Any day now. Almost.
That is, any day now, the creakingly slow mode of the FDA and what seems to be its increased willingness to delay approvals might get fixed, or be on its way to getting fixed.
A new leader for the agency might be appointed. And a revised version of the Prescription Drug User Fee Act (PDUFA) might be approved, which by itself could add to the overworked agency's coffers and speed things up.
In fact, both must happen. But "any day" won't mean next month, or the next, or the next.
PDUFA, enacted in 1992 and first revised in 1997, expires in the fall of this year, which means more pressure on Congress to take steps to ensure PDUFA keeps going for another five years.
As for an FDA head, without which the agency has clomped along for more than a year, two names are hot: Lester Crawford, a veterinarian, who heads Virginia Tech's Center for Food and Nutrition Policy in Alexandria, Va.; and Alastair Wood, vice chancellor and professor of medicine and pharmacology at Vanderbilt University in Nashville, Tenn.
The world of biotechnology could be dealing either with the animal doctor Crawford or with the Republican-sponsored university man Wood, whose post-marketing surveillance position has won the favor of consumer watchdog group Public Citizen. Or, of course, it could be dealing with somebody else entirely although insiders tend to whisper much about Wood (who also is a medical doctor).
Having one warm body or another in the commissioner's chair seems likely to move the approval process for drugs along. The whole idea of PDUFA originally was to jump-start the agency's bureaucratic work, thereby getting treatments to patients sooner rather than later even if not every activist organization agreed with the means.
Approvals since 1992 have been moving faster, at least until 1999. The median time for approval fell from 23 to 11.6 months during that period. But in 2000, it rose 34 percent to 15.6 months. Of 27 drugs that won the FDA's nod in 2000, more than half had been filed before 1998, noted a report by S.G. Cowen Securities. (See BioWorld Financial Watch, Aug. 20, 2001.)
Last month, the FDA reported on its 2001 approvals, breaking them down into two categories. The agency said the Center for Biologics Evaluation and Research (CBER) reviewed 16 biologics license applications (BLAs) in a median time of 13.8 months and approved them in a median time of 20.3 months. Two, classified as priority products, were reviewed in a median time of 11.5 months and approved in 13.2 months.
The agency compared what it called "complex" BLAs to the new drug applications (NDAs) reviewed by the Center for Drug Evaluation and Research (CDER). Last year, the FDA approved 66 NDAs, including 10 priority products that made it through in a median time of six months. The median review time for the others was 12 months, and there was a median of 14 months for approval.
As the FDA and any business owner will be quick to declare, more efficiency demands more money.
When the Food and Drug Modernization Act was passed in 1997, it reauthorized user fees and made other changes, setting the bar higher in terms of evaluation times for regulatory submissions.
Approvals may not have cranked up dramatically as a result of adjusting the goals, but "approvability" has been decided in a timely fashion for whatever that's worth.
Letters denoting the agency's "complete response" (that is, demand for more information) often have come just in time to extend the months required to get the drug on the market. Ditto the "approvable" letters, which eat up time with labeling matters, and of course "non-approvable" letters, which may require entirely new clinical trials, as Goldman Sachs noted in a recent report.
Steve Lawton, vice president of regulatory affairs and general counsel for the Biotechnology Industry Organization (BIO), called the report "a very nice summary of information that's already available."
The FDA, Lawton said, is "finding ways to meet the performance goals without, in their view, the resources to meet the spirit of the law which is thorough interaction with the companies, and final review within those [PDUFA-specified] periods."
BIO, the FDA and pharmaceutical representatives are "working very hard in an effort to understand each other's needs and work out a solution," Lawton told BioWorld Financial Watch, adding that "BIO is committed to an early enactment."
That seems vague enough. What does "early" mean?
"June," Lawton said. The Goldman Sachs report estimates the process will take most of 2002.
Passage of a new PDUFA "obviously depends on whether or not Congress thinks it's important to try to restrict the law to PDUFA, or load it up with other FDA issues."
"We're hoping what they'll do is what they did in PDUFA [version one and version two], and that is to consider the user-fee statute on its own." Lawton acknowledged his reluctance to say too much, since negotiations are still under way.
As many have noted, the FDA needs money. The amount it hoped to garner this fiscal year in user fees (collected when new drug applications are submitted at about $300,000 each, and through continued levies on drugs already marketed) has fallen by about $27 million, to $135 million. But the cost of running the agency has continued to rise, so much that the FDA estimates it could run out of user-fee cash before Congress revamps PDUFA.
Not if BIO and others have their way. Lawton said having a chief of the FDA is important (and BIO hasn't taken a position on which candidate would be the best), but "the whole machine doesn't stop" with one.
"I think people get more naturally conservative," he said. "That seems to be the trend. David Kessler [a former FDA commissioner], for example, took the position that some risk is acceptable, as long as the benefit significantly outweighs the risk. That allowed people to have more comfort in their approval decisions," which in turn could make approvals move more briskly through the agency.
But, at the moment, BIO and others are behind closed doors, hashing out the complexities of a new PDUFA, like labor unions and company officials at work on a new contract.
"We're not finished," Lawton said. "We're deliberating, and there's a lot of good faith in the room. Nothing is stalled."