory programs. We suspected that the report, to be prepared by the Reagan-Udall Foundation, would be a whitewash, but we are pleased to say we were partly wrong.

On the food front, the report echoed criticism from members of Congress, industry and public interest groups that there isn’t a single chain of command among various human food oversight offices, including the Center for Food Safety and Applied Nutrition and the Office of Food Policy and Response.

Now, a diverse group of stakeholders is unhappy with the reorganization plan the FDA announced in January and fleshed out further in late February because it doesn’t fully integrate the all-important food inspection work into the new Human Foods program. 

At a House Oversight Subcommittee hearing in March, Frank Yiannas, who resigned earlier this year as the FDA’s deputy commissioner for food policy, testified that the agency’s ability to protect food safety is hindered by staff turnover, a siloed culture, and a lack of decision-making power. Roberta Wagner, the Consumer Brands Association’s vice president of regulatory and technical affairs, noted that an external study of the FDA has found that the agency’s food regulation suffers from “constant turmoil” and “little motivation.”

One area of FDA dysfunction that has been largely ignored is the Agency's regulation of animals modified with molecular genetic engineering techniques. The Center for Veterinary Medicine's stultifying regulation of these animals as veterinary drugs has virtually destroyed an entire once-promising sector of modern biotechnology – a perfect illustration of how regulators can inflict profound harm on society.  

If Dr. Califf doesn’t correct these shortcomings soon, industry and consumer groups might request that Congress preempt him and do it.

A more comprehensive reorganization and improved supervision might prevent embarrassing regulatory excesses such as the formal warning letter that FDA sent to a Massachusetts bakery for including “love” in its ingredient list. The reason? “‘Love’ is not a common or usual name of an ingredient, and is considered to be intervening material because it is not part of the common or usual name of the ingredient,” it stated. Maybe the staff intended this as a joke, but it’s our tax dollars at work.

The Reagan-Udall report focused its sharpest criticism on the policies of the Center for Tobacco Products for a litany of operational missteps, directionless policymaking, and self-inflicted legal problems. The report even noted “a lack of clarity about the distinction between, and the intersection between, policy and science.” More specifically, the report’s expert panel “was unable to identify a current comprehensive plan that clearly articulates CTP’s priorities, direction for the future, and its near-term and longer-term goals and objectives.”

The FDA’s Feb. 24 response to the report on tobacco policy makes the agency’s widely criticized response to the food report look good by comparison. Rather than show contrition (for his predecessor’s failures), Center for Tobacco Products Director Dr. Brian King doubled down on the regulatory gobbledygook: “Effective immediately, CTP will initiate the development of a comprehensive 5-year strategic plan, building upon the foundation of the center’s previous strategic plans.” We only wish there had been a previous strategic plan! (Our prediction: Expect the FDA to go to Congress for additional funding to implement cherry-picked, largely ineffectual responses to the report.)

The FDA’s recent approach to COVID-19 has also been widely viewed as a disappointment. Perhaps the most egregious failure has been its unwillingness to approve, even under Emergency Use Authorization, a new drug called PEG-lambda interferon that performed well in a medium-sized Phase 3 trial to treat COVID-19 infections. The results were published on Feb. 9:

• Patients who received the drug within seven days of showing symptoms were 51% less likely to be hospitalized or to need an extended visit to an emergency room compared with those given a placebo.
• People given PEG-lambda within three days of the onset of symptoms had a 58% lower risk.
• Vaccinated patients who were treated with PEG-lambda in the study experienced a 51% reduction in hospitalizations relative to the placebo.
• In unvaccinated patients treated within the first three days of symptom onset, there was an 89% reduction compared with the placebo.

In summary, both primary endpoints of the trial — COVID-related hospitalizations and emergency department stays of longer than six hours — were significantly lower in patients who got the drug. Another critical finding was that the patients who received the PEG-lambda experienced no more side effects than those who received a placebo.

One of us (Dr. Miller), a 15-year veteran of the FDA who evaluated drugs in the same class as PEG-lambda, feels that on the basis of publicly available data, it could at least have been granted Emergency Use Authorization.

By contrast, the FDA did grant Emergency Use Authorization to a monoclonal antibody drug that specifically blocks immune complement factor C5a for the treatment of hospitalized COVID patients when initiated within 48 hours of beginning artificial life support. The drug, Gohibic, reduced the risk of death in the sickest patients by 27% compared with placebo during a 28-day period, but missed statistical significance on the trial’s primary endpoint.

Admittedly, the drug is for a much sicker population than PEG-lambda, but consider the list of “the most common adverse reactions” with Gohibic, according to the FDA: “pneumonia, sepsis, delirium, pulmonary embolism, hypertension, pneumothorax, deep vein thrombosis, herpes simplex, enterococcal infection, bronchopulmonary aspergillosis, hepatic enzyme increased, urinary tract infection, hypoxia, thrombocytopenia, pneumomediastinum, respiratory tract infection, supraventricular tachycardia, constipation, and rash.”

PEG-lambda and Gohibic are not directly comparable, but both have the potential to save many lives, and we think both should have been granted Emergency Use Authorization.

The FDA continues to be criticized for its distorted priorities and slow approvals.  A recent example is the Agency’s slow-walking approvals for vaccines to prevent Respiratory Syncytial Virus (RSV) infections, viral enemy number one for children. It results in more pediatric hospitalizations than any other single cause, and pediatricians have long been helpless to stem the tide of RSV-infected newborns who are at particularly high risk for needing to be hospitalized. (The first RSV vaccine, GSK's Arexvy, was finally approved on May 3rd.)

The FDA continues to whistle past the graveyard in its lax oversight of dietary supplements even when they are adulterated or misbranded.  A recent published study of the melatonin concentration in more than two dozen recently launched gummy dietary supplements found that almost all of the products had greater than 10% more melatonin than advertised. One product contained three times the amount the label indicated on the label. 

This is a real public health problem, because large amounts of melatonin have adverse effects in children, which has prompted an exponential increase in poison control calls in recent years.

A reminder to Dr. Califf: Ensuring food safety, regulating tobacco products rationally, and getting new drugs to patients to treat serious illnesses are the foundations of the FDA’s mandate.

Increasingly complex organizational structures, the commissioning of endless reports, and the production of scholarly treatises are the status quo at FDA. What Dr. Califf should be ordering, stat, is bold remedies to the agency’s well-documented shortcomings.

Early in his term last year, a journalist asked Califf about criticism from the public, to which he responded, “I’m 70 years old. I’m relatively impervious to critique.” He went on to say that he considers himself a survivor of “a harrowing confirmation process,” so “what are they going to do to me now?” That sounds as though he intends to continue to lead the agency from the safety of the ivory tower he brought with him from academia. That might afford him comfort, but it may not be conducive to good policymaking or sound regulatory decisions.

An earlier version of this article was published on Issues & Insights.

Jeff Stier is a senior fellow at the Taxpayers Protection Alliance.