Skip to content

Pink Sheet – Breakthrough Denial Doesn't Mean US FDA Won't Bring Full Resources To Application

Pink Sheet – Breakthrough Denial Doesn't Mean US FDA Won't Bring Full Resources To Application

Executive Summary

Agency staff discuss how they offer early development advice to sponsors before a breakthrough decision is made and reassure them if the status is denied.


Sponsors may desire breakthrough status because of the perks that come with it, but US FDA officials said promising non-breakthrough products also could receive a lot of attention to speed them to market.


Billy Dunn, director of the Office of Neurology Products, said his staff does not approach an application differently whether or not it obtains breakthrough status.


“Breakthrough status itself doesn’t really influence the vigor with which we approach a promising therapy,” he said during the recent Biopharma Congress IV, sponsored by Prevision Policy and the Friends of Cancer Research. “Our goal is efficiency. It’s not dogma. … Whether you’re breakthrough or not, you’re going to get that attention.”


Breakthrough product status is intended to allow FDA more involvement early in the development process to potentially help it reach the market faster. To qualify, a product must show preliminary clinical evidence that it may be a substantial improvement over existing therapies.

Dunn Sometimes Reassures Sponsors Who Don’t Obtain Breakthrough Status

Dunn made clear that he was not disparaging the breakthrough program. But he added that the neurology division does not include diseases not considered serious or life-threatening. He said most applications received by the division need the added involvement from FDA staff.


“What I’m bringing up is not criticism at all,” Dunn said. “It’s something that I often reassure sponsors about, which is that although the regulatory threshold for breakthrough designation may not have been reached in certain circumstances, there’s a much broader look at what may be promising about that program and we bring all resources to bear on that.”


The agency’s bar to be named a breakthrough is high, although some have said it is not high enough. (Also see “FDA’s Breakthrough Bar May Be Set Too Low, Jenkins Says” – Pink Sheet, 30 Jun, 2016.)


With the program growing, some stakeholders have asked whether it could be expanded to speed more product reviews. (Also see “PDUFA VII Already: Could Breakthrough Ideas Apply Outside Program?” – Pink Sheet, 26 Aug, 2016.)

Breakthrough May Not Be Fastest Route To Approval

Reminding sponsors that FDA may not necessarily treat a non-breakthrough product differently could be another attempt at slowing the growth of the program, which is resource-intensive.


Dunn appeared to question whether a likely breakthrough product should always apply to enter the program. He said sometimes the effort needed to request the status may actually slow development and approval.


“I don’t want that team that’s responsible for developing this promising drug to spin their wheels in putting the breakthrough package together, because then it will be reviewed by my team who’s responsible for that, taking them away from reviewing the rest of your [data], getting that going as efficiently as possible,” he said.


Dunn said the neurology division makes “very liberal use of the request for preliminary breakthrough advice,” which allows sponsors to gain some insight on whether breakthrough is possible.


“When it’s appropriate we want that package to come in, but that preliminary advice for them I think is very useful and our sponsors have been very receptive to pretty direct feedback about whether they’re going get across the finish line or not for breakthrough,” he said.


James Smith, supervisory medical officer in the Office of New Drugs immediate office, added during the conference that the review division can use the preliminary advice session to give the sponsor hints about where problems may lie in the request.


“The review division can highlight whether or not there are potential sticking points about whether or not something would meet breakthrough based on very preliminary data that we see during that informal [teleconference] and say when you’re putting the package together focus on this because that’s where our question is going to be,” Smith said. “That can really speed efficiencies on both sides.”


FDA created a short form to ask for preliminary breakthrough advice, which also was an attempt to reduce the burden of the program on the agency. (Also see “Breakthrough In Two Pages: FDA Offers Preliminary Advice” – Pink Sheet, 23 Mar, 2016.)


Breakthrough became so popular that FDA was concerned about the resources it required and decided to dedicate revenue from the prescription drug user fee program to hire more reviewers to help deal with the applications. (Also see “FDA’s Breakthrough Workload Will Be Eased By Hiring Reviewers With PDUFA VI Funds” – Pink Sheet, 20 Jul, 2016.)…