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Pink Sheet – PDUFA VII Already: Could Breakthrough Ideas Apply Outside Program?

Pink Sheet – PDUFA VII Already: Could Breakthrough Ideas Apply Outside Program?

Executive Summary

Success of enhanced communications in particular made one stakeholder wonder whether FDA could use it with non-breakthrough applications.


The success of the breakthrough therapies program has stakeholders wondering whether some of its tenets could be applied more broadly.


It is a question that likely will come down to FDA’s ability to handle the additional work, but given the success of the breakthrough program, there likely will be a push from industry and others to expand its concepts beyond the select few in the program.


The issue emerged during an Aug. 15 public meeting on the new agreement between FDA and industry to reauthorize the prescription drug user fee program.


Both sides decided to use fee revenue to hire more review staff, in part so that FDA would have more resources available for breakthrough applications, given the popularity of the program and intense workload it can create for agency staff. (Also see “FDA’s Breakthrough Workload Will Be Eased By Hiring Reviewers With PDUFA VI Funds” – Pink Sheet, 20 Jul, 2016.)


Jeff Allen, president and CEO of the Friends of Cancer Research, the group that championed the breakthrough program as part of PDUFA V, said during the meeting that the agency and stakeholders should explore whether elements of breakthrough could be adapted to other programs.


“We’re certainly seeing something here in terms of the ability to expedite development in these instances,” Allen said. “I hope this is a stepping stone for future programs that could be looked at.”


One of the reasons breakthrough has been so popular – FDA received 441 requests and granted 145 designations as of July 18 – has been the increased involvement by FDA officials throughout the development program.


Allen has heard anecdotes about “how much more the meeting structure in many ways doesn’t apply.”


“It’s almost a breakthrough therapy hotline where reviewers are picking up the phone to ask questions and there’s this back-and-forth that is extremely labor intensive,” he said.


Sponsors in particular like the ability to have more conversations with FDA about what is thought to be a transformational therapy in the hopes of getting it to the market faster.


It is only natural to wonder whether that type of communication or other elements of breakthrough could be applied outside the program, given its success.


Allen said in an Aug. 17 email to the Pink Sheet that “perhaps there are some general or easy to implement approaches … that could be broadly helpful.”


While not in the existing PDUFA renewal, it is possible congress could attempt to add it to the legislative package that will accompany it in 2017. The idea also could signal the beginning of a list of asks for the 2022 PDUFA renewal process.


Sen. Michael Bennet, D-Colo., already has indicated that the breakthrough concept should be implemented across FDA. (Also see “FDA’s Breakthrough Products: Could Patients Drive The Designations?” – Pink Sheet, 13 Mar, 2014.)


The agency has attempted to make itself more available to industry earlier in the development process in recent years.


Its biosimilar program in particular was designed to encourage agency interaction with sponsors well before the marketing application is filed.


The popularity of the product development process also was underestimated. (Also see “Biosimilars Program Could ‘Explode,’ Woodcock Warns Congress” – Pink Sheet, 4 Feb, 2016.)


FDA and industry recently completed renewal discussions for the biosimilar user fee program, which could include changes to help deal with the workload problem. (Also see “Two Out Of Three Ain’t Bad: Biosimilar User Fee Talks Completed” – Pink Sheet, 20 Jun, 2016.)


The breakthrough concept also has moved into the FDA’s device center. It recently created an expedited access pathway, which already is being considered for expansion. (Also see “CDRH’s Expedited Access Pathway: 17 Devices And Counting” – Medtech Insight, 12 May, 2016.)


Early Biomarker Meetings Also Could Expand

More early communications related to biomarker development in PDUFA VI also could apply in other settings, Allen said.


In PDUFA VI, sponsors will be allowed to meet with FDA about the use of novel surrogate endpoints and the possibility of it being used as a primary endpoint. (Also see “Rare Disease Integration Into FDA Reviews Will Grow Under PDUFA VI” – Pink Sheet, 18 Jul, 2016.)


Allen said the idea eventually could expand to include all biomarkers, not just those that could become surrogates.


“I understand why this needs to be a stepping stone because the agency is not resourced to be able to be answering random questions on biomarkers,” he said during the meeting. “There could be more opportunities here in the future, looking at expanding the program beyond just a biomarker used as a surrogate, but for this to be a broader scientific tool to understand the development of new surrogates, not just in the context of that application at hand, but to inform the field moving forward.”


Biomarker development has proven difficult. Since FDA created its approval process, FDA has only qualified six biomarkers.


Changes to the process were included in the House 21st Century Cures legislation, which remains in limbo. (Also see “FDA’s Woodcock Cautions Efforts To ‘Legislate A New Generation Of Biomarkers'” – Pink Sheet, 21 Oct, 2015.)


Rare disease groups also have been asking for an early biomarker qualification meeting, in part to make it more predictable, and potentially allow for more investment. (Also see “Biomarkers For Rare Diseases Get Scaled-Back Plea In New White Paper” – Pink Sheet, 2 Sep, 2013.)


Communication Growth Likely A People Question

Any future expansion of communications with sponsors will depend almost entirely on resources.


PDUFA VI should help. Not only will fees support hiring 230 new full-time equivalents, but the agency also will add a contractor to help with recruitment and retention and create a dedicated unit within the Office of Medical Products and Tobacco to handle recruiting, staffing and retention issues.


FDA already has hundreds of positions it is trying to fill among its rank-and-file and executive areas. (Also see “Show Me The Money: Salaries, Red Tape Challenge FDA Recruiting” – Pink Sheet, 19 Jan, 2015.)…