By Aaron Krol 

February 5, 2015 | Reuters has broken the news that Margaret Hamburg, Commissioner of the Food and Drug Administration since 2009, will be retiring from her post this March, with an official announcement from the White House expected on Friday. Stephen Ostroff, Chief Scientist of the FDA, will reportedly serve as acting commissioner while the Obama administration searches for a permanent successor.

Hamburg's tenure as head of the FDA has been hugely consequential, as the agency has evolved to respond to the long pharmaceutical innovation drought of the 2000's, when new approved drugs came at a trickle and represented few major breakthroughs for patients. Armed with experimental new tools like the breakthrough therapy designation, which creates short-track routes to approval for drugs with the most promising early clinical data, and priority review vouchers, the FDA has earned at least part of the praise for a recent upswing in bringing novel drugs to market, including near-record years for drug approvals in 2012 and 2014. And while the FDA can't take credit for how transformative some of these drugs have been — such as the curative Hepatitis C therapy Sovaldi, new classes of immuno-oncology drugs like Keytruda, and Kalydeco, a poster child for genomic medicine that targets cystic fibrosis mutations — the agency has adapted quickly to the challenges of reviewing new biologic therapies that might involve narrowly targeted companion diagnostics and ultra-rare indications. One reflection of the success of new review strategies is that Congress is now looking to expand them, with major new powers for expedited review included in the draft 21st Century Cures Act.

Hamburg's FDA has also been aggressive in asserting its role in the era of genomic medicine. The agency has taken firm, and controversial, stands on subjects like direct-to-consumer marketing of genetic health tests (banning 23andMe's Personal Genome Service) and the proliferation of non-FDA-cleared sequencing tests (planning to end the "laboratory developed test" exemption from FDA oversight). At the same time, the agency has tried to be flexible in its review process for those companies who want to move genomic technologies through traditional regulatory paths, and new review approaches have opened the door for large numbers of molecular diagnostics and the first FDA-cleared next-generation sequencer.

Outside the realm of drugs and medical devices, Hamburg has also overseen an expansion of the FDA into broader public health concerns. The Tobacco Control Act of 2009 gave the agency the authority to regulate tobacco products for the first time, while the 2010 Affordable Care Act allowed the agency to regulate trans fats and require calorie counts on menus, a signal that the FDA's mandate over food safety will continue to grow beyond adulterants and into nutrition.

Although Hamburg's resignation has not yet been made official, there is already a presumed front runner to succeed her. Robert Califf, a Duke University physician who has headed both the Duke Translational Medicine Institute and the Duke Clinical Research Institute, was previously considered for the post of commissioner in 2009 and is joining the FDA this month as Deputy Commissioner of the Office of Medical Products and Tobacco, the most powerful and influential office in the agency. Califf's leadership roles at Duke have given him experience both in helping to shepherd drugs through clinical trials, and in bridging the gap between academic medical science and drug development, a subject that both President Obama and NIH Director Francis Collins have taken to heart. If he is tapped for the job, his ties to pharma companies through his clinical trials work are likely to come under question during Senate confirmation hearings.

While Hamburg has not shared her reasons for stepping down, her six-year tenure has been one of the longest in FDA history. She will leave behind a notably more agile FDA, but one that is, as always, embroiled in difficult questions about how to balance protecting patients against encouraging innovation. New challenges for the next commissioner are likely to include addressing the medical device market, where the FDA lacks the assortment of tools it has for reviewing new drugs; working with unprecedented volumes of data as genomic medicine continues to pick up speed; and repairing a disjointed food safety system where responsibilities are shared across too many agencies.