The surprise resignation of embattled U.S. Food and Drug Administration Commissioner Lester M. Crawford injects a new element of uncertainty into the regulatory approval process for the anti-obesity drug Acomplia (rimonabant).

Crawford, 67, resigned Sept. 23 only two months after being confirmed by the U.S. Senate, leaving behind an agency whose morale was shaken by controversies including the failure to act promptly on concerns about unsafe medications.

While several recent FDA advisory committee rulings on key drugs have been surprisingly positive for manufacturers, the abrupt change in leadership leaves open the question of whether the agency may now take a more conservative approach to approval of new medicines.

A key test of the regulatory climate in the months ahead is expected to be consideration of Sanofi-Aventis's novel anti-obesity drug Acomplia, which is first endocannabinoid-receptor inhibitor to be brought before it.

Dr. Andrew von Eschenbach, director of the National Cancer Institute, who was immediately nominated by President Bush to be acting FDA director, would no doubt come under stiff Senate questioning about how the agency weighs the risks and benefits of new drugs if nominated as Crawford's permanent successor.

Sen. Charles Grassley of Iowa, chairman of the Senate Finance Committee and a critic of the FDA, said the agency had grown too close to the pharmaceutical industry under Crawford.

"In recent years, the FDA has demonstrated a too-cozy relationship with the pharmaceutical industry and an attitude of shielding rather than disclosing information," said Grassley. "... Now is the time to reform the FDA's culture and reassert that the agency's top priority is what's good for John Q. Public."