Changes at FDA and Challenges on Capitol Hill

One of the last acts of Congress in 2010 was to approve sweeping food safety legislation. The new law provides the Food and Drug Administration with more authority to recall and monitor food products, boosts its inspection force, and strengthens its capacity to halt unsafe imports. This may be the last time for a while that the legislators bolster FDA's oversight capabilities or authorize added resources. With Republicans taking over the House last month and increasing their clout in the Senate, Congressional leaders are contemplating broad federal budget cuts and much more aggressive oversight of administration health policy and regulatory programs. FDA is a prime target as agency critics move to examine an apparent slow-down in new drug approvals and the agency's difficulties in keeping violative products off the market. It's not clear that Congress will even provide the $1.4 billion over five years to hire some 2,000 additional FDA inspectors for the new food safety program.

Jill Wechsler

Similar legislation to strengthen drug safety, moreover, is not likely to move forward in the near future. House Democrats have proposed a bill giving FDA additional enforcement tools over drugs and biologics, including mandatory recall authority, stiffer civil and criminal penalties and authority to subpoena records related to drug violations. But there's not likely to be any action on the measure before 2012 when Congress will face a deadline for renewing prescription drug user fees.

Probing FDA

Meanwhile, new Republican committee chairmen in the House are preparing for extensive oversight hearings on administration healthcare policy and regulatory initiatives. The head of the House Committee on Oversight and Government Reform, Darrell Issa (R-Calif.), has called FDA a "broken bureaucracy" and put the agency on his priority investigation list. Issa was highly critical of FDA officials and pharma executives at hearings before the committee last year on delays in drug recalls by Johnson & Johnson's McNeil unit. Now as panel chairman, he plans to hold FDA officials accountable for such regulatory lapses. In December, Issa sent FDA Commissioner Hamburg a letter questioning FDA oversight of a J&J contract manufacturer and of pharma contracting practices in general. FDA's Office of Criminal Investigations also may draw scrutiny following strong criticism of its operations from Congress' Government Accountability Office (GAO).

Similarly, House Energy and Commerce Committee chairman Fred Upton (R-Mich.) is preparing to scrutinize the administration's health reform legislation, along with "job-killing regulations" that block technological innovation and wasteful programs that warrant budget cuts. FDA approval programs and research policies are fodder for the E&C Health subcommittee, headed by Rep. Joe Pitts (R-Pa.) and Mike Burgess (R-Tex.). In addition, the E&C subcommittee on oversight and investigations may continue the panel's probe into FDA's failure to adequately monitor foreign drug production and clinical research operations.

FDA's progress in creating an approval pathway for biosimilars is another issue of great concern to legislators from both sides of the aisle. E&C members who crafted the reform provision and several Senators involved in the legislation have sent letters to Hamburg clarifying the 12-year data exclusivity provision. The law does not provide for 12 years market exclusivity, they emphasized, and is designed to prevent sponsors from obtaining additional "next generation" patents based on minor product changes.

Changes at FDA

At last year's House hearings on J&J's manufacturing problems, FDA was represented by Principal Deputy Commissioner Joshua Sharfstein, who won plaudits for his command of the issues and knowledge of FDA operations. Now someone else at FDA will have to fill the hot seat at Congressional hearings, following Sharfstein's surprise departure from the agency last month.

Sharfstein was lured away by an offer to head Maryland's health department, a move that capitalizes on his public health roots as Baltimore's health commissioner. In shifting to the state agency, Sharfstein will manage a $7 billion budget and will be involved with implementing the many health reform policies that require state involvement, such as Medicaid expansion and formation of new health insurance exchanges.

At FDA, Sharfstein helped engineer a get-tough compliance policy designed to curb perceptions that FDA was too cozy with industry. The stronger enforcement stance has produced more warning letters citing manufacturing, marketing, and clinical research violations, as well as more criminal investigations of industry. Sharfstein also was involved in strengthening FDA's medical device approval process, a high-profile exercise that remains ongoing, and he was a strong advocate for drug safety and tight curbs on the use of more risky medicines, such as the GlaxoSmithKline's diabetes drug Avandia (rosiglitazone).

Hamburg is using Sharfstein's departure as an opportunity to re-examine the agency's top management structure. Previous commissioners have tried various organizational models, with multiple deputy commissioners and chiefs of staff, and Hamburg may move away from the one-deputy arrangement. Counselor to the commissioner John Taylor is filling Sharfstein's shoes while Hamburg weighs her options, and he is likely to assume a more visible role at the agency in the future. Taylor has had a long career at FDA in legal, enforcement, and regulatory affairs positions under several FDA commissioners during both Democratic and Republican administrations. He rose to be Associate Commissioner for Regulatory Affairs from 2002 to 2005 and then served brief stints at Abbott Laboratories and with the Biotechnology Industry Organization. Taylor returned to FDA in 2009 to be Hamburg's top legal advisor, and the commissioner might very well prefer to have a seasoned enforcement official represent the agency before Congressional committees probing regulatory and safety issues.

More transparency

One of Sharfstein's last official acts at FDA was to unveil the third phase of the agency's transparency initiative, a program he headed as chair of its Transparency Task Force. Launched in June 2009, the initiative has created an FDA Basics web page that presents broad information on agency operations and public health policies. Another innovation is the FDA-TRACK program, which provides the public with measures of the performance and accomplishments of multiple agency offices and regulatory activities.

This latest segment of the project aims to provide sponsors with useful information on FDA policies and procedures. Most of the proposals raise few concerns: FDA will post more information on key staffers and meeting presentations, and will provide a system to answer industry questions quickly. To improve the drug application review process, FDA will clarify standard operating procedures for staff meetings with sponsors about applications, the types of notifications provided to sponsors, such as those for mid-cycle review meetings, and how it informs sponsors whether the review of an application is on track to meet the target action date. A related initiative is to explain the agency's system for developing new guidances and regulations. Still under review are several more complex draft policies, such as whether to set specific timelines for guidance development and how to handle sponsor requests to appeal agency decisions.

More significant for industry is FDA's rejection of two other proposals. The agency decided it will not issue binding advisory opinions on the legality of company marketing and communications activities, as sought by industry and similar to practices by the HHS Inspector General and the Federal Trade Commission. FDA says that it will continue to provide advice on whether pharmaceutical promotional pieces meet regulatory standards, but retains the right to change its opinion later on.

FDA also won't commit to notifying companies in advance of publicly disclosing information about the safety of a regulated product. The agency will try to discuss emerging quality problems with the manufacturer, and the Center for Drug Evaluation and Research still aims to notify sponsors at least 24 hours in advance of plans to post drug safety information. But FDA retains the right to post information about a safety issue before consulting with the company if necessary to protect public health.

Moreover, Sharfstein is leaving FDA without resolving the most contentious disclosure proposals under review by the transparency task force. A May 2010 report on phase two of the initiative sought comments on proposals to make public a broad range of confidential regulatory information, such as when a manufacturer files an investigational application and whether such an application is put on hold, withdrawn or terminated [see Applied Clinical Trials, " View from Washington," July 2010]. FDA also is considering whether to disclose when a company submits a market application for a new drug, biologic, generic drug, or medical device, and if such applications later are withdrawn or abandoned. Most controversial is whether to make public refuse-to-file or complete response letters.

Those issues raise "very interesting legal issues" as well as additional resource requirements, Sharfstein explained at his last FDA media briefing. Agency teams are assessing dozens of comments on these proposals, but a resolution is not expected anytime soon.

Jill Wechsler is the Washington editor of Applied Clinical Trials, (301) 656-4634 jwechsler@advanstar.com