ATTAPULGITE TO LOSE MONOGRAPH STATUS AS ANTIDIARRHEAL INGREDIENT

ATTAPULGITE TO LOSE MONOGRAPH STATUS AS ANTIDIARRHEAL INGREDIENT, FDA indicated to the Nonprescription Drug Manufacturers Association in a Sept. 14 letter. Responding to an Aug. 10 request from NDMA that FDA defer acting on attapulgite in the upcoming OTC antidiarrheal products final monograph to allow for the industry to submit additional efficacy data ("The Tan Sheet" Aug. 23, p. 15), FDA Monograph Review Staff Director William Gilbertson declared that "we must deny your request for the deferment of attapulgite from the final monograph at this time." Gilbertson noted that the "study results and the quality of the data on attapulgite that were reviewed" by a joint meeting of FDA's Nonprescription and Gastrointestinal Drugs Advisory Committees "have raised questions concerning the efficacy of attapulgite." At an April 9 session, the two committees found that attapulgite's effectiveness as an antidiarrheal is unproven in adults based on data from four attapulgite studies, that attapulgite's safety and efficacy in children has not been established, and that additional studies would be needed to support monograph status ("The Tan Sheet" April 12, p. 1). FDA is in "the last stages of completing the rulemaking for OTC antidiarrheal drug products," Gilbertson said, and is "in the process of evaluating the committees' recommendations, which will provide important input into our regulatory decision making." In the April 1986 tentative final monograph for OTC antidiarrheals, FDA moved attapulgite from Category III (data insufficient to permit classification) to Category I (safe and effective). Gilbertson told NDMA, however, that "because the issues regarding attapulgite were only recently addressed in this rulemaking," should "relevant data be submitted to the agency before the effective date of the final monograph, consideration will be given to deferring attapulgite from the effective date of the final monograph . . . until the agency completes its review of the study(s)." The FDAer pointed out that, in a recent telephone call, Office of OTC Drug Evaluation Director Michael Weintraub told NDMA that due to the advisory committees' determination that attapulgite has not been proven safe by existing studies, the association should "prepare more substantial data, using more modem effectiveness criteria, to submit to the agency." A meeting to discuss a potential protocol could be arranged if NDMA decides to conduct such studies, Gilbertson added. In its letter to FDA, NDMA noted that it would be contacting the agency to schedule a meeting to discuss the NDMA Attapulgite Study Group's research agenda for attapulgite. NDMA had requested an OTC feedback meeting with FDA in the summer to discuss the recommendations of the advisory committees; however, that meeting was ultimately postponed. Responding to specific arguments made by NDMA in its August request, Gilbertson said: "Although your letter cites several precedents in which the agency deferred particular ingredients" from final monographs, such as doxylamine succinate as an antihistamine and yellow mercuric oxide as an ophthalmic anti- infective, "it should be noted that in all those cases, data on these ingredients were pending before the agency. This is not the case with attapulgite." Therefore, he continued, "there is no mechanism by which the agency can permit the ongoing marketing of attapulgite-containing antidiarrheal products pending an agency decision on new data submitted after the effective date of the final monograph," particularly if the product is determined to be Category III. Replying to NDMA's request that FDA reopen the administrative record to allow for the submission of additional data, Gilbertson underscored that this procedure is "not intended to stop the OTC drug review process while manufacturers conduct studies or generate new information or data." He continued: "If the agency were to keep an administrative record open in anticipation of expected data from a proposed clinical study -- the results of which may or may not support the upgrading of an ingredient to monograph status -- the OTC drug review would be greatly delayed, thereby prolonging the exposure of consumers to drug products that have not been proven to be safe and effective." Regarding the trade group's suggestion that the antidiarrheal TFM be amended to reclassify attapulgite as Category III, thereby allowing industry additional time to submit data, the FDAer clarified that the purpose of amending a TFM is to "provide a comment period on new data and information already before the agency, not to provide additional time for the submission of new data." Currently, "no new data on attapulgite are pending before the agency," he concluded. In the same letter to NDMA, Gilbertson also noted that antidiarrheal ingredients polycarbophil and calcium polycarbophil would be considered in the final monograph in the "same manner as indicated in this letter for attapulgite".