Food and Drug Administration, HHS § 355.3 modification or alternative procedure § 355.3 Definitions. shall be submitted as a petition in ac- As used in this part: cord with § 10.30 of this chapter. The pe- tition should contain data to support (a) Abrasive. Solid materials that are the modification or data dem- added to dentifrices to facilitate me- onstrating that an alternative proce- chanical removal of dental plaque, de- dure provides results of equivalent ac- bris, and stain from tooth surfaces. curacy. All information submitted will (b) Anhydrous glycerin. An ingredient be subject to the disclosure rules in that may be prepared by heating glyc- part 20 of this chapter. erin U.S.P. at 150 –C for 2 hours to drive off the moisture content. PART 355—ANTICARIES DRUG (c) Anticaries drug. A drug that aids in the prevention and prophylactic PRODUCTS FOR OVER-THE- treatment of dental cavities (decay, COUNTER HUMAN USE caries). (d) Dental caries. A disease of calcified Subpart A—General Provisions tissues of teeth characterized by Sec. demineralization of the inorganic por- 355.1 Scope. tion and destruction of the organic ma- 355.3 Definitions. trix. (e) Dentifrice. An abrasive-containing Subpart B—Active Ingredients dosage form (gel, paste, or powder) for delivering an anticaries drug to the 355.10 Anticaries active ingredients. teeth. 355.20 Packaging conditions. (f) Fluoride. The inorganic form of the Subpart C—Labeling chemical element fluorine in combina- tion with other elements. 355.50 Labeling of anticaries drug products. (g) Fluoride ion. The negatively 355.55 Principal display panel of all fluoride charged atom of the chemical element rinse drug products. fluorine. 335.60 Professional labeling. (h) Fluoride supplement. A special treatment rinse dosage form that is in- Subpart D—Testing Procedures tended to be swallowed, and is pro- 355.70 Testing procedures for fluoride den- moted to health professionals for use in tifrice drug products. areas where the water supply contains AUTHORITY: 21 U.S.C. 321, 351, 352, 353, 355, 0 to 0.7 parts per million (ppm) fluoride 360, 371. ion. (i) Preventive treatment gel. A dosage SOURCE: 60 FR 52507, Oct. 6, 1995, unless form for delivering an anticaries drug otherwise noted. to the teeth. Preventive treatment gels EDITORIAL NOTE: Nomenclature changes to are formulated in an anhydrous glyc- part 355 appear at 69 FR 13717, Mar. 24, 2004. erin base with suitable thickening agents included to adjust viscosity. Subpart A—General Provisions Preventive treatment gels do not con- tain abrasives. § 355.1 Scope. (j) Treatment rinse. A liquid dosage (a) An over-the-counter anticaries form for delivering an anticaries drug drug product in a form suitable for top- to the teeth. ical administration to the teeth is gen- (k) Treatment rinse concentrated solu- erally recognized as safe and effective tion. A fluoride treatment rinse in a and is not misbranded if it meets each concentrated form to be mixed with condition in this part and each general water before using to result in the ap- condition established in § 330.1 of this propriate fluoride concentration speci- chapter. fied in the monograph. (b) References in this part to regu- (l) Treatment rinse effervescent tablets. latory sections of the Code of Federal A fluoride treatment rinse prepared by Regulations are to chapter I of title 21 adding an effervescent tablet (a con- unless otherwise noted. centrated solid dosage form) to water 301 VerDate Aug<31>2005 14:36 May 08, 2008 Jkt 214069 PO 00000 Frm 00311 Fmt 8010 Sfmt 8010 Y:\SGML\214069.XXX 214069 dwashington3 on PRODPC61 with CFR § 355.10 21 CFR Ch. I (4–1–08 Edition) before using to result in the appro- 0.02-percent or 0.05-percent aqueous so- priate fluoride concentration specified lution with a pH of approximately 7. in the monograph. (b) Sodium monofluorophosphate—(1) (m) Treatment rinse powder. A fluoride Dentifrices containing 850 to 1,150 ppm treatment rinse prepared by adding the theoretical total fluorine in a gel or paste powder (a concentrated solid dosage dosage form. Sodium monofluoro- form) to water before using to result in phosphate 0.654 to 0.884 percent with an the appropriate fluoride concentration available fluoride ion concentration = ¥ specified in the monograph. (consisting of PO3 F and F combined) ≥ 800 ppm. [60 FR 52507, Oct. 6, 1995, as amended at 61 FR 52286, Oct. 7, 1996] (2) Dentifrices containing 1,500 ppm the- oretical total fluorine in a gel or paste dosage form. Sodium monofluoro- Subpart B—Active Ingredients phosphate 1.153 percent with an avail- able fluoride ion concentration (con- § 355.10 Anticaries active ingredients. = ¥ sisting of PO3 F and F combined) ≥ The active ingredient of the product 1,275 ppm. consists of any of the following when (c) Stannous fluoride—(1) Dentifrices used in the concentration and dosage containing 850 to 1,150 ppm theoretical form established for each ingredient: total fluorine in a gel or paste dosage (a) Sodium fluoride—(1) Dentifrices con- form. (i) Stannous fluoride 0.351 to 0.474 taining 850 to 1,150 ppm theoretical total percent with an available fluoride ion fluorine in a gel or paste dosage form. So- concentration ≥ 700 ppm for products dium fluoride 0.188 to 0.254 percent with containing abrasives other than cal- an available fluoride ion concentration cium pyrophosphate. ≥ 650 parts per million (ppm). (ii) Stannous fluoride 0.351 to 0.474 (2) Dentifrices containing 850 to 1,150 percent with an available fluoride ion ppm theoretical total fluorine in a pow- concentration ≥ 290 ppm for products dered dosage form. Sodium fluoride 0.188 containing the abrasive calcium to 0.254 percent with an available fluo- ≥ pyrophosphate. ride ion concentration of 850 ppm for (2) Preventive treatment gel. Stannous products containing the abrasive so- fluoride 0.4 percent in an anhydrous dium bicarbonate and a poured-bulk glycerin gel, made from anhydrous density of 1.0 to 1.2 grams per milli- glycerin and the addition of suitable liter. thickening agents to adjust viscosity. (3) Treatment rinses. (i) An aqueous so- (3) Treatment rinse. Stannous fluoride lution of acidulated phosphate fluoride concentrate marketed in a stable form derived from sodium fluoride and containing adequate directions for acidulated with a mixture of sodium mixing with water immediately before phosphate, monobasic, and phosphoric using to result in a 0.1-percent aqueous acid to a level of 0.1 molar phosphate solution. ion and a pH of 3.0 to 4.5 and which yields an effective fluoride ion con- [60 FR 52507, Oct. 6, 1995, as amended at 61 FR centration of 0.02 percent. 52286, Oct. 7, 1996] (ii) An aqueous solution of acidulated phosphate fluoride derived from so- § 355.20 Packaging conditions. dium fluoride acidulated with a mix- (a) Package size limitation. Due to the ture of sodium phosphate, dibasic, and toxicity associated with fluoride active phosphoric acid to a pH of 3.5 and ingredients, the following package size which yields an effective fluoride ion limitations are required for anticaries concentration of 0.01 percent. drug products: (iii) Sodium fluoride 0.02 percent (1) Dentifrices. Dentifrice (toothpastes aqueous solution with a pH of approxi- and tooth powders) packages shall not mately 7. contain more than 276 milligrams (mg) (iv) Sodium fluoride 0.05 percent total fluorine per package. aqueous solution with a pH of approxi- (2) Preventive treatment gels and treat- mately 7. ment rinses. Preventive treatment gel (v) Sodium fluoride concentrate con- and treatment rinse packages shall not taining adequate directions for mixing contain more than 120 mg total fluo- with water before using to result in a rine per package. 302 VerDate Aug<31>2005 14:36 May 08, 2008 Jkt 214069 PO 00000 Frm 00312 Fmt 8010 Sfmt 8010 Y:\SGML\214069.XXX 214069 dwashington3 on PRODPC61 with CFR Food and Drug Administration, HHS § 355.50 (3) Exception. Package size limita- tion into interstate commerce of unap- tions do not apply to anticaries drug proved new drugs in violation of sec- products marketed for professional of- tion 505(a) of the act. fice use only and labeled in accord with (c) Warning. The labeling of the prod- § 355.60. uct contains the following warning (b) Tight container packaging. To min- under the heading ‘‘Warning’’: imize moisture contamination, all fluo- (1) For all fluoride dentifrice (gel, paste, ride powdered dentifrices shall be pack- and powder) products. ‘‘Keep out of aged in a tight container as defined as reach of children under 6 years of age. a container that protects the contents [highlighted in bold type] If more than from contamination by extraneous liq- used for brushing is accidentally swal- uids, solids, or vapors, from loss of the lowed, get medical help or contact a article, and from efflorescence, deli- Poison Control Center right away.’’ quescence, or evaporation under the or- These warnings shall be used in place dinary or customary conditions of han- of the general warning statements re- dling, shipment, storage, and distribu- quired by § 330.1(g) of this chapter. tion, and is capable of tight reclosure. (2) For all fluoride rinse and preventive treatment gel products. ‘‘Keep out of Subpart C—Labeling reach of children. [highlighted in bold type] If more than used for’’ (select ap- § 355.50 Labeling of anticaries drug propriate word: ‘‘brushing’’ or ‘‘rins- products. ing’’) ‘‘is accidentally swallowed, get (a) Statement of identity. The labeling medical help or contact a Poison Con- of the product contains the established trol Center right away.’’ These warn- name of the drug, if any, and identifies ings shall be used in place of the gen- the product as: (select one or both of eral warning statements required by the following: ‘anticavity’ or ‘fluoride’) § 330.1(g) of this chapter.