PART 355—ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371. Source: 60 FR 52507, Oct. 6, 1995, unless otherwise noted. Editorial Note: Nomenclature changes to part 355 appear at 69 FR 13717, Mar. 24, 2004. Subpart A—General Provisions § 355.1 Scope. (a) An over-the-counter anticaries drug product in a form suitable for topical administration to the teeth is generally recognized as safe and effective and is not misbranded if it meets each condition in this part and each general condition established in § 330.1 of this chapter. (b) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21 unless otherwise noted. § 355.3 Definitions. As used in this part: (a) Abrasive. (b) Anhydrous glycerin. (c) Anticaries drug. (d) Dental caries. (e) Dentifrice. (f) Fluoride. (g) Fluoride ion. (h) Fluoride supplement. (i) Preventive treatment gel. (j) Treatment rinse. (k) Treatment rinse concentrated solution. (l) Treatment rinse effervescent tablets. (m) Treatment rinse powder. [60 FR 52507, Oct. 6, 1995, as amended at 61 FR 52286, Oct. 7, 1996] Subpart B—Active Ingredients § 355.10 Anticaries active ingredients. The active ingredient of the product consists of any of the following when used in the concentration and dosage form established for each ingredient: (a) Sodium fluoride Dentifrices containing 850 to 1,150 ppm theoretical total fluorine in a gel or paste dosage form. (2) Dentifrices containing 850 to 1,150 ppm theoretical total fluorine in a powdered dosage form. (3) Treatment rinses. (ii) 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 and which yields an effective fluoride ion concentration of 0.01 percent. (iii) Sodium fluoride 0.02 percent aqueous solution with a pH of approximately 7. (iv) Sodium fluoride 0.05 percent aqueous solution with a pH of approximately 7. (v) Sodium fluoride concentrate containing adequate directions for mixing with water before using to result in a 0.02-percent or 0.05-percent aqueous solution with a pH of approximately 7. (b) Sodium monofluorophosphate Dentifrices containing 850 to 1,150 ppm theoretical total fluorine in a gel or paste dosage form. 3 = − (2) Dentifrices containing 1,500 ppm theoretical total fluorine in a gel or paste dosage form. 3 = − (c) Stannous fluoride Dentifrices containing 850 to 1,150 ppm theoretical total fluorine in a gel or paste dosage form. (ii) Stannous fluoride 0.351 to 0.474 percent with an available fluoride ion concentration ≥290 ppm for products containing the abrasive calcium pyrophosphate. (2) Preventive treatment gel. (3) Treatment rinse. [60 FR 52507, Oct. 6, 1995, as amended at 61 FR 52286, Oct. 7, 1996] § 355.20 Packaging conditions. (a) Package size limitation. (1) Dentifrices. (2) Preventive treatment gels and treatment rinses. (3) Exception. (b) Tight container packaging. Subpart C—Labeling § 355.50 Labeling of anticaries drug products. (a) Statement of identity. (b) Indication. (c) Warning. (1) For all fluoride dentifrice (gel, paste, and powder) products. (2) For all fluoride rinse and preventive treatment gel products. (d) Directions. (1) For anticaries dentifrice products Gel or paste dosage form with a theoretical total fluorine concentration of 850 to 1,150 ppm identified in § 355.10(a)(1), (b)(1), and (c)(1). (ii) Gel or paste dosage form with a theoretical total fluorine concentration of 1,500 ppm identified in § 355.10(b)(2). (iii) Powdered dosage form with a theoretical total fluorine concentration of 850 to 1,150 ppm identified in § 355.10(a)(2). (2) For anticaries treatment rinse products For acidulated phosphate fluoride solution containing 0.02 percent fluoride ion, sodium fluoride 0.05 percent, sodium fluoride concentrate, and stannous fluoride concentrate identified in § 355.10(a)(3)(i), (a)(3)(iv), (a)(3)(v), and (c)(3). (ii) For acidulated phosphate fluoride solution containing 0.01 percent fluoride ion and sodium fluoride 0.02 percent aqueous solution identified in § 355.10(a)(3)(ii) and (a)(3)(iii). (3) For stannous fluoride treatment rinse products. (ii) For powder or effervescent tablets used to prepare treatment rinses. (4) For anticaries preventive treatment gel products. (5) For all concentrated treatment rinse solutions, powders, and effervescent tablets. (e) Additional labeling statements for anticaries drug products. (1) For all preventive treatment gels. (2) For all stannous fluoride treatment rinse, preventive treatment gel, and dentifrice products. (f) Optional additional labeling statements For fluoride treatment rinses and preventive treatment gels. (2) For dentifrice products containing 1,500 ppm theoretical total fluorine. [60 FR 52507, Oct. 6, 1995; 60 FR 57927, Nov. 24, 1995; 61 FR 51187, Oct. 7, 1996; 64 FR 13296, Mar. 17, 1999] § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement of identity required in § 355.50, the following statement shall be prominently placed on the principal display panel: “IMPORTANT: Read directions for proper use.” § 355.60 Professional labeling. (a) The labeling for anticaries fluoride treatment rinses identified in § 355.10(a)(3) and (c)(3) that are specially formulated so they may be swallowed (fluoride supplements) and are provided to health professionals (but not to the general public) may contain the following additional dosage information: Children 3 to under 14 years of age: As a supplement in areas where the water supply is nonfluoridated (less than 0.3 parts per million (ppm)), clean the teeth with a toothpaste and rinse with 5 milliliters (mL) of 0.02 percent or 10 mL of 0.01 percent fluoride ion rinse daily, then swallow. When the water supply contains 0.3 to 0.7 ppm fluoride ion, reduce the dose to 2.5 mL of 0.02 percent or 5 mL of 0.01 percent fluoride ion rinse daily. (b) The labeling for products marketed to health to health professionals in package sizes larger than those specified in § 355.20 shall include the statements: “For Professional Office Use Only” and “This product is not intended for home or unsupervised consumer use.” Subpart D—Testing Procedures § 355.70 Testing procedures for fluoride dentifrice drug products. (a) A fluoride dentifrice drug product shall meet the biological test requirements for animal caries reduction and one of the following tests: Enamel solubility reduction or fluoride enamel uptake. The testing procedures for these biological tests are labeled Biological Testing Procedures for Fluoride Dentifrices (b) The United States Pharmacopeia fluoride dentifrice reference standards along with reference standard stability profiles (total fluoride, available fluoride ion, pH, and specific gravity) required to be used in the biological tests are available to any purchaser upon written request to the United States Pharmacopeial Convention, Inc., 1260 Twinbrook Parkway, Rockville, MD 20852. (c) Alternative testing procedures may be used. Any proposed modification or alternative testing procedures shall be submitted as a petition in accord with § 10.30 of this chapter. The petition should contain data to support the modification or data demonstrating that an alternative testing procedure provides results of equivalent accuracy. All information submitted will be subjected to the disclosure rules in part 20 of this chapter. [60 FR 52507, Oct. 6, 1995, as amended at 68 FR 24879, May 9, 2003; 88 FR 45066, July 14, 2023]