The "drug lag" is back.

The term--biopharma industry shorthand for the belief that new drugs reach the market faster in other countries (especially in Europe) than they do the in U.S.-- was a common refrain in the late 1980s and early 1990s, and the Prescription Drug User Fee Act of 1992 was intended in part to address the perception that US consumers suffered while FDA reviews dragged on.

Some critics of industry question whether a drug lag ever existed, but there is no denying that the perception of one helped shape the legislative climate for FDA in the first half of the 1990s.

There is also no denying that PDUFA ended even the perception of a drug lag. Indeed, a generation of pharmaceutical industry managers grew up in a world where the industry's largest market (the U.S.) was also its fastest growing market, and the one most likely to grant market entry first.

Well, the U.S. is still the largest pharmaceutical market in the world, but it sure isn't the fastest growing. And, after a decade of scrutiny of FDA's post-marketing safety provisions and the enactment of new legislation expanding FDA's authorities and obligations, FDA is routinely missing PDUFA goal dates for the first time. So some in industry are wondering whether the U.S. will start lagging consistently behind other countries in granting market access.

Question Raised During IoM Meeting

Merck EVP Worldwide Regulatory Affairs & Product Safety Peter Honig is one of those who wonder. He raised the possibility of a return of the "drug lag" during a Sept. 2 Institute of Medicine workshop on drug safety, one in a series of updates on IoM's past review of FDA safety regulation.

The Merck exec didn't press his case hard, but he did prompt a response from FDA's top new drug review manager, Office of New Drugs Director John Jenkins.

There are really "two issues people are raising" about new drug reviews, Jenkins noted. One is the undeniable fact that there are some delays associated with new processes and procedures, like the Risk Evaluation & Mitigation Strategies or "safety first" initiative. Jenkins acknowledges that FDA has "taken on a huge process burden" and "the money has not followed at the same pace as the new responsibilities." So some "lag" may be inevitable, at least until resources and habits catch up with the new workflow.

But, Jenkins continued, that isn't really what people worry about. They worry about whether "FDA is becoming more conservative."

And that, Jenkins said, is very hard to quantify, because "we have lagging indicators." Economists, he noted, prefer to focus on leading indicators, but the only was to tell what is happening with approvals is to look at statistics for various application cohorts, and the data inevitably trail months or even years behind the calendar.

So "the most recent data we have is from fiscal 2008, and you really can't see any kind of fall-off or change that is dramatic for first cycle approvals of new molecular entities."

Hard To Measure Cautiousness

But Jenkins didn't just drop the issue there. "It is hard to quantify if my division directors or my office directors are affected by the drug safety debate that has been raging in this country for the last five or six years." The issue "has calmed down a bit recently," Jenkins said, but "have they been impacted?" Are "they less likely to approve a drug today with the same data package that they might have been five years ago?"

"It is impossible to make that assessment because you just can't answer those questions," Jenkins says. "What you have to look at is the data over time to see if you see any trends."

Jenkins noted that he presented an analysis of recent drug approvals last year (during Elsevier Business Intelligence's FDA/CMS Summit for Biopharma Executives in Washington, D.C.). That data showed seven drugs approved in Europe at that time, but not in the U.S., and only two in the U.S. but not Europe ('The Pink Sheet' Jan. 5, 2009).

But that data is "now close to a year old. We've been looking at it again, but we haven't reported any more recent analyses." (That may change Dec. 3, when Jenkins presents during the fifth annual FDA/CMS Summit.)

But even a clear indication that there are more drugs approved in Europe first may not be persuasive. "There are a handful of drugs approved in Europe that we haven't approved," Jenkins said. "We'd be happy to argue in public why we didn't approve them, but we can't always do that."

One of those drugs, Sanofi Aventis' weight loss agent Accomplia , was ultimately withdrawn in Europe for safety reasons. So, Jenkins said, "Only time will tell: are we being too conservative and depriving patients of needed drugs, or are they being too aggressive and going to run into the same safety buzz saw that we blew through in the 2000 decade."

Time will tell indeed, but we want your opinion: respond to our poll and let us know what you think. Is there a drug lag? And if there is, is it because FDA is too conservative or EMEA is too reckless? Look for the results next week.

-Michael McCaughan (m.mccaughan@elsevier.com)

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