PDUFA Hearings Highlight Support and Concerns About Legislation

Posted 02 February 2012 By Alexander Gaffney

The US House Committee on Energy and Commerce (E&C) held a hearing on 1 February 2012 on the Prescription Drug User Fee Act (PDUFA), the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research and Equity Act (PREA). The hearing highlighted the broad support that all three pieces of legislation have in Congress. The hearings also hinted at certain issues that may come to dominate the debate over the coming months, including conflict of interest policies currently in place for advisory committees.

Today's E&C hearing featured several prominent voices, including lengthy testimony from US Food and Drug Administration (FDA) Commissioner Margaret Hamburg, FDA Deputy Commissioner for Global Regulatory Operations and Policy Deborah Autor, as well as representatives from Pfizer, the California Healthcare Institute (CHI), the Biotechnology Industry Association (BIO), the Pew Health Group, the National Organization of Rare Disorders (NORD), the Pharmaceutical Research and Manufacturers of America (PhRMA) and the American Academy of Pediatrics' Committee on Drugs.

Congress is currently looking to reauthorize several pieces of user fee legislation, including PDUFA, in which fees paid by pharmaceutical industry support FDA activities and agency enhancements. FDA has referred to thePDUFA  program as a "net win for consumers and patients," while industry group PhRMA has called the legislation "a great success."

The legislation was submitted to Congress on 13 January, and would reportedly generate more than $299 million dollars in fees over a 5-year period starting in 2013. This figure is almost half of the $595 million currently proposed by FDA and industry for the Medical Device User Fee Act set to go before E&C on 15 February.

Commissioner Hamburg's Testimony to Congress

Hamburg testified in front of the committee at the start of the hearing, and her remarks touched on a wide range of subjects. Hamburg noted the importance of the PDUFA legislation to FDA, remarking that 62% of FDA's approval operations are funded by PDUFA, with the remaining 38% of FDA's budget coming through the congressional appropriations process.

Hamburg said that the proposed PDUFA reauthorization, known as PDUFA V, would be beneficial to both FDA and industry in a number of ways.

Meetings and communications were frequently highlighted. PDUFA allows funding for more pre-submission, mid-cycle and late-cycle meetings and communications with FDA, an adjusts FDA's approval target times accordingly.

PDUFA also provides funding for a number of agency upgrades and improvements. FDA will receive additional funding to enhance its regulatory science initiatives, hire more staff to perform and improve meta-analysis functions within the agency and improve agency capacity to assess biomarkers.

Perhaps the most important development for the agency is that user-fee funding under PDUFA is pegged to inflation. Previous iterations of PDUFA did not contain this provision, which left FDA with comparatively less funding to accomplish its goal at the end of the five year PDUFA term than at the start of that term.

Hamburg's testimony also highlighted some concerns frequently raised by safety and patient advocates. Under PDUFA, FDA would be charged with formulating an enhanced benefit: risk framework, strengthening the drug safety system, issuing guidance relevant to rare of neglected diseases, forming sets of new "patient-reported outcomes" (PROs) and requiring that all industry submissions be entirely electronic.

The enhanced benefit: risk framework has been called for by both patient groups and industry, who charge that it is especially necessary for patients suffering from rare diseases. These patients may be considerably more willing to accept risk than FDA thinks they are.

Congressional Reaction and Further Testimony

Hamburg's testimony was largely met with approval from committee members, though some testy exchanges took place between the Commissioner and several Congressman.

Rep. Burgess (R-TX) said that FDA has been less than forthcoming in cooperating with E&C regarding the tainted Chinese heparin scandal that killed scores of people several years ago. Hamburg fired back, saying that FDA has spent "literally thousands of hours" complying with the committee's requests for information.

Hamburg also responded to Representative Brett Guthrie's (R-KY) questions regarding FDA's use of guidance documents, noting that she believes industry likes them and finds them useful in understanding FDA's current thinking on an issue. Hamburg added that it is also helpful for industry to understand how FDA might formulate future regulations.

In one of the hearing's testier exchanges, Representative Brian Bilbray (R-CA) grilled Hamburg on whether or not FDA would approve aspirin in the current environment, wondering aloud if any existing drug had "saved as many lives as aspirin." "FDA is too risk-focused," said Bilbray. Hamburg largely deflected the questions, noting that she wasn't prepared to speak to that particular case. "Even drugs that the average American would consider safe and routine [...] need to be addressed in an ongoing way," said Hamburg.

Conflict-of-Interest in the Spotlight

The issue of conflicts of interest (COI) came up numerous times throughout the hearing. Representative Phil Gingrey (R-GA) said that current COI policies were hindering the understanding of Advisory Committees and called for caps on the number of COI waivers that FDA can grant to be removed.

Current rules may actually limit the agency in key areas, allowing science to "move beyond the capacity" of experts who are not subject to the COI policies, said Gingrey.

Diane Edquist Dorman of NORD stressed the need for COI reform repeatedly, saying the current COI policies for orphan disease products are "out of balance." Finding non-conflicted experts for extremely small disease classes can be "difficult, if not impossible", said Dorman.

In response to a question from Representative Frank Pallone (D-NJ), Geno Germano of Pfizer said that there was a "need for improvement" in the COI process, but admitted that he didn't think removing COI waiver caps would do much to solve the problem. Obtaining the best expertise for the Advisory Committees is still the best solution, said Germano.

PhRMA representative David Wheadon mirrored these sentiments, saying that industry needs to be able to engage expertise, especially in rare disease classes.

Monitoring Disparities

The issue of disparities in the inspection rates of foreign and domestic manufacturing plants received significant attention from the committee.

US-based manufacturers currently experience factory re-inspections every two years on average, while foreign manufacturers typically are inspected once every decade. In a CNN op-ed posted later in the day, Represenative John Dingell (D-MI) cited a Government Accountability Office report that said that "some of the 3,765 foreign drug establishments in the FDA's database may never have been inspected. An increasing demand, coupled with an expanding globalized drug market, blatantly calls for a more globalized and fully equipped FDA."

"Now, more than ever, U.S. manufacturing facilities should be rewarded, not penalized, for retaining jobs in the United States," said Dingell. "It is not only fair and the right thing to do to protect American competitiveness, it's critically important for the health of American consumers."

Hamburg was quick to note during the hearing that the agency is in need of additional funds to ensure the capability of the agency to monitor clinical trials and inspect foreign manufacturers. "We need additional resources to provide the level of oversight that we believe is adequate," said Hamburg. Parity between domestic and foreign manufacturers would go a long way in securing the domestic drug supply and stemming the flow of manufacturers out of the country.

FDA Reforms?

One idea that received some advocacy at the meeting was proposed by Representative Morgan Griffith (R-VA), who advocated for giving patients the ability to waive their rights to sue a manufacturer for issues relating to safety or efficacy in return for the ability to take experimental drugs. Hamburg said that the agency already adopts a high risk tolerance for drugs if there are no other treatments available, and noted that FDA had not yet considered Griffith's idea.

Hamburg touched on the same subject several other times during the hearing, noting that patient-group-specific risk tolerance levels would be useful. Knowing that certain groups are "willing to accept high levels of risk if there's a benefit payoff" if of particular interest to FDA, said Hamburg.

Several representatives also brought up FDA's ban of Promotine asthma inhalers, which were taken off the market last year in response of the presence of hydrochlorofluorocarbons (HCFCs) in the over-the-counter products.

Representatives Burgess and Mike Ross (D-AR) both raised the Primotine issue, saying that it was less an issue about safety and more of an issue about product affordability. Burgress, a physician, noted that albuterol inhalers are almost twice as expensive as the OTC Primotine inhalers, and require a physician's prescription to obtain which further inflated the cost.

Hamburg responded to Burgess by saying that while numerous factors are involved-including the US Environmental Protection Agency's regulations-FDA was in favor of the action because asthmatics should have their condition managed by a physician.

Some in Congress have called for FDA's mission to be reformed to include job creation, and the idea received significant attention during the hearing. In response to questions from Congressmen, Hamburg said that it is "very hard to factor [jobs] in to this scientific decision-making," and said that efforts to make "job creation" a part of FDA's mission would be "inappropriate." In the question and answer session in the second half of the meeting, David Gollaher of CHI said that he favored using economic metrics as part of FDA's thinking on approvals.

Additional hearings on the PDUFA legislation are not yet scheduled as of this time.

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