approximately four years earlier, as there isalways a delayed effect between the reviewprocess and ultimate approvals. As such, thisyear’s numbers might not say much aboutapproval rates in the future.

Henry Miller, a research fellow at theHoover Institution at Stanford Universityand a former director of the FDA’s Office ofBiotechnology, is blunter: he says trying topredict end-of-year numbers or even ratetrends on the basis of mid-year approvals is nothing more than hand waving.A doubling from mid-point can’t beassumed, he says. He also says that recentannual approval numbers represent too smalla sampling to show a reversal in an overalldecrease in approval numbers since 1996.

A more important long-range predictivenumber, say Miller and Flockhart, is the number of unfilled permanent positionsin top FDA positions, including ‘acting’designations for commissioner, deputycommissioner for operations, and directorand deputy director positions in CDER.

This is “not a healthy situation,” saysMiller, arising from the “refreshing but notaltogether forthright” approach of formercommissioner Mark McClellan, who left inMarch this year. “McClellan denied that the FDA had a problem and emphasizedcommunication with industry,” says Miller.“That’s not what’s needed. What’s needed is a stick to whip the FDA’s risk-aversivepersonnel into a less defensive posture,”as this causes unnecessarily long waits forapprovals. That stick, he says, is leadership.

As a permanent leader, McClellan didspur some movement within the FDA ranks for getting approvals made faster,admits Miller. His influence could be seenlast December, at a time of year when there is a characteristic increase in thenumber of approvals relative to othermonths. December 2003, by contrast,saw only one approval. “The approverswere trying to look good for McClellan [in 2003], and by December there wasnothing left, no applications languishing

that just needed external impetus to getout,” says Miller.

FDA spokesperson Larry Bachorik saidthat the FDA is actively searching forcandidates, and acting commissioner LesterCrawford has been conducting interviews.But there is no time limit for when theacting positions must be filled permanently,so it is “hard to say” when the positionsmight be filled. The commissioner positionis appointed by the White House and thenconfirmed by the Senate, so it will be up tothe president to advance a name for thepermanent position. As this is an electionyear, it is generally thought that even thesearch for a new commissioner will bedelayed until after the identity of the nextadministration is determined.

But will this be too long a hiatus?Maintaining the momentum initiated by McClellan requires a permanentcommissioner, says Flockhart. “‘Acting’ is a major problem. A good commissioner canlead industry in innovation. Not filling [the position] is criminal.”

N E W S & A N A L Y S I S

NATURE REVIEWS | DRUG DISCOVERY VOLUME 3 | AUGUST 2004 | 637

Mid-year at the FDA highlights permanentproblem

Ken Howard

The sigh of relief given by the industry atthe slight upturn in the number of approvalsof new molecular entities (NMEs) in 2003became somewhat muted with the departureof the FDA commissioner, who is widelycredited with trying to make the approvalprocess more efficient. So, can anyconclusions be drawn about the slight dip inNMEs and biopharmaceuticals now underthe remit of Center for Drug Evaluationand Research (CDER) that have beenapproved at the midway stage in 2004 —thirteen drugs — compared with fourteenat the same point in 2003?

One disappointment is that the degree of innovation that shone through the list of approvals in 2003, which included drugssuch as enfuvirtide (Fuzeon; Roche/Trimeris), gefitinib (Iressa; AstraZeneca)and bortezomib (Velcade; Millennium)does not appear to have been maintained in the drugs approved so far this year.(For a full list of approved drugs, seehttp://www.fda.gov/cder/rdmt/)

Apart from that, there are not manyconclusions that can be drawn from thesefigures, according to industry watchers.

On the face of it, the approval numbersare a movement in the right direction, saysDavid Flockhart, professor of medicine andpharmacology at Indiana University Schoolof Medicine. But the current approvalsreflect what the FDA was doing

Approval numbers at this stage tell less of a story than the pitfalls of a potential leadership vacuum.

Henry Miller: the number of ‘acting’ positionsis not a healthy situation for the FDA.

David Flockhart: approval numbers are a stepin the right direction.

For more news and analysis go to

www.nature.com/news

“‘Acting’ is a major problem. A good commissioner can leadindustry in innovation. Not filling[the position] is criminal.”