A draft of the bill to reauthorize FDA's user fee program would add $70 million to the total fee negotiated by the agency and industry in order to pay for additional Rx safety oversight.

FDA and industry have already agreed on user fees of $392.8 million in fiscal 2008, and a bill from Sen. Edward Kennedy, D-Mass., would increase the funds by almost 18 percent in order to give FDA more authority and resources to monitor drug use.

Titled the "Food and Drug Administration Revitalization Act," the ¹ draft legislation is scheduled to be marked up April 18 by Kennedy's Health, Education, Labor and Pensions Committee.

The existing agreement between FDA and industry already triples user fee spending on safety, FDA Commissioner Andrew von Eschenbach noted at a hearing last month (² Also see "Rx Safety Bill Would Require Renegotiation Of User Fees, FDA Tells Senate" - Pink Sheet, 19 March, 2007., p. 3).

Von Eschenbach emphasized that safety mechanisms envisioned by Kennedy would require additional user fees. Industry, already leery of the promotional restrictions and clinical trial requirements contained in the provisions, is likely to look askance at paying significantly more to see them enacted.

Kennedy developed the safety provisions with the committee's ranking member, Sen. Michael Enzi, R-Wyo. Under their bill, reintroduced this year, new drugs would be required to have a Risk Evaluation and Mitigation Strategy. The REMS could range from periodic adverse event reporting to controlled distribution programs, and FDA would be able to impose fines to enforce the provisions.

[Editor's note: Articles about the draft bill first appeared in ³ "The Pink Sheet" DAILY April 11, and coverage of the April 18 mark-up will be available at www.ThePinkSheetDAILY.com. To sign up for a free trial, visit our Web site or call 800-332-2181.]

The bill is the product of many hours of negotiation between senators and stakeholders, but the provisions may still change as the legislation moves towards passage. The omnibus bill faces even more uncertainty in the House, where Energy and Commerce Committee Chairman John Dingell, D-Mich., has not staked out a strong public position on drug safety legislation.

Dingell and Health Subcommittee Chairman Frank Pallone, D-N.J., have indicated they intend to take a substantial amount of time crafting their legislation. The chairmen recently asked FDA when the agency would need to issue furlough notices if the user fee program has not been renewed. While the authority expires at the end of the fiscal year in September, FDA has said it would need to start reductions in force before that if it could not be assured of funding.

Another possibility for PDUFA, albeit remote, would be a one-year extension advocated by a group of academics and ex-FDA staffers in an ⁴ open letter.

Despite the Senate bill's girth, the 227-page legislation is also noteworthy for what it does not include - a pathway allowing FDA to approve follow-on biologics.

Path Seems Further Away For Generic Biologics

The generics industry, members of the payer community and some consumer advocates had been eying the PDUFA bill as a vehicle to pass legislation creating an approval mechanism for generic biologics.

However, in a March 28 letter sent to Kennedy and Enzi, Biotechnology Industry Organization Chief Executive Officer Jim Greenwood urged the senators to consider any follow-on biologics legislation independent of PDUFA to avoid any delays in its reauthorization.

Kennedy held a hearing on the issue in March, but the potential pathway was criticized by Sen. Orrin Hatch, R-Utah, and the brand industry as lacking sufficient provisions for patient safety (⁵ Also see "Generic Biologics: European-Style Regulation Is The Answer, Big Pharma Says" - Pink Sheet, 12 March, 2007., p. 5).

The mark-up in the Health Committee could see an attempt to amend the legislation by attaching the biogenerics bill. However, Sen. Hillary Clinton, D-N.Y., who sits on the committee and is a sponsor of the biogenerics legislation, is also working on alternate legislation with a bipartisan group of committee members (see ⁶ Also see "Follow-On Biologics Alternative Bill Progresses; IP Issues Remain Sticking Point" - Pink Sheet, 16 April, 2007.).

Advocates for a generic biologics pathway continue to press their case on Capitol Hill, and may find a more favorable audience in the House. Pallone, whose committee will begin hearings on the PDUFA bill April 17, the day before the Senate panel marks up its bill, is a cosponsor of the generic biologics legislation.

Former FDA and CMS chief Mark McClellan had predicted that scientific concerns and modest cost savings projections would create hurdles for passage of generic biologics legislation (⁷ Also see "McClellan Sees Roadblocks To Passing Biogenerics Bill This Year" - Pink Sheet, 2 April, 2007., p. 17). FDA, however, appears to be moving forward with its own limited pathway development (⁸ Also see "505(b)(2) Resurrection, FDA Guidance To Bless Follow-On Biologics Pathway" - Pink Sheet, 2 April, 2007., p. 13).

Despite the absence of follow-on biologics from the bill, the generics industry can take some solace in the fact that ANDA user fees, which had been proposed in the administration's budget, were not included in the draft (⁹ [A#00690070001], p. 3).

$1 Bil. Buys You Less Pediatric Exclusivity

The draft bill would also reauthorize the pediatric exclusivity program with modifications that would require drug sponsors to conduct studies earlier in a product's life-cycle in order to receive the incentive.

Under the bill, FDA could not award pediatric exclusivity less than one year before the expiration of an affected patent, and usually could not award exclusivity until pediatric information had been added to a product's label.

The provisions appear designed to address concerns from FDA that it often does not have sufficient time to review the data submitted under the program and concerns from the generic industry that pediatric exclusivity awards at the end of patent life make it difficult to plan ANDA launches.

The changes essentially mean that sponsors would have to complete their pediatric studies 18 months before they often do in order to give FDA time to review and approve the labeling before the cutoff.

The draft bill also caps exclusivity for blockbuster drugs, giving products with more than $1 billion in sales only three months of exclusivity instead of the six months that all products had previously been awarded.

The shorter exclusivity would apply when the "combined annual gross sales for all drugs with the same active moiety exceeded $1,000,000,000 in any calendar year prior to the time the sponsor or holder agrees to a written request" for studies, the draft notes.

Sen. Chris Dodd, D-Conn., a sponsor of the incentive program being reauthorized, expressed interest in shortening exclusivity during a March hearing (¹⁰ [A#00690140012], p. 21). As in the past two iterations of pediatric exclusivity, the new bill reauthorizes the program for five years.

Streamlining FDA's Pediatric Powers

The bill also reauthorizes, permanently, FDA's authority to require pediatric studies of drugs under the Pediatric Research Equity Act, now to be called the Pediatric Research Improvement Act.

At the hearing on pediatric issues, the head of Johnson & Johnson's Pediatric Drug Development Center of Excellence, Samuel Maldonado, said that permanently reauthorizing both programs would spur industry to develop pediatric research expertise (¹¹ Also see "Permanent Pediatric Research Laws Would Spur In-House Units – J&J Exec" - Pink Sheet, 2 April, 2007., p. 20).

PRIA, championed by Sen. Clinton, includes provisions to have FDA better coordinate its consideration of exclusivity-related and mandated studies. FDA has never used its powers to require sponsors to conduct studies, "in part due to the lengthy administrative process required to invoke such authority," Kennedy's office notes.

"PRIA would streamline this administrative process and help get essential pediatric data for important drugs, while preserving the ability of companies to meet and discuss testing with the agency," Kennedy's office states.

FDA Needs To Pick Up The Phone

The draft legislation would also finalize a proposed rule creating a toll-free number for patients to report adverse events.

In 2002, the Best Pharmaceuticals for Children Act mandated that FDA issue a rule establishing a procedure for prescriptions to be dispensed with a phone number allowing patients to contact FDA.

The agency is concerned that the requirement could result in a high volume of calls that would drain resources without producing much worthwhile drug safety data. FDA issued a proposed rule in 2004 on the issue (¹² [A#00660170038], p. 39).

The agency continues to conduct research to refine the wording of the statement (¹³ Also see "Adverse Event Reporting Hotline Being Refined Through FDA Labeling Study" - Pink Sheet, 12 February, 2007., p. 21). However, were the legislation to pass, the existing proposed rule would become effective within 60 days unless FDA finalizes its own rule before then.

The pharmaceutical industry has expressed reservations about the rule out of fear that it might lead to FDA receiving reports about product issues while leaving sponsors uninformed about adverse events. The bill appears to address this concern by exempting from the rule packaging that "includes a toll-free number through which consumers can report complaints to the manufacturer."

- M. Nielsen Hobbs (n.hobbs@elsevier.com)

PDUFA Draft Bill Adds $70 Mil. For Rx Safety To User Fee Totals; Mark-Up Looms

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