Food and Drug Commissioner Margaret Hamburg told agency staffers Thursday she is resigning her post in March after six years in the position.
Hamburg told employees of the FDA in an email that the agency's chief scientist, Stephen Ostroff, will serve as acting commissioner.
She is among the longest-serving commissioners to head the agency and helped oversee the creation of a new food safety system, reforms in how drugs are reviewed and new tobacco regulations.
President Obama named Hamburg to the post in 2009, following a series of high-profile safety problems at the agency ranging from contaminated drugs to salmonella-tainted peppers to peanut butter that required one of the largest food recalls in U.S. history.
Before joining the FDA, Hamburg, 59, was primarily known as a bioterrorism expert who served as New York City health commissioner.