A key point in the debate over renewing the Prescription Drug Fee User Act, or PDUFA, has been the ability of the FDA to review drugs as quickly as possible. Along with the pharmaceutical industry, various members of Congress complain the agency moves too slowly. But a new study in The New England Journal of Medicine contradicts those assumptions and also questions whether the speed of the review process is justified as part of PDUFA reauthorization.
To wit, the study compared first and total regulatory review time among all novel therapeutic applications submitted to the FDA from 2001 to 2010. The upshot? The FDA was approximately two months faster than the other two key agencies - the European Medicines Agency and Health Canada - in issuing approvals. And the FDA was three months faster when examining a sub-sample of therapeutics that had been approved by all three agencies during this time period.
Another interesting point: among therapeutics that had been approved in both the US and Europe, 64 percent were approved for use in the US first. Among those approved in both the US and Canada, 86 percent were approved for use in the US first. As a result, the study authors contend that concerns the FDA has emphasized safety at the expense of efficient approvals is misplaced. PDUFDA, by the way, is up for renewal every five years.
"There are a lot of concerns that FDA has been slowing down, because in the last PDUFDA, safety was emphasized. And so there are concerns that safety is slowing things down," says Joseph Ross, an assistant professor at the Yale University School of Medicine. "But there's not a lot of data is out there. FDA issues reports on performance goals, but they're hard to understand in context. By comparing speed with which FDA is reviewing applications with European and Canadian agencies, we have an ability to benchmark. They serve similar populations and are under similar pressures.
"I think this shows pretty clearly that FDA has not slowed down and is moving at about the exact same speed in this PDUFA period as in the last PDUFA period and, more than that, moving faster than other regulators. But what’s the right speed? I don’t know what that is or what's right or wrong. FDA has to balance these things. But to me, I think the concerns are overstated."
As for the numbers, the authors identified 510 applications for novel therapeutic agents, of which 225 were endorsed by the FDA, 186 by the EMA and 99 by Health Canada. Of these, 289 were unique agents. The median time the FDA took to complete a first review was 303 days, compared with 366 days by the EMA and 352 days by Health Canada. The median total review time was also shorter at the FDA. Among the 289 unique novel therapeutic agents, 190 were approved in both the US and Europe, of which 121, or almost 64 percent, were first approved by the FDA. Meanwhile, 154 were aproved by both the FDA and Health Canada, and 132, or nearly 86 percent, were first approved by the FDA (here is the abstract). Drilling down, the FDA also outperformed the other agencies when reviewing two different therapeutic categories. For cardiovascular, diabetes and endocrine drugs, the FDA median review time was 305 days, compared with 356 for the EMA and 352 for Health Canada. The FDA trailed in total review, though, posting 365 days, compared with 356 for the EMA, although Health Canada posted 472 days.
For oncology meds, the FDA was fasted across the board. When comparing median time, the FDA took 237 days, while the EMA used 384 days and Health Canada needed 345 days. The FDA total time was 264 days, compared with 382 for the EMA and 354 for Health Canada. There were similar contrasts for respiratory and gastrointestinal drugs: median FDA time was 308 days versus 362 for the EMA and 345 days for Health Canada. Total FDA review time was 335 days compared with 362 for EMA and 345 for Health Canada.
Findings were mixed, however, for other categories. For anti-infectives, median FDA time was 275 days versus 348 days for EMA and 245 days for Health Canada. Total FDA review time was 284 days, while EMA took 348 days and Health Canada needed just 245 days. For musculoskeletal and pain drugs, median FDA time was 369 days, while EMA needed 399 days and Health Canada took 411 days. Total FDA time was 431 days versus 399 for the EMA and 478 for Health Canada.
For psychiatric and central nervous system drugs, median FDA review time was 335 days compared with 413 for the EMA and 404 for Health Canada. Total FDA time was 463 days compared with 413 for the EMA and 514 for Health Canada. For all other drugs, the median FDA review time was 303 days versus 345 days for the EMA and 378 for Health Canada. Total FDA review time was 349 days, while the EMA needed 345 days and Health Canada used 402 days.
Ross also pointed out that the study also debunks the notion that drugmakers should seek approval elsewhere first, since he and his colleagues were able to document that, for meds approved in Europe and the US, the available median time was about three months faster in the US. In other words, drugmakers "seem to be going to the agencies at the same time, but their drugs end up becoming available first in the US," he says.
Some numbers: among 289 unique novel therapeutic agents, 190 were approved in both the US and Europe, 154 in both the US and Canada, and 137 in both Europe and Canada. Among meds approved in both the US and Europe, 64 percent were first approved in the US, with the drugs available a median of 96 days earlier in the US. Similarly, among drugs approved in the US and Canada, 86 percent were first approved in the US, and median availability was 355 days earlier in the US.