DEL's AURO-DRI NEEDS ADDITIONAL CONFIRMATORY STUDY

DEL's AURO-DRI NEEDS ADDITIONAL CONFIRMATORY STUDY to support inclusion of the product (5% anhydrous glycerin in 95% isopropyl alcohol) in the tentative final monograph for OTC topical otic drug products for swimmer's ear, FDA told the company in a Nov. 30 letter. Responding to a July 30, 1987 submission from Del Pharmaceuticals that included an Auro-Dri study for preventing swimmer's ear, FDA noted that the study "provides some supportive information on the product's drying effect." However, FDA said it wants "at least one [additional] well-designed confirmatory study" showing the effectiveness of the product on subjects with a history of swimmer's ear. Currently, the ingredients in Auro-Dri are listed in Category III (data insufficient to permit classification). The double-blind, placebo-controlled study submitted by Del in 1987 involved 27 volunteers with unobstructed ear canals. One ear of each subject was filled with warm water. The subjects then tilted their heads to allow the water to run from the ear. Those subjects who retained water were then tested with Auro-Dri. The presence of water was recorded on video tape. Five drops of either water or the product were randomly placed into subjects' ears. After five minutes, subjects' ears were inspected under a microscope and the quantity of water remaining was determined. These results were also recorded on video tape. Del concluded from the study that Auro-Dri was "effective in 22 out of 25 subjects' ears," which translates into an 88% effectiveness rate. In the placebo group, only three of 24 subjects' ears were cleared. Del claimed in its submission that the study results were "very highly significant," according to FDA. While FDA acknowledged that the study contained "some supportive information," the agency outlined additional issues that need to be addressed to prove effectiveness of the product. FDA said that "the position of the [subject's] head and the length of time allowed for the water removal from the ear should be specified." Also, FDA suggested that if Del does not consider Auro-Dri a combination product, product labeling cannot include anhydrous glycerin as an active ingredient. Del would need to show, however, "the basis for [anhydrous glycerin's] use as a vehicle," the letter states. "If you wish to label the product with both ingredients . . . listed as active ingredients," the agency continued, "then a three-treatment study (mixture, glycerin, and isopropyl alcohol) would be necessary." FDA said that "a comparison of treatment to non-treatment would be acceptable" in such a study. FDA also noted that Del must submit proposed labeling for its product so that the agency can determine if labeling for the product is "in accord with the labeling that was proposed in the tentative final monograph." Del Pharmaceuticals said it will continue to market Auro-Dri pending a final monograph decision by FDA, and plans to conduct another clinical study to address FDA's concerns. The company has experienced several regulatory setbacks in the past year related to monograph rulings by FDA on active ingredients included in Del products. In December 1992, FDA published the final monograph for OTC ophthalmic drugs which included no safe and effective ingredients. At the time, Del was in the process of conducting an efficacy study for its yellow mercuric oxide-based Stye ophthalmic ointment ("The Tan Sheet" March 1, p. 12). FDA notified the company's counsel Weil, Gotshal & Manges on Nov. 2 that the data submitted by Del for the treatment of blepharitis or styes with yellow mercuric oxide are "inadequate to support a monograph amendment to include blepharitis and stye indications for OTC ophthalmic emollient ingredients." FDA said Del must "conform to the emollient sections of the final monograph" if it wishes to continue marketing its product without YMO. Earlier this spring, Office of OTC Drug Evaluation Director Michael Weintraub noted in a May 5 letter to the company that the final monograph "also found the stye indication to be nonmonograph." Therefore, Weintraub concluded that "the use of 'stye'. . . in the product's labeling would be misleading and could cause the product to be an unapproved new drug." Also, in November, FDA published the OTC boil treatment final rule without any monograph ingredients ("The Tan Sheet" Nov. 15, p. 4). In support of its Boil-Ease product, Del had submitted three benzocaine efficacy studies that also included data on ichthammol, sulfur and triclosan in January 1989 to support inclusion in the monograph. However, FDA ruled that none of the studies was "adequate" to support monograph status.