FDA May Amend Anticaries Monograph To Allow Combo Antiplaque Products

FDA may be amenable to an oral rinse product that crosses the anticaries and antiplaque/antigingivitis monographs if studies demonstrate safety and efficacy, agency officials told Warner-Lambert at an OTC "feedback" meeting in Rockville, Md. Oct. 8.

Following Warner-Lambert's request the agency amend the anticaries monograph to allow for a cross-over product combining antiplaque essential oils and fluoride, FDA said, the dual monographed product "doesn't seem unreasonable."

"We don't have any problems with the particular kind of product that you are proposing," OTC Drug Products Division Regulatory Counsel Gerald Rachanow said to company execs.

The "first thing that we need to establish is that the product is" generally recognized as safe and effective, Center for Drug Evaluation & Research OTC Drug Product Liaison Robert Sherman noted.

FDA's Dental Plaque Subcommittee has endorsed the concept of an anticaries/antiplaque product as a "rational combination," Sherman pointed out. The advisory group unanimously recommended the possible combination at a May 27-29, 1998 meeting (¹ (Also see "Listerine toothpaste six-month clinical trial necessary for gingivitis claims -- FDA cmte." - Pink Sheet, 1 Jun, 1998.)).

"We are still, in a sense, assessing that recommendation," Sherman noted.

Warner-Lambert Director of Regulatory Affairs Paul Okarma, PhD, urged FDA in written comments to agree to a regulatory pathway that would "harmonize dosage directions between two OTC monographs" so the company may market a product with a "rational combination...that provides both anticaries and antiplaque/antigingivitis benefits."

The anticaries monograph was published Oct. 6, 1995. The antiplaque/antigingivitis monograph, which has undergone extensive advisory consideration in recent years, has yet to become a final rule.

Warner-Lambert markets Listerine mouthwash products including Listerine Antiseptic Mouthrinse with antiplaque/antigingivitis benefits. At the May 1998 Dental Plaque subcommittee meeting, the company proposed a testing protocol for a Listerine antiplaque/antigingivitis toothpaste.

An oral care product, possibly called Listerine Oral Rinse with Fluoride, would combine antiplaque essential oils such as thymol, methyl salicylate, eucalyptol and menthol now used in Listerine mouthwashes with fluoride for anticaries benefits. To do this, W-L asked FDA to amend the anticaries monograph.

The company requested that the final rule's dosage provision for oral rinses - 10 mL two times a day for 60 seconds - be changed to 20 mL twice daily for 30 seconds. An alternate dosing could read: "Vigorously swish milliliters of rinse between your teeth for 30 seconds," Okarma noted.

The W-L exec also asked for an increased allowable pH level, along with the statement: "The active ingredient of the product consists of...an aqueous solution of acidulated phosphate fluoride derived from sodium fluoride acidulated with a mixture of sodium phosphate, dibasic and phosphoric acid to a pH of 3.5 or 4.2 and which yields an effective fluoride ion concentration of 0.01 percent."

Okarma said the company's requests are actually a "slight word change in the existing final rule," noting the ingredients in the proposed product "have all been recognized as Category I for both anticaries and antiplaque/antigingivitis."

An additional issue addressed at the meeting was how to enact the change expeditiously. FDA suggested two options: an amendment to the rule published in the Federal Register and a notice of enforcement policy.

Warner-Lambert noted an enforcement action may permit interim marketing of the product, while it is not clear whether the agency would allow interim marketing during the notice and comment period involved in amending a rule.

"One possible pathway would be simply that you can submit studies" in a citizen petition and wait on FDA's decision to amend the anticaries final monograph, FDA's Sherman stated. "That may not necessarily take any more time than an enforcement action."

Warner-Lambert pointed to ingredients allowed to be marketed before FDA action was taken. Combination hypersensitivity anticaries products, avobenzone sunscreens and cough/cold products, antacids, external analgesics and nighttime sleep-aids all set a precedent, W-L asserted.

OTC Drug Division Deputy Director Linda Katz, MD, suggested once W-L submits a petition and necessary data, "we could get back and talk with you and tell you what your options are."