Margaret Hamburg, one of the  longest-serving commissioners in US Food and Drug Administration (FDA)  history, plans to announce her resignation tomorrow, FDA officials have  confirmed to Regulatory Focus.

Hamburg's final day at the  agency will be in late March 2015, Hamburg wrote in an email. She will be  succeeded on an acting basis by Stephen Ostroff, FDA's chief scientist since  January 2014.

A Long Tenure Hamburg's resignation brings to  an end one of the longest tenures as FDA commissioner of food and drugs in  the agency's history.  According to data analyzed by Regulatory  Focus, Hamburg will be the sixth-longest serving FDA commissioner in  history, the longest-serving (and only the second) female commissioner in the  agency's history, and the second-longest-serving commissioner of FDA's modern  regulatory era.         

Assuming Hamburg leaves office  on 28 March 2015, she will have served in office for 2,140 days. She was  sworn into office on 19 May 2009, and had been the only FDA commissioner to  serve under President Barack Obama.

An Agency in Flux

Hamburg's tenure as  commissioner has been marked by a number of high-profile changes, struggles  and scandals.

She was brought on in the early  days of Obama's push for the Patient Protection and Affordable Care Act  (PPACA), which established a regulatory pathway for biosimilar products.  In 2011, tensions flared between her and Department of Health and Human  Services (DHHS) Secretary Kathleen Sebelius after FDA's approval of an  over-the-counter birth control product was overturned for reasons that  appeared to be more political than scientific.

Hamburg has also overseen  massive legislative changes at FDA. The 2012 passage of the Food and Drug Administration Safety and Innovation Act  (FDASIA) created hundreds of new obligations for the agency, and  also established several new pathways for approvals, such as the breakthrough  therapy designation. The 2013 Drug Quality and  Security Actgave the agency broad new powers to ensure the safety  of the pharmaceutical supply chain and of compounded pharmaceutical products.

Drug and device approvals also  saw marked improvements under Hamburg's tenure, with new drug approvals  experiencing perhaps their best year for approvals ever in 2014, and device  approvals making slow but steady improvements.

Hamburg also oversaw scandals  and problems at FDA during her tenure. FDA was chastised for its lack of  oversight of the pharmaceutical compounding industry, for allegedly spying on  some members of its medical device review divisions, for its approach to  regulating painkillers, and for its regulation of various products and areas.

What's Next?

Hamburg's departure comes at a  particularly tricky time for FDA.

Both the House of  Representatives and Senate are pursuing new legislation aimed at expediting  the processes FDA uses to approve most drugs, and particularly those for  patients with rare or life-threatening diseases. The legislation could have a  massive effect on the way in which FDA regulates almost every medical product  it oversees.

In addition, the agency is  preparing to enter into negotiations with the pharmaceutical and medical  device industries regarding user fees. Under various pieces of legislation-the  Prescription Drug Use Fee Act, the Medical Device User Fee Act,  the Generic Drug User Fee Act and the Biosimilar User Fee Act-FDA  collects fees from pharmaceutical and medical device companies to help it  hire more staff and review new product applications more quickly. In return  for that money, FDA is supposed to adhere to specific timelines for reviewing  products.

The negotiations, which notably  do not involve Congress, are meant to ensure FDA gets sufficient funding to  make improvements, and that industry is assured its funding-which now makes  up more than half of all funding at FDA-is actually resulting in more  efficient regulatory reviews.

Who's Next?

But even more important than what's  next is the question of who's next.

Ostroff, who will serve as acting  commissioner upon Hamburg's departure, is a relatively little-known regulator  outside FDA circles. As of January 2014, he was the chief medical officer of  FDA's food science division, the Center for Food Safety and Applied Nutrition  (CFSAN), and an advisor to FDA's Office of Foods and Veterinary Medicine.

Given Congress' focus on  medical products at the moment, legislators might instead push for someone  who is able to focus more on reforming and accelerating medical product  approvals at FDA.

In a statement, Rep. Fred  Upton, who is leading the House's effort to reform FDA, said he is looking  forward to leadership to "ensure we are firmly on the path to  cures." Sen. Lamar Alexander, who is leading the FDA reform effort from  the Senate side, said he "hopes the president nominates an FDA  Commissioner who will work closely with Congress on finding ways to get safe  medical treatments, devices and drugs to patients more quickly."

Even Obama might be unlikely to  appoint an FDA commissioner who is focused on the regulation of food. As  reported by Regulatory Focus last week, Obama has proposed stripping  FDA of its authority to regulate food products, which would instead be  transferred to a new "Food Safety Administration."

So who might succeed Hamburg?  If rampant speculation is any guide, the agency may already have hired its  next commissioner. Last month, FDA announced it had hired world-renowned  cardiologist Robert Califf to a top role within the agency: deputy  commissioner for medical products and tobacco.

Califf has been considered for  the role of FDA commissioner on two separate occasions.

In appointing his next choice  for FDA commissioner, Obama will also have to grapple with a  Republican-controlled House and Senate, both of which might complicate the  confirmation process. Hamburg, in contrast, was appointed when both chambers  of Congress were overwhelmingly controlled by Democrats.

Read the Reuters  report on Hamburg's expected resignation here.

Hamburg's Resignation Letter to FDA Staff

Dear FDA Colleagues:

It has been a privilege to  serve as your FDA Commissioner for almost six years.  So it is with very  mixed emotions that I write today to inform you that I plan to step down as  FDA Commissioner at the end of March 2015.  As you can imagine, this  decision was not easy.  My tenure leading this Agency has been the most  rewarding of my career, and that is due in no small part to all of you - the  dedicated and hard-working people that make up the heart of this  Agency.  While there is still work ahead (and there always will be), I  know that I am leaving the agency well-positioned to fulfill its  responsibilities to the American public with great success. 

I feel so fortunate to have  worked at an organization as remarkable and productive as the FDA.  The  expertise, dedication and integrity of our people and the unique nature and  scope of FDA's role make this Agency truly special.  Every day, FDA  employees around the world recommit themselves to the Agency's work, to  quality science, to facilitating innovation, and to the protection of public  health.  And because of your dedication and your service, we have been  able to achieve so many significant milestones over the past years.

From creating a modernized  food safety system that will reduce foodborne illness; advancing biomedical  innovation by approving novel medical products in cutting-edge areas; and  responding aggressively to the need to secure the safety of a globalized food  and medical product supply chain, to taking critical steps to reduce the  death and disease caused by tobacco, we have accomplished a tremendous amount  in the last six years.  We can honestly say that our collective efforts  have improved the health, safety and quality of life of the American people.

At the heart of all of  these accomplishments is a strong commitment to science as the foundation of  our regulatory decision-making and of our integrity as an Agency.  And  while there are far too many significant actions, events, and initiatives to  count, there are some highlights of the past years that I particularly want  to mention.

In the foods area, we have  taken critical actions that will improve the safety of the food Americans  consume for years to come.  These include science-based standards  developed to create a food safety system focused on preventing foodborne  illness before it occurs, rather than responding after the fact.  We  have taken several significant steps to help Americans make more informed and  healthful food choices.  These include working to reduce trans fats in  processed foods; more clearly defining when baked goods, pastas and other  foods can be labeled "gluten free;" updating the iconic Nutrition Facts label;  and, most recently, finalizing the rules to make calorie information  available on chain restaurant menus and vending machines.

We have also made great  strides in advancing the safety and effectiveness of medical products. Some  of these important steps include new oversight of human drug compounding and  provisions to help secure the drug supply chain so that we can better help  protect consumers from the dangers of counterfeit, stolen, contaminated, or  otherwise harmful drugs.  We are continuing to increase the speed and  efficiency of medical product reviews.  We just had another strong year  for novel drug approvals, with most of these drugs being approved on or  before their PDUFA goal dates and most being made available to patients in  the United States before they were available to patients in Europe and other  parts of the world.  We launched a powerful new tool to accelerate the  development and review of "breakthrough therapies," allowing FDA to expedite  development of a drug or biologic to help patients with serious or  life-threatening diseases.  In fact, almost half of the novel new drugs  approved in 2014 received expedited review with a combination of breakthrough  designation, priority review and/or fast track status.  These included  drugs for rare types of cancer, hepatitis C, type-2 diabetes and idiopathic  pulmonary fibrosis, as well as a number of groundbreaking vaccines.  We  have also established a regulatory pathway for biosimilar biological products  that will create more options for patients.

On the medical device side,  the average number of days it takes for pre-market review of a new medical  device has been reduced by about one-third since 2010.  The percentage  of pre-market approval (PMA) device applications that we approve annually has  increased since then, after steadily decreasing each year since 2004.   We also published the Unique Device Identification (UDI) final rule that is  intended to improve the tracking and safety of medical devices.  And we  proposed a risk-based framework for laboratory developed tests (LDTs) to help  ensure patients and providers have access to safe, accurate and reliable  tests, while continuing to promote innovation of diagnostic tests to help  guide treatment decisions.

We have ushered in the era  of personalized medicine across all of our medical product centers. For  example, many cancer drugs are increasingly used with companion diagnostic  tests that can help determine whether a patient will respond to the drug  based on the genetic characteristics of the patient's tumor.  A growing  percentage of our recent approvals have involved targeted therapies, offering  many patients more effective response profiles and/or reduced likelihood of  side effects.

We made significant  progress in implementing both the letter and spirit of the Family Smoking  Prevention and Tobacco Control Act.  Our tobacco compliance and  enforcement program has entered into agreements with numerous state and local  authorities to enforce the ban on the sale of tobacco products to children  and teens; conducted close to 240,000 inspections; written more than 12,100  warning letters to retailers; proposed the extremely important foundational  "deeming" rule; and broken new ground for FDA with the launch of the Agency's  first public education campaigns to prevent and reduce tobacco use among our  nation's youth. 

As Commissioner, my goal  has been to shape and support an FDA that is well-equipped to meet the  challenges posed by scientific innovation, globalization, the increasing  breadth and complexity of the products that we regulate, and our new  expanding legal authorities.  I have worked hard to advocate for FDA and  our unique and essential mission, including building new partnerships to  support our work.  The Agency has received numerous votes of confidence  with the bi-partisan enactment of a series of landmark bills extending our  authority in the areas of tobacco, food safety and medical products.  In  addition, we have achieved a dramatic increase in our budget, from some $2.7  billion in FY2009 to almost $4.5 billion in FY2015. 

As hard as it is to leave  this Agency, I am confident that the leadership team that we have in place  will enable FDA to capitalize on, and improve upon, the significant advances  we've made over the last few years.  Many of these leaders have been  with the FDA throughout my tenure, and I am proud to say that we've recently  made some wonderful new additions.

And with respect to the  agency's senior leadership team, I am pleased that Dr. Stephen Ostroff has  agreed to serve as Acting Commissioner when I step down.  Since joining  the Agency in 2013, and most recently serving as FDA's Chief Scientist, Dr.  Ostroff has successfully overseen numerous significant initiatives, while  helping to ensure that scientific rigor, excellence and innovation are  infused across the Agency.  I have every confidence that he will take on  this new role with the same energy, dedication and care.

I want to extend my deepest  gratitude to each and every one of you for your service and for making FDA an  agency that is not only an exciting and rewarding place to work, but also a  place of remarkably meaningful achievement and impact on the health and  well-being of Americans.

Margaret A. Hamburg, M.D.

Commissioner of Food and  Drugs