WASHINGTON — Food and Drug Administration (FDA) Commissioner Lester Crawford resigned unexpectedly yesterday, two months after he survived a tough Senate confirmation. Crawford told his staff that at 67, it was time to step aside.

President Bush appointed Dr. Andrew von Eschenbach, director of the National Cancer Institute, acting commissioner.

Sources familiar with his departure said Crawford was asked to resign.

Crawford's 3 ½-year tenure, first as interim, then permanent, FDA chief, was marked by increasing criticism and a particularly rocky final 12 months. The painkiller Vioxx was pulled off the market for safety problems, and the FDA was embarrassed last fall when its British counterparts shut down a supplier of U.S. flu vaccine for tainted shots. This summer, recalls of malfunctioning heart devices mounted.

Crawford was also accused before his confirmation of having an improper relationship with a female colleague, a charge independent investigators said both parties denied. The final report did note, however, some significant discrepancies between Crawford's testimony and that of others in the commissioner's office.

In August, morale at the agency plummeted after Crawford indefinitely postponed nonprescription sales of the emergency-contraception pill Plan B over objections of staff scientists who had declared the pill safe. The agency's women's-health chief resigned in protest.

The delay also angered Sens. Patty Murray, D-Wash., and Hillary Clinton, D-N.Y., who had allowed Crawford's nomination as commissioner to move forward only after getting a promise that a decision on Plan B would be made by Sept. 1. At the time, Murray said, "This is not only a broken promise to us, but another frightening example of politics trumping science at the FDA."

Yesterday, Murray hailed Crawford's resignation and called on Bush to nominate a replacement who will "show his commitment to putting science ahead of politics."

"Unfortunately, during his tenure, the FDA's reputation as the gold standard in public health has been tarnished."

Despite the controversy surrounding Crawford, the resignation, effective immediately, was a surprise.

A veterinarian who specialized in food safety, he was elevated by Bush from acting commissioner to the full job, in part because his experience was deemed important as the FDA tried to better safeguard the food supply against bioterrorism.

He had worked at the FDA on four occasions over 30 years, at the Agriculture Department and as an adviser to the World Health Organization.

Crawford gave a speech Monday in Washington, D.C., during which he betrayed no sign he was planning to leave.

Health and Human Services Secretary Mike Leavitt accepted Crawford's resignation "with sadness," said department spokeswoman Christina Pearson. Asked if Crawford was forced to resign, Pearson said she couldn't comment further on a personnel issue.

Crawford is the second high-ranking administration official to resign in the past two weeks. Federal Emergency Preparedness Agency Director Michael Brown resigned under pressure because of the agency's performance during and after Hurricane Katrina.

Von Eschenbach, tapped to be the FDA's acting chief, is a cancer survivor and urologic surgeon from Texas who was chief academic officer at the University of Texas M.D. Anderson Cancer Center before moving to the National Cancer Institute.

His tenure isn't immune from controversy, either: Von Eschenbach has said that he hopes by 2015 to make cancer a chronic disease that patients can live with instead of die from. While a laudable goal, many cancer specialists caution science isn't close to achieving it for most cancers.

In a brief farewell message to his staff, Crawford thanked Bush, Leavitt and "the extraordinary people of FDA for the honor of having served with them. ... After 3 ½ years as deputy commissioner, acting commissioner and finally as commissioner, it is time, at the age of 67, to step aside."

Sen. Charles Grassley, R-Iowa, a vocal critic of FDA policies and Crawford, welcomed the departure and said he hoped the new commissioner would reform the agency and take it in a new, and more consumer-oriented direction.

"FDA scientists and employees are by and large hardworking and committed to fulfilling the agency's mission," he said. "They deserve a commissioner who will reinvigorate the agency."

One consumer group lamented Crawford's departure, particularly the loss of his food-safety expertise.

"The agency has had so much turnover in the top spot, and turmoil throughout, that it could have benefited from a period of steady leadership," said Michael Jacobson of the Center for Science in the Public Interest. "The country doesn't need a rudderless FDA."

Material from Seattle Times archives and The Washington Post is included in this report.