FDA Needs Rescuing Now, Former Chiefs Say
Donna Young

WASHINGTON, DC, 26 February 2007 — After years of financial and resource privation and being stuck in a "Bermuda Triangle of continuing resolution," now is the time for Congress and the Bush administration to rescue FDA, said Donald Kennedy, the agency's commissioner 1977–79.

FDA's credibility has been damaged in recent years, he said, partly because of the lack of consistent leadership at the agency and also because of some "unpleasant surprises," such as Merck's sudden withdrawal of Vioxx from the worldwide market in September 2004.

Revelations of conflicts of interest by agency personnel—specifically former FDA commissioner Lester Crawford, who pleaded guilty in October 2006 to charges that he falsely reported ownership of stocks in companies regulated by the agency—and members of FDA drug advisory committees have also brought into question the agency's ability to regulate medications, said Kennedy, editor of Science, the journal of the American Association for the Advancement of Science.

"I also am concerned even more deeply about the tendency of political appointees and officials to rework or reinterpret scientific findings in the pursuit of particular policies," he told an audience at George Washington University in Washington, D.C., which hosted a panel discussion on February 21 with four former FDA commissioners.

"There's a pretty important cart–horse relationship between science and public policy, and the science horse ought to go first," Kennedy contended. "I think the public is concerned and eventually disillusioned when it appears that the public policy cart is coming first."

FDA "lost a lot of credibility" when it failed to take an advisory committee's advice in December 2003 to make Barr Pharmaceuticals' emergency contraceptive Plan B available without a prescription, said David Kessler, the agency's commissioner 1990–97.

Barr in April 2003 sought a change in Plan B's marketing status from prescription to nonprescription without an age restriction.

However, FDA refused that request and issued a "not approvable" letter on May 6, 2004, stating that the company's supplemental new drug application did not contain data demonstrating that the product was safe and effective as a nonprescription drug for women under age 16 years.

Barr submitted an amended application in July 2004 asking FDA to make the drug available without a prescription to women ages 16 years or older.

But on August 26, 2005, Crawford announced that while FDA had concluded that the scientific data were sufficient to support the safe use of Plan B as a nonprescription drug for women 17 years of age or older, the agency was indefinitely delaying taking action on Barr's amended application.

Some lawmakers and consumer groups criticized FDA's postponement of the Plan B decision as a political move rather than a judgement based on science.

On August 24, 2006, FDA announced it was granting nonprescription marketing approval to Plan B for consumers ages 18 years or older.

"If you are going to do something for political reasons . . . at least say that you are doing it for political reasons. Come out, and admit it. Don't do it undercover. Don't put it in the guise of science. You lose credibility," declared Kessler, dean and vice chancellor of medical affairs at the University of California-San Francisco School of Medicine.

FDA's decision-making process is "clearly based in its legal framework," said Jane Henney, the agency's commissioner 1999–2001, but it rests "soundly on the bedrock of scientific evidence."

If there is "even a perception" that FDA's regulatory decisions are not based on science, said Henney, senior vice president for health affairs at the University of Cincinnati in Ohio, "we must do everything we can to turn that around."

The administration, said Frank Young, the agency's commissioner 1984–89, needs to "avoid not only the political meddling, but the lip service." Congress, he added, needs to stop "grandstanding" at hearings.

He called on lawmakers and the administration to work together to provide FDA with stronger enforcement authorities and more funding and resources.

Henney agreed, stating that lawmakers should "not just give this agency more mandates but more resources to do what Congress wants and what the public expects."

The agency's scientists, said Young, chief executive officer of Washington, D.C.-based Cosmos Bio Life Sciences Alliance, should also be provided with adequate training.

"Any discussion of the improvement of FDA without focusing on the professional needs of the people within the agency is a bankrupt suggestion," he said.

The agency's drug reviewers, Young added, should work closely with any scientists at the National Institutes of Health (NIH) who may have been involved in the early development of a medication that is under review by FDA for marketing.

FDA scientists reviewing the postmarketing safety of drugs should also collaborate on information with NIH researchers studying medications, he added.

Congress, Young said, should make the FDA commissioner position a six-year term—a recommendation made by the Institute of Medicine in September 2006.

He called the frequent turnover of commissioners in the past six years "shameful."

"You cannot run an agency in that fashion," Young asserted.

Many of FDA's neglected needs, said Kennedy, are the same as those that have been ignored by Congress and the various administrations since he served as commissioner 30 years ago.

Most prominent among those needs, he said, is an effective national epidemiologic system for tracking and analyzing adverse drug events.

"We don't have anything close to it," Kennedy maintained, noting that FDA has relied on postmarketing data from large insurers like Kaiser Permanente to track safety problems with many drugs, including Vioxx.

Kennedy said he opposes FDA's use of user fees to support the agency's process for reviewing applications for new drugs and biologicals.

"I don't think it's the right way for Congress to exercise its responsibility to all of the people," he argued.

The Prescription Drug User Fee Act (PDUFA)—passed by Congress in 1992, and amended and reauthorized in 1997 and 2002—is due to expire in September unless lawmakers decide to reauthorize it.

Kessler, who was commissioner at the time PDUFA was first enacted, said he thinks that the problems affecting the nation's drug approval and postmarketing safety evaluation processes are "more fundamental" than the issues currently being raised about FDA's use of user fees.

The debate about the nation's medication supply should not be focused on safety, he said, rather, it should be about the right drug, for the right person, for the right disease, at the right dosage.

"The notion that there are going to be drugs that we're going to be able to come up with and have millions and millions of people take safely, the blockbusters, that's the thing that's gotten us into trouble," Kessler said.

"If you try to sell drugs or develop drugs for millions of people for whom a certain percentage are going to benefit but not the vast majority, and they are powerful pharmacological agents, and you have Dorothy Hamill out there doing ice skating and telling you that you are going to be just fine, what do you think is going to happen? Of course there are going to be serious adverse reactions," he said.

Regulators, the pharmaceutical industry, lawmakers, and the public, Kessler said, need to engage in a serious discussion about the economics involved in supporting the current mass-marketing system for drugs, which, he said, is "not a sustainable model."

Kessler said he was "very much opposed" to direct-to-consumer (DTC) advertising while he was commissioner. He noted that the agency loosened its rules on DTC commercials shortly after he left FDA in 1999.

But, Kessler said, DTC advertising has diminished the pharmaceutical industry's credibility and put drug makers "into the cross hairs" of public criticism.

He said many members of the pharmaceutical industry have told him "quietly" that "they regret DTC advertising and wish they weren't in the game."

Although the "genie is out of the bottle" on DTC commercials, Kessler said, FDA and lawmakers need to work with the pharmaceutical industry to place limits on the advertisements so that medications are not marketed as "just another commodity."