21 CFR 310.545

(a) A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses:

(1) Topical acne drug products.

(2) Anticaries drug products—(i) Approved as of May 7, 1991.

(ii) Approved as of October 7, 1996.

(3) Antidiarrheal drug products—(i) Approved as of May 7, 1991.

(ii) Approved as of April 19, 2004; April 18, 2005, for products with annual sales less than $25,000.

(4) Antiperspirant drug products—(i) Ingredients—Approved as of May 7, 1991.

(ii) Approved as of December 9, 2004; June 9, 2005, for products with annual sales less than $25,000.

(5) [Reserved]

(6) Cold, cough, allergy, bronchodilator, and antiasthmatic drug products—(i) Antihistamine drug products—(A) Ingredients.

(B) Ingredients.

(ii) Nasal decongestant drug products—(A) Approved as of May 7, 1991.

(B) Approved as of August 23, 1995.

(C) Approved as of April 11, 2007; October 11, 2007, for products with annual sales less than $25,000. Any ingredient(s) labeled with claims or directions for use for sinusitis or for relief of nasal congestion associated with sinusitis.

(iii) Expectorant drug products.

(iv) Bronchodilator drug products—(A) Approved as of October 2, 1987.

(B) Approved as of January 29, 1996. Any combination drug product containing theophylline (e.g., theophylline and ephedrine, or theophylline and ephedrine and phenobarbital).

(C) Approved as of June 19, 1996. Any ingredient(s) in a pressurized metered-dose inhaler container.

(D) Approved as of October 29, 2001. Any oral bronchodilator active ingredient (e.g., ephedrine, ephedrine hydrochloride, ephedrine sulfate, racephedrine hydrochloride, or any other ephedrine salt) in combination with any analgesic(s) or analgesic-antipyretic(s), anticholinergic, antihistamine, oral antitussive, or stimulant active ingredient.

(7) Dandruff/seborrheic dermatitis/psoriasis drug products.

(8) Digestive aid drug products—(i) Approved as of May 7, 1991.

(ii) Approved as of November 10, 1993.

(iii) Charcoal, activated

(9) [Reserved]

(10) External analgesic drug products—(i) Analgesic and anesthetic drug products.

(ii) Counterirritant drug products.

(iii) Male genital desensitizer drug products.

(iv) Diaper rash drug products. Any ingredient(s) labeled with claims or directions for use in the treatment and/or prevention of diaper rash.

(v) Fever blister and cold sore treatment drug products.

(vi) Insect bite and sting drug products.

(vii) Poison ivy, poison oak, and poison sumac drug products.

(11) [Reserved]

(12) Laxative drug products—(i)(A) Bulk laxatives.

(i)(B) Bulk laxatives—Approved as of March 29, 2007.

(ii) Saline laxative.

(iii) Stool softener.

(iv)(A) Stimulant laxatives—Approved as of May 7, 1991.

(iv)(B) Stimulant laxatives—Approved as of January 29, 1999.

(C) Stimulant laxatives—Approved as of November 5, 2002.

(13) [Reserved]

(14) Oral health care drug products (nonantimicrobial).

(15) Topical otic drug products—(i) For the prevention of swimmer's ear and for the drying of water-clogged ears, approved as of May 7, 1991.

(ii) For the prevention of swimmer's ear, approved as of August 15, 1995.

(16) Poison treatment drug products.

(17) Skin bleaching drug products.

(18) Skin protectant drug products—(i)(A) Ingredients—Approved as of May 7, 1991.

(B) Ingredients—Approved as of June 4, 2004; June 6, 2005, for products with annual sales less than $25,000.

(ii) Astringent drug products.

(iii) Diaper rash drug products.

(iv) Fever blister and cold sore treatment drug products.

(v) Insect bite and sting drug products—(A) Ingredients—Approved as of November 10, 1993.

(B) Ingredients—Approved as of June 4, 2004; June 6, 2005, for products with annual sales less than $25,000.

(vi) Poison ivy, poison oak, and poison sumac drug products—(A) Ingredients—Approved as of November 10, 1993.

(B) Ingredients—Approved as of June 4, 2004; June 6, 2005, for products with annual sales less than $25,000.

(19) [Reserved]

(20) Weight control drug products.

(21) Ophthalmic drug products. (i) Ophthalmic anesthetic drug products.

(ii) Ophthalmic anti-infective drug products.

(iii) Ophthalmic astringent drug products.

(iv) Ophthalmic demulcent drug products.

(v) Ophthalmic vasoconstrictor drug products.

(22) Topical antifungal drug products. (i) Diaper rash drug products. Any ingredient(s) labeled with claims or directions for use in the treatment and/or prevention of diaper rash.

(ii) Ingredients.

(iii) Any ingredient(s) labeled with claims or directions for use on the scalp or on the nails.

(iv) Ingredients.

(23) Internal analgesic drug products—(i) Approved as of November 10, 1993.

(ii) Approved as of February 22, 1999.

(24) Orally administered menstrual drug products—(i) Approved as of November 10, 1993.

(ii) Approved as of February 22, 1999.

(25) Pediculicide drug products—(i) Approved as of November 10, 1993.

(ii) Approved as of June 14, 1994. The combination of pyrethrum extract (formerly named pyrethrins) and piperonyl butoxide in an aerosol dosage formulation.

(26) Anorectal drug products—(i) Anticholinergic drug products.

(ii) Antiseptic drug products.

(iii) Astringent drug products.

(iv) Counterirritant drug products.

(v) Keratolytic drug products.

(vi) Local anesthetic drug products.

(vii) Other drug products.

(viii) Protectant drug products.

(ix) Vasoconstrictor drug products.

(x) Wound healinq drug products.

(xi) Combination drug products. Any combination drug product containing hydrocortisone and pramoxine hydrochloride.

(27) Topical antimicrobial drug products—(i) First aid antiseptic drug products.

(ii) Diaper rash drug products.

(iii) Consumer antiseptic hand wash drug products. Approved as of September 6, 2017.

(iv) Consumer antiseptic body wash drug products. Approved as of September 6, 2017.

(v) [Reserved]

(vi) Health care personnel hand wash drug products. Approved as of December 20, 2018.

(vii) [Reserved]

(viii) Surgical hand scrub drug products. Approved as of December 20, 2018.

(ix) [Reserved]

(x) Patient antiseptic skin preparation drug products. Approved as of December 20, 2018.

(28) Vaginal contraceptive drug products—(i) Approved as of October 22, 1998.

(ii) Approved as of November 5, 2002.

(29) Sunscreen drug products. (i) Ingredients.

(ii) Any ingredients labeled with any of the following or similar claims. Instant protection or protection immediately upon application.

Claims for “all-day” protection or extended wear claims citing a specific number of hours of protection that is inconsistent with the directions for application in 21 CFR 201.327.

(30) [Reserved]

(b) Any OTC drug product that is labeled, represented, or promoted for the uses specified and containing any active ingredient(s) as specified in paragraph (a) of this section is regarded as a new drug within the meaning of section 210(p) of the Federal Food, Drug, and Cosmetic Act (the Act), for which an approved new drug application under section 505 of the Act and part 314 of this chapter is required for marketing. In the absence of an approved new drug application, such product is also misbranded under section 502 of the Act.

(c) Clinical investigations designed to obtain evidence that any drug product labeled, represented, or promoted for the OTC uses and containing any active ingredient(s) as specified in paragraph (a) of this section is safe and effective for the purpose intended must comply with the requirements and procedures governing the use of investigational new drugs set forth in part 312 of this chapter.

(d) Any OTC drug product that is not in compliance with this section is subject to regulatory action if initially introduced or initially delivered for introduction into interstate commerce after the dates specified in paragraphs (d)(1) through (d)(42) of this section.

(1) May 7, 1991, for products subject to paragraphs (a)(1) through (a)(2)(i), (a)(3)(i), (a)(4)(i), (a)(6)(i)(A), (a)(6)(ii)(A), (a)(7) (except as covered by paragraph (d)(3) of this section), (a)(8)(i), (a)(10)(i) through (a)(10)(iii), (a)(12)(i)(A), (a)(12)(ii) through (a)(12)(iv)(A), (a)(14) through (a)(15)(i), (a)(16) through (a)(18)(i)(A), (a)(18)(ii) (except as covered by paragraph (d)(22) of this section), (a)(18)(iii), (a)(18)(iv), (a)(18)(v)(A), and (a)(18)(vi)(A) of this section.

(2) February 10, 1992, for products subject to paragraph (a)(20) of this section.

(3) December 4, 1992, for products subject to paragraph (a)(7) of this section that contain menthol as an antipruritic in combination with the antidandruff ingredient coal tar identified in § 358.710(a)(1) of this chapter. This section does not apply to products allowed by § 358.720(b) of this chapter after April 5, 2007.

(4) February 28, 1990, for products subject to paragraph (a)(6)(iii) of this section, except those that contain ipecac.

(5) September 14, 1993, for products subject to paragraph (a)(6)(iii) of this section that contain ipecac.

(6) December 9, 1993, for products subject to paragraph (a)(6)(i)(B) of this section.

(7) March 6, 1989, for products subject to paragraph (a)(21) of this section, except those that contain ophthalmic anti-infective ingredients listed in paragraph (a)(21)(ii).

(8) June 18, 1993, for products subject to paragraph (a)(21) of this section that contain ophthalmic anti-infective ingredients.

(9) June 18, 1993, for products subject to paragraph (a)(10)(iv) of this section.

(10) June 18, 1993, for products subject to paragraph (a)(22)(i) of this section.

(11) November 10, 1993, for products subject to paragraphs (a)(8)(ii), (a)(10)(v) through (a)(10)(vii), (a)(18)(ii) (except products that contain ferric subsulfate as covered by paragraph (d)(22) of this section and except products that contain calcium acetate monohydrate as covered by paragraph (d)(39) of this section) through (a)(18)(v)(A), (a)(18)(vi)(A), (a)(22)(ii), (a)(23)(i), (a)(24)(i), and (a)(25) of this section.

(12) March 2, 1994, for products subject to paragraph (a)(22)(iii) of this section.

(13) August 5, 1991, for products subject to paragraph (a)(26) of this section, except for those that contain live yeast cell derivative and a combination of hydrocortisone and pramoxine hydrochloride.

(14) September 2, 1994, for products subject to paragraph (a)(26)(vii) and (a)(26)(x) of this section that contain live yeast cell derivative.

(15) September 23, 1994, for products subject to paragraph (a)(22)(iv) of this section.

(16) June 14, 1994, for products subject to paragraph (a)(25)(ii) of this section.

(17) April 19, 2004, for products subject to paragraph (a)(3)(ii) of this section. April 18, 2005, for products with annual sales less than $25,000.

(18) August 15, 1995, for products subject to paragraph (a)(15)(ii) of this section.

(19) October 2, 1987, for products subject to paragraph (a)(6)(iv)(A) of this section.

(20) January 29, 1996, for products subject to paragraph (a)(6)(iv)(B) of this section.

(21) April 21, 1994, for products subject to paragraph (a)(8)(iii) of this section.

(22) April 21, 1993, for products subject to paragraph (a)(18)(ii) of this section that contain ferric subsulfate.

(23) August 23, 1995, for products subject to paragraph (a)(6)(ii)(B) of this section.

(24) October 7, 1996, for products subject to paragraph (a)(2)(ii) of this section.

(25) June 19, 1996, for products subject to paragraph (a)(6)(iv)(C) of this section.

(26) February 22, 1999, for products subject to paragraphs (a)(23)(ii) and (a)(24)(ii) of this section.

(27) [Reserved]

(28) October 22, 1998, for products subject to paragraphs (a)(27) and (a)(28)(i) of this section.

(29) January 29, 1999, for products subject to paragraph (a)(12)(iv)(B) of this section.

(30) November 5, 2002, for products subject to paragraph (a)(12)(iv)(C) of this section.

(31) December 31, 2002, for products subject to paragraph (a)(29)(i) of this section.

(32) June 4, 2004, for products subject to paragraphs (a)(18)(i)(B), (a)(18)(v)(B), and (a)(18)(vi)(B) of this section. June 6, 2005, for products with annual sales less than $25,000.

(33) October 29, 2001, for products subject to paragraph (a)(6)(iv)(D) of this section.

(34) December 9, 2004, for products subject to paragraph (a)(4)(ii) of this section. June 9, 2005, for products with annual sales less than $25,000.

(35) [Reserved]

(36) November 5, 2002, for products subject to paragraph (a)(28)(ii) of this section.

(37) September 25, 2003, for products subject to paragraph (a)(26)(xi) of this section.

(38) October 1, 2007, for products subject to paragraph (a)(12)(i)(B) of this section.

(39) September 6, 2010, for products subject to paragraph (a)(18)(ii) of this section that contain calcium acetate monohydrate, except as provided in § 347.20(b) of this chapter.

(40) December 17, 2012, for products subject to paragraph (a)(29)(ii) of this section. December 17, 2013, for products with annual sales less than $25,000.

(41) September 6, 2017, for products subject to paragraph (a)(27)(iii) or (iv) of this section.

(42) December 20, 2018, for products subject to paragraphs (a)(27)(vi) through (x) of this section.

[55 FR 46919, Nov. 7, 1990]