§ 310.545 21 CFR Ch. I (4–1–19 Edition)

for marketing. In the absence of an ap- Chloroxylenol proved new drug application or abbre- Cloxyquin viated new drug application, such prod- Coal tar uct is also misbranded under section Dibenzothiophene Estrone 502 of the act. Magnesium aluminum silicate (c) Clinical investigations designed Magnesium sulfate to obtain evidence that any drug prod- Phenol uct labeled, represented, or promoted Phenolate sodium for OTC use as a smoking deterrent is Phenyl salicylate safe and effective for the purpose in- Povidone-iodine tended must comply with the require- Pyrilamine maleate ments and procedures governing the Resorcinol (as single ingredient) use of investigational new drugs set Resorcinol monoacetate (as single ingre- dient) forth in part 312 of this chapter. Salicylic acid (over 2 up to 5 percent) (d) After May 7, 1991, any such OTC Sodium borate drug product containing cloves, cori- Sodium thiosulfate ander, eucalyptus oil, ginger (Ja- Tetracaine hydrochloride maica), lemon oil (terpeneless), licorice Thymol root extract, menthol, methyl salicy- Vitamin E late, quinine ascorbate, silver nitrate, Zinc oxide and/or thymol initially introduced or Zinc stearate initially delivered for introduction into Zinc sulfide interstate commerce that is not in (2) Anticaries drug products—(i) Ap- compliance with this section is subject proved as of May 7, 1991. to regulatory action. After December 1, 1993, any such OTC drug product con- Hydrogen fluoride Sodium carbonate taining lobeline (in the form of lobeline Sodium monofluorophosphate (6 percent sulfate or natural lobelia alkaloids or rinse) Lobelia inflata herb), povidone-silver ni- Sodium phosphate trate, silver acetate, or any other in- gredients initially introduced or ini- (ii) Approved as of October 7, 1996. tially delivered for introduction into Calcium sucrose phosphate interstate commerce that is not in Dicalcium phosphate dihydrate compliance with this section is subject Disodium hydrogen phosphate 1 to regulatory action. Phosphoric acid 1 Sodium dihydrogen phosphate [58 FR 31241, June 1, 1993] Sodium dihydrogen phosphate monohydrate Sodium phosphate, dibasic anhydrous rea- § 310.545 Drug products containing gent 1 certain active ingredients offered over-the-counter (OTC) for certain (3) Antidiarrheal drug products—(i) Ap- uses. proved as of May 7, 1991. (a) A number of active ingredients Aluminum hydroxide have been present in OTC drug prod- Atropine sulfate ucts for various uses, as described Calcium carbonate below. However, based on evidence cur- Carboxymethylcellulose sodium rently available, there are inadequate Glycine Homatropine methylbromide data to establish general recognition of Hyoscyamine sulfate the safety and effectiveness of these in- Lactobacillus acidophilus gredients for the specified uses: Lactobacillus bulgaricus (1) Topical acne drug products. Opium, powdered Opium tincture Alcloxa Paregoric Alkyl isoquinolinium bromide Phenyl salicylate Aluminum chlorohydrex Scopolamine hydrobromide Aluminum hydroxide Zinc phenolsulfonate Benzocaine Benzoic acid Boric acid 1 These ingredients are nonmonograph ex- Calcium polysulfide cept when used to prepare acidulated phos- Calcium thiosulfate phate fluoride treatment rinses identified in Camphor § 355.10(a)(3) of this chapter.

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(ii) Approved as of April 19, 2004; April Cedar leaf oil (topical) 18, 2005, for products with annual sales Creosote, beechwood (topical) less than $25,000. Ephedrine (oral) Ephedrine hydrochloride (oral) Attapulgite, activated Ephedrine sulfate (oral) Bismuth subnitrate Racephedrine hydrochloride (oral/topical) Calcium hydroxide Calcium polycarbophil (C) Approved as of April 11, 2007; Oc- Charcoal (activated) tober 11, 2007, for products with annual Pectin sales less than $25,000. Any ingre- Polycarbophil dient(s) labeled with claims or direc- Potassium carbonate tions for use for sinusitis or for relief Rhubarb fluidextract of nasal congestion associated with si- (4) Antiperspirant drug products—(i) nusitis. Ingredients—Approved as of May 7, 1991. (iii) Expectorant drug products. Alum, potassium Ammonium chloride Aluminum bromohydrate Antimony potassium tartrate Aluminum chloride (alcoholic solutions) Beechwood creosote Aluminum chloride (aqueous solution) (aer- Benzoin preparations (compound tincture of osol only) benzoin, tincture of benzoin) Aluminum sulfate Camphor Aluminum sulfate, buffered (aerosol only) Chloroform Sodium aluminum chlorohydroxy lactate Eucalyptol/eucalyptus oil (ii) Approved as of December 9, 2004; Horehound June 9, 2005, for products with annual Iodides (calcium iodide anyhydrous, hydroid- sales less than $25,000. ic acid syrup, iodized lime, potassium io- dide) Aluminum sulfate buffered with sodium alu- Ipecac minum lactate Ipecac fluidextract Ipecac syrup (5) [Reserved] Menthol/peppermint oil (6) Cold, cough, allergy, bronchodilator, Pine tar preparations (extract white pine and antiasthmatic drug products—(i) compound, pine tar, syrup of pine tar, com- Antihistamine drug products—(A) Ingre- pound white pine syrup, white pine) dients. Potassium guaiacolsulfonate Sodium citrate Methapyrilene hydrochloride Squill preparations (squill, squill extract) Methapyrilene fumarate Terpin hydrate preparations (terpin hydrate, Thenyldiamine hydrochloride terpin hydrate elixir) (B) Ingredients. Tolu preparations (tolu, tolu balsam, tolu balsam tincture) Phenyltoloxamine dihydrogen citrate Turpentine oil (spirits of turpentine) Methapyrilene hydrochloride Methapyrilene fumarate (iv) Bronchodilator drug products—(A) Thenyldiamine hydrochloride Approved as of October 2, 1987. (ii) Nasal decongestant drug products— Aminophylline (A) Approved as of May 7, 1991. Belladonna alkaloids Euphorbia pilulifera Allyl isothiocyanate Metaproterenol sulfate Camphor (lozenge) Methoxyphenamine hydrochloride Creosote, beechwood (oral) Pseudoephedrine hydrochloride Eucalyptol (lozenge) Pseudoephedrine sulfate Eucalyptol (mouthwash) Theophylline, anhydrous Eucalyptus oil (lozenge) Theophylline calcium salicylate Eucalyptus oil (mouthwash) Menthol (mouthwash) Theophylline sodium glycinate Peppermint oil (mouthwash) (B) Approved as of January 29, 1996. Thenyldiamine hydrochloride Any combination drug product con- Thymol Thymol (lozenge) taining theophylline (e.g., theophylline Thymol (mouthwash) and ephedrine, or theophylline and Turpentine oil ephedrine and phenobarbital). (C) Approved as of June 19, 1996. Any (B) Approved as of August 23, 1995. ingredient(s) in a pressurized metered- Bornyl acetate (topical) dose inhaler container.

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(D) Approved as of October 29, 2001. Alcohol Any oral bronchodilator active ingre- Aluminum hydroxide dient (e.g., ephedrine, ephedrine hydro- Amylase Anise seed chloride, ephedrine sulfate, Aromatic powder racephedrine hydrochloride, or any Asafetida other ephedrine salt) in combination Aspergillus oryza enzymes (except lactase with any analgesic(s) or analgesic-anti- enzyme derived from Aspergillus oryzae) pyretic(s), anticholinergic, antihis- Bacillus acidophilus tamine, oral antitussive, or stimulant Bean active ingredient. Belladonna alkaloids (7) Dandruff/seborrheic dermatitis/psori- Belladonna leaves, powdered extract Betaine hydrochloride asis drug products. Bismuth subcarbonate Alkyl isoquinolinium bromide Bismuth subgallate Allantoin Black radish powder Blessed thistle (cnicus benedictus) Benzethonium chloride Buckthorn Boric acid Calcium gluconate Calcium undecylenate Capsicum Captan Capsicum, fluid extract of Chloroxylenol Carbon Colloidal oatmeal Cascara sagrada extract Cresol, saponated Catechu, tincture Ethohexadiol Catnip Eucalyptol Chamomile flowers Juniper tar Charcoal, wood Lauryl isoquinolinium bromide Chloroform Menthol Cinnamon oil oleate Cinnamon tincture Methylbenzethonium chloride Citrus pectin Methyl salicylate Diastase Phenol Diastase malt Phenolate sodium Dog grass Pine tar Elecampane Povidone-iodine Ether Resorcinol Fennel acid Sodium borate Galega Sodium salicylate Ginger Thymol Glycine Undecylenic acid Hydrastis canadensis (golden seal) Hectorite (8) Digestive aid drug products—(i) Ap- Horsetail proved as of May 7, 1991. Huckleberry Hydrastis fluid extract Bismuth sodium tartrate Hydrochloric acid Calcium carbonate Iodine Cellulase Iron ox bile Dehydrocholic acid Johnswort Dihydroxyaluminum sodium carbonate Juniper Duodenal substance Kaolin, colloidal Garlic, dehydrated Knotgrass Glutamic acid hydrochloride Lactic acid Hemicellulase Lactose Homatropine methylbromide Lavender compound, tincture of Magnesium hydroxide Linden Magnesium trisilicate Lipase Ox bile extract Lysine hydrochloride Pancreatin Mannitol Pancrelipase Mycozyme Papain Peppermint oil Myrrh, fluid extract of Pepsin Nettle Sodium bicarbonate Nickel-pectin Sodium citrate Nux vomica extract Orthophosphoric acid Papaya, natural (ii) Approved as of November 10, 1993. Pectin

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Peppermint Methapyrilene hydrochloride Peppermint spirit Methyl nicotinate Phenacetin Methyl salicylate Potassium bicarbonate Pectin Potassium carbonate Salicylamide Protease Strong ammonia solution Prolase Tannic acid Rhubarb fluid extract Thymol Senna Tripelennamine hydrochloride Sodium chloride Trolamine salicylate Sodium salicylate Turpentine oil Stem bromelain Zinc sulfate Strawberry Strychnine (vi) Insect bite and sting drug products. Tannic acid Alcohol Trillium Alcohol, ethoxylated alkyl Woodruff Benzalkonium chloride (iii) Charcoal, activated Calamine (9) [Reserved] Ergot fluidextract (10) External analgesic drug products— Ferric chloride Panthenol (i) Analgesic and anesthetic drug prod- Peppermint oil ucts. Pyrilamine maleate Aspirin Sodium borate Chloral hydrate Trolamine salicylate Chlorobutanol Turpentine oil Cyclomethycaine sulfate Zinc oxide Eugenol Zirconium oxide Hexylresorcinol (vii) Poison ivy, poison oak, and poison Methapyrilene hydrochloride Salicylamide sumac drug products. Thymol Alcohol (ii) Counterirritant drug products. Aspirin Benzethonium chloride Chloral hydrate Benzocaine (0.5 to 1.25 percent) Eucalyptus oil Bithionol Calamine (iii) Male genital desensitizer drug Cetalkonium chloride products. Chloral hydrate Benzyl alcohol Chlorobutanol Camphorated metacresol Chlorpheniramine maleate Ephedrine hydrochloride Creosote, beechwood Cyclomethycaine sulfate (iv) Diaper rash drug products. Any in- Dexpanthenol gredient(s) labeled with claims or di- Diperodon hydrochloride rections for use in the treatment and/ Eucalyptus oil or prevention of diaper rash. Eugenol (v) Fever blister and cold sore treatment Glycerin Glycol salicylate drug products. Hectorite Allyl isothiocyanate Hexylresorcinol Aspirin Hydrogen peroxide Bismuth sodium tartrate Impatiens biflora tincture Camphor (exceeding 3 percent) Iron oxide Capsaicin Isopropyl alcohol Capsicum Lanolin Capsicum oleoresin Lead acetate Chloral hydrate Chlorobutanol Mercuric chloride Cyclomethycaine sulfate Methapyrilene hydrochloride Eucalyptus oil Panthenol Eugenol Parethoxycaine hydrochloride Glycol salicylate Phenyltoloxamine dihydrogen citrate Hexylresorcinol Povidone-vinylacetate copolymers Histamine dihydrochloride Pyrilamine maleate Menthol (exceeding 1 percent) Salicylamide

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Salicylic acid (C) Stimulant laxatives—Approved as of Simethicone November 5, 2002. Sulfur Tannic acid Aloe ingredients (aloe, aloe extract, aloe Thymol flower extract) Trolamine salicylate Cascara sagrada ingredients (casanthranol, Turpentine oil cascara fluidextract aromatic, cascara Zirconium oxide sagrada bark, cascara sagrada extract, cas- cara sagrada fluidextract). Zyloxin (11) [Reserved] (13) [Reserved] (14) Oral health care drug products (12) Laxative drug products—(i)(A) (nonantimicrobial). Bulk laxatives. Antipyrine Agar Camphor Carrageenan (degraded) Cresol Carrageenan (native) Dibucaine Guar gun Dibucaine hydrochloride (i)(B) Bulk laxatives—Approved as of Eucalyptol Lidocaine March 29, 2007. Lidocaine hydrochloride Granular dosage forms containing psyllium Methly salicylate (hemicellulose), psyllium hydrophilic Myrrh tincture mucilloid, psyllium seed, psyllium seed Pyrilamine maleate (blond), psyllium seed husks, plantago Sorbitol husks, or plantago seed including, but not Sugars limited to, any granules that are: Tetracaine (1) Swallowed dry prior to drinking liquid, Tetracaine hydrochloride (2) Dispersed, suspended, or partially dis- Thymol solved in liquid prior to swallowing, (15) Topical otic drug products—(i) For (3) Chewed, partially chewed, or unchewed, the prevention of swimmer’s ear and for and then washed down (or swallowed) with the drying of water-clogged ears, ap- liquid, or (4) Sprinkled over food. proved as of May 7, 1991. (ii) Saline laxative. Acetic acid (ii) For the prevention of swimmer’s ear, Tartaric acid approved as of August 15, 1995. (iii) Stool softener. Glycerin and anhydrous glycerin Poloxamer 188 Isopropyl alcohol (iv)(A) Stimulant laxatives—Approved (16) Poison treatment drug products. as of May 7, 1991. Ipecac fluidextract Aloin Ipecac tincture Bile salts/acids Zinc sulfate Calcium pantothenate (17) Skin bleaching drug products. Calomel Colocynth Mercury, ammoniated Elaterin resin (18) Skin protectant drug products— Frangula (i)(A) Ingredients—Approved as of May 7, Gamboge Ipomea 1991. Jalap Allantoin (wound healing claims only) Ox bile Sulfur Podophyllum resin Tannic acid Prune concentrate dehydrate Zinc acetate (wound healing claims only) Prune powder Rhubarb, Chinese (B) Ingredients—Approved as of June 4, Sodium Oleate 2004; June 6, 2005, for products with an- nual sales less than $25,000. (iv)(B) Stimulant laxatives—Approved as of January 29, 1999. Beeswax Bismuth subnitrate Danthron Boric acid Phenolphthalein Cetyl alcohol

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Glyceryl stearate (iv) Fever blister and cold sore treat- Isopropyl palmitate ment drug products. Live yeast cell derivative Shark liver oil Bismuth subnitrate Stearyl alcohol Boric acid Pyridoxine hydrochloride (ii) Astringent drug products. Sulfur Tannic acid Alcohol Topical starch Alum, ammonium Trolamine Alum, potassium Zinc sulfate Aluminum chlorhydroxy complex (v) Insect bite and sting drug products— Aromatics (A) Ingredients—Approved as of November Benzalkonium chloride Benzethonium chloride 10, 1993. Benzocaine Alcohol Benzoic acid Alcohol, ethoxylated alkyl Boric acid Ammonia solution, strong Calcium acetate (except calcium acetate Ammonium hydroxide monohydrate when combined with alu- Benzalkonium chloride minum sulfate tetradecahydrate to provide Camphor an aluminum acetate solution as described Ergot fluid extract in § 347.20(b) of this chapter) Ferric chloride Camphor gum Menthol Clove oil Peppermint oil Colloidal oatmeal Phenol Cresol Pyrilamine maleate Cupric sulfate Sodium borate Eucalyptus oil Trolamine Eugenol Turpentine oil Ferric subsulfate (Monsel’s Solution) Zirconium oxide Honey Isopropyl alcohol (B) Ingredients—Approved as of June 4, Menthol 2004; June 6, 2005, for products with an- Methyl salicylate nual sales less than $25,000. Oxyquinoline sulfate P-t-butyl-m-cresol Beeswax Peppermint oil Bismuth subnitrate Phenol Boric acid Polyoxeythylene laurate Cetyl alcohol Potassium ferrocyanide Glyceryl stearate Sage oil Isopropyl palmitate Silver nitrate Live yeast cell derivative Sodium borate Shark liver oil Sodium diacetate Stearyl alcohol Talc (vi) Poison ivy, poison oak, and poison Tannic acid glycerite sumac drug products—(A) Ingredients— Thymol Topical starch Approved as of November 10, 1993. Zinc chloride Alcohol Zinc oxide Anion and cation exchange resins buffered Zinc phenolsulfonate Benzethonium chloride Zinc stearate Benzocaine Zinc sulfate Benzyl alcohol (iii) Diaper rash drug products. Bismuth subnitrate Bithionol Aluminum hydroxide Boric acid Cocoa butter Camphor Cysteine hydrochloride Cetalkonium chloride Glycerin Chloral hydrate Protein hydrolysate Chlorpheniramine maleate Racemethionine Creosote Sulfur Diperodon hydrochloride Tannic acid Diphenhydramine hydrochloride Zinc acetate Eucalyptus oil Zinc carbonate Ferric chloride

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Glycerin Copper Hectorite Copper gluconate Hydrogen peroxide Corn oil Impatiens biflora tincture Corn syrup Iron oxide Corn silk, potassium extract Isopropyl alcohol Cupric sulfate Lanolin Cyanocobalamin (vitamin B12) Lead acetate Cystine Lidocaine Dextrose Menthol Docusate sodium Merbromin Ergocalciferol Mercuric chloride Ferric ammonium citrate Panthenol Ferric pyrophosphate Parethoxycaine hydrochloride Ferrous fumarate Phenol Ferrous gluconate Phenyltoloxamine dihydrogen citrate Ferrous sulfate (iron) Povidone-vinylacetate copolymers Flax seed Salicylic acid Folic acid Simethicone Fructose Tannic acid Guar gum Topical starch Histidine Trolamine Hydrastis canadensis Turpentine oil Inositol Zirconium oxide Iodine Zyloxin Isoleucine Juniper, potassium extract (B) Ingredients—Approved as of June 4, Karaya gum 2004; June 6, 2005, for products with an- Kelp nual sales less than $25,000. Lactose Lecithin Beeswax Leucine Bismuth subnitrate Liver concentrate Boric acid Lysine Cetyl alcohol Lysine hydrochloride Glyceryl stearate Magnesium Isopropyl palmitate Magnesium oxide Live yeast cell derivative Malt Shark liver oil Maltodextrin Stearyl alcohol Manganese citrate (19) [Reserved] Mannitol (20) Weight control drug products. Methionine Methylcellulose Alcohol Mono- and di-glycerides Alfalfa Niacinamide Alginic acid Organic vegetables Anise oil Pancreatin Arginine Pantothenic acid Ascorbic acid Papain Bearberry Papaya enzymes Biotin Pepsin Bone marrow, red Phenacetin Buchu Phenylalanine Buchu, potassium extract Phosphorus Caffeine Phytolacca Caffeine citrate Pineapple enzymes Calcium Plantago seed Calcium carbonate Potassium citrate Calcium caseinate Pyridoxine hydrochloride (vitamin B6) Calcium lactate Riboflavin Calcium pantothenate Rice polishings Carboxymethylcellulose sodium Saccharin Carrageenan Sea minerals Cholecalcierol Sesame seed Choline Sodium Chondrus Sodium bicarbonate Citric acid Sodium caseinate Cnicus benedictus Sodium chloride (salt)

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Soybean protein Dichlorophen Soy meal Menthol Sucrose Methylparaben Thiamine hydrochloride (vitamin B1) Oxyquinoline Thiamine mononitrate (vitamin B1 mono- Oxyquinoline sulfate nitrate) Phenol Threonine Phenolate sodium Tricalcium phosphate Phenyl salicylate Tryptophan Propionic acid Tyrosine Propylparaben Uva ursi, potassium extract Resorcinol Valine Salicylic acid Vegetable Sodium borate Vitamin A Sodium caprylate Vitamin A acetate Sodium propionate Vitamin A palmitate Sulfur Vitamin E Tannic acid Wheat germ Thymol Xanthan gum Tolindate Yeast Triacetin Zinc caprylate (21) Ophthalmic drug products. (i) Oph- Zinc propionate thalmic anesthetic drug products. (iii) Any ingredient(s) labeled with Antipyrine claims or directions for use on the Piperocaine hydrochloride scalp or on the nails. (ii) Ophthalmic anti-infective drug (iv) Ingredients. products. Camphorated metacresol Boric acid Chloroxylenol Mild silver protein m-cresol Yellow mercuric oxide Nystatin (iii) Ophthalmic astringent drug prod- (23) Internal analgesic drug products— ucts. (i) Approved as of November 10, 1993. Infusion of rose petals Aminobenzoic acid Antipyrine (iv) Ophthalmic demulcent drug prod- Aspirin, aluminum ucts. Calcium salicylate Codeine Polyethylene glycol 6000 Codeine phosphate (v) Ophthalmic vasoconstrictor drug Codeine sulfate products. Iodoantipyrine Lysine aspirin Phenylephrine hydrochloride (less than 0.08 Methapyrilene fumarate percent) Phenacetin (22) Topical antifungal drug products. Pheniramine maleate Pyrilamine maleate (i) Diaper rash drug products. Any ingre- Quinine dient(s) labeled with claims or direc- Salsalate tions for use in the treatment and/or Sodium aminobenzoate prevention of diaper rash. (ii) Approved as of February 22, 1999. (ii) Ingredients. Any atropine ingredient Alcloxa Any ephedrine ingredient Alum, potassium Aluminum sulfate (24) Orally administered menstrual drug Amyltricresols, secondary products—(i) Approved as of November 10, Basic fuchsin 1993. Benzethonium chloride Benzoic acid Alcohol Benzoxiquine Alfalfa leaves Boric acid Aloes Camphor Asclepias tuberosa Candicidin Asparagus Chlorothymol Barosma Coal tar Bearberry (extract of uva ursi)

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Bearberry fluidextract (extract of bearberry) Benzyl alcohol Blessed thistle (cnicus benedictus) Benzyl benzoate Buchu powdered extract (extract of buchu) Chlorophenothane (dichlorodiphenyl tri- Calcium lactate chloroethane) Calcium pantothenate Coconut oil soap, aqueous Capsicum oleoresin Copper oleate Cascara fluidextract, aromatic (extract of Docusate sodium cascara) Formic acid Chlorprophenpyridamine maleate Isobornyl thiocyanoacetate Cimicifuga racemosa Picrotoxin Codeine Collinsonia (extract stone root) Sabadilla alkaloids Corn silk Sulfur, sublimed Couch grass Thiocyanoacetate Dog grass extract Ethyl nitrite (ii) Approved as of June 14, 1994. The Ferric chloride combination of pyrethrum extract (for- Ferrous sulfate merly named pyrethrins) and piperonyl Gentiana lutea (gentian) butoxide in an aerosol dosage formula- Glycyrrhiza (licorice) tion. Homatropine methylbromide (26) Anorectal drug products—(i) Anti- Hydrangea, powdered extract (extract of hy- cholinergic drug products. drangea) Hydrastis canadensis (golden seal) Atropine Hyoscyamine sulfate Belladonna extract Juniper oil (oil of juniper) Magnesium sulfate (ii) Antiseptic drug products. Methapyrilene hydrochloride Boric acid Methenamine Boroglycerin Methylene blue Hydrastis Natural estrogenic hormone Phenol Niacinamide Resorcinol Nutmeg oil (oil of nutmeg) Sodium salicylic acid phenolate Oil of erigeron Parsley (iii) Astringent drug products. Peppermint spirit Tannic acid Pepsin, essence Phenacetin (iv) Counterirritant drug products. Phenindamine tartrate Phenyl salicylate Camphor (greater than 3 to 11 percent) Piscidia erythrina Hydrastis Pipsissewa Menthol (1.25 to 16 percent) Potassium acetate Turpentine oil (rectified) (6 to 50 percent) Potassium nitrate (v) Keratolytic drug products. Riboflavin Saw palmetto Precipitated sulfur Senecio aureus Sublimed sulfur Sodium benzoate (vi) Local anesthetic drug products. Sodium nitrate Sucrose Diperodon Sulferated oils of turpentine Phenacaine hydrochloride Taraxacum officinale Theobromine sodium salicylate (vii) Other drug products. Theophylline Collinsonia extract Thiamine hydrochloride Escherichia coli vaccines Triticum Lappa extract Turpentine, venice (venice turpertine) Leptandra extract Urea Live yeast cell derivative (ii) Approved as of February 22, 1999. Mullein Any atropine ingredient (viii) Protectant drug products. Any ephedrine ingredient Bismuth oxide (25) Pediculicide drug products—(i) Ap- Bismuth subcarbonate proved as of November 10, 1993. Bismuth subgallate Bismuth subnitrate Benzocaine Lanolin alcohols

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(ix) Vasoconstrictor drug products. Tribromsalan Triclocarban Epinephrine undecylenate (x) Wound healinq drug products. Triple Dye Undecoylium chloride iodine complex Cholecalciferol Cod liver oil (iv) Consumer antiseptic body wash Live yeast cell derivative drug products. Approved as of Sep- Peruvian balsam tember 6, 2017. Shark liver oil Cloflucarban Vitamin A Fluorosalan (xi) Combination drug products. Any Hexachlorophene combination drug product containing Hexylresorcinol hydrocortisone and pramoxine hydro- Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol) chloride. Iodine tincture (27) Topical antimicrobial drug prod- Methylbenzethonium chloride ucts—(i) First aid antiseptic drug prod- Nonylphenoxypoly (ethyleneoxy) ucts. ethanoliodine Phenol (greater than 1.5 percent) Ammoniated mercury Phenol (less than 1.5 percent) Calomel (mercurous chloride) Poloxamer iodine complex Merbromin (mercurochrome) Povidone-iodine (5 to 10 percent) Mercufenol chloride (ortho- Secondary amyltricresols chloromercuriphenol, ortho- Sodium oxychlorosene hydroxyphenylmercuric chloride) Tribromsalan Mercuric chloride (bichloride of mercury, Triclocarban mercury chloride) Triclosan Mercuric oxide, yellow Triple Dye Mercuric salicylate Undecoylium chloride iodine complex Mercuric sulfide, red Mercury (v) [Reserved] Mercury oleate (vi) Health care personnel hand wash drug products. Approved as of December Nitromersol 20, 2018. Para-chloromercuriphenol Phenylmercuric nitrate Cloflucarban Thimerosal Fluorosalan Vitromersol Hexachlorophene Zyloxin Hexylresorcinol Iodine complex (ammonium ether sulfate (ii) Diaper rash drug products. and polyoxyethylene sorbitan monolaurate) Para-chloromercuriphenol Iodine complex (phosphate ester of Any other ingredient containing mercury alkylaryloxy polyethylene glycol) (iii) Consumer antiseptic hand wash Methylbenzethonium chloride drug products. Approved as of Sep- Nonylphenoxypoly (ethyleneoxy) tember 6, 2017. ethanoliodine Phenol Cloflucarban Poloxamer-iodine complex Fluorosalan Secondary amyltricresols Hexachlorophene Sodium oxychlorosene Hexylresorcinol Tribromsalan Iodine complex (ammonium ether sulfate Triclocarban and polyoxyethylene sorbitan Triclosan monolaurate) Undecoylium chloride iodine complex Iodine complex (phosphate ester of (vii) [Reserved] alkylaryloxy polyethylene glycol) (viii) Surgical hand scrub drug prod- Methylbenzethonium chloride ucts. Approved as of December 20, 2018. Nonylphenoxypoly (ethyleneoxy) ethanoliodine Cloflucarban Phenol (greater than 1.5 percent) Fluorosalan Phenol (less than 1.5 percent) Hexachlorophene Poloxamer iodine complex Hexylresorcinol Povidone-iodine (5 to 10 percent) Iodine complex (ammonium ether sulfate Secondary amyltricresols and polyoxyethylene sorbitan Sodium oxychlorosene monolaurate)

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Iodine complex (phosphate ester of (ii) Any ingredients labeled with any alkylaryloxy polyethylene glycol) of the following or similar claims. In- Methylbenzethonium chloride stant protection or protection imme- Nonylphenoxypoly (ethyleneoxy) diately upon application. ethanoliodine Phenol Claims for ‘‘all-day’’ protection or Poloxamer-iodine complex extended wear claims citing a specific Secondary amyltricresols number of hours of protection that is Sodium oxychlorosene inconsistent with the directions for ap- Tribromsalan plication in 21 CFR 201.327. Triclocarban Triclosan (30) [Reserved] Undecoylium chloride iodine complex (b) Any OTC drug product that is la- beled, represented, or promoted for the (ix) [Reserved] uses specified and containing any ac- (x) Patient antiseptic skin preparation tive ingredient(s) as specified in para- drug products. Approved as of December graph (a) of this section is regarded as 20, 2018. a new drug within the meaning of sec- Cloflucarban tion 210(p) of the Federal Food, Drug, Fluorosalan and Cosmetic Act (the Act), for which Hexachlorophene an approved new drug application Hexylresorcinol under section 505 of the Act and part Iodine complex (phosphate ester of 314 of this chapter is required for mar- alkylaryloxy polyethylene glycol) Iodine tincture (USP) keting. In the absence of an approved Iodine topical solution (USP) new drug application, such product is Mercufenol chloride also misbranded under section 502 of Methylbenzethonium chloride the Act. Nonylphenoxypoly (ethyleneoxy) (c) Clinical investigations designed ethanoliodine to obtain evidence that any drug prod- Phenol uct labeled, represented, or promoted Poloxamer-iodine complex for the OTC uses and containing any Secondary amyltricresols active ingredient(s) as specified in Sodium oxychlorosene Tribromsalan paragraph (a) of this section is safe and Triclocarban effective for the purpose intended must Triclosan comply with the requirements and pro- Triple dye cedures governing the use of investiga- Undecoylium chloride iodine complex tional new drugs set forth in part 312 of Combination of calomel, oxyquinoline ben- this chapter. zoate, triethanolamine, and phenol deriva- (d) Any OTC drug product that is not tive in compliance with this section is sub- Combination of mercufenol chloride and sec- ondary amyltricresols in 50 percent alcohol ject to regulatory action if initially in- (28) Vaginal contraceptive drug prod- troduced or initially delivered for in- ucts—(i) Approved as of October 22, 1998. troduction into interstate commerce after the dates specified in paragraphs Dodecaethylene glycol monolaurate (poly- (d)(1) through (d)(42) of this section. ethylene glycol 600 monolaurate) (1) May 7, 1991, for products subject Laureth 10S to paragraphs (a)(1) through (a)(2)(i), Methoxypolyoxyethyleneglycol 550 laurate (a)(3)(i), (a)(4)(i), (a)(6)(i)(A), Phenylmercuric acetate Phenylmercuric nitrate (a)(6)(ii)(A), (a)(7) (except as covered by Any other ingredient containing mercury paragraph (d)(3) of this section), (a)(8)(i), (a)(10)(i) through (a)(10)(iii), (ii) Approved as of November 5, 2002. (a)(12)(i)(A), (a)(12)(ii) through Octoxynol 9 (a)(12)(iv)(A), (a)(14) through (a)(15)(i), (29) Sunscreen drug products. (i) Ingre- (a)(16) through (a)(18)(i)(A), (a)(18)(ii) dients. (except as covered by paragraph (d)(22) of this section), (a)(18)(iii), (a)(18)(iv), Diethanolamine methoxycinnamate (a)(18)(v)(A), and (a)(18)(vi)(A) of this Digalloyl trioleate Ethyl 4-[bis(hydroxypropyl)] aminobenzoate section. Glyceryl aminobenzoate (2) February 10, 1992, for products Lawsone with dihydroxyacetone subject to paragraph (a)(20) of this sec- Red petrolatum tion.

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(3) December 4, 1992, for products sub- (15) September 23, 1994, for products ject to paragraph (a)(7) of this section subject to paragraph (a)(22)(iv) of this that contain menthol as an anti- section. pruritic in combination with the anti- (16) June 14, 1994, for products subject dandruff ingredient coal tar identified to paragraph (a)(25)(ii) of this section. in § 358.710(a)(1) of this chapter. This (17) April 19, 2004, for products sub- section does not apply to products al- ject to paragraph (a)(3)(ii) of this sec- lowed by § 358.720(b) of this chapter tion. April 18, 2005, for products with after April 5, 2007. annual sales less than $25,000. (4) February 28, 1990, for products (18) August 15, 1995, for products sub- subject to paragraph (a)(6)(iii) of this ject to paragraph (a)(15)(ii) of this sec- section, except those that contain ipe- tion. cac. (19) October 2, 1987, for products sub- ject to paragraph (a)(6)(iv)(A) of this (5) September 14, 1993, for products section. subject to paragraph (a)(6)(iii) of this (20) January 29, 1996, for products section that contain ipecac. subject to paragraph (a)(6)(iv)(B) of (6) December 9, 1993, for products sub- this section. ject to paragraph (a)(6)(i)(B) of this (21) April 21, 1994, for products sub- section. ject to paragraph (a)(8)(iii) of this sec- (7) March 6, 1989, for products subject tion. to paragraph (a)(21) of this section, ex- (22) April 21, 1993, for products sub- cept those that contain ophthalmic ject to paragraph (a)(18)(ii) of this sec- anti-infective ingredients listed in tion that contain ferric subsulfate. paragraph (a)(21)(ii). (23) August 23, 1995, for products sub- (8) June 18, 1993, for products subject ject to paragraph (a)(6)(ii)(B) of this to paragraph (a)(21) of this section that section. contain ophthalmic anti-infective in- (24) October 7, 1996, for products sub- gredients. ject to paragraph (a)(2)(ii) of this sec- (9) June 18, 1993, for products subject tion. to paragraph (a)(10)(iv) of this section. (25) June 19, 1996, for products subject (10) June 18, 1993, for products subject to paragraph (a)(6)(iv)(C) of this sec- to paragraph (a)(22)(i) of this section. tion. (11) November 10, 1993, for products (26) February 22, 1999, for products subject to paragraphs (a)(8)(ii), subject to paragraphs (a)(23)(ii) and (a)(10)(v) through (a)(10)(vii), (a)(18)(ii) (a)(24)(ii) of this section. (except products that contain ferric (27) [Reserved] subsulfate as covered by paragraph (28) October 22, 1998, for products sub- (d)(22) of this section and except prod- ject to paragraphs (a)(27) and (a)(28)(i) ucts that contain calcium acetate of this section. monohydrate as covered by paragraph (29) January 29, 1999, for products subject to paragraph (a)(12)(iv)(B) of (d)(39) of this section) through this section. (a)(18)(v)(A), (a)(18)(vi)(A), (a)(22)(ii), (30) November 5, 2002, for products (a)(23)(i), (a)(24)(i), and (a)(25) of this subject to paragraph (a)(12)(iv)(C) of section. this section. (12) March 2, 1994, for products sub- (31) December 31, 2002, for products ject to paragraph (a)(22)(iii) of this sec- subject to paragraph (a)(29)(i) of this tion. section. (13) August 5, 1991, for products sub- (32) June 4, 2004, for products subject ject to paragraph (a)(26) of this section, to paragraphs (a)(18)(i)(B), (a)(18)(v)(B), except for those that contain live yeast and (a)(18)(vi)(B) of this section. June cell derivative and a combination of 6, 2005, for products with annual sales hydrocortisone and pramoxine hydro- less than $25,000. chloride. (33) October 29, 2001, for products sub- (14) September 2, 1994, for products ject to paragraph (a)(6)(iv)(D) of this subject to paragraph (a)(26)(vii) and section. (a)(26)(x) of this section that contain (34) December 9, 2004, for products live yeast cell derivative. subject to paragraph (a)(4)(ii) of this

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section. June 9, 2005, for products with used to treat or prevent this condition, annual sales less than $25,000. quinine sulfate has caused adverse (35) [Reserved] events such as transient visual and au- (36) November 5, 2002, for products ditory disturbances, dizziness, fever, subject to paragraph (a)(28)(ii) of this nausea, vomiting, and diarrhea. Qui- section. nine sulfate may cause unpredictable (37) September 25, 2003, for products serious and life-threatening hyper- subject to paragraph (a)(26)(xi) of this sensitivity reactions requiring medical section. intervention and hospitalization; fa- (38) October 1, 2007, for products sub- talities have been reported. The risk ject to paragraph (a)(12)(i)(B) of this associated with use of quinine sulfate, section. in the absence of evidence of its effec- (39) September 6, 2010, for products tiveness, outweighs any potential ben- subject to paragraph (a)(18)(ii) of this section that contain calcium acetate efit in treating and/or preventing this monohydrate, except as provided in benign, self-limiting condition. Based § 347.20(b) of this chapter. upon the adverse benefit-to-risk ratio, (40) December 17, 2012, for products any drug product containing quinine or subject to paragraph (a)(29)(ii) of this quinine sulfate cannot be considered section. December 17, 2013, for products generally recognized as safe for the with annual sales less than $25,000. treatment and/or prevention of noc- (41) September 6, 2017, for products turnal leg muscle cramps. subject to paragraph (a)(27)(iii) or (iv) (b) Any OTC drug product that is la- of this section. beled, represented, or promoted for the (42) December 20, 2018, for products treatment and/or prevention of noc- subject to paragraphs (a)(27)(vi) turnal leg muscle cramps is regarded as through (x) of this section. a new drug within the meaning of sec- [55 FR 46919, Nov. 7, 1990] tion 201(p) of the Federal Food, Drug, and Cosmetic Act (the act), for which EDITORIAL NOTE: For FEDERAL REGISTER ci- tations affecting § 310.545, see the List of CFR an approved application or abbreviated Sections Affected, which appears in the application under section 505 of the act Finding Aids section of the printed volume and part 314 of this chapter is required and at www.govinfo.gov. for marketing. In the absence of an ap- EFFECTIVE DATE NOTE: At 61 FR 9571, Mar. proved new drug application or abbre- 8, 1996, in § 310.545 in paragraph (a)(6)(ii)(B), viated new drug application, such prod- the entry for ‘‘l-desoxyephedrine (topical)’’ uct is also misbranded under section was stayed until further notice. 502 of the act. (c) Clinical investigations designed § 310.546 Drug products containing ac- tive ingredients offered over-the- to obtain evidence that any drug prod- counter (OTC) for the treatment uct labeled, represented, or promoted and/or prevention of nocturnal leg for OTC use for the treatment and/or muscle cramps. prevention of nocturnal leg muscle (a) Quinine sulfate alone or in com- cramps is safe and effective for the pur- bination with vitamin E has been pose intended must comply with the re- present in over-the-counter (OTC) drug quirements and procedures governing products for the treatment and/or pre- the use of investigational new drugs vention of nocturnal leg muscle set forth in part 312 of this chapter. cramps, i.e., a condition of localized (d) After February 22, 1995, any such pain in the lower extremities usually OTC drug product initially introduced occurring in middle life and beyond or initially delivered for introduction with no regular pattern concerning into interstate commerce that is not in time or severity. There is a lack of ade- compliance with this section is subject quate data to establish general rec- to regulatory action. ognition of the safety and effectiveness of quinine sulfate, vitamin E, or any [59 FR 43252, Aug. 22, 1994] other ingredients for OTC use in the treatment and/or prevention of noc- turnal leg muscle cramps. In the doses

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