Enhancing New Drug Development

FDA once again approved more innovative new drugs this past year, beating a near record set in 2014. Yet, John Jenkins, director of the Office of New Drugs (OND) in The Center for Drug Evaluation and Research (CDER), is concerned if this pace of development will continue.  

CDER approved 45 new molecular entities (NMEs) and biotech therapies, including more than 20 orphan drugs. In the process, the agency met all review timeframes and goals set by the Prescription Drug User Fee Act (PDUFA V). Almost all NMEs were assessed in the first review cycle, Jenkins reported at the FDA/CMS Summit in December 2015, and more new drugs reached the market first in the United States. Jenkins noted that expectations are high for continued gains, as requests remain high from sponsors for breakthrough drug designations, a program that has led to the approval of approximately 30 innovative products over the past four years.

The Center for Biologics Evaluation and Research (CBER) also approved more than a dozen new biologics, vaccines, blood products, and diagnostics.  This last item supports the drive for personalized medicine, which relies on the development of innovative in vitro diagnostics and combination products. FDA is pursuing initiatives to better coordinate oversight of drugs, biologics, and medical devices, with particular attention to reducing redundancies in manufacturing inspections and data requirements.

Seeking “me-betters”

One concern for Jenkins is that sponsors tend to shy away from developing the third or fourth drug in a class, which can limit patient choice in important, widely used drug classes such as beta blockers, anti-inflammatories, and statins. He would like to see investment in more “me-better” drugs-as opposed to “me-too” medicines-to expand treatment options for patients and to boost competition among manufacturers.

“Choice is a good thing,” Jenkins commented, as later drugs in a class often enhance safety or efficacy for certain individuals. The move away from “me-too” drugs, he said, is “not necessarily good for public health.” He acknowledged, though, that the development of “me-better” therapies might be challenging and costly due to requests for extensive safety data. Further guidance from FDA, he said, should help sponsors by making clear where to set the bar for information and by not asking for more studies than are really needed.

A continued rise in new drug approvals, moreover, may fall short, said Jenkins, due to a fairly flat rate in submissions to the agency. Even though FDA oversees approximately 7000 commercial investigational new drug applications (INDs) for drugs and biologics, Jenkins pointed out that actual submissions generally total approximately 35–40 applications a year. CDER has approximately 30 NMEs under review at any given time, he said, but it “can’t approve more NMEs every year if it doesn’t get more applications.”

He also cited manufacturing issues as a prime cause for delay in approving important new therapies. Scheduling timely preapproval plant inspections is a challenge within the six-month review timeframe for breakthrough drugs, he said, noting that it’s “often manufacturing and inspections that are the rate-limiting steps” for expedited approvals-and not clinical development. And small biotech companies that rely on contract manufacturers have run into difficulties when inspectors uncover GMP issues at the contracted production facility.

But the biggest concern for CDER’s new drug review program, Jenkins observed, is inadequate staff to handle a rising workload. Difficulties in recruiting and retaining capable analysts and scientists leaves CDER short by some 1000 authorized employees. At the same time, the agency faces growing requests from sponsors to meet with review staff, and limited resources to support the breakthrough drug program.

CDER might be able to manage its workload better if it could post information on why it does or does not approve a breakthrough drug designation request, Jenkins commented. Sponsors tend to announce only when they succeed, and limited information on why some drug candidates don’t qualify as breakthroughs encourages excessive submissions. And too much focus on breakthroughs, said Jenkins, can leave valuable therapies “on the shelf.”