Posted 03 July 2017
By Michael Mezher
Despite being consistently ranked among the world's fastest regulators, the US Food and Drug Administration (FDA) is often criticized for being slow and bureaucratic.
In an analysis published in The BMJ last week, Thomas Marciniak, a retired team leader within FDA's Division of Cardiovascular and Renal Products, and Victor Serebruany, a professor at Johns Hopkins University, attempt to debunk some of these claims.
"This crude depiction ignores industry's contribution to the clock after clinical trials are completed but before the FDA receives the formal application," they write.
Instead, the authors argue that there's little room on FDA's end to speed the review of new drugs.
"It may be possible to accelerate drug approvals in other ways, such as changing processes earlier in the development programme, before the end of the pivotal trials," they write, while cautioning that lowering FDA's standards to speed reviews "may prove costly for patients and healthcare budgets."
The authors reached their conclusion after looking at the submission and review timelines for the 15 novel cardiorenal drugs reviewed by FDA between 2011 and 2015.
On average, drugmakers took 12 months, with a median of eight months, to submit a new drug application (NDA) for novel cardiorenal drugs between 2011 and 2015.
But, the authors say this time was highly variable across submissions, with a standard deviation of 12 months. In a few cases, submissions took more than a year after pivotal trials wrapped up to be sent to FDA, and one drug, Corlanor (ivabradine), was submitted to FDA 51 months after completing its last pivotal trial.
While much of this time is spent performing data analysis and writing up the trial report for the submission, the authors point to Eliquis (apixaban) and Xarelto (rivaroxaban), both of which were submitted to FDA just four months after completing pivotal trials, as examples where industry could improve its efficiency.
On FDA's end, the authors break up the review time into two segments: the agency's scientific review and decision to approve or reject the application.
Here, the authors found that FDA largely met its review goals under the Prescription Drug User Fee Act, taking an average of seven months to complete the scientific review for new drugs plus three months for agency management to reach a decision to approve or reject the drug.
However, the authors found there was much less variability in the length of time FDA took for both these parts of the review, with a standard deviation of two months for FDA's scientific review and one month for its management's decision making.
The authors also found that resubmissions were the only area where FDA added significant amounts of time to the approval timeline. But, while applications that required resubmission took 50-100% longer than other applications to be approved, the authors say it's a blurred line in terms of who's responsible for the delays.
"On the one hand, the drug sponsor should have identified the trial problems before submission and acted on them. On the other hand, closer collaboration between the sponsor and FDA during the initial submission might have facilitated first round approval," they write.