DRUG USER FEE REVIEW TIMES MAY BE RIPE FOR OVERSIGHT FROM REPUBLICANS: IS FDA STRETCHING DEADLINES?; KESSLER'S MOVE TO CLINTON PUTS FDA IN PRECARIOUS POSITION

FDA's progress in meeting its drag user fee review goals are a potential lightning rod for an efficiency-espousing, business- oriented Republican Congress.

As a supplementary budget program with a government commitment to efficiency, the user fee program provides a perfect target for Republican oversight. In addition it is timely because there are indications that FDA may be tailoring its review schedules to meet user fee deadlines without making as much progress toward faster drug approvals as the industry supporters of user fees had hoped.

Approximately six "approvable" NDAs for new molecular entities and 11 "approvable" NDAs for non-NMEs are pending at FDA. That may provide an opening for critics to charge that FDA looks as if it is making its primary objective getting drugs to the "approvable" stage.

FDA's review performance goals, which were developed in consultation with industry, are laid out in a Sept. 14, 1992 letter to Rep. Dingell (D-Mich.) from FDA Commissioner Kessler. The letter was an addendum to the drug user fee bill (HR 5952) ("The Pink Sheet" Sept. 12, 1992, p. 5). For products subject to user fees, FDA's review timeclock stops when it completes its first action on an application, either "approvable", approval, "nonapprovable" or not approved, and only restarts after the company has resolved outstanding issues such as appropriate labeling or manufacturing concerns.

Several companies have begun questioning the fairness of stopping the review clock while labeling and manufacturing issues are being worked out because resolution of these issues is not entirely under the companies' control.

Another issue that the pharmaceutical industry may take to Capitol Hill is the increasing amount of data that FDA is requiring of firms to get products approved. Agency requests for more data from animal studies before the initiation of human clinical trials have been a recent sore point with biotech companies.

Related to the amount of preclinical work, a trend has been observed of more Phase I studies being conducted outside the U.S. ("The Pink Sheet" April 11, T&G-2).

The increasing requirements are based on troubling preclinical studies with some drugs as well as the failure to predict that Lilly/Oclassen's hepatitis B drug fialuridine would cause liver and pancreatic injuries and deaths in clinical trial patients. While an investigating committee of the Democratic House (Rep. Towns' Government Operations subcommittee) was preparing further hearings on the FIAU trials, a Republican House may be more likely to look into the severity of FDA's attempt to prevent a repeat of the situation.

FDA is a target to the Republicans partially because of Commissioner Kessler' s visibility, and the image that he has cultivated as a surprise, Republican-appointed consumerist in a Democratic administration.

The commissioner has had set-tos with several leading Congressional Republicans, including Sen. Hatch (D-Utah), who has been critical of several Kessler initiatives including the dietary supplement act. Georgia Republican Rep. Gingrich, who is slated to become Speaker of the House, recently characterized FDA's activist role in the regulation of health products as bloated and unfair.

One interesting early indication of Kessler's ability and desire to weather the Republican controlled Congress may derive from the reaction to an upcoming feature on the commissioner on "60 Minutes." A segment is expected in late November or December.

The TV spot could give Kessler some protection as too visible a consumerist for the Republicans to attack. Just as likely, it could provide Kessler with an opportune time to begin to look for a way out of a job that is going to be less pleasant, with less chance of getting through his final agenda items.

The anti-smoking/nicotine program and patient drug labeling are believed to be two of Kessler's remaining goals for his tenure. Neither would go very far under the glare of the Republican Congress.

The drug patient labeling/information project was just beginning to get untracked again this month after a year-long delay. As part of an information-gathering process for developing the proposal, FDAers met with representatives from the Pharmaceutical Research & Manufacturers of America on Nov. 9. PhRMA is likely to object to FDA's medication guide idea if the industry has to incur the expense of standardizing the information for patients. The mandatory Patient Package Insert program proposed during the Carter Administration was strongly opposed by industry.

Defending the agency's ability to meet user fee commitments, FDA officials have been taking the public position that the agency is ahead of schedule in fulfilling its part of the agreement.

At a recent PDA/FDA meeting, Center for Drug Evaluation & Research Deputy Director for Review Management Murray Lumpkin said that for the FY 1993 cohort of 87 original and supplemental applications -these form the baseline for the user fee program and no performance goals were assigned -- 58% received a first action within the 12-month timeframe that FDA has committed to meet for 55% of NDAs and PLAs received during FY 1994 ("The Pink Sheet" Sept. 26, T&G-3).

Lumpkin noted that of the 12 NMES approved through August 1994, seven were filed in fiscal 1993 after user fee collection began and were reviewed in an average of 12.3 months, much less than the average time of 26.5 months for NMES approved in 1993. The average time to first action for the seven NMEs was 11.6 months (the times for Prograf injection and capsule NDAs were averaged). Lumpkin also reported the agency's success in its user fee goal of reducing the backlog of overdue applications.

A General Accounting Office report was commissioned by outgoing House Government Operations Subcommittee Chairman Towns (D-N.Y.). Towns criticized FDA's method of clocking review times as inadequate to measure how long it takes for drugs to be available to the public ("The Pink Sheet" Aug. 29, T&G-2).

The GAO report recommends that to better measure the timeliness of the approval process, the user fee act should be amended to require that Congress receive more information, such as length of the IND phase.

The agency is supposed to get another user fee efficiency analysis from the HHS Inspector General. The IG expects to issue the study in July, according to its FY 1995 work plan.