PART 333—TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371. Source: 52 FR 47322, Dec. 11, 1987, unless otherwise noted. Subpart A [Reserved] Subpart B—First Aid Antibiotic Drug Products § 333.101 Scope. (a) An over-the-counter first aid antibiotic drug product in a form suitable for topical administration is generally recognized as safe and effective and is not misbranded if it meets each of the conditions in this subpart and each of the general conditions established in § 330.1. (b) References in this subpart to regulatory sections of the Code of Federal Regulations are to chapter I of title 21 unless otherwise noted. § 333.103 Definitions. As used in this subpart: First aid antibiotic. [52 FR 47322, Dec. 11, 1987, as amended at 64 FR 403, Jan. 5, 1999] § 333.110 First aid antibiotic active ingredients. The product consists of any of the following active ingredients within the specified concentration established for each ingredient and in the specified dosage form: (a) Bacitracin ointment containing, in each gram, 500 units of bacitracin in a suitable ointment base. (b) Bacitracin zinc ointment containing, in each gram, 500 units of bacitracin zinc in a suitable ointment base. (c) Chlortetracycline hydrochloride ointment containing, in each gram, 30 milligrams of chlortetracycline hydrochloride in a suitable ointment base. (d) Neomycin sulfate ointment containing, in each gram, 3.5 milligrams of neomycin in a suitable water soluble or oleaginous ointment base. (e) Neomycin sulfate cream containing, in each gram, 3.5 milligrams of neomycin in a suitable cream base. (f) Tetracycline hydrochloride ointment containing, in each gram, 30 milligrams of tetracycline hydrochloride in a suitable ointment base. [52 FR 47322, Dec. 11, 1987, as amended at 53 FR 18838, May 25, 1988; 64 FR 403, Jan. 5, 1999] § 333.120 Permitted combinations of active ingredients. The following combinations are permitted provided each active ingredient is present within the established concentration and in the specified dosage form, and the product is labeled in accordance with § 333.160. (a) Combinations of antibiotic active ingredients. (2) Bacitracin-neomycin sulfate-polymyxin B sulfate ointment containing, in each gram, in a suitable ointment base the following: (i) 500 units of bacitracin, 3.5 milligrams of neomycin, and 5,000 units of polymyxin B; or (ii) 400 units of bacitracin, 3.5 milligrams of neomycin, and 5,000 units of polymyxin B; (3) Bacitracin-polymyxin B sulfate topical aerosol containing, in each gram, 500 units of bacitracin and 5,000 units of polymyxin B in a suitable vehicle, packaged in a pressurized container with suitable inert gases. (4) Bacitracin zinc-neomycin sulfate ointment containing, in each gram, 500 units of bacitracin and 3.5 milligrams of neomycin in a suitable ointment base. (5) Bacitracin zinc-neomycin sulfate-polymyxin B sulfate ointment containing, in each gram, in a suitable ointment base the following: (i) 400 units of bacitracin, 3 milligrams of neomycin, and 8,000 units of polymyxin B; or (ii) 400 units of bacitracin, 3.5 milligrams of neomycin, and 5,000 units of polymyxin B; or (iii) 500 units of bacitracin, 3.5 milligrams of neomycin, and 5,000 units of polymyxin B; or (iv) 500 units of bacitracin, 3.5 milligrams of neomycin, and 10,000 units of polymyxin B; (6) Bacitracin zinc-polymyxin B sulfate ointment containing, in each gram, 500 units of bacitracin and 10,000 units of polymyxin B in a suitable ointment base. (7) Bacitracin zinc-polymyxin B sulfate topical aerosol containing, in each gram, 120 units of bacitracin and 2,350 units of polymyxin B in a suitable vehicle, packaged in a pressurized container with suitable inert gases. (8) Bacitracin zinc-polymyxin B sulfate topical powder containing, in each gram, 500 units of bacitracin and 10,000 units of polymyxin B in a suitable base. (9) Neomycin sulfate-polymyxin B sulfate ointment containing, in each gram, 3.5 milligrams of neomycin and 5,000 units of polymyxin B in a suitable water miscible base. (10) Neomycin sulfate-polymyxin B sulfate cream containing, in each gram, 3.5 milligrams of neomycin and 10,000 units of polymyxin B in a suitable vehicle. (11) Oxytetracycline hydrochloride-polymyxin B sulfate ointment containing, in each gram, 30 milligrams of oxytetracycline and 10,000 units of polymyxin B in a suitable ointment base. (12) Oxytetracycline hydrochloride-polymyxin B sulfate topical powder containing, in each gram, 30 milligrams of oxytetracycline and 10,000 units of polymyxin B with a suitable filler. (b) Combinations of first aid antibiotic active ingredients and local anesthetic active ingredients. (2) Bacitracin-neomycin sulfate-polymyxin B sulfate ointment containing, in each gram, in a suitable ointment base the following: (i) 500 units of bacitracin, 3.5 milligrams of neomycin, 5,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient; or (ii) 400 units of bacitracin, 3.5 milligrams of neomycin, 5,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient. (3) Bacitracin-polymyxin B sulfate topical aerosol containing, in each gram, 500 units of bacitracin and 5,000 units of polymyxin B and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient in a suitable vehicle, packaged in a pressurized container with suitable inert gases. (4) Bacitracin zinc-neomycin sulfate-polymyxin B sulfate ointment containing, in each gram, in a suitable ointment base the following: (i) 400 units of bacitracin, 3 milligrams of neomycin, 8,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient; or (ii) 400 units of bacitracin, 3.5 milligrams of neomycin, 5,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient; or (iii) 500 units of bacitracin, 3.5 milligrams of neomycin, 5,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient; or (iv) 500 units of bacitracin, 3.5 milligrams of neomycin, 10,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient; (5) Bacitracin zinc-polymyxin B sulfate ointment containing, in each gram, 500 units of bacitracin, 10,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient in a suitable ointment base. (6) Neomycin sulfate-polymyxin B sulfate cream containing, in each gram, 3.5 milligrams of neomycin, 10,000 units of polymyxin B, and any single generally recognized as safe and effective amine or “caine”-type local anesthetic active ingredient in a suitable vehicle. [52 FR 47322, Dec. 11, 1987; 52 FR 48792, Dec. 24, 1987, as amended at 53 FR 18838, May 25, 1988; 55 FR 9722, Mar. 15, 1990; 55 FR 40381, Oct. 3, 1990; 55 FR 50172, Dec. 5, 1990; 64 FR 403, Jan. 5, 1999] § 333.150 Labeling of first aid antibiotic drug products. (a) Statement of identity. (b) Indications. (c) Warnings. (1) “For external use only. Do not use in the eyes or apply over large areas of the body. In case of deep or puncture wounds, animal bites, or serious burns, consult a doctor.” (2) For products containing chlortetracycline hydrochloride or tetracycline hydrochloride. (3) For any product containing bacitracin, bacitracin zinc, neomycin, neomycin sulfate, polymyxin B, and/or polymyxin B sulfate. (d) Directions. For ointment and cream products. (2) For powder products. (3) For aerosol products. (e) The word “doctor” may be substituted for the word “physician” in any of the labeling statements in this subpart. [52 FR 47332, Dec. 11, 1987, as amended at 61 FR 58472, Nov. 15, 1996] § 333.160 Labeling of permitted combinations of active ingredients. Statements of identity, indications, warnings, and directions for use, respectively, applicable to each ingredient in the product may be combined to eliminate duplicative words or phrases so that the resulting information is clear and understandable. (a) Statement of identity. (b) Indications. (1) For permitted combinations identified in § 333.120(a). (2) For permitted combinations identified in § 333.120(b). (c) Warnings. (d) Directions. Subpart C—Topical Antifungal Drug Products Source: 58 FR 49898, Sept. 23, 1993, unless otherwise noted. § 333.201 Scope. (a) An over-the-counter antifungal drug product in a form suitable for topical administration is generally recognized as safe and effective and is not misbranded if it meets each of the conditions in this subpart and each general condition established in § 330.1 of this chapter. (b) Reference in this subpart to regulatory sections of the Code of Federal Regulations are to chapter I of title 21 unless otherwise noted. § 333.203 Definitions. As used in this subpart: (a) Antifungal. (b) Athlete's foot. (c) Dermatophyte. (d) Fungus. (e) Jock itch. (f) Ringworm. § 333.210 Antifungal active ingredients. The active ingredient of the product consists of any one of the following within the specified concentration established for each ingredient: (a) Clioquinol 3 percent. (b) Haloprogin 1 percent. (c) Miconazole nitrate 2 percent. (d) Povidone-iodine 10 percent. (e) Tolnaftate 1 percent. (f) Undecylenic acid, calcium undecylenate, copper undecylenate, and zinc undecylenate may be used individually or in any ratio that provides a total undecylenate concentration of 10 to 25 percent. (g) Clotrimazole 1 percent. [58 FR 49898, Sept. 23, 1993, as amended at 67 FR 5943, Feb. 8, 2002] § 333.250 Labeling of antifungal drug products. (a) Statement of identity. (b) Indications. (1) For products containing any ingredient identified in § 333.210 labeled for the treatment of athlete's foot, jock itch, and ringworm. (A) “Athlete's foot,” athlete's foot (dermatophytosis),” “athlete's foot (tinea pedis),” or “tinea pedis (athlete's foot)”; (B) “Jock itch,” “jock itch (tinea cruris),” or “tinea cruris (jock itch)”; or (C) “Ringworm,” “ringworm (tinea corporis),” or “tinea corporis (ringworm).”) (ii) In addition to the information identified in paragraph (b)(1)(i) of this section, the labeling of the product may contain the following statement: (Select one of the following: “Relieves,” “For relief of,” “For effective relief of,” or “Soothes,”) (select one or more of the following: “Itching,” “scaling,” “cracking,” “burning,” “redness,” “soreness,” “irritation,” “discomfort,” “chafing associated with jock itch,” “itchy, scaly skin between the toes,” or “itching, burning feet”). (2) For products containing the ingredient identified in § 333.210(e) labeled for the prevention of athlete's foot. (ii) In addition to the information identified in paragraph (b)(2)(i) of this section, the labeling of the product may contain the following statement: “Clears up most athlete's foot infection and with daily use helps keep it from coming back.” (c) Warnings. (1) For products containing any ingredient identified in § 330.210. (ii) “For external use only.” (iii) “Avoid contact with the eyes.” (2) For products labeled according to paragraph (b)(1) of this section for the treatment of athlete's foot and ringworm. (3) For products labeled according to paragraph (b)(1) of this section for the treatment of jock itch. (4) For products labeled according to paragraph (b)(2) of this section for the prevention of athlete's foot. (5) For products containing the ingredient identified in § 333.210(a) labeled according to paragraph (b)(1) of this section. (ii) “Do not use for diaper rash.” (d) Directions. (1) For products labeled according to paragraph (b)(1) of this section for the treatment of athlete's foot, jock itch, and ringworm. (2) For products labeled according to paragraph (b)(2) of this section for the prevention of athlete's foot. (e) The word “physician” may be substituted for the word “doctor” in any of the labeling statements in this section. [58 FR 49898, Sept. 23, 1993, as amended at 65 FR 52305, Aug. 29, 2000] § 333.280 Professional labeling. The labeling provided to health professionals (but not to the general public) may contain the following additional indication: (a) For products containing haloprogin or miconazole nitrate identified in § 333.210 (a) and (c). Candida albicans (b) [Reserved] Subpart D—Topical Acne Drug Products Source: 56 FR 41019, Aug. 16, 1991, unless otherwise noted. § 333.301 Scope. (a) An over-the-counter acne drug product in a form suitable for topical application is generally recognized as safe and effective and is not misbranded if it meets each of the conditions in this subpart and each general condition established in § 330.1 of this chapter. (b) References in this subpart to regulatory sections of the Code of Federal Regulations are to chapter I of title 21 unless otherwise noted. § 333.303 Definitions. As used in this subpart: (a) Acne. (b) Acne blemish. (c) Acne drug product. (d) Acne pimple. (e) Blackhead. (f) Whitehead. § 333.310 Acne active ingredients. The active ingredient of the product consists of any of the following: (a) Benzoyl peroxide, 2.5 to 10 percent. (b) Resorcinol, 2 percent, when combined with sulfur in accordance with § 333.320(a). (c) Resorcinol monoacetate, 3 percent, when combined with sulfur in accordance with § 333.320(b). (d) Salicylic acid, 0.5 to 2 percent. (e) Sulfur, 3 to 10 percent. (f) Sulfur, 3 to 8 percent, when combined with resorcinol or resorcinol monoacetate in accordance with § 333.320. [75 FR 9776, Mar. 4, 2010] § 333.320 Permitted combinations of active ingredients. (a) Resorcinol identified in § 333.310(b) may be combined with sulfur identified in § 333.310(f). (b) Resorcinol monoacetate identified in § 333.310(c) may be combined with sulfur identified in § 333.310(f). [75 FR 9776, Mar. 4, 2010] § 333.350 Labeling of acne drug products. (a) Statement of identity. (b) Indications. (1) “For the” (select one of the following: “management” or “treatment”) “of acne.” (2) In addition to the information identified in paragraph (b)(1) of this section, the labeling of the product may contain any one or more of the following statements: (i) (Select one of the following: “Clears,” “Clears up,” “Clears up most,” “Dries,” “Dries up,” “Dries and clears,” “Helps clear,” “Helps clear up,” “Reduces the number of,” or “Reduces the severity of”) (select one or more of the following: “acne blemishes,” “acne pimples,” “blackheads,” or “whiteheads”) which may be followed by “and allows skin to heal.” (ii) “Penetrates pores to” (select one of the following: “eliminate most,” “control,” “clear most,” or “reduce the number of”) (select one or more of the following: “acne blemishes,” “acne pimples,” “blackheads,” or “whiteheads”). (iii) “Helps keep skin clear of new” (select one or more of the following: “acne blemishes,” “acne pimples,” “blackheads,” or “whiteheads”). (iv) “Helps prevent new” (select one or more of the following: “acne blemishes,” “acne pimples,” “blackheads,” or “whiteheads”) which may be followed by “from forming.” (v) “Helps prevent the development of new” (select one or more of the following: “acne blemishes,” “acne pimples,” “blackheads,” or “whiteheads”). (c) Warnings. (1) For products containing any ingredients identified in § 330.310. (i) The labeling states “For external use only.” (ii) The labeling states “When using this product [bullet] skin irritation and dryness is more likely to occur if you use another topical acne medication at the same time. If irritation occurs, only use one topical acne medication at a time.” (2) For products containing sulfur identified in § 333.310(e) and (f). (i) The labeling states “Do not use on [bullet] broken skin [bullet] large areas of the skin.” (ii) The labeling states “When using this product [bullet] apply only to areas with acne.” (3) For products containing any combination identified in § 333.320. (ii) The labeling states “Stop use and ask a doctor [bullet] if skin irritation occurs or gets worse.” (4) For products containing benzoyl peroxide identified in § 333.310(a). (i) The labeling states “Do not use if you [bullet] have very sensitive skin [bullet] are sensitive to benzoyl peroxide.” (ii) The labeling states “When using this product [bullet] avoid unnecessary sun exposure and use a sunscreen [bullet] avoid contact with the eyes, lips, and mouth [bullet] avoid contact with hair and dyed fabrics, which may be bleached by this product [bullet] skin irritation may occur, characterized by redness, burning, itching, peeling, or possibly swelling. Irritation may be reduced by using the product less frequently or in a lower concentration.” (iii) The labeling states “Stop use and ask a doctor if [bullet] irritation becomes severe.” (d) Directions. (1) For products applied containing any ingredient identified in § 333.310. (2) For products applied and left on the skin containing benzoyl peroxide identified in § 333.310(a). (i) The labeling states the directions in paragraph (d)(1) of this section. (ii) The labeling states “[bullet] if going outside, apply sunscreen after using this product. If irritation or sensitivity develops, stop use of both products and ask a doctor.” (3) For products applied and removed from the skin containing any ingredient identified in § 333.310. (4) Optional directions. Sensitivity Test for a New User. [56 FR 41019, Aug. 16, 1991, as amended at 75 FR 9776, Mar. 4, 2010]