House lawmakers, FDA officials and industry stakeholders all praised the success of the agency’s breakthrough designation in lowering drug development times, and stressed that the pending Prescription Drug User Fee Agreement (PDUFA) will bring important resources to the breakthrough effort. The widespread commitment to the designation at a House hearing Wednesday (March 22) is likely to please FDA Commissioner-nominee Scott Gottlieb, who has proposed sweeping reforms to build upon the breakthrough program, which he has said speeds drug entry to market.

But FDA drug center chief Janet Woodcock also cautioned the program can only be expanded so far. At Wednesday’s hearing, an Energy & Commerce Democrat called on the agency to carry over certain elements of the breakthrough designation to support generic development. Woodcock cautioned such efforts might open the agency up to lawsuits from brand companies.

FDA’s breakthrough designation was created by the Food and Drug Administration Safety and Innovation Act (FDASIA) and allows for expedited development and review of drugs intended to treat a serious or life-threatening disease, and which preliminary clinical research indicates may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Lawmakers were quick to praise the commitment to supporting the breakthrough designation included in the pending drug user fee agreement. “I am pleased that PDUFA VI will continue to build upon the success of the breakthrough therapy program,” E&C health subcommittee Chairman Michael Burgess (R-TX) said in his opening statement.

The PDUFA VI commitment letter promises additional resources for the program to ensure its sustained success. “Additional resources will enable the Agency to continue to work closely with sponsors throughout the breakthrough therapy designation, development, and review processes. Both FDA and the regulated industry are committed to ensuring the expedited development and review of innovative therapies for serious or life-threatening diseases or conditions by investing additional resources into the breakthrough therapy program,” the PDUFA commitment letter states.

Woodcock called the breakthrough therapy “extremely successful” in shortening development times. She noted that the programs become “one of the most popular components of the human drug review program.”

“What I’ll say about [the breakthrough program] is that it is probably the first program that has really shortened drug development. As we’ve all said, drug review isn’t the problem. It occurs now in a timely manner –predictable manner — based on PDUFA. But drug development is still a very gnarly problem. It takes too long and it costs too much and there are many failures. Breakthrough has been the first program actually (where) drug development time has been shortened. And you’ve heard that before this committee from a number of witnesses. (It has taken) several years off of drug development and the overall time it takes to get those drugs,” Woodcock told lawmakers Wednesday.

Development time was 2.2 years shorter for approved breakthrough cancer drugs according to research conducted by Friends of Cancer Research, the group’s President and CEO Jeff Allen told lawmakers Wednesday.

Woodcock said the new prescription user fee agreement will continue to build on that program.

“The PDUFA VI agreement provides dedicated funding to ensure the sustained success of the [Breakthrough] program. Additional resources will enable FDA to increase review staff and to supplement resources for clinical pharmacology, statistics, and product quality. This renewed commitment will enable the Agency to continue to work closely with sponsors to ensure expedited development and review of breakthrough therapies for serious or life-threatening diseases,” Woodcock’s testimony states.

The Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO) also praised the program Wednesday.

“As a cornerstone of the PDUFA V agreement, the breakthrough therapy program has been a profound success. The response to the program has been remarkable–a sign of the swift pace of new scientific advances–and substantially more resource intensive for FDA to manage than anticipated. No additional resources were provided for this function in PDUFA V. PDUFA VI will dedicate significant new resources to the program to ensure that the workload is manageable and patients continue to gain expedited access to treatments for serious and life-threatening diseases that are currently without adequate treatment option,” PhRMA’s testimony states.

Rep. Kurt Schrader (D-OR) called on FDA to apply portions of the breakthrough program to speed development of generics. “Say we are able to encourage a [generic] manufacturer to come to market … once they’re there it would be nice if you use that breakthrough approach that’s been so successful to also hasten things too. To help us encourage them to come to market and be successful, if they knew that breakthrough approach is going to be applied that that might incentive things also,” Schrader said.

However, Woodcock cautioned that such an action may open the agency up to legal challenges. “Sometimes there are unintended consequences…because there’s such a commercial hit that the innovators take when they get a generic competition on the market, that any provisions that they can sue us about or send us citizen petitions or obstruct a process, cause delays and I believe that needs to be taken into account as you think about incentivizing,” Woodcock said.

Gottlieb, who has been a frequent critic of FDA’s review process, has praised the breakthrough designation, particularly as it has been used by the agency’s oncology center.

“I believe better science and better drugs, at least as it relates to the oncology division, instigated a lot of FDA’s regulatory adjustment. But also, to some degree, it was enabled by implementation of the ‘Breakthrough’ process. And I believe that no FDA division has more fully embraced these methods and the spirit of that law than FDA’s cancer group,” Gottlieb said in a May 2016 speech.

Gottlieb has also laid out FDA reform steps he says would build on the success of the breakthrough program, including: reorganizing FDA around disease; basing clinical reviews around particular approaches to drug development; revamping how biomarkers are qualified; and pursuing new statistical approaches. (See Inside Health Policy’s previous in-depth look at what Gottlieb will mean for FDA reform). 

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