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November 07, 2011

Reaction to PDUFA V Signals Harmony on Most Issues but Some Discontent with Risk Evaluation

Agency expects to finalize fifth authorization of Prescription Drug User Fee Act and send it to Congress by January '12.

Reaction to PDUFA V Signals Harmony on Most Issues but Some Discontent with Risk Evaluation

All are eager to see Congress approve PDUFA V early next year, and prospects of this are looking good. [SwitchPhotography - Fotolia.com]

  • FDA’s proposed fifth authorization of the Prescription Drug User Fee Act (PDUFA V) largely drew support from drug developers and patient groups during the agency’s meeting held October 24 and in written comments sent in through October 31. All are eager to see Congress approve it early next year, even as they differ over how to evaluate the benefits and risks of new drugs.

    The proposed PDUFA V Reauthorization Performance Goals and Procedures for Fiscal Years 2013 through 2017 was hammered out earlier this year along with the Biotechnology Industry Organization (BIO) and Pharmaceutical Research and Manufacturers of America (PhRMA). It would give FDA another $100 million in user fees toward hiring additional review staff for drug applications. User fees in the current PDUFA IV totals $2.9 billion.

    PDUFA V will also require more communication between drug companies seeking approval and the agency. FDA, BIO, and PhRMA signed a Draft Commitment Letter pushing back the start of FDA’s clock for its first review cycle to after its 60-day administrative filing review period. Once the clock starts, drug developers and FDA officials must meet three times: at presubmission and late-cycle meetings as well as at newly required mid-cycle meetings, about two weeks after the agency holds its own internal mid-cycle review.

    In return FDA committed to reviewing and acting on 90% of standard NME, NDA, and BLA submissions within 10 months—12 months from the date of filing—and on 90% of priority NME, NDA, and BLA submissions within six months—eight months from date of filing.

    The agency plans to finalize PDUFA V and forward it to Congress by January 15, 2012. “PhRMA urges Congress to act expeditiously to reauthorize PDUFA, passing a bill that includes the carefully negotiated PDUFA V performance goals letter,” David Wheadon, M.D., svp, scientific and regulatory affairs, told the FDA. “PhRMA further urges Congress to refrain from adding additional provisions that could create excessive regulatory burdens or uncertainty for the agency as well as industry and other stakeholders or that could delay the legislative process.”

  • Protecting Consumers

    The prospect of the addition of further guidelines that PhRMA refers to as excessive regulatory burdens is unlikely, since those likeliest to seek any such rules—consumer groups—have little sway with the Republican-controlled House of Representatives. While the Senate is Democrat-controlled, it too isn’t likely to risk the wrath of drug developers or its access to their campaign cash before 2012 elections by siding with consumer groups. That bodes well for Congressional reauthorization of PDUFA V before it expires on September 30, 2012.

    Addressing FDA at the hearing, Sally Greenberg, executive director of the National Consumers League, faulted the agency for not including consumer and patient groups along with BIO and PhRMA when it put together the PDUFA V framework.

    “As a result, several patient safety and consumer protection initiatives that were put forward were never discussed in the formal dialogue with industry,” Greenberg said. “We believe that the PDUFA proposal should not be moved forward without these additional provisions.”

    Among suggestions were that FDA should:

    • set aside part of the user fees to hire staffers to review all direct-to-consumer ads for drugs before they reach the public;
    • convert data captured on the Medwatch system for recording adverse effects to more commonly used electronic formats so that trends can be better identified; and
    • devote another portion of user fees to examine the safety of off-label prescribing and add rules informing consumers of available alternatives, evidence supporting product use, approval status/use in other countries, and implications for insurance coverage.

    “While it is important to have an efficient and timely approval process, there is still, in our view, too little emphasis on performance goals aimed at improving the safety and efficacy of drugs,” Greenberg added.

    Not so, counter drug developers and some patient groups. BIO and PhRMA have criticized the agency for rules passed under the Food and Drug Administration Amendments Act (FDAAA) of 2007. They contend that while these were developed to protect patients, the guidelines have slowed down drug reviews and led to more rejections. FDAAA gave FDA the authority to require post-approval studies, establish active surveillance of approved drugs, and require a Risk Evaluation and Mitigation Strategy (REMS) for drugs connected to greater safety risks.

  • Bolstering REMS

    In a survey BIO commissioned last year, 81% of respondents said FDA did not begin REMS discussions early enough to allow adequate time for dialogue. At the PDUFA V hearing, PhRMA praised the new proposal for committing FDA to a public process to standardize REMS. The aim is to reduce red tape for healthcare providers and patients.

    By the end of fiscal 2013, FDA plans to issue guidance on determining whether a REMS is necessary to ensure that the benefits of a drug outweigh the risks. By the end of FY 2014, FDA will issue guidance on methodologies for assessing those REMS deemed necessary.

    If it’s serious about improving REMS, the FDA should consider many of the constructive suggestions of the American Pharmacists Association. It released a “white paper” report in May recommending the standardization of REMS programs, components, and processes; establishment of a central repository or clearinghouse for all REMS related information; and encouragement of more personal consultations with patients. It also suggested that compensation models be established that afford providers staff and resources to implement REMS programs.

  • Establishing a Role for Patients

    While consumer and patient groups were unhappy about being left out of the process of drafting PDUFA V, they applauded the proposal for committing to incorporate patient perspectives in reviewing new drugs. With PDUFA V, FDA expects to develop a set of disease areas that warrant “a more systematic and expansive approach to obtaining the patient perspective on disease severity or unmet medical need.”

    Marc Boutin, evp and COO of the National Health Council, told GEN: “At the strong urging of the patient advocacy community, the FDA and industry agreed to the development of a decision framework that will more systematically allow FDA to take into account input from patients and consumers and more appropriately determine the benefits and risks in the therapeutic context.”

    The decision process for reviewing new treatments “will also be transparent, so patients will better understand why a particular drug was or was not approved,” Boutin added. The National Health Council is an umbrella for about 50 patient groups among more than 100 national health-related organizations.

    In a September 27 letter to FDA, a coalition of 32 patient groups proposed that patient input be solicited when an IND is filed and any point when FDA decides, based on risk-related issues, that it must disapprove or delay the start of a clinical trial or suspend an existing trial.

    Another FDA commitment that has drawn support from industry and patient groups is the agency’s five-year plan to develop a structured benefit/risk assessment in the new drug approval process. FDA said it will publish its draft plan for public comment by the end of the first quarter of FY 2013, with implementation by September 30, 2013, the end of that fiscal year.

    Since the concerns of patient groups are largely in synch with those of drug developers, PDUFA V holds more potential than PDUFA IV ever did for the partnership long envisioned between government, industry, and supporters within the patient community. Consumer advocates still fight an uphill battle for tougher regulation of the industry, however. While consumer groups may not get all their demands met, they could still exert influence to advance some of their goals.

    For all involved the aim should be to fulfill what FDA calls the spirit of the original PDUFA authorized in 1992, which was articulated most recently by CDER director Janet Woodcock, M.D., in testimony July 7 to the House: “speeding patient access to drugs shown to be safe and effective for the indicated uses.”

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