President Obama’s pick to lead the Food and Drug Administration inched closer to confirmation late Monday, despite loud protests from Senate Democrats who said the agency needs a crusader who will rein in and regulate prescription painkillers that are feeding the nation’s heroin epidemic.

The Senate voted, 80-6, to advance Robert M. Califf’s nomination, setting up a vote to confirm him later this week.

Mr. Obama nominated Dr. Califf, a cardiologist and current No. 2 at the agency, in September, and he breezed through a committee vote in January.

While Senate Health Committee Chairman Lamar Alexander, Tennessee Republican, and others touted Dr. Califf’s credentials, several lawmakers raised questions about his long tenure at Duke University, where he led a clinical research center that received a large share of its funding from the pharmaceutical industry.

Others, including Democratic presidential contender Bernard Sanders of Vermont, questioned his prior work as a consultant to drug companies, saying he wouldn’t rein in skyrocketing costs, although the campaigning senator missed Monday’s vote.

Sens. Edward J. Markey, Massachusetts Democrat, and Sen. Joe Manchin III, West Virginia Democrat, pushed back the hardest.

They said Dr. Califf’s industry ties made him a poor choice to “shake up” the agency, which they accused of rubber-stamping new painkillers without the input of outside experts and erring in its decision to approve use of OxyContin by children as young as 11.

“Enough is enough. This whole culture has to change,” Mr. Markey said.

Democratic Sens. Bill Nelson of Florida and Richard Blumenthal of Connecticut also voted “no,” as did Republican Sens. Rob Portman of Ohio and Kelly Ayotte of New Hampshire, who are locked in tough re-election battles and have made fighting the opioid epidemic a key part of their platforms.

Senate Majority Leader Mitch McConnell’s push to confirm Mr. Obama’s pick stood in stark contrast to the bitterly partisan battle over how to replace late conservative Supreme Court Justice Antonin Scalia, with GOP leaders saying the president should leave the nomination to the next president.

Yet lawmakers from both parties have sounded the alarm over the proliferation of opioid painkillers and heroin, which affect the body in similar ways and are causing frequent overdoses.

As it stands, 44 people die from prescription opioid overdoses in the U.S. each day, according to the Centers for Disease Control.

“The FDA plays a critical role in this epidemic it’s fostered this drug addiction more than any other agency,” Mr. Manchin said.

Mr. Manchin said Monday he wants to impose a fee on opioid manufacturers that will be used to fund drug-abuse treatment centers.

Sen. Shelley Moore Capito, West Virginia Republican, said Dr. Califf would be a good fit for her state, despite her Democratic counterpart’s opposition.

“Dr. Califf knows West Virginia. He has worked on projects to improve health outcomes with West Virginians in areas such as diabetes and heart disease,” she said. “I also expect Dr. Califf to be an innovative leader in the area of pain management and look forward to working with him to strengthen our efforts to combat opioid abuse.”

Dr. Califf earlier this month pledged to reform the FDA’s approach to opioids, including the use of warning labels and requiring outside experts to approve opioids that do not have abuse-deterrent properties.

Mr. Markey said the notion of “abuse-deterrent” opioids was an oxymoron, like “jumbo shrimp,” and that he planned to use the nomination as a springboard for a yearlong fight that could bleed into the appropriations process.

“We’re gonna wage our battle, but this is the beginning of a long struggle that I think, ultimately, we’re going to win,” he said.

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