President Joe Biden announced Friday he is nominating Robert Califf to again serve as commissioner of the Food and Drug Administration.
"As the FDA considers many consequential decisions around vaccine approvals and more, it is mission critical that we have a steady, independent hand to guide the FDA," said Biden in a statement. "I am confident Dr. Califf will ensure that the FDA continues its science and data drive decision-making."
Califf, who previously helmed the FDA in the final year of the Obama administration, is seen as a status quo choice.
Independent experts say Califf has decades of experience in the development and conduct of clinical trials. That resume has brought Califf in frequent contact with both the FDA and the pharmaceutical industry he would be charged with regulating.
Biden faced a Nov. 15 deadline to nominate a permanent commissioner to an overwhelmed agency steering decisions on critical COVID-19 vaccines and tests.
If confirmed, Califf would oversee an agency that regulates one-fourth of every dollar spent in the United States. And he would oversee the FDA at a time of deep distrust stemming from a tsunami of misinformation in America and the agency’s own pandemic missteps.
Acting Commissioner Janet Woodcock has temporarily captained the agency for 10 months, nearly as long as her confirmed predecessor Stephen Hahn. Woodcock can remain in place as long as it takes for Califf to be confirmed. Woodcock was once seen as a front-runner for the post, but her stewardship of the agency’s drug regulatory center during the approvals of addictive opioids and the authorization of hydroxychloroquine under President Donald Trump, despite her successful efforts to pare back the drug’s usage to only hospital settings, were among the issues hurting her chances.
Biden said Friday Woodcock did "an incredible job leading the agency during what has been a busy and challenging time."
Califf had such strong bipartisan support that when Trump took office in early 2017, many pharmaceutical and medical device industry officials expressed hope he would continue on as the FDA’s leader.
“My feeling about Califf is that he’s a political compromise. His nomination shows the power of pharma. But despite his close ties to pharma, he has always talked about the importance of solid scientific evidence,” said Diana Zuckerman, president of the National Center for Health Research, a think tank in Washington, D.C. “I have some confidence that Dr. Califf is not someone who likes controversy. That is different than Dr. Woodcock who doesn’t seem to mind controversy at all. I'm hopeful he will really focus on the science in a way that has been missing lately at FDA.”
Califf is a longtime cardiologist and a professor in the school of medicine at Duke University. Califf also served as founding director of the Duke Clinical Research Institute, a partnership between the university and pharmaceutical companies with the goal of innovating clinical trial design. He led it for a decade. The research institute receives about half of its funding from the pharmaceutical industry and half from the government, according to a 2020 report. He founded the Clinical Trials Transformation Initiative, a collaboration between the FDA and Duke on improving the speed and reducing the cost of clinical trials, which collaborates with pharmaceutical companies.
Califf is also an executive at Verily Life Sciences, formerly Google Life Sciences, an Alphabet Inc. company.
In addition to his experience at the FDA, Califf has consulted for several pharmaceutical companies, including Amgen, AstraZeneca, Eli Lilly, Johnson & Johnson, and Sanofi-Aventis, critics at the advocacy group Public Citizen noted.
“Califf was a poor choice for FDA commissioner when he was nominated by Obama in 2015 and he remains a poor choice today,” said Michael Carome, director of Public Citizen’s Health Research Group, in a statement. "Califf must not be allowed to again pass through the revolving door between the FDA and regulated industries."
One of the most controversial episodes in Califf’s brief tenure was the approval of eteplirsen, a rare disease drug made by Sarepta Therapeutics that showed no clinical benefit but was strongly backed by a vocal group of parents of children with Duchenne muscular dystrophy. Woodcock, then director of the FDA’s Center for Drug Evaluation and Research, overruled the agency's career scientists, and Califf allowed the decision to stand.
Califf justified that decision in an interview earlier this year by saying he deferred to the typical FDA chain of command.
“I had to spend many, many hours over the Sarepta decision during my tenure, and the whole basis for my not intervening in the dispute between the center director and the staff at the FDA was that there actually is a literal chain of command,” he said. “The statute directs it to the secretary. The secretary delegates to the commissioner as a matter of form. When it comes to individual product decisions, 99.9 percent of the time the commissioner defers to the center director to make the final decision.”
But Califf has in several public statements voiced support for more patient input at the FDA.
Critics say this advocacy is often financed by the pharmaceutical industry, and the FDA often does not distinguish between authentic advocacy and these conflicts of interest.
Califf has also called for other changes to clinical trials supported by the pharmaceutical company, including greater reliance on real-world evidence pulled from electronic health records outside of a clinical trial and on biomarkers, biological signals a drug is working before it shows a clinical benefit.
“Of course, the devil’s always in the details. It’s fine to be supportive, for example, of biomarkers as a way to get information about potential benefits but it needs to be backed up by solid science," said Zuckerman.
At the FDA, Califf would likely have to respond to an ongoing investigation by the Health and Human Services inspector general into the approval of the Alzheimer’s drug aducanumab. It was approved through FDA’s accelerated approval pathway based on the difference it made with a controversial biomarker, amyloid plaques.
Califf came to serve at the FDA in 2015 during a controversy over continued opioid approvals amid a raging overdose epidemic.
Some senators sensitive to the overdose epidemics back home opposed his confirmation because of his industry ties.
Sen. Joe Manchin III, D-W.Va, has already come out against Califf's nomination.
"Dr. Califf’s nomination makes no sense as the opioid epidemic continues to wreak havoc on families across this country with no end in sight. 2020 was the deadliest year on record," he said in a statement Friday. "I have made it abundantly clear that correcting the culture at the FDA is critical to changing the tide of the opioid epidemic.… His nomination is an insult to the many families and individuals who have had their lives changed forever as a result of addiction."
In 2016, Manchin and Edward J. Markey, D-Mass., both opposed Califf’s confirmation and argued that Califf was unlikely to make changes at the agency to reduce access to opioid pain killers. Manchin and Sen. Bernie Sanders, I-Vt., both threatened to filibuster his nomination.
But the majority of sitting senators, including current Senate Health, Education, Labor and Pensions Chairwoman Patty Murray of Washington and Senate Minority Leader Mitch McConnell of Kentucky, praised Califf’s leadership experience and regulatory know-how when the Senate confirmed him 89-4 in February 2016.
In response to concerns that the FDA had failed to correct course after its approvals contributed to the opioid epidemic, Califf outsourced action to the National Academies of Sciences, Engineering, and Medicine, which came up with new recommendations for opioid approvals.
They were fiercely opposed by the pharmaceutical industry and the patient advocacy groups they fund.