7-25-2013 - Pink Sheet - FDA’s Breakthrough Designations Face Question Of Review Resources | Friends of Cancer Research

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7-25-2013 - Pink Sheet - FDA’s Breakthrough Designations Face Question Of Review Resources

7-25-2013 - Pink Sheet - FDA's Breakthrough Designations Face Question of Review Resources

July 25, 2013

By Derrick Gingery

Woodcock says FDA will manage breakthrough applications along with its entire portfolio of submissions, but some stakeholders express concern about whether the demands of the exceedingly popular program will affect the agency’s handling of other applications.

FDA is facing questions about whether the growing number of breakthrough designations has pulled resources away from other applications, an indication there may be concerns about the demands the program is placing on the agency.

A breakthrough designation allows the product sponsor easier and more-frequent interaction with FDA officials and streamlined development, if early clinical evidence indicates a major improvement over existing therapy.

Industry’s interest and FDA’s embrace of the program, designed for products showing dramatic improvements over existing therapies, has far out-paced expectations.

Early projections were that FDA might designate two to four breakthrough products per year when the program was included in the 2012 FDA Safety and Innovation Act. However, in the year since FDASIA became law, the agency has designated 25 products as breakthroughs and received 77 requests ("FDA “Breakthrough Therapy” Designations" — Pharmaceutical Approvals Monthly, July 2013).

The stunning pace of designations has some in industry questioning whether FDA can handle the workload presented by the large group of breakthrough applications along with the goals of other submissions it reviews.

Janet Woodcock, director of the Center for Drug Evaluation and Research, said July 24 that agency staff also have acknowledged the resource issue breakthrough creates.

She said after participating in a Capitol Hill briefing organized by the Friends of Cancer Research that breakthrough applications are just another part of FDA’s overall workload.

“We have a body of work we have to do,” Woodcock said. “We just do the best we can. It’s a portfolio we have to manage.”

Jay Siegel, head of global regulatory affairs at Johnson & Johnson, said it is clear that FDA is spending more time on breakthrough applications, but ultimately it should pay off with time saved later.

He also reiterated that breakthrough drugs are not the only important products looking for FDA action.

“I’m inclined to think that maybe … the overall amount of resources spent will not be that much more,” Siegel said. “Often that type of close partnership will lead to a more efficient resolution of processes and problems.”

Siegel said after the briefing there is no way to determine at this point that breakthrough is negatively impacting anything else at FDA. He also said industry is monitoring many of the new systems put in place by FDASIA, including a new review model for NDAs and BLAs.

Delays and other problems should be caught relatively quickly.

The Pharmaceutical Research and Manufacturers of America and Biotechnology Industry Organization created a database to track participating applications and trends ("PhRMA, BIO’s PDUFA V Application Tracker Could Inform “Course Corrections”" — "The Pink Sheet" DAILY, Jun. 25, 2013).

Siegel said he was more worried about the impact of the agency funding lost to the budget sequester.

FDA lost $209 million in FY 2013 when the mandatory cuts went into effect, including $82 million in user fees. A congressional effort is underway to exempt fee revenue in future years ("FDA Sequestration Relief Bill In House Would Free User Fees, But “Pay For” Remains Question Mark" — "The Pink Sheet" DAILY, Jul. 19, 2013).

FDA Changed To Accommodate Science’s Change

With breakthrough applications, FDA no longer spends much of its time debating whether a product actually works, potentially saving time. But Woodcock said there still are trade-offs.

“New questions are arising so it’s also very important for us to pull out this group and work on a truly new development pathway,” she said during the briefing. “We’re always short of resources … but I do think some of the activities that we have done in the past will not be the activities that we do in the future.”

The new pathway is necessary because drug development is expanding to include new targeted therapies based on the basic science of a disease. FDA changed its regulatory approach to accommodate it, Woodcock said.

“If that prediction is true, we will gradually develop a new pathway for development that is more efficient,” she said. “The hope and belief is that this probably reflects the investment in science that has been made over the past 40 years.”

Woodcock said recently that targeted therapies are expected to emerge as a significant category of breakthrough products ("“Breakthrough” Therapies: Pharmacyclics Gains More Access, Certainty For Ibrutinib" — "The Pink Sheet," Jun. 10, 2013).

Manufacturing Is Hurdle For Breakthroughs

Manufacturing issues remain a hurdle for breakthrough sponsors, but they and FDA also view it as a potential opportunity.

The speed a manufacturing facility must be ready to scale up and inspected is among the problems. FDA already has said that manufacturing facilities likely will have to be ready faster than they normally would to cater to a breakthrough application ("Industry Wants A Breakthrough Therapy, Even Without All The Standards" — "The Pink Sheet," Oct. 29, 2012).

Jeffrey Leiden, CEO of Vertex Pharmaceuticals Inc., said the breakthrough process could usher in manufacturing process and facility upgrades.

“I see part of the breakthrough process as being … how do we do manufacturing differently so it’s not quite as cumbersome, so it is easier to inspect,” he said. “While I do see it as a challenge, sometimes those challenges become opportunities to streamline the process.”

Woodcock also said the agency will once again mount an effort to boost the manufacturing enterprise. She said changes could be made that would prevent scale-up for mass production from being a major issue.

“It may well be that breakthrough is an opportunity that will motivate folks to put the effort in,” she said.