President Biden on Friday nominated former Food and Drug Administration commissioner Robert M. Califf to return as the agency’s head, ending a difficult, months-long search to find a leader for the sprawling bureaucracy on the pandemic’s front lines.

In a statement, Biden said Califf “has the experience and expertise to lead the Food and Drug Administration during a critical time in our nation’s fight to put an end to the coronavirus pandemic.”

Califf, 70, a renowned cardiologist and researcher, is senior adviser for Verily, a research organization devoted to the life sciences, and Google Health. He served as FDA commissioner during the last year of the Obama administration. He spent most of his career at Duke University School of Medicine, where he founded the Duke Clinical Research Institute, one of the largest academic clinical trial operations in the world.

Many FDA experts welcomed the nomination, seeing Califf as an experienced hand who is unlikely to make abrupt changes as the agency navigates a tumultuous period marked by high-pressure reviews of coronavirus vaccines and therapies and hot-button issues involving Alzheimer’s treatments, opioids and tobacco products. An expert on clinical trials and other types of health data, Califf is likely to press for better evidence in assessing drugs and devices and to improve the nation’s cumbersome testing system.

But critics said the FDA needs fresh leadership and direction and that Califf’s longtime links to the drug industry make him the wrong choice.

“I have made it abundantly clear that correcting the culture at the FDA is critical to changing the tide of the opioid epidemic,” Sen. Joe Manchin III (D-W.Va.) said in a statement. “Dr. Califf’s nomination and his significant ties to the pharmaceutical industry take us backwards, not forward.”

Sen. Richard Blumenthal (D-Conn.), who along with Manchin voted against Califf in 2016, said he has the same “grave reservations” now as he did last time. Democratic Sens. Maggie Hassan (D-N.H.) and Edward J. Markey (D-Mass) also expressed qualms, primarily because of the FDA’s record on opioids, but did not say how they would vote.

But Califf got support from Sen. Patty Murray (D. Wash.), chair of the Committee on Health, Education, Labor and Pensions, which will consider his nomination.

“Dr. Califf has led the agency before, and was confirmed last time around in a strong, bipartisan vote,” she said. “I look forward to working with him to see our nation through this pandemic and to tackle other critical challenges like the ongoing opioid crisis, rising youth tobacco use, high drug prices, health inequities, and more.”

Califf also has strong support among agency insiders and many health groups.

Matthew L. Myers, president of Campaign for Tobacco-Free Kids, called the veteran cardiologist a strong tobacco-control advocate who understands “the urgent need for action to eliminate all flavored tobacco products, including flavored e-cigarettes, menthol cigarettes and flavored cigars.”

Califf, an avid fan of Duke basketball, is known for a laconic, low-key demeanor. Confirmed as FDA commissioner in 2016 by 89 to 4, he was backed by most Democrats and got strong support from Republicans who saw him as an accomplished scientist who was not hostile to drug companies. That pattern could repeat itself. In a White House briefing on Friday, press secretary Jen Psaki expressed confidence Califf would be confirmed again.

Califf’s name was rarely heard in connection with the top job until recently. He does not provide the racial diversity Biden said was a top priority in filling critical posts. And he was in the commissioner’s job for too short a time to have made a significant imprint on the agency, according to several people inside and outside the FDA.

“He was frustrated by not being able to get stuff done as we were heading” into the 2016 election, said a former FDA official who spoke on the condition of anonymity to discuss internal agency matters. “We could not do anything controversial.”

In his previous time at the FDA, Califf pushed steps to combat the opioid epidemic, including requiring “black box” warnings on the dangers of mixing opioids and benzodiazepines; worked to streamline trials and issued a long-delayed plan for regulating e-cigarettes.

If Califf is confirmed, he will find an agency staff exhausted by two years of pandemic-related political and scientific crises and an array of unfinished non-covid work, including decisions about which vaping products can stay on the market.

Janet Woodcock, a 35-year veteran of the FDA and former head of the agency’s powerful Center for Drug Evaluation and Research, has been acting commissioner since January and initially was a top contender for the nomination. She was derailed, to the dismay of some senior FDA officials, by opposition from a handful of Democrats led by Manchin, who attacked the longtime drug regulator for the what he viewed as the agency’s lax approach to opioids.

Administration officials in recent months considered a long list of potential candidates before settling on Califf.

“I think he would be terrific,” said Harlan Krumholz, a cardiologist at Yale School of Medicine. “It is critically important to have a commissioner who can step in and knows the job and knows how to make policy decisions.”

Even some of the agency’s toughest critics say Califf is acceptable.

“Rob Califf is a good choice,” said Aaron S. Kesselheim, a professor of medicine at Harvard Medical School who has faulted the FDA for approving drugs on what he considers flimsy evidence. “Califf certainly spent the vast majority of his early career working on clinical trials … and understands the value of rigorous data.”

But others expressed strong opposition, calling on the Senate to reject his nomination.

“Califf has a long history of extensive financial ties to Big Pharma, most significantly through pharmaceutical industry funding of the Duke Clinical Research Institute,” said Michael Carome, director of nonprofit Public Citizen’s Health Research Group, a consumer advocacy organization. “We need someone to tilt in the opposite direction and be more pro-public health and less pro-regulated industry.”

The Duke institute, which conducts clinical trials in more than 40 countries, receives funding from a broad range of sources, including the pharmaceutical industry. Califf has consulted for several pharmaceutical firms, including Merck and Eli Lilly. Since 2014, he has received more than $93,000 in consulting fees and travel and lodging expenses from drug companies, according to the federal government’s Open Payments database. He also serves on the board of two biotech companies.

During his confirmation process in 2015, Califf said drug company dollars did not influence the outcome of his academic research and that he had donated consulting fees to charities.

Eric G. Campbell, a University of Colorado health-policy expert who has done extensive research on the impact of financial conflicts of interest in medicine, said Califf’s past ties with industry should not disqualify him.

“To my knowledge those relationships have been fully discussed and widely debated in the academic and political arena,” Campbell said, adding that many academic trials are underwritten by drug companies.

Califf’s supporters say his experience strengthens his hand in dealing with the industry. The agency must be “skeptical and rigorous,” but also work with manufacturers, which “are the ones delivering the products,” Krumholz said.

“Robert Califf is a former treating physician, one of the top trialists in the world, and has proven himself to be an effective leader of the FDA in the past,” said Ellen Sigal, chair of Friends of Cancer Research.

Califf joined the FDA in early 2015 as deputy commissioner for medical products and tobacco. When he was nominated to be FDA commissioner by President Barack Obama in the fall of 2015, he ran into roadblocks from a handful of Democratic senators unhappy about the FDA’s record on opioids and Califf’s industry links. Besides Manchin and Blumenthal, Edward J. Markey (D-Mass.), along with former Republican Sen. Kelly Ayotte (N.H.). Sen. Bernie Sanders (I-Vt.) delayed Califf’s nomination but did not vote on his confirmation.

If Califf is nominated, he will have to divest financial holdings that could pose a conflict of interest and recuse himself from certain decisions, under federal ethics rules.

Califf, during his stint as FDA commissioner, became embroiled in one of the most contentious episodes in the history of the agency — the accelerated approval in 2016 of a controversial drug for Duchenne muscular dystrophy, a terminal disease that usually affects men.

Woodcock, as head of the drug center, approved the drug, called eteplirsen, despite vociferous opposition from agency scientists and outside experts, who argued there was insufficient evidence the treatment worked. The emotionally fraught dispute wound up with Califf, who said in a September 2016 memo that both sides made reasonable arguments, but that Woodcock had not overstepped her authority and that he was deferring to her.

A similar controversy occurred in the spring when the FDA approved a controversial Alzheimer’s drug over the objections of its outside advisory committee.

The episodes underscore an ongoing challenge for the FDA: How to speed drugs to patients with calamitous diseases while upholding stringent standards. Critics say those standards already have been weakened, but some patient groups say they welcome the agency’s flexibility, especially on diseases such as cancer and Alzheimer’s.

If confirmed, Califf, who has long argued that better evidence leads to better decisions, will almost certainly push to augment clinical trial data with “real-world evidence,” which taps into insurance records, clinical practice and electronic health data to get a clearer picture of how drugs, devices and other medical interventions work. He has criticized the nation’s clinical trial system as costly and overly complex, saying the flaws hurt the coronavirus response because many studies did not produce useful results.

At Verily and Google Health, Califf’s main responsibilities are to advise corporate leaders about the clinical aspects of the products and services the companies are exploring, according to a spokesperson for Verily. For one Verily initiative, called Project Baseline, researchers working with Stanford and Duke universities are trying to “create a map of human health” by studying 10,000 volunteers over four years using a variety of tools.

Califf, a native of South Carolina and a graduate of Duke and the university’s medical school, became known in the 1980s and 1990s for leading large trials, including ones testing clot-busting drugs for heart attacks. Mark McClellan, who was FDA commissioner during the George W. Bush administration, said Califf managed to organize hundreds of hospitals around the world at a time when facilities communicated via fax machines.

Califf has been known to get into intense debates before highly competitive basketball games. One such discussion, before Califf joined the FDA, resulted in his having to wear a University of Maryland T-shirt all day after Maryland beat Duke.

In December 2016, just before leaving the FDA, Califf talked to The Washington Post about his experience. “Everyone who knows me knows I have just had fun every day on the job,” he said.

Tyler Pager and Rachel Roubein contributed to this report.