Hamburg, The Atypical Commissioner, Receives Atypically Fond Farewell

Margaret Hamburg’s background in public health, as opposed to academic medicine, was off-putting to some in pharma initially, but she leaves the agency in March with high drug approval numbers, initiatives to improve the OTC monograph and switch programs and increased enforcement in the supplement manufacturing arena.

FDA Commissioner Margaret Hamburg will step down from the agency’s helm at the end of March, leaving behind a record that indicates a public health official can successfully run a public health agency to industry’s liking – trade groups played up her commitment to expedited drug approval pathways, record high drug approvals and regulatory science in comments on her departure.

Stephen Ostroff, FDA’s chief scientist, will serve as acting commissioner upon her departure (Also see "FDA’s Acting Chief Scientist Offers Vaccine Continuity As Goodman Departs" - Pink Sheet, 9 Jan, 2014.). The White House declined to comment on any plans to nominate a new permanent commissioner at its Feb. 5 press briefing, but indicated anyone they did bring forward would have bipartisan appeal.

Ostroff was chief medical officer for the Center for Food Safety and Applied Nutrition and worked with the Division of Dietary Supplement Program in the agency’s 2013 investigation of a link between OxyElite Pro, a sports nutrition product manufactured by [USPlabs LLC], and cases of acute non-viral hepatitis (Also see "DMAA Product OxyElite Pro Named Potential Link In Acute Hepatitis Cases" - Pink Sheet, 9 Oct, 2013.).

“Steve’s a good guy to work with,” said Daniel Fabricant, then DDSP director at FDA and now head of the Natural Products Association.

Consumer health care product manufacturers’ interests are in good hands with Ostroff as acting commissioner, Fabricant says.

“He gets public health. He gets the balance between prevention and protection of public health, that you can’t just have an adversarial relationship with industry,” he said.

The Consumer Healthcare Products Association, Pharmaceutical Research and Manufacturers of America, Biotechnology Industry Organization and Generic Pharmaceutical Association, all praised Hamburg after the news of her retirement broke and while industry’s general pleasure with Hamburg might not seem out of place today, at the time of Hamburg’s 2009 nomination by the Obama administration there was concern by industry that she did not have the resume best suited to the job.

“During her tenure, the agency has made important progress toward expanding consumer care through OTC medicines – in particular with prescription-to-OTC switches. Just in the last two years, the FDA has approved four successful switches, and we are very optimistic about additional opportunities for future switches,” CHPA President and CEO Scott Melville said in a statement.

FDA launched two initiatives with significant potential to boost the OTC industry’s profile during Hamburg’s tenure: considering changes to facilitate additional OTC switches and looking at solutions for the inefficient and stalled OTC monograph system.

Fabricant said while he was with FDA, Hamburg backed increasing the agency’s dietary supplement good manufacturing inspections and tightening enforcement of the industry. “She did a great job,” he said, adding that under Hamburg “the needle was moved on” increasing regulatory compliance in the industry.

Unique Background For FDA Commissioner

Speculation had been that newly appointed Deputy Commissioner for Medical Products and Tobacco, Robert Califf, may be in line to permanently succeed Hamburg even before her Feb. 5 resignation announcement (Also see "FDA Lands Duke’s Califf As Top Deputy, Potential Next Commissioner" - Pink Sheet, 26 Jan, 2015.).

While it may seem ironic, Hamburg’s nomination was unique as most of FDA’s pervious leaders have hailed from the world of academic medicine, a world more relatable and perhaps seen as more in line with the missions of the pharmaceutical industry than a public health-focused professional.

Hamburg’s background included time as New York City’s Health Commissioner, expertise in bioterrorism preparedness research, and a stint as an assistant secretary for policy and evaluation in HHS in the Clinton administration.

In a New England Journal of Medicine piece shortly after her confirmation she indicated she would put public health ahead of user fee goals (Also see "Public Health Trumps User Fee Goals, FDA Leaders Say – But That May Be Good News For Sponsors" - Pink Sheet, 1 Jun, 2009.).

At the time of her nomination and confirmation, Steve Grossman, president of the regulatory consultancy HPS Group, said there were accusations that she wasn’t qualified for the position. He took to his FDA Matters blog to argue otherwise.

“The point would be people were saying she was unqualified or less well qualified and I was responding, no, it’s just because you’re assuming that the same people should always be FDA commissioner and actually what she brings to the job is different and there is even an argument that its better,” Grossman said.

Grossman felt that Hamburg’s experience as NYC public health commissioner prepared her for running FDA in valuable ways that a career in academic or clinical medicine might not have prepared her.

“Academic medicine, in a leadership position, involves balancing interests within your institution,” he explained, but a city health department functions more like the FDA. “In a city health department you are dealing largely with externally driven forces – whether it’s the city council, the mayor, a food crisis, bird flu, whatever – and you live by the unexpected and your ability to respond to the unexpected.”

Hamburg had additional operational preparation for the FDA job because “running a city department is hierarchical and reports into a political structure,” Grossman said.

Grossman said he believes this background has helped Hamburg cope with the crises she faced as commissioner. “I’m not saying she is more or less successful than the others but I’ve seen the background she’s had play out favorably as you go through the crises of the last half dozen years.”

Industry Cites Record High Approvals, Breakthrough Program

The bon voyage comments from industry groups seem to indicate that companies feel it worked out just fine for them after all.

“BIO extends our thanks and gratitude to Dr. Margaret Hamburg for her nearly six years of public service as the Commissioner of the FDA. … Dr. Hamburg fulfilled these duties well and served at a time of historic advances in biotechnology and regulatory science,” BIO President and CEO Jim Greenwood said.

“Of particular note, Dr. Hamburg presided over the implementation of the Food and Drug Administration Safety and Innovation Act (FDASIA) and the successful launch of the breakthrough therapy designation program and other expansions of expedited approval pathways. These programs have proven invaluable in bringing groundbreaking new therapies to patients more efficiently, while maintaining the FDA’s high standards for safety and efficacy. In 2014, the FDA approved more than 40 new drugs, the most in nearly two decades,” Greenwood noted (Also see "FDA Solidifies 2014 As Breakthrough Year With December Drug Approval Rush" - Pink Sheet, 5 Jan, 2015.).

Lakshman Ramamurthy, director of FDA Regulatory Policy at Avalere, also cited the breakthrough program as the pharmaceutical highlight of Hamburg’s tenure, and indicative of her flexibility and support of innovation (Also see "‘Breakthrough’ Drugs Get ‘Road-MaPP’ – Complete With Communication Timetable" - Pink Sheet, 29 Jul, 2014.).

Ramaruthy also credited Hamburg’s public health experience with opening up the door for patients to more directly communicate with FDA. “I think it really became more open and transparent agency in that sense,” he said (Also see "FDA Seeks New Ways To Involve Patients In Regulatory Process" - Pink Sheet, 3 Nov, 2014.).

Overseeing an expansion of FDA’s expedited approval programs for innovative drugs, including Breakthrough, her dedication to advancing regulatory science and globalization and harmonization as well as a committee to transparency, were cited by Friends of Cancer Research as some of Hamburg’s accomplishments (Also see "FDA Has Regulatory Science Plan; Now It Needs Funding" - Pink Sheet, 6 Oct, 2010.).

Hamburg also received praise from key congressional leaders in the House Energy & Commerce Committee and the Senate Health Education Labor and Pensions Committee, which have jurisdiction over the agency.

Hamburg’s nearly six-year tenure brought stability back to an agency that had recently seen commissioners serve for much shorter stints, Grossman said. She also helped restore progress and prestige to an agency plagued by crises including heparin contamination and the Vioxx withdrawal, he argued.

Daniel Kracov, head of the FDA and healthcare practice at Arnold & Porter LLP, said, “from a drug and device perspective I think she’s done a good job. … I think they get to a significant degree that there is a very significant demand out there for getting new treatments to patients as quickly as possible, that’s been a very significant focus.”

However, Kracov – unlike the big industry groups – said Hamburg’s tenure has been a “mixed bag.”

“I think there’s been some areas in which the agency has been less receptive to ways in which the regulatory burden can be reduced while still maintaining the quality and integrity of product,” he said.

One area where FDA is lagging is promotion and communication issues. Regarding “the onerous restrictions on the ability of pharma and device companies to engage in scientific exchange,” Kracov said.

“I think there is a lot of unfinished business there. I think the First Amendment, case law is getting out ahead of where the agency is and it would be better if the agency responded to that rather than courts making policy in that area ultimately,” Kracov said. “It may ultimately be a matter for a legislative resolution” (Also see "FDA Reassessing Off-Label Policies To Address First Amendment Concerns" - Pink Sheet, 23 Apr, 2014.).

The one group that was particularly happy to see Hamburg go was Public Citizen, who said the commissioner was too cozy with industry.

“Too often, the FDA has succumbed to industry and political pressures, implementing policies and taking actions that tilt too far toward the bottom-line interests of pharmaceutical and medical device companies, and away from protecting public health. Transparency of agency decision-making also has suffered with Hamburg at the helm,” Michael Carome, Public Citizen’s Health Research Group director said.

Biosimilars, GDUFA, Compounding Also Key Legacies

Regulatory science and globalization were key initiatives spearheaded by Hamburg (Also see "FDA Globalization Efforts Gain Traction Even As Budget Request Emphasizes Old Inspection Model" - Pink Sheet, 21 Feb, 2011.).

However, she will also be remembered for presiding over the FDA during a time when a biosimilar pathway was being shaped and implemented and the first generic drug user fees and biosimilar user fees programs were implemented, though such programs weren’t necessarily her own doing.

For better or worse Hamburg will likely also be remembered for her handling of the outbreak of fungal meningitis that resulted from contaminated compounded drugs which ushered in new legislation and new authorities to FDA to oversee certain compounding facilities.

HELP Committee Chair, Sen. Lamar Alexander, R-Tenn., noted that he and Hamburg worked together to find a solution to prevent another compounding crisis like the 2012 outbreak in comments on her resignation, though during that period Hamburg, Lamar and House Republicans did not always see eye to eye (Also see "FDA Wants Compounding Authority Clarified, Congress Not So Sure It’s Necessary" - Pink Sheet, 14 Nov, 2012.).

Another more controversial stain on her FDA tenure may be the agency’s approval of the first single-entity, hydrocodone extended-release product, Zogenix Inc.’s Zohydro, amidst concerns of abuse of opioid products (Also see "Abuse-Deterrent Testimony: Hamburg Defends Opioid Policy On The Hill" - Pink Sheet, 14 Mar, 2014.)).

Hamburg leaves the agency just as it may have to deal with a new wave of biomedical reform taking shape in Congress, as it also simultaneously prepares to negotiate the next set of drug user fee legislation in 2016 (Also see "New Rx Approval Standards, Faster Pathways Offered In Cures Legislation" - Pink Sheet, 2 Feb, 2015.).