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FDA’s NONPRESCRIPTION DRUG ADVISORY COMMITTEE TO HOLD INAUGURAL MEETING DEC. 15-16, INDUSTRY LIAISON REP SAYS; 10-MEMBER COMMITTEE ROSTER NOT YET DISCLOSED

Executive Summary

FDA's Nonprescription Drug Advisory Committee is scheduled to hold its inaugural meeting on Dec. 15-16. The agency has not yet officially announced the dates for the meeting because the process of selecting, clearing and approving committee member appointments is not complete. The industry liaison member to the committee, Clairol VP-R&D Edward Marlowe, reported on the upcoming meeting to the Nonprescription Drug Manufacturers Association Legal Section meeting in Washington, D.C. on Sept. 16. One of the main agenda items for the opening meeting, Marlowe reported, will be a "major presentation" by NDMA. Marlowe was chosen to be the industry liaison before he recently assumed a position outside the OTC drug field. NDMA has not indicated whether it will seek another representative actively involved in the OTC area. Marlowe was the president of consumer R&D through 1991 at Warner-Lambert. Although Marlowe did not provide details of NDMA's planned presentation, it is likely to be designed to try to define a framework for the advisory committee's functions. One of NDMA's outside attorneys, Peter Hutt (Covington & Burling) has extensive experience with the start-up of an advisory committee review process. As FDA chief counsel in the early 1970's, Hutt played a major role at the start of the OTC Review process and the establishment of the advisory panels for that review. Hutt advised the panels at that time about that nature of their reviews and the relationship between advisory committee decisions and subsequent FDA actions based on those discussions. Marlowe noted that FDA has changed the size, composition and name of the advisory committee since it was first proposed in September 1991. The agency initially asked for nominations for six voting members. The agency is now planning to have 10 voting members, with experts in biopharmaceutics and clinical pharmacology; representatives from dermatology, epidemiology, internal medicine, obstetrics and gynecology, and pediatrics. The addition of the pediatrician represents acceptance of a suggestion made by NDMA last year ("The Pink Sheet" Nov. 18, T&G-1). There will also be a pharmacy representative and a voting consumer advocate, Marlowe observed. The consumer advocate "will also be a professional from one of these disciplines." Marlowe noted that "we hope to have the names of the members soon." He could not specify "what 'soon' means." FDA can wait right until the last moment to announce the members without missing the mid-December meeting dates. The agency convened a similar inaugural meeting of its Generic Drugs Advisory Committee in mid-December of 1990 with only 15 days advance notice of the meeting and final committee membership. Potential topics for the OTC advisory committee, Marlowe speculated, "will be Rx-to-OTC switches"; "amendments to monographs"; "new claims -- non-sedating or less-sedating antihistamines could be presented"; "safety studies like the ones on benzoyl peroxide"; "clinical evaluations, such as the studies to support antihistamine efficacy"; "pediatric dosing"; "harmonizing" with international regulations; and "alternative methods for animal testing." Marlowe noted that the formation of the new organization within FDA (the Office of OTC Drugs) and the convening of the new advisory committee provide a "mega-opportunity" for the industry to shape the future of OTC regulation. Industry has the opportunity to work with FDA "on the management systems" from the ground up, Marlowe suggested, "so that we have priorities for our products, so that we have timeliness for our products." Contrasting the future for OTC reviews against "the horror stories" from NDA reviews in the new drug evaluation effort, Marlowe said that "we can set up meeting schedules that are realistic." Some precedents for Rx-to-OTC switch criteria have already been set by the decisions of the last decade, and the staff of the Office of OTC Drugs are continuing to work on defining the information that they will want to see when approval decisions are transferred from the NDA drug review offices. FDA's director of the monograph review, William Gilbertson identified over a dozen types of information that FDA expects in Rx-to-OTC switch applications in February 1991. Among his suggested criteria were data showing a "large margin of safety," a safety profile at high doses, and worldwide marketing and experience data ("The Pink Sheet" Feb. 4, T&G-15). Speaking at a Sept. 15 NDMA symposium on Rx-to-OTC switches, FDA consultant Michael Weintraub, MD, outlined three general characteristics for good OTC switch candidates: consistency, simplicity and safety. Weintraub, a clinical pharmacologist and investigator from the University of Rochester, is working at FDA and continues to be the leading candidate to head FDA's new Office of OTC Drugs. Weintraub suggested that small standard deviations in pharmacodynamics/pharmacokinetics would indicate a consistent, predictable effect in a broad range of patients. He explained that for a switch candidate to fit into his "consistency model," it should have certain pharmacokinetic characteristics that he described as "not necessary...but important considerations." Absorption of the drug should be "rapid and complete," he noted, "because slow absorption means inconsistent absorption." In addition, he said that medications with a "low level of first-pass hepatic extraction and metabolism will be more likely to provide a consistent response." To assure consistency, FDA would like to see OTC switch candidates studied in clinical trials using an "all-comer" patient population, Weintraub noted. "These would be typical medication users of both sexes across the expected age spectrum with varying severity of the treatable indication," he explained. "Innovations in clinical trial methodology allow these all-comer studies to approximate more closely the true-life OTC situation." Regarding simplicity, Weintraub suggested that ingredients with "one primary pharmacologic effect that leads to a defined clinical response or set of responses" make better switch candidates. Such products, he noted, are easier for consumers to use, have less problematic side effects and avoid confusion in OTC labeling. "In theory, a simple medication means that a large percentage of the population would achieve clinical benefit over a narrow dose range," Weintraub elaborated. "However, a simple medication should also have a relatively flat dose or concentration versus response relationship." Acknowledging that the two goals "are incompatible," he suggested that "this is a situation where the art of drug development and the art of regulatory science... must come into play." Safety issues to be considered include the potential for patient mis-diagnosis and the resulting likelihood of delays in seeking necessary treatment. Weintraub also pointed to the importance of consumer education in labeling and advertising when there are clearly recognizable patient groups for which a switch candidate should be contraindicated. Weintraub indicated that FDA would like to see foreign clinical data and labeling so that the agency can anticipate problems in the increasingly multi-ethnic U.S. population. "Whether you call that ethnopharmacology or use some other term," he said, "I believe that purchaser safety may depend on such data." Marlowe listed eight elements for switch applications: (1) market research to define the target population; (2) diagnosis information -- can the consumer diagnose the condition or is it previously diagnosed by the physician; (3) adverse drug reaction reports -- "hopefully on a worldwide basis, if the data are available;" (4) safety tests to support the OTC use; (5) potential warnings on drug or food interactions and dosing information about how and when to take the product; (6) dose-ranging studies -- "FDA is constantly asking what is the minimum effective dose."; (7) clinical protocols: double-blind cross-over studies where appropriate; (8) statistical methodology -- "this should not be an afterthought, this should be included when you decide the protocols."
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