Sharfstein, appointed by President Barack Obama in 2009, has emphasized public health and safety in the FDA's oversight of drugs and medical devices. He also has pushed for greater transparency in the agency's decision making.
The former Baltimore health commissioner will be named head of Maryland's department of health and mental hygiene. Maryland Governor Martin O'Malley, a Democrat, has scheduled a news conference for Wednesday to announce the appointment.
Sharfstein declined to comment and referred questions to the Maryland governor's office.
Obama named Sharfstein the top deputy to FDA Commissioner Margaret Hamburg, another public health specialist. The pair took over an agency criticized as too slow to tackle drug safety problems and widely viewed as underfunded.
The FDA oversees about 25 percent of the U.S. economy including prescriptions and over-the-counter drugs, medical devices, most foods and many other consumer products.
Under Hamburg and Sharfstein, the agency has become more aggressive in its oversight of companies for product safety problems, shoddy manufacturing and misleading advertisements. That focus was expected to continue while Hamburg remains in charge. Hamburg told the Reuters Health Summit in November she had no plans to leave the FDA's top post.
Sharfstein, during his two-year tenure, led a drive to make the FDA more open about its decisions and testified before Congress on high-profile issues. He criticized Johnson & Johnson for its handling of recalls of over-the-counter medicines at a hearing in September. (Reporting by Lisa Richwine and Susan Heavey, Editing by Maureen Bavdek)