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Sequestration Remains Major Challenge to FDA’s Mission


By Mari Serebrov
Washington Editor

With sequestration all but wiping out the 6 percent increase the FDA received in drug user fees for fiscal 2013, the agency is struggling to keep up with a medical revolution spurred by scientific advances and the potential of personalized medicine, Janet Woodcock, director of the agency’s drug review center, told a House subcommittee Friday.

The task could be even more challenging in fiscal 2014, as sequestration is endangering up to $112 million in FDA user fees, Rep. Kathy Castor (D-Fla.) said at the Energy and Commerce’s Health Subcommittee hearing on the implementation of the 2012 FDA Safety and Innovation Act (FDASIA). (Some of that cut would come from food and tobacco user fees.)

Of the $209 million the FDA lost to sequestration in the past budget year, $85 million was in user fees, with about $56 million coming from fees for prescription drugs, generics, biosimilars and medical devices, according to written FDA testimony submitted to the subcommittee.

While the sequestered fees can’t be used to pay down the deficit, which is the intent of sequestration, they will remain off-limits to the FDA until Congress re-appropriates them. In the meantime, the loss of the funding puts key commitments negotiated under FDASIA at risk, Woodcock said.

One of the areas impacted is rare diseases. The FDA’s Center for Drug Evaluation and Research (CDER) works with drugmakers on a case-by-case basis to design clinical trials involving diseases that affect small patient populations. As part of its FDASIA commitment, CDER set up a rare disease staff, but Woodcock said sequestration has hampered efforts to get that staff fully up and running.

CDER isn’t the only FDA unit suffering under sequestration. Jeffrey Shuren, director of the agency’s medical device center, testified that the sequester will keep the Center for Devices and Radiological Health (CDRH) from meeting its FDASIA user fee goals. Many device programs already have been affected by the across-the-board cuts, and it’s getting to the point of turning lights off in some of CDRH’s labs, he said.

Castor expressed frustration that the user fees were cut by the sequestration. “This is not smart,” she said, adding that this is a bad time to shortchange the FDA, given its increased responsibilities and the ongoing evolution of science.

Although user fees don’t contribute to the budget deficit, which the sequester is aimed at reducing, the White House Office of Management and Budget determined that they should be subject to the sequestration knife. Several lawmakers, from both sides of the political aisle, are pushing to have the fees protected from future cuts. (See BioWorld Today, Oct. 18, 2013, and Nov. 1, 2013.)

Despite the reduction in user fees, the FDA is making progress on many of its FDASIA goals and is doing its best to meet the ambitious time frames set by Congress, Woodcock said, as she held up a many-page spreadsheet listing all the law’s mandates.

Some of the accomplishments she mentioned include:

starting a pilot of a new review program for new molecular entities;

implementing the breakthrough therapy designation for products addressing serious or life-threatening diseases – the FDA has received about 100 applications for the new designation, granted designation to 25 drugs and recently approved the first two; (See BioWorld Today, Nov. 14, 2013.)

streamlining the vetting process for advisory committee members, reducing the number of vacancies;

approving 12 drugs for rare diseases on the basis of surrogate endpoints, with one of those being approved via the Animal Rule, which requires no human trials;

granting 24 qualified infectious disease product designations;

beefing up the generic drug review staff and acting on 900 of the 2,500 applications caught in a backlog of abbreviated new drug applications (ANDAS).

The agency also reported advances in biosimilars. As of Sept. 17, it had received 56 requests for an initial meeting to discuss biosimilar development programs related to 13 different reference biologics and had held 47 initial meetings with sponsors. It also had received 17 investigational new drug (IND) applications for biosimilar development programs, with other development programs proceeding under pre-INDs.

Some of the progress has created frustration for industry, Woodcock acknowledged, especially in the area of generic drug reviews. With 8,000 items pending in the generic review program, she said staff had to limit communication with sponsors, otherwise the reviews would never get done.

The drug center will notify generic sponsors when an ANDA is approaching specific review steps, but it can no longer field thousands of questions from industry if it hopes to get through the backlog, Woodcock said.

Risk Aversion Is Risk Itself

One of the big threats to public health is regulators being too averse to risk, according to senior officials at the European Medicines Agency (EMA).

Risk aversion could lead regulators to deny approval, withdraw a drug from the market or restrict its use “when it would in fact have caused more good than harm,” the EMA said, citing an article by senior officials that was published Friday in Nature Reviews Drug Discovery.

An unwillingness to accept some uncertainty increases “opportunity costs,” the EMA officials said. Such costs are incurred when a regulator’s request for additional data reduces the R&D resources a company has, derailing the development of other drugs that could have brought public health gains.

The EMA recommends that regulators be allowed to factor opportunity costs into the standards for evaluating a drug’s benefit-risk profile and in individual approval decisions. Other recommendations include:

defining ways to systematically include the patient perspective on the level of acceptable risk linked to a medicine;

developing methodologies that combine patients’ values with the interpretation of the data;

developing the concept of “tolerability of risk” thresholds for evaluating drugs, recognizing that zero-risk situations don’t exist in the real world.

Noting the shift in regulation toward surveillance of safety and effectiveness in the real world, the EMA officials said faster decisionmaking, risk-minimization measures and robust tools to generate real-time knowledge “should reduce the perceived need for risk aversion at the initial stage of licensing.”

Earlier Access Needed

A report by an expert group with the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) is pushing for earlier patient access to innovative drugs that address unmet medical needs. The agency’s Expert Group on Innovation in the Regulation of Healthcare urged the government to launch an early access scheme for unlicensed medicines as soon as possible and consider including a special designation for therapies that may qualify for early access. The group also encouraged MHRA to press the European Medicines Agency on launching adaptive licensing at the earliest opportunity.