FDA OFFICES OF SUPPLEMENTAL APPROVALS WOULD BE ESTABLISHED BY AMENDED KASSEBAUM BILL; "MEDGUIDE" WOULD BE BLOCKED BY COATS AMENDMENT

FDA would be required to establish offices of supplemental approval in each of its centers under the version of Sen. Kassebaum's (R-Kan.) FDA reform bill that emerged from committee mark-up March 28. The provision is part of an amendment promoting the submission and approval of NDA supplements that was introduced by Sen. Kennedy (D-Mass.) and approved on a voice vote.

"One of the most contentious issues in this debate has been the issue of off-label promotion," Kennedy stated. "Whatever side you take, all of us should be able to agree that it is best when products are used for supplemental indications based on carefully controlled studies that meet the FDA's rigorous approval standards." The idea of devoting FDA staff to supplemental indications was raised by representatives of the Patients' Coalition during the Feb. 22 Labor & Human Resources hearing on off-label uses ("The Pink Sheet" Feb. 26, p. 5).

Under the Kennedy amendment, FDA would be required to issue performance standards for supplemental reviews and guidances to industry explaining the requirements for supplemental applications within 180 days of the enactment of the amended bill.

FDA also would be required to work with NIH and other medical and scientific organizations to "identify published and unpublished studies that could support a supplemental application, and to encourage sponsors to make application or conduct further research in support of an application based, in whole or in part, on such studies."

An amendment proposed by Sen. Kennedy to extend FDA approval deadlines and remove the "hammer" mandating third-party reviews if the agency fails to meet statutory deadlines was rejected along party lines. Kennedy also outlined a series of changes to the bill that he plans to introduce when the bill reaches the floor.

The amended Kassebaum bill passed mark-up with bipartisan support on a 12-4 vote. While Kennedy, the committee's ranking Democrat, opposed the legislation, Sens. Mikulski (D-Md.), Dodd (D-Ct.) and Harkin (D-Iowa) voted for the bill along with Republican committee members. Floor time has reportedly been scheduled for mid-April.

The amended bill also establishes an office within the Center for Drug Evaluation & Research to regulate radiopharmaceuticals, pursuant to a proposal introduced by Sens. Gregg (R-N.H.), Ashcroft (R-Mo.) and Frist (R-Tenn.) and accepted on a voice vote. FDA would also be required to promulgate regulations governing the approval of radiopharmaceuticals designed for diagnosis and monitoring.

Implementation of FDA's Aug. 24, 1995 "MedGuide" proposal on patient prescription drug information would be stalled by the bill, under an amendment submitted by Sen. Coats (R-Ind.) and accepted on a 13-3 vote. The Coats rule, which received support from both the pharmaceutical and pharmacy industries, requires a committee formed from industry, health professionals and consumer groups to "develop a long-range plan to achieve goals consistent with the goals of the FDA's proposed rule."

FDA could move forward on its prescription drug labeling plan if a substitute proposal is not submitted by the private committee within four months. The agency also would review the private-sector program, and could implement MedGuide if it felt that the results were inadequate.

Kennedy, who voted against the amendment with Sens. Pell (D-R.I.) and Simon (D-Ill.), argued that FDA should not be excluded from the process of developing consumer information. The measure was supported by all the Republican senators, along with Democrats Dodd, Mikulski, Harkin and Wellstone (D-Minn.).

Independent centers for education and research on drugs, devices and biological products would be established by the bill under an amendment proposed by Sen. Frist and accepted by voice vote. Frist indicated that grants awarded under the bill would be used to perform studies inadequately addressed by corporate research, such as product comparisons and dosage studies.

Committee members stressed that the establishment of such centers would be dependent upon the appropriation of already limited funds. The bill authorizes appropriations of $9 mil. for FY 1997, $12 mil. for FY 1998 and $15 mil. for both FY 1999 and FY 2000. Federally funded research centers have been championed by Georgetown University Pharmacy Department Chairman Raymond Woosley, MD, who testified at Senate FDA reform hearings on off-label uses Feb. 22 ("The Pink Sheet" Feb. 26, p. 4).

An amendment co-sponsored by Sens. Simon and Frist reauthorizes the clinical pharmacology program for the next two years. That amendment also passed on a voice vote.

Future FDA Commissioners would have a term limit of five years and would undergo confirmation by the Senate under a Coats amendment.

The Commissioner could be reappointed for a second five-year term, but would have to undergo a new confirmation process. The amendment, which would not apply to sitting Commissioner Kessler, was passed by a vote of 9-7, with Michigan Sen. Abraham the only Republican voting against the measure, and Sen. Simon the sole Democrat to vote in favor.

Support for granting votes to advisory committee industry representatives was voiced by Sen. Coats in response to an amendment proposed by Sen. Wellstone to make patient representatives on advisory committees voting members. To resolve that issue during mark-up, Sen. Kassebaum moved to strike the language on patient and industry advisory committee reps from the bill, restoring the status quo for the time being.

A three-year pilot program for third-party review of medical devices would be established by an amendment proposed by Sen. Coats. Democratic Sens. Dodd, Mikulski and Wellstone joined the committee's Republicans in supporting the proposal.

Sen. Harkin, who noted that he could support an experiment in third-party review, opposed the amendment citing particular concern over the provision that the reviewing third party would contract its services directly with the manufacturer. Harkin also argued that FDA should retain the decision over which reviews are contracted out; the Coats amendment allows manufacturers to decide whether FDA or a third party would review the device application. The House bill follows Coats' approach for all products.

Movement toward international harmonization agreements is supported by the bill, under a "sense of the committee" amendment introduced by Gregg and accepted by voice vote. "The committee would urge that the Secretary of Health and Human Services regularly participate in meetings with other foreign governments to discuss and reach agreement on methods and approaches to harmonize regulatory requirements," the bill now states.

The latest Kassebaum mark has removed language that would allow approval of new uses of approved drugs based on common medical practice and expert opinions. That change was among the amendments requested by the Patients' Coalition in a March 15 letter to Labor & Human Resources Committee members.

The bill also removes provisions that would have required FDA to set performance standards for action on "letters, telephone calls, requests for meetings, and the scheduling of requested meetings." In his opening statement, Kennedy complained that the Kassebaum bill, despite "laudable" goals, "imposes a massive new structure of red tape and micromanagement on the agency" by adding expanded bureaucratic requirements.