FDA's Approvable Problem - Pharmaceutical Executive

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FDA's Approvable Problem


Pharmaceutical Executive


Still, not everyone inside pharma sees a conspiracy, or even a controversy, in the new wave of approvable letters. Gretchen Dieck, vice president of safety and risk management at Pfizer, said that to make a fair assessment, you'd have to examine each NDA on its own terms. "The drug development process is long—and not a straight line," Dieck said. "Something can come up, such as new side effects with a class of drugs or new surrogate markers, and the agency will say, 'You need to address this in your clinical trial.' It's not necessarily a matter of negligence on the part of the drugmaker."

Safety, Politics, or Both?


Mark Senak, Blogger
The explanation most often heard for the spike in approvable letters is the obvious one: that FDA has raised the bar for drug safety. This takes account of both the scientific and the political aspects of the issue. Most letters ask for additional data either about a specific "safety signal" or about more general heart and liver toxicity. At the same time, the agency is seen as desperate to rehabilitate its image as a guardian of public health—and, ironically, "above" politics.

"Vioxx and other episodes shook confidence in the agency, and took it from being a gold standard to having a very tarnished image," said Mark Senak, senior vice president at Fleishman-Hillard and EyeonFDA.com blogger. But Senak also points to other factors that likely play a role. "Coinciding with that was the fact that for the past six years, FDA has been rudderless at the top," with a series of short-lived or interim heads until Andrew von Eschenbach's confirmation last spring.

Nor has drug-safety been the only area in which politics has appeared to intervene, Senak point out. The typically hush-hush process of drug approval burst wide open in 2004 during the machinations around the review of Plan B as an over-the-counter "morning after" pill. The acting director of the Center for Drug Evaluation and Review (CDER) sent it back, asking for more safety data related to its use by teenage girls—a decision widely viewed as a sop to President Bush's abstinence-only fundamentalist base. The ensuing protests from scientists both inside and outside FDA raised still-unanswered questions about the degree to which the agency is influenced by the administration's own political agenda.

"Congress began scrutinizing the internal process at FDA," said Senak, "and it saw a lot of things it did not like. Enforcement of regulations was down. People who were not experts but political appointees were inserted into advisory committees. There was a wave of whistle-blowers and a general degradation of morale."

There has been a prolonged and unprecedented public airing of internal disagreements about drug approval, with the drug-safety camp in open strife with the drug-review camp. "The agency has been called out on this by Congress. There have been specific charges that it suppresses safety information, or at least dissent," said attorney Daniel Kracov, head of Arnold & Porter's pharmaceutical practice. "It is a very difficult atmosphere to make tough decisions about drug safety, and this may induce too much caution on FDA's part."

Still, neither Senak nor Kracov believes that there has been a single order from on high to turn the ship around on safety. Speaking for FDA, Dr. John Jenkins, who has headed the Office of New Drugs at CDER since 2002, says there has not been. He emphasizes that each NDA is evaluated individually, and the agency doesn't set a target for how many drugs will be approved each year. Yet he acknowledged that public concerns over drug safety have had an effect. "The calls for having more certainty about safety than may have been required in the past are in the minds of decision makers when reviewing drugs," he said.


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