A Bigger, Bolder Agency

When a salmonella contamination hit pistachio nuts a few months ago, FDA moved quickly to recall products and shut down processors. These days, officials are sending out more warning letters, as well as taking bolder enforcement actions and a more proactive approach to health emergencies such as swine flu. Make no mistake: There's a new sheriff in town, and principal deputy commissioner Joshua Sharfstein set the tone early with several high-visibility actions pending confirmation of Margaret (Peggy) Hamburg for the top spot. Their task is now to restore the agency's image, both with the public and at its new White Oak, MD, campus.

Jill Wechsler

Since coming to FDA at the end of March, Sharfstein has promised aggressive action to ensure food and drug safety; he responded to criticism of FDA's process for regulating medical devices by supporting a review of research requirements for device classes. During the same period, FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) sent letters admonishing 14 drug companies about their inappropriate use of sponsored links on Internet search engines such as Google. The criticism comes from presenting information on drug benefits on an initial posting while requiring at least one click to disclose risks. Marketers contended that FDA was ignoring the communications capabilities of Internet technology, but consumer advocates cheered the policy as necessary for balancing information on drug risks and benefits.

During the swine flu outbreak, Sharfstein authorized emergency access to antiviral drugs and diagnostics, and established response teams under the guidance of Jesse Goodman—the newly named deputy commissioner for scientific and medical programs and acting chief medical officer at the agency—to facilitate development of new vaccines, antivirals, diagnostics, and other products needed in a pandemic. (See "Science and Swine Flu, page, 22.) FDA moved quickly to approve Sanofi Pasteur's new vaccine manufacturing facility in Pennsylvania, and threatened fines and criminal action against anyone seeking to tap into public fears by marketing products that made unapproved claims about preventing or curing influenza.

Visible support

Congressional leaders are also seeking to bolster FDA leadership and authority. The Senate moved quickly to confirm Hamburg as FDA commissioner last month, stressing the need for a strong agency to deal with food and drug safety issues. At a very friendly confirmation hearing before the Senate Health, Education, Labor and Pensions (HELP) Committee, Hamburg promised to tackle the challenges arising from the globalization of food and drug production, to strengthen FDA's science base, to review flu vaccine options, and to balance innovation with regulation. She emphasized that she would be the FDA commissioner, and not hand responsibility for drugs off to Sharfstein, as some had speculated. She also displayed some feistiness in her hearing, maintaining that FDA "is the appropriate agency to regulate tobacco," despite objections from Republicans about giving that task to an organization charged with ensuring public health.

Hamburg and Sharfstein are starting out with strong backing from the White House, from Health and Human Services, and from leading legislators on both sides of the aisle. FDA's leaders will be visiting Capitol Hill frequently in coming months to justify their budget requests and discuss a number of reform proposals currently on the table. Several bills seek to expand global inspections of food and drug producers, and would give FDA added enforcement authority to retain suspect products, issue subpoenas, and expand manufacturer registration. Bill sponsors have proposed additional user fees on food processors and importers to support these activities—a move opposed by some food companies as well as some farm-state legislators.

Science and Swine Flu

Despite concerns about drugs from overseas, some legislators continue to press FDA to take steps to ensure the safety and quality of less costly prescription drugs available abroad. The 2010 budget proposal includes $5 million to support FDA planning for a safe importation program with the aim of making this long-debated policy a reality.

The Obama administration's determination to reform the nation's healthcare system will involve FDA in a number of issues. The potential for savings from the speedier approval of generic drugs and from authorization of follow-on biologics will put those topics on the front burner, and proposals to curb DTC advertising are likely to resurface, particularly if analysts can demonstrate that marketing curbs would reduce spending and enhance the safe use of medicines.

Hamburg and Sharfstein should get some help in dealing with Congress from new senior counsel David Dorsey. Formerly a top staffer to HELP Committee chairman Edward Kennedy (D-MA), Dorsey played a lead role negotiating bills to authorize user fees, pediatric studies, and the FDA Amendments Act (FDAAA) of 2007, as well as working closely with Kennedy on his proposal for authorizing biosimilars.

Building on FDAAA

Current legislative proposals would enhance FDA enforcement powers beyond the increased fines and criminal penalties authorized by FDAAA. So far, FDA has not brought a case under this new authority, but "when we need to use it, we will," said Deborah Autor, director of the Office of Compliance in FDA's Center for Drug Evaluation and Research (CDER).

"Enforcement will increase," she promised at the April annual meeting of the Food and Drug Law Institute (FDLI).

Autor pointed to a rise in injunctions, investigator disqualifications, and warning letters, and advised companies to avoid getting the agency's "big stick" by being proactive about compliance. In five years, her staff has grown from 150 to 250, increasing its capacity to take regulatory action. As of April 14, 2009, CDER had issued almost 40 warning letters—that's nearly half the 87 sent out in all of 2008. Autor cites the agency's speedy action in halting production and requiring recalls due to repeat manufacturing violations by KV Pharmaceuticals. Similarly, the agency moved quickly to close down Coast IRB following revelations that this independent review board had approved a fictitious study presented in a sting operation by the Government Accountability Office. Data integrity also is important, Autor said, advising due diligence by companies involved in corporate mergers and acquisitions to verify the quality of submissions to the agency.

In addition, FDA's campaign to remove unapproved drugs from the market remains a high priority. Even though this effort has affected over 200 manufacturers and involved actions against 12 classes of drugs, "we still see industry as somewhat complacent," Autor said. She stressed that manufacturers must understand that FDA approval is imperative for all drugs.

Globalization of drug manufacturing and product testing is another issue that further stresses FDA oversight capacity. Foreign drug manufacturing sites now exceed registered domestic facilities, and the volume of drug products made overseas continues to rise. FDA is boosting staff in its overseas offices, and plans more aggressive monitoring of foreign operations and tactics (such as Chinese "show" and "shadow" factories—a clean facility presented to FDA inspectors that masks production at a shoddy plant). However, the agency emphasizes that manufacturers are wholly responsible for the ingredients and the quality of their finished products. "Look for red flags," Autor advised. Lax regulation in a market or a significant decline in an important ingredient may be open invitations to dishonest behavior.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com