Recruiting and retaining top scientists with the expertise needed to review applications for emerging technologies, like gene and cell-based therapies, is the U.S. Food and Drug Administration's greatest concern right now, the agency's top leaders said.
While advocates of the FDA have called for ensuring that the agency is adequately funded, Acting Commissioner Ned Sharpless said he is more worried about attracting experienced scientists to work at his agency and keeping them on board.
Ned Sharpless, acting commissioner, U.S. FDA
"The FDA is well-supported to do what we need to do today," Sharpless said June 4 at the BIO International Conference in Philadelphia. "But the problem is we are being asked to take on a lot of new stuff."
He noted that the FDA is wrangling with regulating software and 3D printed medical devices, electronic cigarettes and therapies that are increasingly being developed for an individual patient.
"And all of those innovative areas require new expertise and knowledge," Sharpless said.
While the 21st Century Cures Act, signed in December 2016 by then-President Barack Obama, granted the FDA new hiring authorities, which allows it to be more flexible with bringing on certain employees, Sharpless said he was concerned about it also creating staffing and compensation inequities.
He said expanding the Cures Act's authorities would be valuable to the FDA, particularly as it seeks to hire the experts it needs.
Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said one of the most damaging impacts on the agency's ability to hire and retain top scientists was the 35-day government shutdown, in which over 7,000 of the agency's staff were furloughed from Dec. 22, 2018, to Jan. 25, 2019, while some others worked without pay.
"In a full employment economy like we have right now, people lose interest in coming to a government job," Marks said June 4 during a separate session at the conference. "When you have shutdowns that last several weeks, that's a bad thing. It dissuades people."
Marks said the FDA lost promising job candidates "who had shown interest, but their deciding factor was they could be furloughed for several weeks."
During the shutdown, the FDA "kept it together with Scotch tape and chewing gum," Marks said, but the agency was "very touch and go at the end" and nearly ran out of funding, added Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research.
She said the shutdown was very hard on FDA employees' morale.
Overlapping expertise needed
Marks noted that his center is increasingly confronted with regulating products that overlap among the key areas it regulates of blood, vaccines and gene and cell-based therapies.
"It's tremendously exciting times," he said.
But, Marks said, the FDA is struggling with how it will staff up quickly to address that steep growth in those areas.
He acknowledged that it takes up to two years to properly train new scientists to be able to provide the right answers to companies working in the new technical areas of innovation.
"We want the people meeting with you to have good advice and telling you the right answers," he told biopharmaceutical companies at the BIO conference.
Marks said he anticipates having to increase his scientific staff by up to 50% in the next two years because of the increase in companies pursuing gene and cell-based therapies and other emerging technologies.
While the FDA values the people it brings on board from academia, "we love it when we get people from industry because they come with a lot of experience and they bring practical knowledge," he said.
People who have worked in the biopharmaceutical industry "understand what it means to be on a production floor and why it's so challenging to make biologic products," Marks said.
"That type of experience is invaluable," he said. "We would love to get more people from industry."
Therapies for one
Woodcock noted that the FDA is grappling with how to regulate potentially curative therapies being developed in academic settings for individual patients with extremely rare diseases.
"We're really rushing to get policy together because this came upon us faster than one might have anticipated," she said.
The FDA is up against an environment where academic investigators are more easily able to sequence a patient's genome but have never before conducted a clinical trial for a new molecular entity.
She pointed to the recent case of where Harvard University neurogeneticist Timothy Yu found a successful way to treat a young girl with Batten disease, an inherited and fatal neurodegenerative disease.
Woodcock said the FDA has discussed the experimental antisense oligonucleotide treatment with Yu and said he recognizes that as it becomes more readily known, there will be an up swell in demand for it.
"We're trying to get policies together on a therapy that is not being developed for commercial but for an N=1, or a bespoke therapy for a single individual," Woodcock said. "We're beginning to learn the molecular basis and the heterogeneity of a lot of rare life-threatening illnesses."
"We need to figure out ways to see how those therapies can be delivered in an effective way consistent with some business model," Marks added.
The FDA will need to determine what types of preclinical and clinical data will be needed and what manufacturing procedures will be required, "and how we would wiggle our way through to treating people we might not have clinical data for in that construct but we have clinical data for something close," he said.
"We want to get it right because if we get it wrong too often we don't want to set things back," Marks said. "There's not a lot of room for error here."
Woodcock noted that there are some major questions the FDA cannot answer: Who is going to pay for the therapies, how will the drugs be administered in perpetuity, and if people survive, how are they going to keep getting the products?
"Those are questions for the larger healthcare system," she said.