CIBA-GEIGY's ACUTRIM MAY REMAIN ON THE MARKET WITHOUT APPROVED NDA, PRIOR TO FINAL MONOGRAPH; PHENYLPROPANOLAMINE IN OROS POSES NO SAFETY RISK, FDA SAYS

FDA is formally dropping a regulatory action against Ciba-Geigy's Acutrim, the agency told the firm in a Nov. 26 letter. The OTC phenylpropanolamine weight control product may therefore remain on the market without an NDA, until publication of a final monograph on OTC weight control products. In a regulatory letter issued May 26, FDA had told the firm that because Acutrim employs Alza's "new and unique" OROS timed-release dosage system, the product is a new drug requring an approved NDA for continued marketing. At that time, FDA Center for Drugs & Biologics Office of Compliance Director Daniel Michaels stated that "such drug when incorporating the OROS delivery system is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use" as stated in Acutrim labeling ("The Pink Sheet" May 28, p. 3). In a May 18 letter to FDA, Ciba-Geigy cited the agency's preamble to the Miscellaneous Internal Panel report on OTC weight control products, which stated that sustained-release products containing the maximum 75 mg daily dosage of phenylpropanolamine would require NDAs upon publication of a final monograph. Ciba-Geigy asserted that the preamble "makes no distinctions among timed-release technologies or systems." Further, the company said the panel report "does not purport to cover inactive ingredients or timed-release technology." Retracting FDA's position on Acutrim, Michaels stated in his Nov. 26 letter: "We intended the policy statement set out in the Weight Control Drug Products Panel Report . . . to apply only to dosage forms then on the market. However, we now realize that our position could have been stated more clearly. In view of the fact that there appears to be no safety risk arising from the use in Acutrim of the osmotic release oral system (OROS), and in view of the arguably ambiguous language in the panel report, we do not believe that regulatory action is indicated at the present time." In affirming that Oros does not pose a safety risk with Acutrim, FDA indicated it is more comfortable with the Alza delivery system. Ciba-Geigy began discussions with FDA over the status of Acutrim after the withdrawal from European markets of Merck's Oros/Indocin product, Osmosin, and several agency inspections of Ciba-Geigy plants. Ciba-Geigy asserted in its letter to FDA in May that technology in the Acutrim timed-release system is similar to other timed-release products on the market which have not incurred regulatory action in advance of the final monograph. FDA may have decided it was more expeditious to hold off on Acutrim rather than initiating regulatory action against the various other OTC timed release products on the market. We intended the policy statement sat out in the Weight Control Drug Products Panel Report (47 FR 8466 at 8468) to apply only to dosage forms than on the market. However, we now realize that our position could have been stated more clearly. In view of the fact that there appears to be no safety risk arising from the use in ACUTRIM of the osmotic release oral system (OROS), and in view of the arguably ambiguous language in the Panel Report, we do not believe that regulatory action is indicated at the present time. FDA Center for Drugs and Biologics Office of Compliance Director Daniel Michels in a Nov. 26 letter to Ciba-Geigy