PART 352—SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE [STAYED INDEFINITELY] Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371. Source: 64 FR 27687, May 21, 1999, unless otherwise noted. Effective Date Note: At 68 FR 33381, June 4, 2003, part 352 was stayed until further notice, effective June 4, 2004. Subpart A—General Provisions § 352.1 Scope. (a) An over-the-counter sunscreen drug product in a form suitable for topical administration 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. § 352.3 Definitions. As used in this part: (a) Minimal erythema dose (MED). (b) Product category designation (PCD). (1) Minimal sun protection product. (2) Moderate sun protection product. (3) High sun protection product. (c) Sunscreen active ingredient. (d) Sun protection factor (SPF) value. i.e. Subpart B—Active Ingredients § 352.10 Sunscreen active ingredients. The active ingredient of the product consists of any of the following, within the concentration specified for each ingredient, and the finished product provides a minimum SPF value of not less than 2 as measured by the testing procedures established in subpart D of this part: (a) Aminobenzoic acid (PABA) up to 15 percent. (b) Avobenzone up to 3 percent. (c) Cinoxate up to 3 percent. (d) [Reserved] (e) Dioxybenzone up to 3 percent. (f) Homosalate up to 15 percent. (g) [Reserved] (h) Menthyl anthranilate up to 5 percent. (i) Octocrylene up to 10 percent. (j) Octyl methoxycinnamate up to 7.5 percent. (k) Octyl salicylate up to 5 percent. (l) Oxybenzone up to 6 percent. (m) Padimate O up to 8 percent. (n) Phenylbenzimidazole sulfonic acid up to 4 percent. (o) Sulisobenzone up to 10 percent. (p) Titanium dioxide up to 25 percent. (q) Trolamine salicylate up to 12 percent. (r) Zinc oxide up to 25 percent. [64 FR 27687, May 21, 1999] Effective Date Note: At 67 FR 41823, June 20, 2002, § 352.10 was amended by revising paragraphs (f) through (n), effective Sept. 1, 2002. This amendment could not be incorporated because at 66 FR 67485, Dec. 31, 2001, the effective date was stayed until further notice. For the convenience of the user, the revised text is set forth as follows: § 352.10 Sunscreen active ingredients. (f) Ensulizole up to 4 percent. (g) Homosalate up to 15 percent. (h) [Reserved] (i) Meradimate up to 5 percent. (j) Octinoxate up to 7.5 percent. (k) Octisalate up to 5 percent. (l) Octocrylene up to 10 percent. (m) Oxybenzone up to 6 percent. (n) Padimate O up to 8 percent. § 352.20 Permitted combinations of active ingredients. The SPF of any combination product is measured by the testing procedures established in subpart D of this part. (a) Combinations of sunscreen active ingredients. (2) Two or more sunscreen active ingredients identified in § 352.10(b), (c), (e), (f), (i) through (l), (o), and (q) may be combined with each other in a single product when used in the concentrations established for each ingredient in § 352.10. The concentration of each active ingredient must be sufficient to contribute a minimum SPF of not less than 2 to the finished product. The finished product must have a minimum SPF of not less than the number of sunscreen active ingredients used in the combination multiplied by 2. (b) Combinations of sunscreen and skin protectant active ingredients. (c) [Reserved] [64 FR 27687, May 21, 1999, as amended at 68 FR 33380, June 4, 2003] Effective Date Note: At 67 FR 41823, June 20, 2002, § 352.20 was amended by revising paragraphs (a)(1) through (a)(2), effective Sept. 1, 2002. This amendment could not be incorporated because at 66 FR 67485, Dec. 31, 2001 the effective date was stayed until further notice. For the convenience of the user, the text is set forth as follows: § 352.20 Permitted combinations of active ingredients. (a) Combinations of sunscreen active ingredients. (2) Two or more sunscreen active ingredients identified in § 352.10(b), (c), (e), (g), (j) through (m), (o), and (q) may be combined with each other in a single product when used in the concentrations established for each ingredient in § 352.10. The concentration of each active ingredient must be sufficient to contribute a minimum SPF of not less than 2 to the finished product. The finished product must have a minimum SPF of not less than the number of sunscreen active ingredients used in the combination multiplied by 2. Subpart C—Labeling § 352.50 Principal display panel of all sunscreen drug products. In addition to the statement of identity required in § 352.52, the following labeling statements shall be prominently placed on the principal display panel: (a) For products that do not satisfy the water resistant or very water resistant sunscreen product testing procedures in § 352.76 For products with SPF values up to 30. (2) For products with SPF values over 30. (b) For products that satisfy the water resistant sunscreen product testing procedures in § 352.76. (2) “SPF (insert SPF value of the product, as stated in paragraph (a)(1) or (a)(2) of this section, after it has been tested using the water resistant sunscreen product testing procedures in § 352.76).” (c) For products that satisfy the very water resistant sunscreen product testing procedures in § 352.76. (2) “SPF (insert SPF value of the product, as stated in paragraph (a)(1) or (a)(2) of this section, after it has been tested using the very water resistant sunscreen product testing procedures in § 352.76).” § 352.52 Labeling of sunscreen drug products. (a) Statement of identity. (b) Indications. (1) For products containing any ingredient in § 352.10. 1 1 (ii) For products that satisfy the water resistant testing procedures identified in § 352.76. (iii) For products that satisfy the very water resistant testing procedures identified in § 352.76. (2) Additional indications. (i) For products that provide an SPF of 2 to under 12. (ii) For products that provide an SPF of 12 to under 30. (iii) For products that provide an SPF of 30 or above. (c) Warnings. (1) For products containing any ingredient in § 352.10. (ii) “Stop use and ask a doctor if [bullet] rash or irritation develops and lasts”. (2) For products containing any ingredient identified in § 352.10 marketed as a lip protectant or lipstick. (d) Directions. (1) For products containing any ingredient in § 352.10. (ii) “[bullet] children under 6 months of age: ask a doctor”. (2) In addition to the directions provided in § 352.52(d)(1), the following may be used for products containing any ingredient in § 352.10. (3) If the additional directions provided in § 352.52(d)(2) are used, the phrase “and as needed” in § 352.52(d)(1) is not required. (4) For products marketed as a lip protectant or lipstick. (e) Statement on product performance For products containing any ingredient identified in § 352.10, the following PCD labeling claims may be used under the heading “Other information” or anywhere outside of the “Drug Facts” box or enclosure. (i) For products containing active ingredient(s) that provide an SPF value of 2 to under 12. (ii) For products containing active ingredient(s) that provide an SPF value of 12 to under 30. (iii) For products containing active ingredient(s) that provide an SPF value of 30 or above. (2) For products containing any ingredient identified in § 352.10, the following labeling statement may be used under the heading “Other information” or anywhere outside of the “Drug Facts” box or enclosure. (f) Products labeled for use only on specific small areas of the face (e.g., lips, nose, ears, and/or around eyes) and that meet the criteria established in § 201.66(d)(10) of this chapter. (1) The labeling shall meet the requirements of § 201.66(c) of this chapter except that the title, headings, and information described in § 201.66(c)(1), (c)(3), and (c)(7) may be omitted, and the headings, subheadings, and information described in § 201.66(c)(2), (c)(4), (c)(5), and (c)(6) may be presented as follows: (i) The active ingredients (§ 201.66(c)(2) of this chapter) shall be listed in alphabetical order. (ii) The heading and the indication required by § 201.66(c)(4) of this chapter may be limited to: “Use [in bold type] helps protect against sunburn.” For a lip protectant product, the heading and the indication required by § 201.66(c)(4) may be limited to: “Use [in bold type] helps protect against sunburn and chapped lips.” (iii) The “external use only” warning in § 201.66(c)(5)(i) of this chapter may be omitted. (iv) The subheadings in § 201.66(c)(5)(iii) through (c)(5)(vii) of this chapter may be omitted, provided the information after the heading “Warnings” states: “Keep out of eyes.” and “Stop use if skin rash occurs.” (v) The warning in § 201.66(c)(5)(x) of this chapter may be limited to the following: “Keep out of reach of children.” (vi) For a lip protectant product or lipstick, the warnings “Keep out of eyes” in § 352.52(f)(1)(iv) and “Keep out of reach of children” in § 352.52(f)(1)(v) and the directions in § 352.52(d) may be omitted. (2) The labeling shall be printed in accordance with the requirements of § 201.66(d) of this chapter except that any requirements related to § 201.66(c)(1), (c)(3), and (c)(7), and the horizontal barlines and hairlines described in § 201.66(d)(8), may be omitted. [64 FR 27687, May 21, 1999, as amended at 68 FR 33380, June 4, 2003] § 352.60 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) In addition, the labeling of the product may contain any of the “other allowable statements” that are identified in the applicable monographs. (2) For permitted combinations containing a sunscreen and a skin protectant identified in § 352.20(b), any or all of the applicable indications for sunscreens in § 352.52(b) and the indication for skin protectants in § 347.50(b)(2)(i) of this chapter should be used. For products marketed as a lip protectant, the indication in § 352.52(f)(1)(ii) should be used. (c) Warnings. (d) Directions. [64 FR 27687, May 21, 1999, as amended at 68 FR 33380, June 4, 2003] Subpart D—Testing Procedures § 352.70 Standard sunscreen. (a) Laboratory validation. i.e. (b) Preparation of the standard homosalate sunscreen. Composition of Preparation A and Preparation B of the Standard Sunscreen Ingredients Percent by weight Preparation A Lanolin 5.00 Homosalate 8.00 White petrolatum 2.50 Stearic acid 4.00 Propylparaben 0.05 Preparation B Methylparaben 0.10 Edetate disodium 0.05 Propylene glycol 5.00 Triethanolamine 1.00 Purified water U.S.P 74.30 (2) Preparation A and preparation B are heated separately to 77 to 82 °C, with constant stirring, until the contents of each part are solubilized. Add preparation A slowly to preparation B while stirring. Continue stirring until the emulsion formed is cooled to room temperature (15 to 30 °C). Add sufficient purified water to obtain 100 grams of standard sunscreen preparation. (c) Assay of the standard homosalate sunscreen. (1) Preparation of the assay solvent. (2) Preparation of a 1-percent solution of the standard homosalate sunscreen preparation. (3) Preparation of the test solution (1:50 dilution of the 1-percent solution). (4) Spectrophotometric determination. (5) Calculation of the concentration of homosalate. Concentration of homosalate = absorbance × 50 × 100 × 172 = percent concentration by weight. § 352.71 Light source (solar simulator). A solar simulator used for determining the SPF of a sunscreen drug product should be filtered so that it provides a continuous emission spectrum from 290 to 400 nanometers similar to sunlight at sea level from the sun at a zenith angle of 10° it has less than 1 percent of its total energy output contributed by nonsolar wavelengths shorter than 290 nanometers; and it has not more than 5 percent of its total energy output contributed by wavelengths longer than 400 nanometers. In addition, a solar simulator should have no significant time-related fluctuations in radiation emissions after an appropriate warmup time, and it should have good beam uniformity (within 10 percent) in the exposure plane. To ensure that the solar simulator delivers the appropriate spectrum of UV radiation, it must be measured periodically with an accurately-calibrated spectroradiometer system or equivalent instrument. § 352.72 General testing procedures. (a) Selection of test subjects (male and female). Selection of Fair-skin Subjects Skin Type and Sunburn and Tanning History (Based on first 30 to 45 minutes sun exposure after a winter season of no sun exposure.) I—Always burns easily; never tans (sensitive). II—Always burns easily; tans minimally (sensitive). III—Burns moderately; tans gradually (light brown) (normal). IV—Burns minimally; always tans well (moderate brown) (normal). V—Rarely burns; tans profusely (dark brown) (insensitive). VI—Never burns; deeply pigmented (insensitive). (2) A medical history shall be obtained from all subjects with emphasis on the effects of sunlight on their skin. Ascertain the general health of the individual, the individual's skin type (I, II, or III), whether the individual is taking medication (topical or systemic) that is known to produce abnormal sunlight responses, and whether the individual is subject to any abnormal responses to sunlight, such as a phototoxic or photoallergic response. (b) Test site inspection. (c) Informed consent. (d) Test site delineation Test site area. (2) Test subsite area. (e) Application of test materials. (f) Waiting period. (g) Number of subjects. (h) Response criteria. (i) Rejection of test data. § 352.73 Determination of SPF value. (a)(1) The following erythema action spectrum shall be used to calculate the erythema effective exposure of a solar simulator: V i V i 0.094 (298 - l ) V i 0.015 (139 - l ) (2) The data contained in this action spectrum are to be used as spectral weighting factors to calculate the erythema effective exposure of a solar simulator as follows: (b) Determination of MED of the unprotected skin. n (c) Determination of individual SPF values. SPF value = the ratio of erythema effective exposure (Joules per square meter) (MED(PS)) to the erythema effective exposure (Joules per square meter) (MED(US)). (d) Determination of the test product's SPF value and PCD. i.e. § 352.76 Determination if a product is water resistant or very water resistant. The general testing procedures in § 352.72 shall be used as part of the following tests, except where modified in this section. An indoor fresh water pool, whirlpool, and/or jacuzzi maintained at 23 to 32 °C shall be used in these testing procedures. Fresh water is clean drinking water that meets the standards in 40 CFR part 141. The pool and air temperature and the relative humidity shall be recorded. (a) Procedure for testing the water resistance of a sunscreen product. (1) Apply sunscreen product (followed by the waiting period after application of the sunscreen product indicated on the product labeling). (2) 20 minutes moderate activity in water. (3) 20-minute rest period (do not towel test sites). (4) 20 minutes moderate activity in water. (5) Conclude water test (air dry test sites without toweling). (6) Begin solar simulator exposure to test site areas as described in § 352.73. (b) Procedure for testing a very water resistant sunscreen product. (1) Apply sunscreen product (followed by the waiting period after application of the sunscreen product indicated on the product labeling). (2) 20 minutes moderate activity in water. (3) 20-minute rest period (do not towel test sites). (4) 20 minutes moderate activity in water. (5) 20-minute rest period (do not towel test sites). (6) 20 minutes moderate activity in water. (7) 20-minute rest period (do not towel test sites). (8) 20 minutes moderate activity in water. (9) Conclude water test (air dry test sites without toweling). (10) Begin solar simulator exposure to test site areas as described in § 352.73. § 352.77 Test modifications. The formulation or mode of administration of certain products may require modification of the testing procedures in this subpart. In addition, alternative methods (including automated or in vitro procedures) employing the same basic procedures as those described in this subpart may be used. Any proposed modification or alternative procedure 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 procedure provides results of equivalent accuracy. All information submitted will be subject to the disclosure rules in part 20 of this chapter.