Margaret Hamburg

FDA Commissioner Margaret Hamburg delivered this year’s keynote speech in front of a packed room of pharma and bioscience personnel at the 46th annual meeting of the Drug Information Association, which opened Monday morning. Hamburg started her speech by explaining how her earliest goal as FDA chief was to build the field of regulatory science—an area hasn’t received the focus or the dollars it needs to advance.

“How do we make sure that we fully translate research into real-world products and programs that really matter?” Hamburg asked. “We all recognize that a gap has formed between bioresearch and the development of those products. With the disclosure of knowledge and capabilities emerging from many domains in research from around the globe comes the fundamental question: How do we make sure that we fully translate the potential and promise of that research into a real world product and program that really matters?”

Hamburg noted that a gap has formed between biomedical research and the development of new medical products, and urged industry to work with government to help close that gap.

She also said that industry is lacking the science and tools to assess and evaluate safety and efficacy. In other words, the US needs to beef up its regulatory science. “Billions of dollars have been invested in biomedical research, but this research will not translate into real life therapies for those that need them until we make an appropriate investment in regulator science,” Hamburg said. “We can no longer rely on techniques and approaches of the 20th century for the preventions, treatments and cures of the 21st century.”

According to the commissioner, new advancements in regulatory science can make the difference in speeding evaluation of new products, tracking safety, recognizing potential problems early on, and helping hone in on drugs that work or that have specific side effects to a targeted sub-population of patients.

Hamburg listed some opportunities for regulatory sciences.

1. Promising research is underway using stem cells for brain function loss in the case of Parkinson’s disease and treating other medical conditions.
2. NIH, industry, and foundation are working together to create an artificial pancreas for juvenile diabetes, which would continuously monitor patients’ blood sugar and automatically inject the proper amount of insulin.
3. Basic research is identifying potential tumor markers to indicate whether a patient’s cancer will respond to a specific therapy.

However, she pointed out that none of these treatments will come to fruition unless regulatory science is improved to help turn raw research into actual products.

She talked about FDA’s new initiative to work with TB researchers and companies to help create combination products, thereby fast-tracking much-needed treatments to patients in underdeveloped countries. “In might not be a sexy as discovery, but regulatory science is a dynamic and essential part of our scientific enterprise,” Hamburg said. “We want FDA to serve as a gateway, not a barrier, to the products that people need and count on every day.”

Hamburg said that the number of foreign products product US patients use has increased significantly. “The numbers are mind-boggling,” she said.

Global Security

“This year, about 80 percent of the active pharmaceutical in drugs we consume come from outside of our borders,” Hamburg noted. while acknowledging the recent mess with the tainted heparin and the growing number of counterfeit drugs. She said that oversight has to keep up with the growing global economy. This includes adding more sophisticated security strategies and establishing foreign offices.

“FDA will never have the resources to inspect every foreign manufacturer or every shipment of product from overseas,” Hamburg said. “The truth is that we need new approaches.”

She suggested building a global channel that everyone shares, and building stronger relationships with sister regulatory bodies and overseas pharma companies.

“Today, we are involved in a large amount of international activities including efforts to harmonize scientific standards, share technical expertise, and provide training in applicable regulatory disciplines and import requirements,” Hamburg said. “Public health protection is a global endeavor…that is a win-win situation for all involved”

The stated aim is to assist FDA’s Division of Drug Marketing, Advertising, and Communications (DDMAC) in its efforts to deter promotional activities. DDMAC examines promotional pieces submitted to the agency, scans ads and TV commercials informally, and monitors drug company exhibits and programs at medical meetings. An important source of information is all the complaints the division receives are from industry competitors who see another company getting away with off-label promotion or unfair comparisons. It’s impossible for DDMAC to catch everything, and certainly not what’s said in meetings between doctors and sales reps or at sponsored dinner programs.

To kick off the Bad Ad program, which was announced last month, DDMAC staffers will give talks and distribute educational materials to providers at medical conventions and society meetings. A brochure advises doctors on how to recognize misleading promos: omitting risks, overstating effectiveness, promoting off-label uses, or making misleading comparative claims. FDA is making it easy for doctors to squeal about objectionable messages by establishing a special call-in number and email address.

It’s not yet clear if the campaign will generate a lot of finger-pointing—or if it does, how DDMAC will deal reports that are vague and undocumented (anonymous calls are okay). Marketers fear that doctors will file complaints based on misunderstandings and personal prejudices. Supporters of the program anticipate that marketers and sales reps will modify their pitches if they think that their audience is taking a much closer look at what they say. But free-speech advocates like the Washington Legal Foundation fear it will chill open exchange of health information, which can be useful.

The Bad Ad campaign fits FDA’s effort to step up enforcement, as Commissioner Margaret Hamburg promised a year ago. The agency has issued 186 warning letters so far this year, putting it on track to meet last year’s record of 570 enforcement missives, according to BNet Pharma. And more of those are coming from DDMAC, which doubled its warning-letter rate to 41 in 2009, vs. 21 the year before. Many recent letters challenge Internet marketing, an activity that remains on FDA’s radar screen. In April, DDMAC sent a long warning letter to Novartis challenging the company’s use of Web sites to promote unapproved uses and to make unsubstantiated claims for Gleevec. FDA plans to develop guidelines on Internet promotion and use of social media by drug marketers, but it’s proving to be a complicated business.

The cover story by Jill Wechsler was supplemented by some amazing photos by DC-based editorial and portrait photographer Stephen Voss. I found him after doing some general searches on Google and instantly fell in love with his style of photography, which skews a bit on the dark side (as in contrast, not The Force)

The only thing I asked of Stephen was to make sure he captured Dr. Hamburg as a power player. He succeeded in spades, and I was blown away by the stunning photo of her—all smiles—against a lovely earth-tone wall. Check out some of the outtakes from the shoot after the jump. Enjoy the shots.

FDA officials have been promising stiffer enforcement of manufacturing and marketing requirements for several months, and commissioner Margaret Hamburg is moving full-speed ahead to fulfill those predictions. Last month, FDA announced it will issue warning letters quickly when it finds violations and will require manufacturers to respond promptly. Too many serious violations “have gone unaddressed for far too long,” including failings with product quality, adulteration and false and misleading labeling and advertising, Hamburg commented at a meeting sponsored by the Food and Drug Law Institute. The commissioner wants to limit all the back-and-forth wrangling with regulated companies that delays compliance. And if there’s a situation that raises serious health and safety issues, FDA may launch a recall or seizure before even issuing a warning letter, she warned.

Under the new program, manufacturers will have 15 working days after receiving an inspection report to respond to any cited violations. If FDA doesn’t receive a sufficient response in that timeframe, the agency will issue a warning letter. The 15-day policy was described in an Aug.10 Federal Register notice and will apply to violation notices issued after Sept. 15.

On its part, FDA will try to promptly reinspect or investigate a company’s efforts to correct violations. If the problems are not corrected, though, the agency won’t just issue another warning letter, but will look at penalties, seizure, closures or other action.

Carrot for Compliance
In addition to waving a bigger stick, FDA wants to encourage pharma companies to quickly address violations by establishing a formal process for resolving enforcement actions. After determining that problems cited in a warning letter have been corrected, beginning this month the agency will state that compliance in a formal close-out letter and post the information on its website. This gives companies an official statement to show investors and customers that they’re back in FDA’s good graces, and that a facility or product is no longer tainted.

Another important change is to end the extra legal review of warning letters before they are sent out. The Bush administration revised procedures so that the FDA chief counsel examined all warning letters, a policy that was criticized for delaying and reducing agency enforcement actions against industry. “This created very cumbersome practices without a lot of benefit,” Hamburg commented. Now each FDA center will review and identify those warning letters should go to the chief counsel because they raise “novel, complex and sensitive issues,” such as an activity involved in a lawsuit or recently established by legislation.

Hamburg hopes that these policies will spur speedy corrective efforts by cited companies and encourage broader compliance throughout industry. Publicizing agency enforcement actions, she said, will increase public confidence in the agency and better educate patients and consumer about potential risks in medical products.

Faster review of violations and follow-up to corrective actions will require more resources, which Hamburg says are now available due to FDA budget increases. The food safety legislation before Congress also will give the agency some additional enforcement tools.

Hamburg expects an initial increase in warning letters but hopes that the volume will level off over the long run as industry recognizes that a strong compliance program is good for business and for consumers. FDA’s success in spurring compliance “should be measured not by the number of warning letters or injunctions or seizures,” she said, but by “our impact on the health and welfare of the public.” Failure to meet FDA standards means that a company is “putting the public at risk” and also “jeopardizing the public’s confidence in your industry.”

Typical of new administrations, FDA commissioner Margaret Hamburg is moving around some staff functions and bringing in new faces, but holding off on major reorganizational changes at the agency. There will be a new “food czar”—a deputy commissioner of food—but not a comparable official in charge of drugs, biologics and medical devices. Hamburg also is looking for a politically savvy health expert to head up a new Center for Tobacco Products, plus other newcomers to direct revised operations for managing policy, budget, science and communications functions in the FDA commissioner’s office.

The departure of the remaining top staffers under the previous administration—chief of staff Susan Winckler, policy chief Randall Lutter and chief of operations John Dyer—facilitates these changes. Budget development will shift to the policy office to better meet demands from Congress for more detailed information on how FDA will spend all the added money it’s seeking. An office of external affairs will handle FDA’s relations with the media, health professionals and interest groups, and a new Office of Special Medical Programs is slated to absorb a number of cross-cutting programs—bioresearch monitoring, combination products, orphan drugs and pediatrics.

That will leave chief scientist Jesse Goodman to focus on innovation and counter-terrorism, in charge of FDA’s Critical Path Initiative and pandemic response. Goodman also will head up a new office of scientific integrity that will resolve scientific disputes within the agency, and share oversight of the Center for Toxicological Research in Arkansas.

But Hamburg’s main focus clearly is on improving food safety and oversight. The commissioner proposed these changes to the secretary of Health and Human Services (HHS) in June, just as the Obama administration rolled out new proposals from its food safety working group to better control food-borne illness. As part of the initiative, FDA issued a long-awaited final rule for reducing salmonella contamination in eggs and promised new guidance on ways to prevent E.coli contamination of tomatoes, melons and leafy greens.

At the same time, Hamburg announced the return of former FDA official and food regulatory expert, Michael Taylor, as a special advisor on foods. The expectation is that Taylor will be new food czar, overseeing the Center for Food Safety and Nutrition (CFSAN) and the Center for Veterinary Medicine (CVM), along with extensive food-related oversight provided by FDA’s field force. Taylor comes to FDA with the benefit of experience as administrator of the Department of Agriculture’s Food Safety and Inspection Services (FSIS) as well as FDA deputy commissioner for policy in the early 1990s. As an academic for the last 10 years, Taylor has been involved in food safety research and policy. He has backed proposals to create a single federal agency governing food safety, but says that’s off the table for now.

Bigger Budget

Hamburg will have support for reorganization and expansion in the form of a $3 billion budget for the coming year. House and Senate spending bills provide FDA with $2.3 billion in appropriated funds plus some $600 million in user fees. The legislators specify increases in funds for generic drug approvals and instruct FDA to use much of the added money to increase inspections of food and drug operators, examine more imports, upgrade lab equipment and improve information technology.

There are special earmarks for research on food-borne contaminants, neuroblastoma, dietary guidelines and the impact of Risk Evaluation and Mitigation Strategies for drugs. The Senate bill earmarks $18 million for the Critical Path Initiative, along with research on tropical diseases, tuberculosis treatment, antibiotics and the bioequivalence of anti-epileptic drugs.

Differences in the specifics will be ironed out this fall, with an eye to approving final agency funding before the new fiscal year begins Oct. 1 – a major accomplishment after years of missed funding deadlines.

One lead initiative is to define FDA’s “global footprint” for dealing with food safety and drug and medical product development on an international basis. Establishing overseas offices is just one aspect of developing a comprehensive strategic approach to addressing global health issues, Hamburg explained. These hubs provide more on-the-ground understanding of local developments and will permit more “nimbleness” in a crisis, she pointed out. But FDA also needs to develop partnerships with sister regulatory agencies to promote harmonization and provide assistance and capacity-building in countries with less developed regulatory frameworks.

Tackling tobacco
A high priority for FDA is to develop a framework for regulating tobacco products. Hamburg feels strongly that FDA, as a science-based public health regulatory agency, is the appropriate organization to address the “important public health problems” raised by tobacco use. The agency is still developing staffing plans and the rollout for a new tobacco center, but Hamburg believes that the new legislation provides the necessary tools and authorities, and does not “overload the plate” at FDA. She does not expect to take resources from other areas to support tobacco regulation, or that broader organizational changes will be needed.

Despite the heightened focus on food safety and tobacco regulation, the drug and medical product area is crucial to FDA’s mission, Hamburg emphasized, adding that “I do not see us stepping away from that important component.” She regards industry as “absolutely key partners in what we do” and aims “to get more involved in issues of innovation and in providing swift reviews of new products.” This a good time, she feels, to take a new look at the Critical Path Initiative and at how FDA can leverage emerging science and technology to strengthen new product development and review, as well as postmarket surveillance and product communication.

In the marketing and promotion area, Hamburg said she “cares deeply about making sure consumers get access to appropriate and adequate information about the choices they need to make.” Yet she is concerned that in a world with such a wide array of media outlets such as blogs, Web sites, and 24-hour cable TV, “it is very easy for inaccurate information to get out there. We have a real responsibility to make sure that where we have authority and opportunity, we provide the clearest and most accessible public health message possible.” Hamburg wants to work more with drug companies and advertising firms to ensure that any information on medical products is accurate and reliable and reflects available scientific data.

Hamburg also anticipates a closer working relationship with the Centers for Medicare and Medicaid Services (CMS) to help move medical products “out of the review process and into the market place.” Early discussions can help CMS understand what new products will emerge, and which may enable them to streamline their own procedures for review and reimbursement, she explained.

The commissioner recognizes the importance of having the resources to attract and retain the expertise needed to accomplish these many goals. She hopes that her leadership will be marked by a “strong and clear emphasis on science-based decision making.” If there’s a question about the safety or efficacy of a drug on the market, though, “I will not have any hesitancy about examining it closely,” she warned.

Setting up a new tobacco center will take some juggling, Hamburg acknowledges, but it is a high priority. How FDA takes on these new responsibilities will be looked at as a measure of FDA’s leadership. “FDA needs to make significant strides in order to accomplish its mission in a global world,” said Hamburg