99-12853. Sunscreen Drug Products For Over-The-Counter Human Use; Final Monograph  

  • [Federal Register Volume 64, Number 98 (Friday, May 21, 1999)]
    [Rules and Regulations]
    [Pages 27666-27693]
    From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
    [FR Doc No: 99-12853]
    
    
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    DEPARTMENT OF HEALTH AND HUMAN SERVICES
    
    Food and Drug Administration
    
    21 CFR Parts 310, 352, 700, and 740
    
    [Docket No. 78N-0038]
    RIN 0910-AA01
    
    
    Sunscreen Drug Products For Over-The-Counter Human Use; Final 
    Monograph
    
    AGENCY: Food and Drug Administration, HHS.
    
    ACTION: Final rule.
    
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    SUMMARY: The Food and Drug Administration (FDA) is issuing a final rule 
    in the form of a final monograph establishing conditions under which 
    over-the-counter (OTC) sunscreen drug products are generally recognized 
    as safe and effective and not misbranded as part of FDA's ongoing 
    review of OTC drug products. FDA is issuing this final rule after 
    considering public comments on the agency's proposed regulation, which 
    was issued in the form of a tentative final monograph, and new data and 
    information on sunscreen drug products that have come to the agency's 
    attention. FDA is also issuing final rules regarding the labeling of 
    certain cosmetic products to inform consumers that these products do 
    not provide protection from the sun.
    
    EFFECTIVE DATES:  This regulation is effective May 21, 2001 for parts 
    310, 352, and 700 and is effective May 22, 2000 for part 740.
    
    FOR FURTHER INFORMATION CONTACT: John D. Lipnicki, Center for Drug 
    Evaluation and Research (HFD-560), Food and Drug Administration, 5600 
    Fishers Lane, Rockville, MD 20857, 301-827-2222.
    
    SUPPLEMENTARY INFORMATION: 
    
    I. Introduction
    
        In the Federal Register of August 25, 1978 (43 FR 38206), FDA 
    published, under Sec. 330.10(a)(6) (21 CFR 330.10(a)(6)), an advance 
    notice of proposed rulemaking (ANPRM) to establish a monograph for OTC 
    sunscreen drug products, together with the recommendations of the 
    Advisory Review Panel on OTC Topical Analgesic, Antirheumatic, Otic, 
    Burn, and Sunburn Prevention Drug Products (the Panel), which was the 
    advisory review panel that evaluated data on the active ingredients in 
    this drug class. The agency's proposed regulation for OTC sunscreen 
    drug products, in the form of a tentative final monograph, was 
    published in the Federal Register of May 12, 1993 (58 FR 28194).
        In the Federal Register of June 8, 1994 (59 FR 29706), the agency 
    proposed to amend the tentative final monograph (and reopened the 
    comment period until August 22, 1994) to remove five sunscreen 
    ingredients because of a lack of interest in establishing United States 
    Pharmacopeia (USP) monographs: Digalloyl trioleate, ethyl 4-
    [bis(hydroxypropyl)] aminobenzoate, glyceryl aminobenzoate, lawsone 
    with dihydroxyacetone (interest was subsequently shown in developing a 
    monograph for lawsone and dihydroxyacetone), and red petrolatum. The 
    agency also reiterated that all sunscreen ingredients must have a USP 
    monograph before being included in the final monograph for OTC 
    sunscreen drug products. This final rule includes those sunscreen 
    ingredients that have USP monographs.
        In the Federal Register of September 16, 1996 (61 FR 48645), the 
    agency amended the proposed rule to include avobenzone as a single 
    ingredient and in combination with certain other sunscreen ingredients 
    (interim marketing was allowed in the Federal Register of April 30, 
    1997 (62 FR 23350)). In the Federal Register of October 22, 1998 (63 FR 
    56584), the agency proposed to amend the tentative final monograph to 
    include zinc oxide as a single ingredient and in combination with any 
    proposed Category I sunscreen active ingredient except avobenzone.
        In the Federal Register of April 5, 1994 (59 FR 16042), the agency 
    reopened the administrative record and announced a public meeting to 
    discuss ultraviolet A (UVA) radiation claims and testing procedures. In 
    the Federal Register of August 15, 1996 (61 FR 42398), the agency 
    reopened the administrative record and announced a public meeting to 
    discuss the photochemistry and photobiology of sunscreens.
        This final monograph completes the tentative final monograph except 
    for
    
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    certain testing issues and UVA labeling, which the agency will discuss 
    in future issues of the Federal Register. Until then, UVA labeling may 
    continue in accord with the tentative final monograph and its 
    amendments. The agency advises that on or after May 21, 2001, no OTC 
    drug product that is subject to the monograph and that contains a 
    nonmonograph condition may be initially introduced or initially 
    delivered for introduction into interstate commerce unless it is the 
    subject of an approved new drug application or abbreviated new drug 
    application. Further, any OTC drug product subject to this monograph 
    that is repackaged or relabeled after the effective date of the 
    monograph must be in compliance with the monograph regardless of the 
    date the product was initially introduced or initially delivered for 
    introduction into interstate commerce. Manufacturers are encouraged to 
    comply voluntarily as soon as possible.
        In response to the proposed rule on OTC sunscreen drug products and 
    subsequent reopenings of the administrative record, the agency received 
    433 comments. The comments included four petitions (Refs. 1 through 4) 
    requesting consideration of sunscreen ingredients that have been 
    marketed in Europe but not in the United States. The status of these 
    petitions is discussed in section II.C, comment 13 of this document. 
    One manufacturer requested an oral hearing before the Commissioner of 
    Food and Drugs if the agency mandated a limit on sun protection factor 
    (SPF) values in this final rule. Copies of the information considered 
    by the Panel, the comments and petitions, and the hearing request are 
    on public display in the Dockets Management Branch (HFA-305), Food and 
    Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. 
    All ``OTC Volumes'' cited throughout this document refer to information 
    on public display.
        A number of comments were filed in the Dockets Management Branch 
    after the dates the administrative record had officially closed. The 
    agency has considered these comments as ``feedback'' communications 
    under the OTC drug review procedures, as discussed in the Federal 
    Register of September 29, 1981 (46 FR 47740), and clarified in the 
    Federal Register of April 1, 1983 (48 FR 14050). When ``feedback'' 
    material submitted after an administrative record has officially closed 
    directly influences or forms one of the bases for the agency's decision 
    on a matter in an OTC drug rulemaking proceeding, the agency adds it to 
    the administrative record without submission of a formal petition by an 
    interested party.
        The agency has included these data and information in the 
    administrative record and addressed them in this document. The agency 
    has considered the request for an oral hearing in its response to the 
    comment and believes it has adequately responded to the manufacturer 
    and that a hearing is not needed. As discussed in section II.G, comment 
    29 of this document, the agency is allowing the marketing of OTC 
    sunscreen drug products with SPF values above 30 under one collective 
    term (i.e., ``30 plus'' or ``30 +''). The agency will also consider 
    including labeling in the monograph with actual label SPF values on 
    products with SPF values over 30 when adequate data are submitted to 
    substantiate a testing procedure applicable to SPF values over 30.
    
    II. The Agency's Conclusions on the Comments
    
    A. General Comments on OTC Sunscreen Drug Products
    
        1. Several comments asked that the agency either exempt currently 
    marketed sunscreen products from the requirement for redetermining the 
    SPF or provide a 2-year implementation period. One comment requested a 
    3-year implementation period. The comments contended that the proposed 
    12-month implementation period would result in lost business and a 
    serious economic hardship for manufacturers, estimated to be 35 million 
    dollars for reformulating, retesting, and relabeling sunscreen 
    products.
        The agency agrees with the comments that the proposed 12-month 
    implementation period may cause undue economic burden on some 
    manufacturers of these products without a corresponding benefit to 
    consumers (see section VII of this document). As discussed in section 
    VII, a 24-month effective date would allow most firms to relabel 
    products during a normal relabeling cycle without incurring additional 
    costs. Accordingly, the final rule will be effective 24 months from the 
    date of this publication. Because this final rule provides testing 
    procedures that were proposed in the tentative final monograph, 
    currently marketed products that have already been tested by those 
    procedures will not need to be retested. However, sunscreen products 
    that have not been tested will need to be tested using the methods 
    described in this document. The agency intends to propose modified test 
    procedures in a future issue of the Federal Register and any necessary 
    retesting time will be specified when the final rule for testing 
    procedures publishes.
        2. Several comments recommended modifications to the definition of 
    minimal erythema dose (MED) in proposed Sec. 352.3(a). Some comments 
    objected to the presumption that erythema is a ``diffusing'' reaction 
    that starts from within the exposed site and moves outward in a dose 
    dependent manner, i.e., ``redness reaching the borders of the exposure 
    site.'' Other comments asserted that the definition is too limiting 
    because it may not be appropriate for all solar simulator 
    configurations (e.g., no template). Many comments recommended the 
    definition of MED used by the European Trade Association COLIPA (Ref. 
    5): ``The quantity of radiant energy required to produce the first 
    perceptible, unambiguous redness reaction with clearly defined 
    borders.'' Another comment recommended ``erythema-effective ultraviolet 
    radiation'' in place of ``radiant energy.''
        The agency agrees that the proposed definition of MED should be 
    modified for the reasons discussed by the comments and is revising 
    Sec. 352.3(a) in this final rule, as follows: ``Minimal erythema dose 
    (MED). The quantity of erythema-effective energy (expressed in Joules 
    per square meter) required to produce the first perceptible redness 
    reaction with clearly defined borders.'' The agency considers this 
    definition broad enough to encompass tests conducted with solar 
    simulator configurations with no template and consistent with COLIPA's 
    definition.
        3. One comment noted that the wavelength ranges for UVA, UVB, and 
    UVC radiation in the tentative final monograph differed from the 
    official ranges of the Commission International de L'Eclairage (CIE), 
    which are: (1) UVC-radiation of less than 280 nanometers (nm), (2) UVB-
    280 to 315 nm, and (3) UVA-315 to 400 nm. The comment mentioned the 
    agreement reached at the 11th International Congress on Photobiology 
    (Ref. 6) on the short wavelength end of UVB radiation (280 or 290 nm) 
    and suggested that the scientific evidence supports 320 nm as the long-
    wavelength boundary of UVB radiation.
        The agency agrees with the comment that the scientific evidence 
    supports 320 nm as the long-wavelength boundary of UVB radiation. 
    However, the short-wavelength boundary for UVB radiation has been 
    accepted as either 280 or 290 nm. Given that the comment did not 
    provide a compelling reason to change the proposed definition of UVB 
    radiation, the agency will continue to
    
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    define the boundaries of UVB radiation as 290 to 320 nm.
        4. Comments requested the agency to amend the definition of a 
    sunscreen active ingredient in proposed Sec. 352.3(c) to include 
    mechanisms other than absorption, to expand the UV range to include UVA 
    radiation, and to provide a minimum SPF value requirement. The comments 
    added that some proposed Category I active ingredients (e.g., menthyl 
    anthranilate and titanium dioxide) do not meet the proposed definition, 
    and that the definition is not interpretable without specifications for 
    measuring 85 percent absorbance.
        The agency discussed the need to modify the definition in a 1996 
    proposed amendment of the tentative final monograph (61 FR 48645 at 
    48646). The agency agrees that modifications should be to: (1) Include 
    mechanisms other than absorption, (2) redefine wavelengths, and (3) 
    remove the percent absorbance requirement. The agency does not agree 
    that a minimum SPF value should be included in the definition because 
    this information is more appropriately a characteristic of the final 
    formulation. Therefore, the agency has revised proposed Sec. 352.3(c) 
    in this document, to read: ``Sunscreen active ingredient. An ingredient 
    listed in Sec. 352.10 that absorbs, reflects, or scatters radiation in 
    the ultraviolet range at wavelengths of 290 to 400 nanometers.''
        5. One comment recommended that the agency reevaluate statements in 
    the tentative final monograph on the harmful nature of tanning. The 
    agency discussed the harmful effects of UV radiation-induced tanning in 
    the tentative final monograph (58 FR 28194 at 28238 to 28239). The 
    comment suggested that a natural tan reduces cumulative sun exposure 
    and may potentiate sunscreen effectiveness. The comment did not, 
    however, provide data or references to support this claim or to 
    otherwise cause the agency to change its position.
        6. One comment requested that the final monograph require 
    expiration dating and storage information in the labeling of OTC 
    sunscreen drug products. The comment noted that under 21 CFR 211.137, 
    OTC drug products with data demonstrating stability for 3 years and 
    without labeled dosage limitations are not required to include an 
    expiration date in their labeling. The comment stated that it was aware 
    of numerous cases that suggest these products may not be stable for 3 
    years.
        The agency requested the comment to provide data and information 
    about the specific products it was aware of (Ref. 7), but none were 
    subsequently provided. The agency is not currently aware of stability 
    problems that would require expiration dating for OTC sunscreen drug 
    products but will address such a requirement if data become available. 
    All sunscreen active ingredients included in the final monograph also 
    have a USP monograph that contains packaging and storage requirements 
    and standards for products containing these ingredients.
        7. Comments recommended that the agency establish procedures for 
    ensuring batch-to-batch SPF test results, and that it approve testing 
    laboratories and regulate their performance.
        Regulations already exist to assure that each batch of drug product 
    meets established specifications for the identity and strength of each 
    active ingredient. Specifically, 21 CFR 211.160 requires that product 
    specifications and laboratory controls be established and performed. 
    Although the agency would not require SPF testing on human subjects for 
    every batch produced, manufacturers need to assure conformance to their 
    finished product specifications. Further, any changes to the batch 
    formula would, at a minimum, require review and documentation by the 
    manufacturer's quality control unit to determine if SPF retesting is 
    necessary. Finally, 21 CFR 211.180 provides for the inspection of 
    records pertaining to production, control, and distribution of batches 
    of drug products. Thus, testing laboratories are subject to these 
    regulations.
    
    B. Comments on the Drug/Cosmetic Status of Sunscreen Products
    
        8. One comment questioned whether sunscreen products should be 
    regulated as drugs. The comment asserted that such products are not 
    active in the mitigation or elimination of a disease condition, and 
    that sunscreen products have no more affect on the structure and 
    function of the body than ``being in physical shade.''
        The basis for the agency's determination that products intended for 
    use as sunscreens are subject to regulation as drugs under section 
    201(g)(1) of the Federal Food, Drug, and Cosmetic Act (the act) (21 
    U.S.C. 321(g)(1)) is set forth at length in the tentative final 
    monograph (58 FR 28194 at 28203 to 28206). Essentially, sunscreen 
    active ingredients affect the structure and function of the body by 
    absorbing, reflecting, or scattering the harmful, burning rays of the 
    sun, thereby altering the normal physiological response to solar 
    radiation. Proper use of sunscreen ingredients (see section II.L, 
    comment 51 of this document) may help to prevent skin damage and may 
    help reduce the risk of skin lesions, skin cancer, and other disease 
    conditions. Products that are marketed to achieve these important 
    health benefits meet the definition of a drug under section 
    201(g)(1)(B) and (g)(1)(C) of the act.
        9. One comment disagreed with the agency's tentative conclusion 
    that products containing a sunscreen ingredient, but labeled for the 
    purpose of obtaining an ``even tan,'' are subject to regulation as 
    drugs. According to the comment, such a product is subject to 
    regulation as a drug only if it bears a claim to treat or prevent 
    sunburn. The comment asserts that this has been the agency's consistent 
    approach since 1940.
        Another comment stated that sunless tanning products, used to 
    impart color without exposure to the sun, could be improved by adding a 
    sunscreen to provide users protection during their normal outside 
    activities. The comment requested that such products should be regarded 
    as cosmetics, because they would be used primarily for a cosmetic 
    effect, with the sunscreen protection serving only a secondary purpose.
        The agency thoroughly discussed the regulatory status of 
    ``tanning'' products, including the basis for withdrawing its 1940 
    advisory opinion on sunburn and suntan preparations, in the tentative 
    final monograph (58 FR 28194 at 28203 to 28207, 28293 to 28294). As 
    discussed in the tentative final monograph, the presence of a sunscreen 
    active ingredient, in conjunction with labeling claims that the product 
    may be used, e.g., to permit tanning or to acquire an even tan, 
    generally establishes that the product's intended use is that of a 
    drug. Such products suggest, among other things, that the ingredients 
    in the product will allow the consumer to stay in the sun longer 
    without suffering skin damage (58 FR 28194 at 28204). Likewise, 
    products that claim to accelerate or stimulate the tanning process are 
    claiming, either expressly or impliedly, to stimulate the production of 
    melanin in the body. Such a claim to affect the structure or function 
    of the body renders the product subject to regulation as a drug under 
    section 201(g)(1) of the act (see 58 FR 28194 at 28293). Finally, a 
    sunless tanning product that contains a sunscreen ingredient, to 
    provide protection to the consumer, is subject to regulation as a drug. 
    The idea that the sunburn protection offered by the product may only be 
    a ``secondary'' feature for the consumer is not relevant. If an 
    intended use of the product is to provide users with sun protection 
    when they go
    
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    outside (as the comment suggests), then the product is subject to 
    regulation as a drug.
        On the other hand, products that do not make express or implied sun 
    protection claims, and do not contain sunscreen ingredients, may be 
    regarded as cosmetics under section 201(i) of the act. If the product 
    is intended solely to provide cosmetic effects on the skin (e.g., to 
    moisturize the skin while sunbathing), or solely to impart color to the 
    skin without exposure to the sun or other sources of light (i.e., 
    sunless tanning), then the product may be marketed as a cosmetic. Such 
    products, however, must include a warning statement (discussed in this 
    section, comment 10 of this document) to inform the consumer that the 
    product does not provide any protection against sunburn. Products 
    marketed to enhance or permit tanning that do not contain a sunscreen 
    ingredient must be reviewed on a case-by-case basis to determine 
    whether the product is intended solely to provide a cosmetic benefit 
    (such as moisturizing) or whether the product is intended to enhance or 
    permit tanning by some other mechanism of action.
        The comments offered no other reasoning and no data to the 
    contrary, other than to suggest that the agency's approach would 
    encourage manufacturers to remove sunscreen ingredients from suntan 
    products and, thereby, expose consumers to even higher levels of 
    harmful ultraviolet rays. The agency is not persuaded that a 
    significant number of manufacturers will choose to reformulate their 
    products, to make them less safe for consumers, as a result of this 
    final rule. Moreover, consumers will continue to have an array of 
    sunscreen-containing products from which to choose. Finally, as 
    discussed below, certain tanning products (including sunless tanning 
    products) that do not contain sunscreen ingredients must bear a 
    prominent warning to the consumer. This will ensure that the consumer 
    is fully informed as to which products offer sun protection and which 
    do not.
        10. One comment requested that the signal word ``Caution'' replace 
    the signal word ``Warning'' preceding the following statement for 
    suntanning preparations: ``Warning--This product does not contain a 
    sunscreen and does not protect against sunburn.'' The comment stated 
    that the word ``Warning'' suggests safety hazards associated with these 
    products that are unrelated to sunburn. Another comment petitioned to 
    add a second sentence to the warning: ``Tanning in sunlight or under 
    tanning lamps can cause skin cancer and premature skin aging-even if 
    you don't burn.'' The comment concluded that the availability of 
    tanning products without a protective sunscreen ingredient is a serious 
    health issue and detrimental to public health. A third comment objected 
    to any such warnings on tanning products.
        The agency considers it an important public health issue that users 
    of suntanning products be alerted when these products do not contain a 
    sunscreen and do not protect against sunburn or other harmful effects 
    to the skin. Because suntanning products are intended for repeated use 
    under the sun or suntanning lamps while acquiring a tan, the agency 
    considers failure to provide information on hazards associated with 
    repeated, unprotected exposure to UV radiation to be a failure to 
    reveal material facts (see sections 201(n), 502(a), and 602(a) of the 
    act (21 U.S.C. 352(a) and 362(a))), especially in light of the 
    representations that are made for the product (e.g., suntanning). 
    Therefore, the agency is requiring the labeling of suntanning 
    preparations that do not contain a sunscreen ingredient (Sec. 740.19 
    (21 CFR 740.19)) to bear the following: ``Warning--This product does 
    not contain a sunscreen and does not protect against sunburn. Repeated 
    exposure of unprotected skin while tanning may increase the risk of 
    skin aging, skin cancer, and other harmful effects to the skin even if 
    you do not burn.'' The agency considers this information to be 
    sufficiently important, for safety reasons, to require a 12-month 
    effective date (as opposed to 24 months for the balance of the rule) 
    and to require the strongest possible signal word, i.e., ``Warning.''
        11. One comment disagreed with the proposal that hair care and nail 
    products that contain a sunscreen ingredient for a nontherapeutic use 
    (e.g., to protect the color of the product), and that use the term 
    ``sunscreen'' in the labeling, must describe in the labeling the 
    functional role of the sunscreen. According to the comment, it is 
    highly unlikely that consumers would think that these products are 
    intended to protect the skin. If this requirement were finalized, the 
    comment requested that the agency permit the term ``sunscreen'' to 
    appear once anywhere in the labeling, with the purpose of the sunscreen 
    explained elsewhere in the labeling.
        The agency disagrees with the premise of this comment. The use of 
    the term ``sunscreen'' in labeling suggests that the product in some 
    way will protect the consumer from the harmful effects of the sun. The 
    health risks associated with relying on a product for protection from 
    the sun, when in fact the product does not provide such protection, are 
    sufficiently serious to require the type of disclosure outlined in the 
    proposed rule. Information about the purpose of a sunscreen ingredient 
    in a hair care or nail product will be useful to consumers to inform 
    them that the ingredient protects only the hair or only the color of 
    the product.
        This information need appear only once and can appear anywhere in 
    the labeling, provided the qualifying purpose appears prominently and 
    conspicuously and in conjunction with the word ``sunscreen.'' The 
    information may, e.g., be combined in a single statement, e.g., 
    ``Contains a sunscreen--to protect product color.'' This will ensure 
    that consumers will see and readily associate the two pieces of 
    information.
        12. Two comments objected to the use of an OTC drug rulemaking 
    process to change cosmetic labeling requirements, i.e., the addition of 
    a warning on certain tanning products and the labeling requirements for 
    hair care or nail products that contain a sunscreen for a 
    nontherapeutic use.
        The agency addressed this procedural concern, which was also raised 
    in response to the ANPRM, at length in the tentative final monograph 
    (58 FR 28194 at 28201 to 28202). The industry and consumers have had 
    ample notice of the fact that this proceeding included several cosmetic 
    labeling issues that arise out of the same facts and findings at issue 
    in developing the OTC drug monograph. It is not uncommon for the agency 
    to address in an OTC rulemaking document the status of, or the 
    regulation of, products that fall outside of the monograph. In this 
    instance, the cosmetic labeling issues were so closely related to the 
    OTC drug issues that a separate proceeding would have been overly 
    duplicative and inefficient.
    
    C. Comments on Specific Sunscreen Active Ingredients
    
        13. Several comments noted that FDA had deferred a decision on the 
    citizen petitions requesting that sunscreen active ingredients marketed 
    solely in foreign countries be included in the OTC sunscreen monograph. 
    The comments urged FDA answer these petitions and establish a policy 
    concerning the inclusion of OTC sunscreens based solely on foreign data 
    and marketing experience.
        In the Federal Register of October 3, 1996 (61 FR 51625), the 
    agency published an ANPRM that addressed establishing eligibility 
    criteria for considering additional OTC conditions (i.e., OTC drug 
    active ingredients, indications, dosage forms, dosage
    
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    strengths, routes of administration, and active ingredient 
    combinations) in the OTC drug monograph system. These proposed criteria 
    would address how foreign or domestic OTC marketing experience could be 
    used to support the inclusion of an ingredient in an OTC drug 
    monograph. Specifically, the criteria would address how OTC marketing 
    experience in the United States or abroad could be used to meet the 
    statutory requirement under section 201(p) of the act of marketing ``to 
    a material extent'' and ``for a material time.'' ``Material extent'' 
    and ``material time'' are needed to qualify a specific OTC drug 
    condition for consideration under the OTC drug monograph system.
        The decision on whether to proceed with a final rulemaking on this 
    subject will be based, in part, on the information and comments 
    submitted in response to the notice of proposed rulemaking that the 
    agency is preparing for publication in a future issue of the Federal 
    Register. Resolution of the pending sunscreen petitions must await the 
    outcome of any final rulemaking on this subject.
        14. One comment requested that the agency adopt simpler, more user-
    friendly, names for several sunscreen ingredients: (1) Roxadimate for 
    ethyl-[bis(hydroxypropyl)] aminobenzoate, (2) lisadimate for glyceryl 
    aminobenzoate, and (3) diolamine methoxycinnamate for diethanolamine 
    methoxycinnamate. The comment claimed that these names had been adopted 
    or designated by the United States Adopted Names (USAN) Council. The 
    comment also requested that if USAN adopts a name for 
    phenylbenzimidazole sulfonic acid, FDA adopt this name as well. The 
    comment also suggested the use of the acronyms ``TEA'' and ``DEA'' for 
    triethanolamine and diethanolamine, respectively.
        The agency is including in this final monograph only those active 
    ingredients that are the subject of an official USP compendial 
    monograph that sets forth its standards of identity, strength, quality, 
    and purity (see section I of this document). In the Federal Register of 
    June 8, 1994, FDA deleted ethyl-[bis(hydroxypropyl)] aminobenzoate and 
    glyceryl aminobenzoate from the tentative final monograph due to the 
    lack of interest in establishing USP monographs for these ingredients. 
    Moreover, two sunscreen ingredients (including diethanolamine 
    methoxycinnamate) have been deferred from the final monograph due to 
    the lack of a current or proposed compendial monograph. Therefore, the 
    issue of whether a ``user-friendly'' name for these ingredients should 
    be developed or adopted need not be resolved in this proceeding at this 
    time. Similarly, TEA and DEA need not be addressed in this proceeding, 
    as triethanolamine is not a sunscreen active ingredient, and 
    diethanolamine is only used in the ingredient diethanolamine 
    methoxycinnamate which, as discussed, is not a monograph ingredient at 
    this time.
        With respect to the comment on the monograph ingredient 
    phenylbenzimidazole sulfonic acid, the agency agrees that if USAN or 
    the USP were to adopt a different or alternative name for this 
    ingredient, such a name could be used in the labeling of a product that 
    contains this ingredient. As discussed in comment 30 of the tentative 
    final monograph (58 FR 28194 at 28207 to 28209), the agency is using 
    the compendial name as the established name for each active ingredient.
        15. Two comments requested that the term ``PABA'' continue to be 
    allowed in labeling. The comments stated that the name aminobenzoic 
    acid is meaningless to consumers and physicians, who over the years 
    have learned to recognize this ingredient on the label as PABA. One 
    comment recommended the use of aminobenzoic acid in the ingredient list 
    and the use of PABA in other communications about the product. The 
    comment added that the term ``PABA-free'' should be allowed on products 
    that do not contain aminobenzoic acid. The other comment proposed 
    either to permit the listing of the ingredient as PABA or, if that is 
    unacceptable, as PABA (aminobenzoic acid).
        In comment 30 of the tentative final monograph (58 FR 28194 at 
    28207 to 28209), the agency discussed the issue of the appropriate 
    established name for this and other sunscreen ingredients. As the 
    agency stated in that discussion, the recognized compendial name for 
    aminobenzoic acid no longer includes the term PABA.
        The agency acknowledges, however, that the term PABA formerly was 
    part of the established name for this ingredient and that the use of 
    the term in consumer labeling has continued despite the change in the 
    compendial name. In addition, the agency agrees with the comment that 
    many consumers have learned to recognize this ingredient as, and only 
    as, PABA. The agency also recognizes that consumers seeking to avoid 
    the use of this ingredient for health-related reasons (e.g., allergy) 
    may, in this case, be misled if the term PABA were no longer permitted. 
    Some consumers may believe that a product that lists aminobenzoic acid 
    as an ingredient, but does not list PABA, is PABA-free. If such a 
    consumer has an allergy to aminobenzoic acid, the individual may suffer 
    adverse health consequences.
        For these reasons, and especially in light of the potential safety 
    concerns for certain consumers, the agency concludes that wherever the 
    ingredient aminobenzoic acid appears in the labeling of an OTC 
    sunscreen drug product, including labeling that notes the absence of 
    this ingredient, the descriptive term PABA must immediately follow the 
    established name, i.e., ``Aminobenzoic acid (PABA).'' Thus, e.g., a 
    product that is currently marketed as ``PABA-free'' would now be 
    required to state that the product is ``Aminobenzoic acid (PABA)-
    free.'' This convention will allow consumers to begin to recognize that 
    the ingredient they may wish to avoid is ``aminobenzoic acid.'' After a 
    sufficient period of time, the agency will revisit the need for 
    consumer labeling to continue to bear the descriptive term PABA.
        16. One comment stated that claims of protection by artificial 
    melanin, melanin-containing products, and antioxidants should be 
    enumerated, well regulated, and defined.
        The agency agrees with the comment, but these claims are not 
    covered by this final monograph. Melanin and artificial melanins are 
    not recognized sunscreen active ingredients. Any product containing 
    melanin or artificial melanins as active ingredients and making sun 
    protection claims would have to seek marketing approval under a new 
    drug application (NDA).
        The agency is aware that claims of protection from antioxidants are 
    used in the labeling of some cosmetic products with or without a 
    sunscreen. The agency will ascertain the nature of any such claims 
    (drug or cosmetic) on a case-by-case basis.
        17. Several comments objected to the agency's proposal that OTC 
    sunscreen drug products must contain less than 500 parts per billion 
    (ppb) of N-methyl-N-nitrosoaminobenzoate octyl ester (NMPABAO) for 
    several reasons: (1) Toxicological studies indicate that NMPABAO does 
    not have mutagenic or suspected carcinogenic potential (Ref. 8), (2) 
    NMPABAO may be present in sunscreens containing padimate O only in 
    small amounts (ppb range) and the risks associated with NMPABAO are 
    very low, (3) NMPABAO decomposes quickly when exposed to UV radiation, 
    and (4) industry is aware not to formulate with known nitrosating 
    agents in the presence of amines in order to avoid nitrosamine 
    contamination of its products. Some comments stated that FDA's own 
    conclusions in the tentative
    
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    final monograph concerning the safety of both NMPABAO and padimate O do 
    not support the imposition of concentration limits for NMPABAO in 
    sunscreens nor do they justify the high cost of analyzing each batch of 
    sunscreen product for NMPABAO. One comment contended that any proposed 
    limit should apply to all nitrosamines and not just NMPABAO. The 
    comment stated that nitrosamines can be formed from any secondary or 
    tertiary amine. Several sunscreen active ingredients contain this 
    moiety in their chemical structure and many inactive ingredients are 
    secondary or tertiary amines. The comment concluded that targeting 
    NMPABAO falsely conveys that padimate O is a unique concern, resulting 
    in manufacturers using other ingredients to avoid costly testing and 
    negative implications.
        In the tentative final monograph, the agency did not propose a 
    concentration limit on NMPABAO. Rather, based on concerns that had been 
    raised, the agency asked for comment on whether it should consider 
    proposing a fixed limit. As discussed in the tentative final monograph 
    (58 FR 28194 at 28288 to 28293), toxicological studies support the 
    agency's belief that the risk associated with NMPABAO contamination of 
    sunscreen drug products is very low due to NMPABAO's low mutagenicity 
    and carcinogenicity potential and rapid decomposition in the presence 
    of UV radiation. The agency has not become aware of any new data or 
    information since the publication of the tentative final monograph 
    suggesting a safety concern with NMPABAO in sunscreen drug products. 
    Therefore, the agency has decided not to propose or otherwise include 
    in this final monograph a requirement that OTC sunscreen drug products 
    must contain less than 500 ppb of NMPABAO.
        In the tentative final monograph (58 FR 28194 at 28292), the agency 
    discussed its analysis for NMPABAO in 25 commercially available 
    sunscreen products. Of the 11 samples found to be contaminated with 
    NMPABAO, the four highest contained 2-bromo-2-nitro-1,3-propanediol, an 
    indirect nitrosating agent. The agency concluded that there would be no 
    nitrosamine contamination if these products were formulated without the 
    nitrosating agent. As noted by several of the comments, the industry is 
    aware not to formulate with known nitrosating agents in the presence of 
    amines in order to avoid nitrosamine contamination of its products.
        18. One comment submitted a reference to a subchronic oral toxicity 
    study in rats conducted with padimate O which a chemical manufacturer 
    had submitted to the Toxic Substance Control Act 8(e) coordinator of 
    the United States Environmental Protection Agency for consideration. 
    The study was a 4-week repeated dose study at doses of 0, 100, 300, and 
    1,000 milligrams (mg)/kilogram (kg)/day of padimate O administered by 
    gavage in a corn oil vehicle (10 to 15 rats/group/sex). The study 
    included a 4-week recovery period to assess the persistence or 
    reversibility of any toxic effects. At the end of the 4-week treatment 
    period, toxic effects were seen in four target organs: Testes, 
    epididymis, spleen, and liver. The no-observed-effect-level in this 
    study was 100 mg/kg/day for both males and females. Toxic effects 
    appeared reversible in the animals necropsied after the 4-week recovery 
    period with the exception of marked epididymal hypospermia at the 1,000 
    mg/kg/day dose (5/5 animals).
        The clinical relevance of this animal toxicity study is difficult 
    to assess. Padimate O was administered chronically and at very high 
    oral doses. Under normal use conditions, sunscreen drug products 
    containing padimate O are applied topically and used intermittently. In 
    addition, pharmacokinetic parameters were not calculated and the 
    different routes of administration (oral in this study versus topical 
    for sunscreen products) preclude calculation of a ``safety margin'' on 
    the basis of dose per unit of body weight or surface area. Similarly, 
    kinetic data are not available for a comparison of serum levels of drug 
    or metabolites. Literature searches indicate no published information 
    on the kinetics of padimate O with topical application in man. If 
    percutaneous absorption of padimate O does occur in man, it seems 
    likely that the peak and/or cumulative levels achieved with sunscreen 
    usage would be quite low compared to the systemic exposure achieved in 
    this animal toxicity study. Further, it is not known whether the 
    irreversible epididymal hypospermia found in the 1,000 mg/kg/day group 
    would also be reversible with more time.
        The agency has determined that this study does not present 
    sufficient data to exclude padimate O from the final monograph and that 
    an adequate safety margin exists for its use as an OTC sunscreen 
    ingredient.
        19. Two comments submitted safety and/or efficacy data to support 
    Category I status for micronized titanium dioxide (Refs. 9 and 10). One 
    comment stated that micronized titanium dioxide is not a new material 
    but is a selected distribution of existing material that provides 
    higher SPF values while being transparent and esthetically pleasing on 
    the skin. The comments added that micronized titanium dioxide meets all 
    safety and efficacy criteria and also meets the USP specifications for 
    purity except pure water content.
        Another comment asserted for the following reasons that micronized 
    titanium dioxide is a new ingredient with several unresolved safety and 
    efficacy issues: (1) It does not meet the definition of a sunscreen 
    opaque sunblock, (2) there is no control of particles to agglomerate, 
    which is critical to effectiveness, (3) no standards exist to ensure 
    integrity of coatings, (4) there are no performance-based standards of 
    identity; micronized titanium dioxide is not included in the USP, (5) 
    its photocatalyst potential, and (6) the potential for the smaller 
    particle size to accumulate under the skin.
        The agency finds the data with the comments supportive of monograph 
    status for micronized titanium dioxide. Acute animal toxicity, 
    irritation, sensitization, photoirritation, photosensitization, and 
    human repeat insult patch and skin penetration studies revealed no 
    deleterious effects. SPF values for four product formulations 
    containing from 4.4 to 10 percent micronized titanium dioxide were from 
    9 to 24 and support effectiveness as a sunscreen ingredient.
        The agency is aware that sunscreen manufacturers are using 
    micronized titanium dioxide to create high SPF products that are 
    transparent and esthetically pleasing on the skin. The agency does not 
    consider micronized titanium dioxide to be a new ingredient but 
    considers it a specific grade of the titanium dioxide originally 
    reviewed by the Panel. Fairhurst and Mitchnick (Ref. 11) note that 
    ``fines'' have been part of commercially used titanium dioxide powders 
    for decades, and that a micronized product simply refers to a 
    refinement of particle size distribution. Based on data and information 
    presented at the September 19 and 20, 1996, public meeting on the 
    photobiology and photochemistry of sunscreens (Ref. 12), the agency is 
    not aware of any evidence at this time that demonstrates a safety 
    concern from the use of micronized titanium dioxide in sunscreen 
    products. While micronized titanium dioxide does not meet the proposed 
    definition of a sunscreen opaque sunblock, the agency has not included 
    the use of this term in the final monograph (see section II.L, comment 
    52 of this document). The potential for titanium dioxide particles to 
    agglomerate in formulation, which could result in lower SPF values, is 
    addressed by the final product SPF test.
    
    [[Page 27672]]
    
     The SPF data that the agency reviewed (Ref. 9) did not indicate such a 
    problem.
        Micronized titanium dioxide meets current USP monograph 
    specifications for titanium dioxide with the exception that the 
    material contains more associated water. In both the July through 
    August 1996 and 1998 issues of the Pharmacopeial Forum (Refs. 13 and 
    14), the United States Pharmacopeial Convention published in-process 
    revision proposals to make the monograph for titanium dioxide more 
    applicable to ingredients used in sunscreen drug products. The agency 
    will work with the USP in the future to update this monograph as 
    necessary.
        20. One comment stated that it is unnecessary to set the maximum 
    limit of titanium dioxide at 25 percent.
         The Panel discussed the safety and effectiveness of 2 to 25 
    percent titanium dioxide in the ANPRM (43 FR 38206 at 38250) and the 
    agency concurred with the Panel's findings in the tentative final 
    monograph (58 FR 28194 at 28295). The comment submitted no data and the 
    agency has no data to support the use of titanium dioxide in sunscreen 
    drug products at concentrations higher than 25 percent.
    
    D. Comments on Dosages for Sunscreen Drug Products
    
        21. Several comments objected to the minimum concentration 
    requirements for sunscreen active ingredients when used in combination 
    because they: (1) Are a less effective measurement of effectiveness 
    than a performance based SPF test, (2) impact on creativity and 
    innovation of new formulations (technological advances since 
    publication of the 1978 ANPRM have resulted in higher SPF values using 
    lower concentrations of active ingredients), (3) increase potential for 
    irritation and allergic reactions due to unnecessarily high 
    concentration levels of active ingredients, (4) contradict FDA's 
    position that the lowest effective dose of an active ingredient be used 
    to produce the desired treatment effect, (5) result in higher 
    manufacturing and consumer costs due to unnecessary levels of active 
    ingredients, and (6) affect international harmonization because Canada, 
    Australia, and the European Union have no concentration minimums for 
    active ingredients when used in combination.
        One comment petitioned the agency to amend proposed Sec. 352.20 of 
    the tentative final monograph to include a provision for formulating 
    combination sunscreen products at lower minimum concentrations. Two 
    comments submitted efficacy data to support lower concentrations of 
    sunscreen active ingredients when used in combination. One comment 
    (Ref. 15) submitted in vitro SPF testing data for several different 
    combinations. Although these data showed a statistically significant 
    increased efficacy for lower than minimum concentrations, they were not 
    predictive of the SPF values that would be obtained with human testing 
    and, therefore, were not used to support lower concentrations of 
    sunscreen active ingredients when used in combination. The other 
    comment (Ref. 16) submitted in vivo SPF testing data conducted 
    according to the procedure proposed in the tentative final monograph 
    (58 FR 28194 at 28298 to 28301) in which a selected cross section of 
    active ingredients were tested in pairs by substituting water or the 
    solvent system for the active ingredients. The data were evaluated 
    using a matched pairs comparison statistical hypothesis test procedure 
    and demonstrated that concentrations of sunscreen active ingredients 
    lower than the minimum concentrations proposed in Sec. 352.20(a)(2) for 
    combination products can provide a significant contribution to product 
    effectiveness.
        The agency recognizes that technological advances in sunscreen 
    formulation technology since 1978 have resulted in the ability to 
    formulate products with lower concentrations of active ingredients and 
    higher SPF values. The agency also recognizes that final product 
    testing, and not the concentration of the active ingredients in the 
    combination, ensures product effectiveness.
        Due to the recent advances in sunscreen formulation and the data 
    referenced previously, the agency is concerned that setting minimum 
    concentration requirements for active ingredients in sunscreen 
    combination drug products could subject consumers to unnecessary levels 
    of active ingredients. Therefore, the agency is only requiring the 
    maximum concentration limits in Sec. 352.10 for sunscreen active 
    ingredients when used in combination with another sunscreen or when the 
    combination is used with any other permitted active ingredient. 
    However, any such ingredient used in combination with one or more 
    sunscreen active ingredients must be consistent with the regulations in 
    Sec. 330.10(a)(4)(iv), i.e., each of the combined active ingredients 
    must make a contribution to the claimed effect, the combining of active 
    ingredients must not decrease the safety or effectiveness of any 
    individual active ingredient, and the combination must provide rational 
    concurrent therapy for a significant proportion of the target 
    population. Although the agency needs assurance that each ingredient is 
    contributing to the effectiveness of the product, it does not want to 
    impose unnecessary testing requirements on sunscreen product 
    manufacturers. Therefore, the agency is removing the minimum 
    concentration requirement for sunscreen active ingredients proposed in 
    Sec. 352.20 and is adding the requirement that: (1) The concentration 
    of each active sunscreen ingredient used in a combination product must 
    be sufficient to contribute a minimum SPF of not less than 2 to the 
    finished product, and (2) the finished product must have a minimum SPF 
    of not less than the number of the sunscreen active ingredients used in 
    combination multiplied by 2.
    
    E. Comments on Labeling and Testing Procedures for UVA Sunscreen Drug 
    Products
    
        22. In the sunscreen tentative final monograph (58 FR 28194 at 
    28232 and 28233), the agency proposed to allow claims relating to 
    ``broad spectrum protection'' or ``UVA radiation protection'' for 
    sunscreen products: (1) Containing sunscreen active ingredients with 
    absorption spectra extending to 360 nm or above, and (2) that 
    demonstrate meaningful UVA radiation protection using appropriate 
    testing procedures to be developed. The agency received numerous 
    comments concerning such claims and current scientific evidence 
    implicates UVA radiation as a major cause of, among other things, 
    photoaging of the skin (Refs. 17 through 20).
        In the Federal Register of September 16, 1996, and October 22, 
    1998, the agency proposed a specific skin damage and premature skin 
    aging claim for sunscreen products containing specific concentrations 
    of avobenzone or zinc oxide based upon the submission of data to 
    support claims of UVA radiation protection in such products. The agency 
    will address comments pertaining to measurement of UVA radiation 
    protection in sunscreen products and related UVA radiation protection 
    claims in a future issue of the Federal Register. Until then, UVA 
    labeling may continue in accord with the tentative final monograph and 
    its amendments.
    
    F. General Comments on the Labeling of Sunscreen Drug Products
    
        23. Several comments requested that products containing sunscreen 
    ingredients as an adjunct to their main purpose (e.g., a daily 
    moisturizer or a lipstick with a sunscreen) be considered ``secondary 
    sunscreens'' (intended only for incidental or casual sun exposure), and 
    should be subject to different
    
    [[Page 27673]]
    
    labeling requirements from ``primary'' sunscreen products. A number of 
    comments likewise contended that some of the labeling requirements for 
    ``beach'' or ``primary'' sunscreen products are not appropriate for 
    ``non-beach'' or ``secondary'' sunscreen products.
        For example, the comments stated that neither the proposed 
    ``Recommended Sunscreen Product Guide'' nor any other references to 
    sunburn or sunburn protection should be required for secondary 
    sunscreens. Some suggested that the warnings be reduced for secondary 
    sunscreens to a statement such as ``For external use only, keep out of 
    eyes. Discontinue use if signs of irritation appear.'' One comment 
    recommended that the statement of identity for a secondary sunscreen 
    should be its cosmetic function, e.g., ``moisturizer.'' Another 
    recommended stating the primary (cosmetic) function first, then the 
    secondary (drug) function, e.g., ``moisturizing face cream with 
    sunscreen (or with SPF ____ sunscreen).''
        The comments also suggested that secondary products be permitted to 
    bear certain labeling claims relating to aging, such as ``Helps reduce 
    the chance of skin aging caused by incidental (or casual) exposure to 
    the sun,'' or ``Helps reduce premature aging from incidental (or 
    casual) exposure to the sun.'' Some also requested the option of being 
    allowed to relate skin aging claims directly to sun exposure, to inform 
    consumers more clearly that sun protection is not the primary attribute 
    of the product, e.g., ``Provides moisture to facial skin throughout the 
    day while protecting facial skin from skin aging due to exposure to 
    sun.'' Other comments recommended that the proposed ``Sun alert'' 
    statement or other references to ``skin cancer'' or other cancers 
    should not be required for secondary products.
        On the other hand, the agency also received comments opposing the 
    idea of recognizing ``primary'' and ``secondary'' or ``beach'' and 
    ``non-beach'' categories of sunscreen products. One comment stated that 
    any product containing a sunscreen for the purpose of protection from 
    the sun's harmful effects should be held to the same standards as other 
    sunscreen products. Another comment disagreed with the idea of allowing 
    different sets of claims for ``primary'' and ``secondary'' products. 
    According to this comment, claims such as ``Helps reduce the chance of 
    skin aging'' are drug claims and should be regulated as such. Finally, 
    one comment stated that any sunscreen product (primary or secondary) 
    must have an SPF of 15 to 30 or higher to provide adequate protection, 
    whether for continuous beach exposure or everyday (incidental) sun 
    exposure.
        The agency agrees that all sunscreen products (whether drug only or 
    drug-cosmetic) should be held to the same standards (e.g., active 
    ingredient(s), testing requirements, and labeling). Regardless of what 
    type of product a consumer chooses for sun protection, the essential 
    information relevant to sun protection is the same. Thus, to ensure 
    that consumers are adequately protected from overexposure to the sun, 
    all products intended for use as sunscreens should have similar 
    labeling requirements, irrespective of their method of use and 
    irrespective of whether the sunscreen use is considered primary or 
    secondary to the product. Consistent with this approach, the agency has 
    developed uniform, streamlined labeling for all sunscreen products (see 
    sections II.I through II.L of this document).
        The agency also notes, however, that a number of the labeling 
    issues raised in these comments, including the issue of the 
    ``Recommended Sunscreen Product Guide,'' are addressed elsewhere in 
    this document. In addressing these issues, the agency gave careful 
    consideration to the wide variety of products marketed for sunscreen 
    uses.
        Finally, the agency notes that under the recently issued 
    standardized OTC drug product labeling format (Sec. 201.66 (21 CFR 
    201.66)), manufacturers will not be allowed to commingle drug and 
    cosmetic claims within the ``Drug Facts'' portion of the labeling.
        24. One comment requested clarification of the agency's discussion 
    of the term ``anti-aging'' as a claim or as part of a trade name (58 FR 
    28194 at 28287). The comment was concerned that products containing no 
    sunscreen active ingredients and no sunscreen claims, but which are 
    sold under ``anti-aging'' trade names, would be subject to regulation 
    under the OTC drug sunscreen monograph.
        The use of ``anti-aging'' language in a product that made no 
    sunscreen claims and contained no sunscreen active ingredients would 
    not, as the comment asked, cause the product to fall within the scope 
    of the OTC sunscreen drug monograph. Such a product may, however, be 
    subject to regulation as a drug and as a new drug, under section 
    201(g)(1) and (p) of the act, or as a cosmetic under section 201(i), or 
    as both a drug and a cosmetic, depending upon all of the circumstances 
    surrounding its distribution. A product that is marketed under the 
    final OTC sunscreen drug monograph, but which uses anti-aging language 
    in the labeling to suggest or imply an unapproved therapeutic or 
    physiologic effect, would likely be subject to regulatory action as an 
    unapproved new drug (58 FR 28194 at 28286 to 28287; see comments 37 and 
    38 in section II.I of this document).
        25. Three comments contended that the terms ``natural,'' ``non-
    chemical,'' and ``chemical free'' are false and misleading in the 
    labeling of OTC sunscreen drug products. The comments requested the 
    agency to restrict the use of these terms, especially for sunscreen 
    products containing titanium dioxide and zinc oxide.
        Generally, the appropriateness of these terms requires case-
    specific analysis to determine whether their use would render the 
    product false or misleading in any particular (see sections 502(a) and 
    602(a) of the act). The agency notes, however, that the use of the 
    terms ``non-chemical'' and ``chemical-free'' in the labeling of an OTC 
    sunscreen drug product, to describe the ingredients contained in the 
    product, is likely to be considered unacceptable. Sunscreen drug 
    products contain active (and often inactive) ingredients that have been 
    obtained through a chemical process, or that have been formulated into 
    the finished product through a chemical process. The term ``natural'' 
    is more likely to require context-specific analysis, particularly when 
    used in labeling to describe certain cosmetic aspects or uses of a 
    sunscreen product. The term ``natural,'' however, would not be 
    permitted to appear within the required OTC drug labeling of a 
    sunscreen product and is not considered to be interchangeable with any 
    of the final sunscreen monograph language.
        26. Four comments opposed any labeling that a sunscreen product 
    ``does not provide UVA protection,'' contending that FDA's policy does 
    not require disclaimers of broader purposes for which products are not 
    useful. One comment added that an SPF 15 product must block UVA 
    radiation to be effective in preventing sunburn.
        Two comments argued that a ``negative warning'' would be useful and 
    necessary to warn and protect consumers and suggested ``Does not 
    provide broad spectrum UVA protection,'' or ``Caution: This product 
    does not provide protection from the recognized dangers of UVA rays 
    which may contribute to skin cancer and other chronic skin disease.''
        Labeling should primarily direct consumers towards the purposes for 
    which a product is considered useful. However, in establishing the 
    conditions for the safe and effective use of an OTC
    
    [[Page 27674]]
    
    drug product, the agency also must take into account, among other 
    things, the context in which a product is customarily marketed and the 
    potential that consumers may use the product for a use for which it may 
    not be beneficial (see sections 201(n) and 502(a) of the act; 
    Sec. 330.10(a)(3)).
        With these factors in mind, the agency will further evaluate 
    whether ``negative warnings'' or disclosure statements are needed when 
    it completes the UVA portion of the sunscreen monograph in a future 
    issue of the Federal Register.
        27. Four comments contended that the signal words ``Indications'' 
    and ``Directions'' are not needed, take up valuable label space, and 
    should either not be required or be optional, especially for sunscreen-
    containing drug products that have some ``traditional'' cosmetic uses 
    (e.g., lipsticks).
        The agency allows the signal word ``Use'' or ``Uses'' in place of 
    ``Indication'' or ``Indications.'' This short signal word is useful for 
    consumers, appropriate for dual use products, and does not clutter 
    label space. Likewise, the agency concludes that the signal word 
    ``Directions'' is useful for consumers and does not clutter label space 
    (64 FR 13254 at 13264 to 13268, March 17, 1999). The agency is 
    including Sec. 352.52(f) in this final monograph to provide labeling 
    modifications for sunscreen products that meet the small package 
    specifications in Sec. 201.66(d)(10) and are labeled for use on 
    specific small areas of the face (e.g., lips, nose, ears, and/or around 
    eyes). These products include many traditional cosmetics (e.g., 
    lipstick or eye makeup) that may contain sunscreens. These products 
    will be allowed to present a condensed ``Uses'' section and may omit 
    directions for use if they are marketed in a lipstick form.
        28. One comment requested that the monograph include professional 
    labeling for both UVB and UVA radiation protection to assist health 
    professionals to select appropriate products. The comment recommended 
    inclusion of the absorption spectrum of each sunscreen in the product 
    and suggested that the labeling include information that the product: 
    (1) Protects against drug-induced photosensitization reactions induced 
    by UV radiation in the ranges ____ nm to ____ nm, and (2) other 
    truthful and nonmisleading statements describing both UVB and UVA 
    radiation protection against photosensitization reactions.
        The agency did not propose professional labeling in the tentative 
    final monograph, but did ask for data to be submitted (58 FR 28194 at 
    28210 and 28245). No data were received. The agency will consider 
    including this type of professional labeling in the monograph in the 
    future when specific supportive data are provided.
    
    G. Comments on Sunscreen Drug Products With High SPF Values
    
        29. Numerous comments objected to the proposed maximum SPF value of 
    30 for OTC sunscreen drug products. The comments requested either that 
    the agency adopt no limit or a limit of SPF 50, for the following 
    reasons: (1) UV radiation exposure is increasing due to both lifestyle 
    changes and depletion of the atmospheric ozone layer, (2) skin cancer 
    rates are increasing and there is no safe threshold to prevent cancer, 
    (3) people using an SPF 30 sunscreen will have slight sunburn after 
    receiving their 30 MED and therefore should have available sunscreens 
    with higher SPF values, (4) high SPF sunscreens are needed for 
    extremely sun-sensitive people during periods of unavoidable intense or 
    lengthy sun exposure, and because of less than ideal usage by consumers 
    due to misjudging of their skin type and/or inadequate/infrequent 
    application, (5) there is a significant variation of skin types, 
    sensitivities, and UV radiation exposures among people, (6) formulation 
    techniques can increase SPF values without necessarily increasing 
    ingredient concentrations, (7) current information does not support an 
    association between high SPF products and safety concerns, and (8) high 
    SPF products provide for greater relative exposure times and decreased 
    UV radiation transmission. Three comments (Refs. 21, 22, and 23) 
    submitted supporting data.
        Some comments stated that ``High SPF'' (i.e., above SPF 30) 
    products are on the market and used by consumers, and that limiting SPF 
    values would stifle sunscreen product development and preventative 
    health benefits. Other comments argued that sunscreens with high SPF 
    values provide increased protection from ultraviolet radiation effects 
    such as photoimmunosuppression and are needed by those with 
    ``dermatological problems.''
        In contrast, some comments supported the agency's proposal to limit 
    SPF values to 30 to stop the promotional ``bidding war'' or 
    ``horsepower race.'' Another comment contended that real consumer 
    benefit is achieved through appropriate balance of SPF, substantivity, 
    UVA radiation protection, irritation potential, and cost, whereas SPF 
    values above 30 provide only ``incremental benefit'' and an unnecessary 
    increase in drug exposure.
         The data provided by the comments in support of allowing numerical 
    values above 30 were of only limited use. Data from a field survey of 
    62 sunbathers on Miami's South Beach during July 1993 (Ref. 21) did not 
    provide any reliable conclusions on the frequency or extent of solar 
    overexposure by light-skinned individuals or a benefit provided by 
    sunscreen products with an SPF value above 30 as: (1) The sample size 
    was small and the survey population did not represent a random sample, 
    (2) the MED was not determined under controlled conditions or 
    standardized procedure, and (3) full-day UVB radiation exposure was 
    based on crude extrapolation of weather data.
        Data from MED determinations on 1,332 people with skin types I, II, 
    and III, and UV radiation data for the month of June 1974 in 5 cities 
    in the United States (Ref. 22), support the contention that a sizeable 
    population may exist that is at risk to more than 30 MED's of UV 
    radiation per day. However, the data are insufficient for extrapolation 
    to the general population. The small sample size in this study limits 
    the sensitivity of the study and the study population did not represent 
    a random sample.
        Finally, data from animal studies (Ref. 23) showed that: (1) 
    Limiting sunscreen protection to SPF 30 may not be prudent if UV 
    radiation damage is not related to SPF; (2) a greater amount of 
    sunscreen is needed to completely inhibit some of the nonerythemogenic 
    damage caused by UV radiation, and (3) nonerythemogenic effects (e.g., 
    photoimmunosuppression) occur with suberythemal doses of UV radiation 
    (as can be obtained with the use of low or high SPF sunscreens). While 
    the agency agrees that higher SPF values may provide for greater 
    relative exposure times, the SPF test is not the appropriate 
    measurement of protection from nonerythemogenic damage because SPF is 
    only a measure of erythema. The agency finds that the data from these 
    studies were not sufficient to either support or dismiss limiting the 
    maximum SPF value in this final rule.
        The agency continues to agree with the comments about overall 
    increases in both UV radiation exposure (58 FR 28194 at 28223), skin 
    cancer rates (58 FR 28194 at 28227), and the variation of skin types, 
    sensitivities, and UV radiation exposures among people (58 FR 28194 at 
    28222). The agency also agrees with the comment that a person using an 
    SPF 30 sunscreen could have a slight sunburn after being exposed to 
    their 30 MED (i.e., after their skin receives a MED). However, the 
    agency continues to believe that an SPF 30 sunscreen product provides 
    adequate
    
    [[Page 27675]]
    
    protection for the majority of consumers even under extreme conditions, 
    less than ideal usage, or in varying weather conditions (58 FR 28194 at 
    28225).
        On the other hand, the agency is also aware that many OTC sunscreen 
    products with SPF values above 30 are currently marketed and are 
    increasingly used by consumers. Numerous comments from health 
    professionals, consumers, and industry provide actual use information 
    in support of SPF values above 30 for what may be a substantial number 
    of sun-sensitive people in this country. Further, as numerous comments 
    noted: (1) There is a lack of data to correlate higher than SPF 30 
    sunscreen products with corresponding safety problems, and (2) modern 
    formulation techniques have resulted in higher SPF values using lower 
    active ingredient concentrations.
        Because of the numerous concerns from health professionals, new 
    data to support the need for SPF values above 30, and the lack of data 
    concerning safety problems with such SPF values, the agency concludes 
    that OTC sunscreen drug products with SPF values above 30 should be 
    available for those sun-sensitive consumers who require such products 
    based upon personal knowledge of their skin's susceptibility to 
    sunburn, experience with specific products, planned sun exposure, or 
    the recommendation of a health professional. The agency agrees with the 
    comments that higher SPF values generally can provide for greater 
    relative exposure times and decreased UV radiation transmission. 
    However, the agency continues to believe that the additional sunburn 
    protection provided by an SPF 30 sunscreen and, e.g., an SPF 50 
    sunscreen (i.e., about a 1.3 percent increase in absorption of 
    erythemal UV radiation) is extremely small for most people. The agency 
    is also concerned about the ability of current testing methods to 
    accurately and reproducibly determine SPF values for high SPF products 
    (see section II.M, comment 53 of this document). In addition, 
    nonlinearity of the SPF rating system is a concept difficult to explain 
    in the limited space on a product label. Therefore, the agency 
    concludes that the label SPF declaration for sunscreens with SPF values 
    above 30 should be limited to one collective term, which appears in 
    Sec. 352.50(a) of this document as follows: ``For products with SPF 
    values over 30. ``SPF 30'' (select one of the following: ``plus'' or 
    ``+''). Any statement accompanying the marketed product that states a 
    specific SPF value above 30 or similar language indicating a person can 
    stay in the sun more than 30 times longer than without sunscreen will 
    cause the product to be misbranded under section 502 of the Federal 
    Food, Drug, and Cosmetic Act (the act).''
        Numerous comments from dermatologists asked that a specific SPF 50 
    product be allowed to remain on the market because it is needed for the 
    ``ultrasensitive patient'' and for patients with ``dermatological 
    problems.'' The agency has previously discussed the use of high SPF 
    sunscreen drug products to protect consumers with photosensitivity 
    diseases (58 FR 28194 28225) and the need to provide data for such uses 
    (see section II.F, comment 28 of this document) as the absorption 
    spectrum of a specific product, not necessarily the SPF, may be the 
    more clinically significant factor for such people.
        As discussed previously in this comment 29 of section II.G of this 
    document, the agency has concluded that the use of SPF label values 
    above 30 in OTC drug products is not supported at this time. The 
    agency, however, invites interested persons to continue developing the 
    test methods needed to measure high SPF values, and to submit the data 
    in support of such methods to FDA. If test methods are developed, the 
    agency also invites interested persons to consider proposed methods for 
    communicating in labeling the level of protection associated with high 
    SPF values (given the nonlinear nature of the SPF rating system). These 
    and other well-supported improvements to the methodology for accurately 
    and reproducibly measuring SPF values will be addressed, as 
    appropriate, in future issues of the Federal Register. Until then, OTC 
    sunscreen drug products are permitted to be labeled with SPF values no 
    higher than ``30+'' or ``30 plus.''
        Finally, the agency does not agree with the argument that limiting 
    SPF values would stifle sunscreen product development and preventative 
    health benefits. Undue emphasis for sunburn protection should not be 
    placed upon SPF value alone (i.e., ``single focus products''). As noted 
    by another comment, consumer benefit is achieved through appropriate 
    balance of several factors, including substantivity, UVA radiation 
    protection, and irritation potential.
    
    H. Comments on Water Resistant Labeling and Testing for Sunscreen Drug 
    Products
    
        30. One comment agreed and several disagreed with proposed 
    Sec. 352.52(e)(2)(iii) and (e)(3)(iii) concerning sweat resistant 
    claims based upon water resistance testing instead of a specific sweat 
    resistance test. One comment submitted data from two sweat resistance 
    studies and two water resistance studies (Ref. 24) utilizing methods 
    proposed by the Panel in the ANPRM (43 FR 38206) and involving a total 
    of 117 subjects. The comment concluded that the water resistance test 
    is less stressful than the sweat resistance test.
        The agency does not find the data submitted in the studies 
    sufficient to support the comment's contention. The studies each 
    comprised distinct subject populations and addressed a single variable, 
    i.e., the effect of water exposure or induced sweating on a product's 
    SPF. Therefore, a comparison of mean SPF values across studies is not 
    the appropriate measure of relative ``stress'' associated with these 
    variables. The agency believes that a randomized, two-period crossover 
    study design in a single patient population would better have addressed 
    the comment's contention. Further, the Panel's sweat and water 
    resistance protocols provide qualitative information and were not 
    designed to provide comparative assertions requiring valid statistical 
    inferences. Thus, the agency is allowing water and sweat resistant 
    claims based upon the water resistance test procedures in Sec. 352.76 
    of this document.
        31. One comment contended that the ``water resistant'' labeling 
    proposed in Sec. 352.50(b)(1) and (c)(1) should not be required for 
    products labeled or purchased for uses other than swimming or bathing.
        The agency notes that the water resistance statements referenced by 
    the comment were not required unless the manufacturer wished to make 
    water resistant claims in the labeling of its sunscreen products. This 
    final rule also will not require a manufacturer to make a water 
    resistance claim for its sunscreen product, even if the product is 
    determined to be water resistant. However, a manufacturer wishing to 
    make water resistance claims must comply with Secs. 352.50(b) or (c) 
    and 352.52(b)(1)(ii) or (b)(1)(iii) of this document, as applicable for 
    ``water resistant'' or ``very water resistant'' products.
        32. Several comments urged the agency to return to the 
    ``waterproof'' and ``water resistant'' label claims proposed by the 
    Panel and to limit the labeled SPF value to only the SPF after water 
    resistance testing. Another comment requested only general guidelines 
    for claims such as ``water resistant'' or ``sweat resistant'' on the 
    basis that such claims reflect the inherent characteristics of specific 
    formulations and not sunscreen ingredients.
    
    [[Page 27676]]
    
        The agency thoroughly discussed use of the terms ``waterproof'' and 
    ``water resistant'' in the tentative final monograph (58 FR 28194 at 
    28228). The comments did not present any arguments or data that the 
    agency did not previously consider. In addition, the agency points out 
    that performance claims such as these for OTC sunscreen drug products 
    are based on final product formulation.
        The agency agrees with the comments that the more relevant SPF 
    value for products labeled ``water resistant'' or ``very water 
    resistant'' is the SPF value of the final product formulation following 
    water resistance testing. Therefore, in this document the agency is 
    limiting the SPF label declaration to the SPF after water resistance 
    testing and is modifying the testing procedures in Sec. 352.76 to 
    reflect deletion of the proposed dual SPF testing requirement for 
    sunscreen products with water resistant claims.
        33. Two comments suggested that ``water resistant'' labeling be 
    permitted for drug products retaining at least 80 percent of their SPF 
    value after static testing in pools and that any product meeting this 
    criterion could also be labeled ``sweat proof.'' The comments further 
    suggested that the term ``very water resistant'' should be permitted 
    for products retaining 90 to 98 percent of their SPF after testing.
        The agency disagrees with the comments. Simple immersion provides 
    neither an aqueous shear stress nor thermal challenge, and thus is an 
    inadequate assessment of water resistance. In addition, no 
    justification was offered for the respective threshold values of 80 
    percent and 90 to 98 percent.
        34. Several comments contended that the water resistance testing 
    procedures in Sec. 352.76 should be amended to allow for continuation 
    of the water exposure regimen beyond the 80 minute total and suggested 
    that the ``very water resistant'' claim be expanded beyond 80 minutes 
    for products meeting such testing requirements. One comment provided 
    data (Ref. 24) to support extended water resistance claims. Another 
    comment also proposed a testing protocol (Ref. 25) for an additional 
    claim of ``rubproof'' or ``abrasion proof.''
        The agency does not concur with an expansion of the ``very water 
    resistant'' claim. Although data submitted by the comment (Ref. 24) 
    show that under testing conditions products may retain their SPF values 
    for up to 270 minutes of water exposure, no usage data were presented 
    to refute the Panel's determination of an 80 minute upper exposure 
    limit (58 FR 28194 at 28277). In addition, the agency believes that for 
    consumers to compare products with multiple performance 
    characteristics, a labeling claim of ``very water resistant'' is best 
    supported by a uniform testing standard. Should the agency receive data 
    in the future indicating customary usage patterns in excess of 80 
    minutes of water exposure, it will reconsider this limit.
        35. One comment disagreed with the agency's proposal in the 
    tentative final monograph (58 FR 28194 at 28278) that manufacturers 
    determine the waiting periods for the most effective use of their 
    sunscreen products (i.e., the time between application and exposure to 
    the sun or water, if applicable). This information would then be 
    included in the directions for the product. The comment asserted there 
    is no reason to require a ``time versus efficacy'' study for every 
    sunscreen formula because studies show that products maintain their 
    efficacy for up to 8 hours.
        In the tentative final monograph, the agency did not propose a 
    specific method or testing procedure for the determination of a proper 
    waiting period because of the variation in sunscreen product dosage 
    forms and formulations. Instead, the agency allowed manufacturers to 
    make this determination. However, the agency did propose in 
    Sec. 352.52(d)(2) that a waiting period before sun or water exposure, 
    if applicable, be included in the labeling of sunscreen products for 
    their most effective use. In this final rule, the agency has included 
    the requirement for a waiting period in the sunscreen product 
    application statement in proposed Sec. 352.52(d)(1) for the reasons 
    stated in the tentative final monograph (58 FR 28278). The agency 
    continues to allow the manufacturer to determine both the necessity for 
    this statement (based on the product's formulation and dosage form) and 
    how the waiting period, if applicable, is determined.
    
    I. Comments on Indications for Sunscreen Drug Products
    
        36. One comment urged the agency to more strongly state the 
    effectiveness of sunscreens (a specific claim was not suggested). The 
    comment cited a controlled study of a broad spectrum, SPF 17 sunscreen 
    on 431 Caucasian subjects over one summer in Australia (Ref. 26). The 
    study showed that the group using the sunscreen had significantly fewer 
    solar keratoses and more remissions than the control group. Another 
    comment expressed concern that use of the term ``help prevent skin 
    damage'' may mislead consumers to think that these products prevent 
    skin cancer and premature skin aging.
        The agency agrees that solar keratoses are a clinical sign of skin 
    damage. However, although sunscreens are associated with a 
    statistically significant decrease in solar keratoses after 1 or 2 
    years, the solar keratoses reduction in this study was small and 
    neither the clinical nor biological significance of this reduction has 
    been established. Most solar keratoses never become skin cancers and 
    typically resolve spontaneously (Refs. 27 and 28).
        Because of the wide variability possible in the formulation of 
    sunscreen products, not all sunscreen products are identical in their 
    UV radiation absorption characteristics. Sunscreen products may contain 
    active ingredients that absorb in different regions of the UVB 
    radiation spectrum (the primary cause of sunburn) or absorb in both the 
    UVB and different regions of the UVA radiation spectrum. Therefore, 
    even the degree/type of UV radiation protection reported in one study 
    using a specific sunscreen formulation may not be relevant to all 
    possible sunscreen products within the scope of this final monograph. 
    Further, the agency does not believe that it is prudent to extrapolate 
    claims for skin cancer or skin aging based upon a test designed to only 
    measure erythema (i.e., the SPF test).
        The agency has reviewed information concerning the mechanisms of 
    skin cancers and photoaging. UV radiation appears to have a dual role 
    in the induction of skin cancers as it can cause several varieties of 
    direct DNA damage (Refs. 23 and 29 through 32) plus suppress the immune 
    response to developing skin cancers (Refs. 33 through 37). This immune 
    suppression may be a critical variable as skin cancers, unlike other 
    cancer types, evoke a strong immune response (especially by Langerhans 
    cells and T-lymphocytes) (Ref. 38). In photoaging, there are multiple 
    sites in the skin that can be damaged by UV radiation (Ref. 17). For 
    example, recent studies support the concept that specific UV radiation-
    induced enzymes (i.e., matrix metalloproteinases) can mediate 
    connective tissue damage and result in the premature aging effects seen 
    in skin exposed to UV radiation (Refs. 19 and 20). These data also 
    suggest that these mechanisms of carcinogenesis and photoaging can 
    occur from doses of UV radiation below that required to produce sunburn 
    (i.e., suberythemal doses). Thus, even if no sunburn has occurred with 
    the use of a sunscreen, the consumer cannot assume that sun-induced 
    skin damage that might contribute to the eventual development
    
    [[Page 27677]]
    
    of skin cancer or signs of photoaging has not occurred.
        The agency agrees with the comment that terms such as ``help 
    prevent skin damage'' may mislead consumers to think that sunscreen use 
    alone will prevent skin cancer and premature skin aging. However, the 
    agency believes that an appropriate statement can be used to inform 
    consumers that sunscreens may reduce the risks of skin aging, skin 
    cancer, and other harmful effects from the sun when used in a regular 
    program that includes limiting sun exposure and wearing protective 
    clothing (see section II.L, comment 51 of this document).
        37. Several comments expressed concern that the statements ``Allows 
    you to stay in the sun up to (insert SPF of product up to 30) times 
    longer than without sunscreen protection'' and ``Provides up to (insert 
    SPF of product up to 30) times your natural protection from sunburn'' 
    in proposed Sec. 352.52(b)(1)(iii) and (b)(1)(iv) may mislead consumers 
    as to the amount and degree of protection sunscreen products provide. 
    The comments were concerned that this message will convey a more 
    expansive meaning than intended and that consumers might be misled 
    about how long they can stay in the sun without risking any sun-induced 
    skin injury. One comment expressed additional concern because the SPF 
    value is only a laboratory test of a few minutes duration.
        One comment also objected to the unqualified use of terms such as 
    ``shields from,'' ``protects from,'' ``filters'' or ``screens out'' the 
    ``sun's rays,'' ``sun's harsh rays,'' or ``sun's harmful rays'' to 
    ``help prevent skin damage'' proposed in Sec. 352.52(b)(1)(v) and 
    (b)(1)(vi). The comment expressed concern that these unqualified terms 
    could imply complete protection from the sun's harmful rays and may 
    mislead consumers by inducing a false sense of security when using 
    sunscreen products.
        As discussed in section II.I, comment 36 of this document, the 
    agency believes that sunscreen use alone will not prevent all of the 
    possible harmful effects due to the sun. Variation between individuals, 
    UV radiation absorption and substantivity of sunscreen products, 
    exposure conditions, and conditions of use cannot promise a precise 
    result for each individual. Thus, the agency agrees that these 
    statements could provide the wrong message and a false sense of 
    security to some consumers. The agency therefore is not including 
    proposed Sec. 352.52(b)(1)(iii) through (b)(1)(vi) in this final rule 
    and considers these and similar statements to be nonmonograph. For the 
    same reasons, the agency also considers extended wear claims concerning 
    a specific number of hours of ``protection'' (or similar terminology) 
    or an absolute claim such as ``all-day protection'' to be nonmonograph. 
    Instead, the agency is including an accurate, simpler, and less 
    confusing indication statement in this final rule using two bulleted 
    statements under the ``Uses'' heading, as follows: ``[bullet] helps 
    prevent sunburn'' and ``[bullet] higher SPF gives more sunburn 
    protection''.\1\
    ---------------------------------------------------------------------------
    
        \1\ See Sec. 201.66(b)(4)
    ---------------------------------------------------------------------------
    
        38. Several comments contended that terms such as ``skin aging,'' 
    ``wrinkling,'' ``premature skin aging,'' or ``photoaging'' should be 
    permitted as indications for sunscreens, especially if protection is 
    provided in the UVA II (320 to 340 nm) radiation region. One comment 
    suggested that a label claim such as ``Helps reduce the chance of skin 
    aging caused by incidental (or casual) exposure to the sun'' may help 
    to further position the product as a cosmetic for consumers. The 
    comment also suggested an indication statement: ``Excessive, chronic 
    sun exposure can lead to premature photoaging of the skin, 
    characterized by drying, wrinkling and thinning of the skin. Regular 
    use of a sunscreen can help protect against this condition.''
        The agency discussed the use of terms such as ``skin aging,'' 
    ``wrinkling,'' ``premature skin aging,'' or ``photoaging'' on sunscreen 
    products in the tentative final monograph (58 FR 28194 at 28236 and 
    28287). As discussed in the response to comments 36 and 37, the agency 
    has determined that the labeling should describe the product's use in 
    preventing sunburn. A more expansive set of indications is currently 
    unsupported. The agency notes, however, that the final ``Sun alert'' 
    statement (discussed in section II.L, comment 51 of this document) does 
    provide the consumer with information about the role of sunscreens in 
    reducing skin aging, in a context that ensures that the information 
    will not be misleading. The agency, however, is continuing to consider 
    whether certain sunscreens may provide protection against photoaging 
    (58 FR at 28287) and has discussed this in tentative final monograph 
    amendments for certain sunscreens containing avobenzone or zinc oxide 
    based upon specific data submitted to the agency (see section II.E, 
    comment 22 of this document). The agency will evaluate this issue 
    further when it completes the UVA portion of the sunscreen monograph, 
    in a future issue of the Federal Register.
        39. Several comments contended that the extensive labeling proposed 
    in the tentative final monograph was excessive. For environmental 
    concerns, the comments objected to the use of extra packaging materials 
    as a method of including added labeling. One comment disagreed with the 
    need for a specific statement of product indications on individual 
    units of non-beach products properly labeled with an SPF value, and 
    cited limitations on labeling space. The comment suggested that 
    manufacturers be given the option to provide off-package information at 
    the point-of-sale rather than be required to place the statement(s) on 
    each individual unit of the product.
        To balance the environmental and regulatory concerns, the agency 
    has streamlined labeling in this final monograph by significantly 
    reducing the amount of required labeling and making optional other 
    labeling that was proposed as required in the tentative final 
    monograph. The agency is also including Sec. 352.52(f) in this final 
    monograph to provide for additional labeling accommodations for 
    sunscreen products that meet the small package specifications in 
    Sec. 201.66(d)(10) and are labeled for use on specific small areas of 
    the face (e.g., lips, nose, ears, and/or around eyes) (see section IV, 
    comment 6 of this document).
    
    J. Comments on Warnings for Sunscreen Drug Products
    
        40. One comment asked the agency to permit reduced warning 
    statements for lip balm products containing sunscreens based on their 
    safe market history. The comment argued that lip balms are not applied 
    to the eye area, and thus extensive eye warnings are not required. Two 
    comments cited the long history of safe use of lipstick products 
    containing sunscreens and suggested the reduced warning, ``Discontinue 
    use if signs of irritation appear.''
        The agency discussed its rationale for proposing an eye warning for 
    sunscreen-containing lip balms in comment 52 of the tentative final 
    monograph (58 FR 28194 at 28229 to 28232), noting that some lip balms 
    could be used on other areas of the face. However, the agency has 
    received neither data concerning adverse reactions due to the use of 
    sunscreen-containing lip balms near the eyes, nor information that such 
    products are normally used in the eye area. These products also are 
    consistent with the factors described in the final OTC standardized 
    content and format labeling rule (64 FR 13254 at 13270) for considering 
    additional labeling modifications. Accordingly, this final monograph 
    allows sunscreen-containing
    
    [[Page 27678]]
    
    lipsticks to omit the eye warning in proposed Sec. 352.52(c)(1)(i). As 
    discussed in Section II.J, comment 42 of this document, the wording of 
    this warning is modified in this final monograph. For lip balms, the 
    agency expects to adopt the same modification when it issues the final 
    monograph on OTC skin protectant drug products.
        The proposed warning in Sec. 352.52(c)(1)(iii) is now stated as a 
    bullet under the ``Stop use and ask a doctor if'' subheading as 
    follows: ``[bullet] rash or irritation develops and lasts.'' This 
    warning appears in Sec. 352.52(c)(1)(ii) in this document. Finally, 
    lipsticks (and lip balms, which will be addressed in the final 
    monograph on OTC skin protectant drug products) will not be required to 
    bear the ``For external use only'' warning. Accordingly, in this final 
    monograph, Sec. 352.52(c)(2) allows lipsticks to omit the warning in 
    Sec. 201.66(c)(5)(i).
        41. One comment requested that an eye irritancy warning need not be 
    required for products that contain titanium dioxide as the sole active 
    ingredient. The comment stated that titanium dioxide is an inert 
    inorganic oxide (and thus is chemically distinct from all other 
    Category I sunscreen active ingredients, which are organic compounds) 
    and is an FDA approved color additive for the eye area in both drugs 
    and cosmetics. The comment argued that determination of eye irritancy 
    should be based on total product formulation. A second comment 
    concurred that the labeling for inorganic sunscreens, which are not eye 
    irritants, should be differentiated from organic sunscreens, which may 
    be irritants in the eye.
        The agency agrees that the eye warning (proposed in 
    Sec. 352.52(c)(1)(ii)) is based on total formulation, not simply 
    presence of an ingredient. The agency's rationale was discussed in 
    comments 52 and 62 of the tentative final monograph (58 FR 28194 at 
    28229 to 28232 and 28241). Accordingly, this final monograph requires 
    all sunscreen-containing drug products to bear the eye warning in 
    Sec. 352.52(c)(1)(i). Only products formulated as a lipstick (and lip 
    balms, which will be addressed in the final monograph on OTC skin 
    protectant drug products) may omit this warning (see Sec. 352.52(c)(3) 
    of this document). The agency will consider omitting the eye warning 
    requirement for a particular formulation if data submitted in an NDA 
    deviation (Sec. 330.11 (21 CFR 330.11)) from the sunscreen monograph 
    demonstrate it is not an eye irritant.
        42. One comment suggested restating the proposed warnings in 
    Sec. 352.52(c)(1) more concisely, as follows: ``For external use only. 
    Keep out of eyes. If contact occurs, rinse thoroughly with water. If 
    irritation or rash occurs, discontinue use. Consult a doctor if problem 
    persists.''
        Since the tentative final monograph was published, the agency has 
    published a final rule revising the format and content requirements for 
    OTC drug product labeling (64 FR 13254). Section 201.66(c)(5)(i) 
    requires the warning ``For external use only'' for all topical drug 
    products not intended for ingestion. Therefore, it is not necessary to 
    state that warning in this document and the warning in proposed 
    Sec. 352.52(c)(1)(i) is not included in this final monograph. The 
    agency is shortening the proposed warning in Sec. 352.52(c)(1)(ii). 
    This warning appears in Sec. 352.52(c)(1)(i) in this document as a 
    bullet under the ``When using this product'' subheading as follows: 
    ``[bullet] keep out of eyes. Rinse with water to remove.'' The agency 
    is stating the proposed warning in Sec. 352.52(c)(1)(iii) as a bullet 
    under the ``Stop use and ask a doctor if'' subheading as follows: 
    ``[bullet] rash or irritation develops and lasts.'' This warning 
    appears in Sec. 352.52(c)(1)(ii) in this document. Section 
    201.66(c)(5)(x) requires the ``Keep out of reach of children'' and 
    accidental ingestion warning set forth in 21 CFR 330.1(g) for these 
    products.
        43. One comment contended that the proposed warning about 
    swallowing in Sec. 352.52(c)(1)(i) would not be needed for so-called 
    secondary sunscreen products because adults using these products 
    (which, according to the comment, have traditionally been marketed as 
    cosmetics) would know not to ingest them.
        As discussed in section II.J, comment 42 of this document, the 
    warning proposed in Sec. 352.52(c)(1)(i) has been superseded by the 
    warning required by Sec. 201.66(c)(5)(i). The new required warning no 
    longer contains the statement about not swallowing the product.
    
    K. Comments on Directions for Sunscreen Drug Products
    
        44. Two comments stated that the proposed directions in 
    Sec. 352.53(d)(4) for lipsticks and make-up preparations are 
    unnecessary because these products are marketed primarily for their 
    cosmetic uses, which are self-evident. One comment contended that it is 
    unlikely that consumers will modify their habits of lipstick 
    application and usage simply because the product contains a sunscreen. 
    The other comment argued that failure to follow directions for these 
    products is unlikely to have serious consequences.
        The agency has determined that directions for use in the labeling 
    of lipstick products containing sunscreens would provide minimal 
    benefit to consumers and the omission of a directions statement is not 
    likely to have serious consequences (see section II.J, comment 40 of 
    this document). However, the agency believes that directions would be 
    useful for make-up products containing sunscreens because of the wide 
    variety of make-up products that are available. Therefore, the agency 
    is revising proposed Sec. 352.52(d)(4) to read: ``For products 
    formulated as a lipstick. The directions in paragraphs (d)(1) and 
    (d)(2) of this section are not required.'' The agency expects to 
    finalize the same modifications for lip balm products when it finalizes 
    the monograph for OTC skin protectant drug products.
        45. Several comments contended that the proposed direction, 
    ``Children under 2 years of age should use sunscreen products with a 
    minimum SPF of 4,'' is misleading and has no scientific basis. Some 
    comments stated that the direction implies that an SPF 4 may be 
    adequate for children and noted that the Skin Cancer Foundation advises 
    use of SPF 15 or higher for both children and adults. The American 
    Academy of Dermatology questioned why children should not have the 
    benefit of a more highly protective sunscreen. Other comments suggested 
    that this direction should only be required for products with an SPF 
    lower than 4 because it would be nonsensical and a waste of label space 
    on products with higher SPF values.
        The agency agrees with the comments that this direction could 
    mislead parents into believing SPF 4 is adequate for children under 2 
    years of age. Therefore, the agency concludes it is not appropriate and 
    is not including it in Sec. 352.52(d) in this document.
        46. One comment stated that the words, ``adults and children 6 
    months of age and over'' in proposed Sec. 352.52(d)(1) are unnecessary 
    because there is a separate statement, ``Children under 6 months of 
    age: consult a doctor.'' Another comment suggested that lengthy 
    directions for use by children 6 months to 2 years of age are not 
    appropriate for many product types (e.g., a daily facial moisturizer 
    with a sunscreen) and should be revised to ``For adult use only.'' 
    Another comment added that when ``For adult use only'' is used, then 
    warning and cautionary statements concerning use by children would not 
    be needed.
    
    [[Page 27679]]
    
        The agency agrees with the comment that the statement, ``Children 
    under 6 months of age: consult a doctor,'' provides sufficient 
    information regarding the age limit for use and is retaining it under 
    Sec. 352.52(d) as a bullet with a small modification as follows: 
    ``[bullet] children under 6 months of age: ask a doctor''. Therefore, 
    the agency is removing the phrase, ``Adults and children 6 months of 
    age and over.'' The proposed directions for children 6 months to 2 
    years of age referred to by the comments in Sec. 352.52(d)(1), (d)(2), 
    (d)(3), and (d)(5) stated: ``Children under 2 years of age should use 
    sunscreen products with a minimum SPF of 4.'' As discussed in section 
    II.K, comment 45 of this document, the agency concluded that this 
    direction was misleading and did not include it in Sec. 352.52(d) in 
    this document. The agency finds it unnecessary to include the direction 
    ``For adult use only'' in this document because there are only two age 
    groups in the directions: Children under 6 months of age and all other 
    users of the product.
        47. One comment argued that the direction ``apply generously'' may 
    be responsible for some skin irritation complaints from consumers. 
    However, the comment did not provide data to support its position. The 
    comment contended that application of smaller amounts of sunscreen may 
    provide adequate coverage, but that in the case of sun protection, it 
    may be best to err on the generous side. Another comment maintained 
    that applying too little sunscreen may significantly lower protection 
    in a geometric rather than a linear fashion, e.g., an SPF 25 sunscreen 
    applied half as thick as the amount applied for the SPF test may only 
    have the effect of SPF 8.
        The agency agrees with the comments that adequate sunscreen should 
    be applied to achieve full labeled SPF protection. Therefore, the 
    agency concludes that the directions in Sec. 352.52(d)(1) of this final 
    monograph to apply ``liberally'' or ``generously'' convey the 
    appropriate message to ensure that consumers adequately apply the 
    sunscreen.
        48. One comment stated that the agency should permit firms to 
    provide reapplication instructions based on substantiation information 
    the firm possesses. The comment noted that some products may not need 
    to be applied as frequently as some select time period.
        The agency is including a general reapplication direction in 
    Sec. 352.52(d)(2). Manufacturers who have data to support reapplication 
    instructions based on specific substantiation information may submit 
    that information for approval via an NDA deviation as provided in 
    Sec. 330.11.
    
    L. Comments on Product Performance Statements for Sunscreen Drug 
    Products
    
        49. Several comments recommended revisions to proposed 
    Sec. 352.52(e), the statement on product performance. For example, some 
    comments suggested that multiple superlative category designations 
    (e.g., ``high,'' ``very high,'' and ``ultra high'') may foster consumer 
    confusion about the level of protection each SPF provides. Other 
    comments stated that the current SPF scale does not encourage consumers 
    to use higher SPF products. Other comments disagreed with the 
    indication ``permits no tanning.''
        The agency has revised proposed Sec. 352.52(e) in this document by 
    condensing the five proposed product categories to three broader ones, 
    and has generalized the category designations. The new categories are: 
    minimal sunburn protection for products with SPF 2 to under 12; 
    Moderate sunburn protection for products with SPF 12 to under 30; high 
    sunburn protection for products with SPF 30 or above. These product 
    category designations (PCD) should appear under the ``Other 
    information'' heading and may also appear on the PDP. Further, products 
    are now described as providing minimal, moderate, or high protection 
    against tanning, thus deleting the reference to tanning prevention that 
    was proposed in Sec. 352.52(b)(2)(v)(B).
        50. Many comments opposed the ``recommended sunscreen product 
    guide'' in proposed Sec. 352.52(e)(4). Some comments noted that the 
    guide is incomplete because it only considers skin type and not 
    duration of exposure, season, geographic location, and other factors 
    that influence choice of product. Other comments stated that the guide 
    is deceptive and may encourage inappropriate use of lower SPF's for 
    protection. Several comments stated that labeling for many products is 
    too small to accommodate the guide. Other comments suggested that 
    information in the guide should be disseminated to consumers through 
    point of sale, television, and weather programs, rather than being 
    required in product labeling.
        The agency recognizes that various factors influence the purchase 
    of a sunscreen product, including skin type, geographic location, hours 
    exposed to the sun, and sun reflections. While the product guide was 
    intended as a general guidance for using these products, the agency 
    acknowledges that the guide is incomplete and could be confusing and 
    misleading to consumers. Accordingly, the agency is not including the 
    recommended sunscreen product guide in this document.
        51. Many comments requested that the ``Sun alert'' in proposed 
    Sec. 352.52(e)(6) be voluntary instead of required labeling and 
    suggested this information could better be disseminated at the point of 
    purchase or through consumer education programs. Some comments stated 
    that the ``Sun alert'' is too weak and suggested alternate language. 
    One comment observed that the ``Sun alert'' fails to warn consumers 
    that UV radiation may harm the immune system, impairing the body's 
    ability to fight infectious disease. The comment did not provide data 
    to support this claim.
        The agency agrees that the ``Sun alert'' should be optional on 
    product labeling. Further, the agency has reevaluated the ``Sun alert'' 
    and concludes that its purpose should be to describe the role of 
    sunscreens in a total program to reduce harmful effects from the sun. 
    Marks (Ref. 39) has noted that sunscreens ``are normally recommended 
    for use as an adjunct to other protection,'' such as clothing, hats, 
    and avoidance of the sun near midday. The agency agrees with this 
    concept, as do many researchers (Ref. 40), the American Academy of 
    Dermatology (Ref. 41), Centers for Disease Control (Ref. 41), and the 
    Governments of Australia and New Zealand (Ref. 42). For this reason, 
    the agency has revised the ``Sun alert'' to include other protective 
    actions consumers can take, and has clarified possible results. The 
    agency is including skin cancer in the ``Sun alert'' instead of the 
    body's ability to fight infectious disease because, to date, skin 
    cancer is the best documented adverse effect of UV radiation on the 
    immune system (Ref. 43). Accordingly, Sec. 352.52(e)(2) in this 
    document provides the following optional ``Sun alert,'' which should 
    appear under the ``Other information'' heading and may also appear on 
    the PDP: ``Limiting sun exposure, wearing protective clothing, and 
    using sunscreens may reduce the risks of skin aging, skin cancer, and 
    other harmful effects of the sun.'' The agency encourages sunscreen 
    manufacturers to voluntarily include this ``Sun alert'' in the labeling 
    and to otherwise make it available at point of purchase and through 
    consumer education programs.
        52. Several comments suggested that the term ``sunblock,'' proposed 
    in the definition in Sec. 352.3(d) and as a labeling statement for 
    products containing titanium dioxide that provide an SPF of 12 to 30 in 
    Sec. 352.52(e)(5), not be included in the final monograph. Some
    
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    comments argued that the term is unclear and may mislead and confuse 
    consumers into thinking that the product blocks all of the sun, when in 
    fact it does not. One comment stated that no product available totally 
    blocks sun damage. Numerous other comments contended that the term 
    ``sunblock'' should be applied to all sunscreen ingredients that 
    provide an SPF of 12 or higher, as such products block at least 90 
    percent of the sun's UV rays. One of the comments submitted a study 
    (Ref. 44) to show that micronized titanium dioxide absorbs short 
    wavelength UV radiation and reflects and scatters long wavelengths, 
    thereby functioning similarly to chemical UVB radiation sunscreens. The 
    comment contended that the method in which micronized titanium dioxide 
    performs as a sunscreen active ingredient further justifies the use of 
    the term ``sunblock'' for all sunscreen products with an SPF of 12 or 
    higher.
        The agency has decided not to include the term ``sunblock'' in the 
    final monograph and now considers this term nonmonograph. The agency's 
    intention in the tentative final monograph was to provide information 
    to consumers on the method of product performance, not to imply greater 
    protection from using a product labeled as a ``sunblock.'' The agency 
    is concerned that the term ``sunblock'' on the label of sunscreen drug 
    products will be viewed as an absolute term which may mislead or 
    confuse consumers into thinking that the product blocks all light from 
    the sun. For example, consumers might view an SPF 15 product labeled as 
    a sunblock as superior to a product labeled as an SPF 30 broad spectrum 
    sunscreen. As nonmonograph labeling, the term ``sunblock'' cannot 
    appear anywhere in product labeling.
        In addition, the proposed definition of ``sunscreen opaque 
    sunblock'' in Sec. 352.3(d) applied only to titanium dioxide and is 
    inconsistent with how micronized titanium dioxide functions as an 
    sunscreen active ingredient (Ref. 44). Further, it is the radiation 
    from the UV portion (290 to 400 nm) of the sun's spectrum that reaches 
    the earth's surface and may produce skin erythema, melanogenesis, and 
    cancer. The agency believes that claims of protection beyond 400 nm 
    (i.e., protection from visible and infra red light) are nonmonograph 
    and not within the scope of this document. Therefore, to provide clear 
    and consistent labeling, the agency is not including proposed 
    Secs. 352.3(d) and 352.52(e)(5) in this document.
    
    M. Comments on Testing Procedures for Sunscreen Drug Products
    
        53. Several comments questioned the ability of current testing 
    methods to accurately and reproducibly determine SPF values for high 
    SPF products. Some comments contended that the spectra of currently 
    used solar simulators (especially around 290 nm and above 350 nm) could 
    cause overestimation of SPF for high SPF sunscreens and recommended use 
    of a specifications table that provided percent of erythemal 
    contribution by wavelength regions. Other comments submitted data in 
    support of a high-SPF sunscreen control following concerns expressed by 
    the agency in the proposed rule (58 FR 28194 at 28253 and 28254) that 
    data were not sufficient to demonstrate that the testing methods used 
    to evaluate sunscreen drug products with SPF values up to 15 are 
    equally applicable to evaluating sunscreen drug products with SPF 
    values above 15. Several comments submitted data and information that 
    questioned the ability of current testing methods to accurately and 
    reproducibly determine SPF values for high SPF products and requested 
    significant changes to proposed subpart D of Sec. 352.70. Other 
    comments requested changes to the testing procedures proposed in 
    subpart D of the sunscreen monograph that were unrelated to products 
    with high SPF values.
        The agency believes that the test method proposed in the tentative 
    final monograph (TFM), for measuring SPF values up to 30, represents at 
    this time a straightforward, well-understood, and sound method for 
    measuring these values. The agency therefore is finalizing the method 
    proposed in the TFM. The agency recognizes, however, that testing 
    methods in this area are evolving and that a number of comments raised 
    useful ideas for proposed improvements in the accuracy and 
    reproducibility of the agency's methodology. As discussed in response 
    to comment 29 of section II.G of this document, the agency is also 
    inviting interested persons to continue working on improving SPF 
    testing methods, toward the development of accurate methods for 
    measuring high SPF values. In future issues of the Federal Register, if 
    appropriate, the agency will consider proposed improvements to its 
    testing methodology.
        54. One comment contended that the calculation of erythema 
    effective exposure (E) serves no practical purpose in the calculation 
    of SPF because the E constant is common to both the numerator and 
    denominator of the equation. Another comment stated that the definition 
    of E is incorrect because it is defined as ``dose'' (Joules/square 
    meter (m2)) on the left side of the equation E =  
    Vi () * I (), whereas the right side of 
    the equation is in terms of irradiance (Watts/m2). The 
    comment also stated that the unit of time exposure (seconds) is missing 
    on the right side of the equation.
        The agency acknowledges that this calculation is not technically 
    necessary if the solar simulator emission spectrum does not change 
    between exposures to protected and unprotected skin. The same result 
    can then be obtained by measuring the difference (i.e., ratio) in time 
    required to produce erythema on protected versus unprotected skin. 
    However, the agency finds that the calculation of E provides valuable 
    information and is necessary to demonstrate how the MED was determined 
    during SPF testing. The agency agrees with the comment concerning the 
    missing variable of time (in seconds) in the calculation of E and, 
    accordingly, has modified the equation in Sec. 352.73 of this document 
    to read as follows: `` E =  Vi () * I 
    () * texp''
    
    III. Recent Developments
    
        In the Federal Register of October 22, 1998, the agency proposed to 
    amend the tentative final monograph to include zinc oxide as a single 
    ingredient and in combination with any proposed Category I sunscreen 
    active ingredient except avobenzone. Two comments supported the 
    proposal. One comment disagreed with the agency's exclusion of 
    avobenzone from combinations with zinc oxide. Two of the comments urged 
    the agency to expeditiously review and approve a citizen petition (Ref. 
    45) to recognize this combination.
        The agency has informed the petitioner that it is unable to approve 
    the combination without appropriate UVA radiation effectiveness data to 
    demonstrate the UVA radiation protection potential of zinc oxide in 
    combination with avobenzone (Ref. 46). The agency will reconsider this 
    combination for monograph status upon receipt of the appropriate data.
        This final rule includes monograph conditions for zinc oxide as a 
    sunscreen active ingredient at concentrations up to 25 percent when 
    used alone or in combination with any monograph sunscreen active 
    ingredient except avobenzone.
    
    IV. Additional Changes
    
        1. The agency has determined that for an active ingredient to be 
    included in an OTC drug final monograph it is necessary to have 
    publicly available
    
    [[Page 27681]]
    
    chemical information that can be used by all manufacturers to determine 
    that the ingredient is appropriate for use in their products. 
    Compendial monographs include an ingredient's official name, chemical 
    formula, and analytical chemical tests to confirm the quality and 
    purity of the ingredient. These monographs establish public standards 
    for the strength, quality, purity, and packaging of ingredients and 
    drug products available in the United States.
        In the Federal Register of June 8, 1994, FDA deleted digalloyl 
    trioleate, ethyl 4-[bis(hydroxypropyl)] aminobenzoate, glyceryl 
    aminobenzoate, lawsone with dihydroxyacetone, and red petrolatum from 
    the tentative final monograph due to the lack of interest in 
    establishing USP compendial monographs for these ingredients. Lawsone 
    with dihydroxyacetone subsequently remained under agency consideration 
    due to increased interest by manufacturers in establishing a compendial 
    monograph. Of the 18 remaining sunscreen active ingredients under 
    consideration in the tentative final monograph (58 FR 28194 at 28295, 
    amended at 61 FR 48645 and 63 FR 56584), 16 (aminobenzoic acid, 
    avobenzone, cinoxate, dioxybenzone, homosalate, menthyl anthranilate, 
    octocrylene, octyl methoxycinnamate, octyl salicylate, oxybenzone, 
    padimate O, phenylbenzimidazole sulfonic acid, sulisobenzone, titanium 
    dioxide, trolamine salicylate, and zinc oxide) currently have 
    compendial monographs. Two (diethanolamine methoxycinnamate and lawsone 
    with dihydroxyacetone) do not have a current or proposed compendial 
    monograph.
        The agency is including in Sec. 352.10 of this document the 16 
    sunscreen active ingredients that currently have a compendial 
    monograph. The agency is reserving the appropriate paragraphs in 
    proposed Sec. 352.10 for the two active ingredients without compendial 
    monographs in case a monograph is developed for either ingredient. 
    Dihydroxyacetone has been proposed for a compendial monograph, but none 
    has been proposed for lawsone. Because these two active ingredients are 
    used in conjunction, lawsone must have a compendial monograph in order 
    for lawsone with dihydroxyacetone to be included in the sunscreen final 
    monograph.
        2. The agency has revised proposed Sec. 352.52(b) in response to 
    comments requesting reduction, streamlining, and flexibility of 
    sunscreen labeling and in accordance with new data reviewed by the 
    agency (see section II.I of this document). The agency has revised 
    proposed Sec. 352.52(b)(1) by: (1) Deleting references to any other 
    indication except that pertaining to the prevention of sunburn (see 
    section II.I, comment 37 of this document), (2) adding (in 
    Sec. 352.52(b)(2) of this final rule) guidance on SPF selection due to 
    simplification of the PCD in proposed Sec. 352.52(e)(1) and deletion of 
    the Recommended Product Guide in proposed Sec. 352.52(e)(4) (see 
    section II.L, comments 49 and 50 of this document), and (3) deleting 
    the quantitative claims (i.e., ``up to (insert SPF of product up to 30) 
    times'') and terms such as ``screens,'' ``shields,'' etc., concerning 
    sunburn protection throughout proposed Sec. 352.52(b) (see section 
    II.I, comment 37 of this document).
        3. The tentative final monograph allowed reduced labeling 
    directions on sunscreen products if formulated as a make-up 
    preparation, lipstick, lip balm, or skin preparation and labeled with 
    claims relating only to the prevention of ``lip damage,'' 
    ``freckling,'' or ``uneven coloration.'' Because there is no convincing 
    evidence that SPF testing predicts protection from anything but sunburn 
    (see section II.I, comment 36 of this document), the agency is not 
    including proposed Sec. 352.52(b)(1)(v), (b)(1)(vi), (d)(4), and (d)(5) 
    in this document. The agency will consider including such claims in the 
    monograph when specific supportive data are provided or a specific 
    clinically relevant final formulation test is developed.
        4. Numerous comments requested deletion of the dual SPF testing of 
    water resistant products in proposed Sec. 352.50(b)(2) and (c)(2). The 
    agency agrees with the comments (see section II.H, comment 32 of this 
    document) and has revised proposed Secs. 352.50(b)(2) and (c)(2) and 
    352.76 to require only the SPF value after water resistant testing. 
    Further, the agency has modified and made optional the reapplication 
    directions in proposed Secs. 352.52(d)(1) and (d)(2) (see section II.K, 
    comment 48 of this document). These changes to proposed Sec. 352.52(d) 
    provide flexibility by allowing manufacturers to expand on 
    reapplication information necessary for specific sunscreen formulations 
    and by equalizing requirements between products with and without water 
    resistance claims and between sunscreen drug and drug-cosmetic 
    products. Thus, the water resistance labeling in Sec. 352.52(b)(1)(ii) 
    and (b)(1)(iii) of this document should also serve as a directive for 
    reapplication of the product. In summary, for products making water 
    and/or sweat resistance claims, the agency has modified and combined 
    water resistance statements formerly in proposed Sec. 352.52(e)(2), 
    (e)(3), (d)(1), and (d)(2) into Sec. 352.52(b)(1)(ii) and (b)(1)(iii) 
    in this document.
        5. The agency has modified references to ``tanning'' and ``prolongs 
    exposure time'' in proposed Sec. 352.52(b)(2) by combining the PCD 
    claim in Sec. 352.52(e)(1) of this document with either the phrase 
    ``protection against sunburn'' or ``protection against sunburn and 
    tanning.'' Based upon current information, the agency believes that the 
    terms proposed in the tentative final monograph could send the wrong 
    message relative to the dangers of even suberythemal UV radiation 
    exposure and give consumers a false sense of security concerning sun 
    exposure and sunscreen use. The agency has reduced and simplified the 
    other optional, additional indications in proposed Sec. 352.52(b)(2) to 
    reflect a modified, simpler, combined version of the PCD in proposed 
    Sec. 352.52(e)(1) (see section II.L, comment 49 of this document) and 
    the ``Recommended Product Guide'' in proposed Sec. 352.52(e)(4) (see 
    section II.L, comment 50 of this document). Because the agency has 
    deleted reference to use of the term ``Sunblock'' in proposed section 
    Sec. 352.52(e)(5) (see section II.L, comment 52 of this document), it 
    has deleted reference to ``Reflects the burning rays of the sun'' in 
    proposed Sec. 352.52(b)(3) for the same reasons.
        6. Several comments requested labeling exemptions or flexibility 
    for packages that are too small to accommodate all required 
    information. Some comments specifically requested flexible labeling for 
    products based upon their intended use, such as lipsticks and lip 
    balms.
        As discussed in the final rule establishing standardized format and 
    content requirements for the labeling of OTC drug products (64 FR 13254 
    at 13267 to 13268 and 13289), the agency has established specifications 
    for small packages in Sec. 201.66(d)(10). The agency also stated in the 
    final labeling rule that it will consider additional approaches for 
    accommodating certain small-package products in their respective OTC 
    drug monograph proceedings.
        The agency considers the required OTC drug labeling information 
    essential for the safe and effective use of these products and 
    important to consumers for selection of an appropriate product. 
    Nevertheless, the agency agrees that excessive labeling requirements 
    may discourage manufacturers from marketing certain products, such as 
    lipsticks or lip balms containing sunscreens, which provide significant 
    public health benefit.
        In this OTC drug rulemaking, the agency has included several 
    accommodations for products such as
    
    [[Page 27682]]
    
    lipsticks (and lip balms, which will be addressed in the final 
    monograph on OTC skin protectant drug products), taking into 
    consideration the intended uses of these products, the limited areas to 
    which these products are applied, and the overall safety profile of 
    these products, and other factors described in the final OTC labeling 
    rule (64 FR 13254 at 13270). The agency is including Sec. 352.52(f) in 
    this document to provide for labeling modifications for sunscreen 
    products that meet the small package specifications in 
    Sec. 201.66(d)(10) and are labeled for use on specific small areas of 
    the face (e.g., lips, nose, ears, and/or around eyes).
        7. The agency has revised Secs. 700.35 and 740.19 (21 CFR 700.35 
    and 740.19) in response to comments requesting clarification on whether 
    certain products will be subject to regulation as drugs (see section 
    II.B, comments 8 through 11 of this document). Section 700.35 has been 
    revised to make clear that, generally, products that make sun 
    protection claims, whether express or implied, are subject to 
    regulation as drugs. Only those products that contain a sunscreen 
    ingredient solely for a nontherapeutic, nonphysiologic use (e.g., as a 
    color additive, or to protect the color of the product such as in a 
    nail polish or hair coloring product) (see 58 FR at 28205), and which 
    include a labeling statement that accurately describes that use, may be 
    marketed as cosmetic products. Section 740.19 has been revised to make 
    clear that the term ``suntanning preparations'' does not include 
    products intended to provide sun protection or otherwise to affect the 
    structure or any function of the body. Suntanning preparations include 
    gels, creams, liquids, and other topical products that are intended to 
    provide cosmetic effects on the skin while tanning through exposure to 
    UV radiation (e.g., moisturizing or conditioning), or that are intended 
    to give the appearance of a tan by imparting color through the 
    application of approved color additives (e.g., dihydroxyacetone) 
    without the need for exposure to UV radiation (i.e., sunless tanning 
    products).
    
    V. Conclusion
    
        The agency is issuing a final monograph establishing conditions 
    under which OTC sunscreen drug products are generally recognized as 
    safe and effective and not misbranded; 16 ingredients listed in 
    Sec. 352.10 are currently a monograph condition. Any drug product 
    labeled, represented, or promoted for use as an OTC sunscreen drug that 
    contains any of the nonmonograph ingredients listed in 
    Sec. 310.545(a)(29), or that is not in conformance with the monograph 
    (21 CFR part 352), may be considered a new drug within the meaning of 
    section 201(p) of the act and misbranded under section 502 of the act. 
    Such a drug product cannot be marketed for OTC sunscreen use unless it 
    is the subject of an approved application under section 505 of the act 
    (21 U.S.C. 355) and 21 CFR part 314 of the regulations. An appropriate 
    citizen petition to amend the monograph may also be submitted in accord 
    with 21 CFR 10.30 and Sec. 330.10(a)(12)(i). The agency will address 
    sunscreen active ingredients that have foreign marketing experience and 
    data at a future time. Any OTC sunscreen drug product initially 
    introduced or initially delivered for introduction into interstate 
    commerce after the effective date of the final rule for 
    Sec. 310.545(a)(29) or this document that is not in compliance with the 
    regulations is subject to regulatory action.
    
    VI. References
    
        The following references are on display in the Dockets Management 
    Branch (address above) and may be seen by interested persons between 9 
    a.m. and 4 p.m., Monday through Friday.
        1. Comment No. CP1, Docket No. 78N-0038, Dockets Management 
    Branch.
        2. Comment No. CP2, Docket No. 78N-0038, Dockets Management 
    Branch.
        3. Comment No. CP3, Docket No. 78N-0038, Dockets Management 
    Branch.
        4. Comment No. CP7, Docket No. 78N-0038, Dockets Management 
    Branch.
        5. Comite de Liaison des Associations Europeenes de L'Industrie 
    de la Parfumerie, des Produits Cosmetiques et de Toilette (COLIPA), 
    SPF Test Method (Draft), The Recommendations of the COLIPA Task 
    Force ``Sun Protection Measurement,'' December 1992 in Comment No. 
    C00365, Docket No. 78N-0038, Dockets Management Branch.
        6. Peak, M. J., and J. C. van der Leun, ``Boundary Between UVA 
    and UVB,'' in Frontiers of Photobiology, edited by A. Shima et al., 
    Excerpta Medica, Amsterdam, pp. 425-427, 1993.
        7. Comment No. LET 135, Docket 78N-0038, Dockets Management 
    Branch.
        8. Dunkel, V.C. et al., ``Evaluation of the Mutagenicity of an 
    N-Nitroso Contaminant of the Sunscreen Padimate O,'' Environmental 
    and Molecular Mutagenesis, 20:188-198, 1992.
        9. Comment No. C00364, Docket No. 78N-0038, Dockets Management 
    Branch.
        10. Comments No. C00397 and SUP21, Docket No. 78N-0038, Dockets 
    Management Branch.
        11. Fairhurst, D., and M. Mitchnick, ``Particulate Sun Blocks: 
    General Principles,'' in Sunscreens: Development, Evaluation, and 
    Regulatory Aspects, Marcel Dekker, Inc., New York, pp. 313-352, 
    1997.
        12. Comment No. TR3, Docket No. 78N-0038, Dockets Management 
    Branch.
        13. Pharmacopeial Forum, United States Pharmacopeial Convention, 
    Inc., Rockville, MD, 22(4):2635-2636, July through August 1996.
        14. Pharmacopeial Forum, United States Pharmacopeial Convention, 
    Inc., Rockville, MD, 24(4):6547-6548, July through August 1998.
        15. Comment No. C00406, Docket No. 78N-0038, Dockets Management 
    Branch.
        16. Comment No. C00404, Docket No. 78N-0038, Dockets Management 
    Branch.
        17. Kligman, L. H., and A. M. Kligman, ``Ultraviolet Radiation-
    Induced Skin Aging,'' in Sunscreens: Development, Evaluation, and 
    Regulatory Aspects, Lowe, N. J., N. A. Shaath, and M. A. Pathak, 
    eds., Marcel Dekker, Inc., New York, pp. 117-137, 1997.
        18. Lavker, R., and K. Kaidbey, ``The Spectral Dependence for 
    UVA-Induced Cumulative Damage in Human Skin,'' The Journal of 
    Investigative Dermatology, 108:17-21, 1997.
        19. Fisher, G. J. et al., ``Pathophysiology of Premature Skin 
    Aging Induced by Ultraviolet Light,'' The New England Journal of 
    Medicine, 337:1419-1428, 1997.
        20. Lowe, N. J. et al., ``Low Doses of Repetitive Ultraviolet A 
    Induce Morphologic Changes in Human Skin,'' Journal of the American 
    Academy of Dermatology, 105:739-743, 1995.
        21. Comment No. C00282, Docket No. 78N-0038, Dockets Management 
    Branch.
        22. Comment No. C00365, Docket No. 78N-0038, Dockets Management 
    Branch.
        23. Comment No. C00531, Docket No. 78N-0038, Dockets Management 
    Branch.
        24. Comment No. C00128, Docket No. 78N-0038, Dockets Management 
    Branch.
        25. Comment No. SUP16, Docket No. 78N-0038, Dockets Management 
    Branch.
        26. Thompson, S. C., J. D. Jolley, and R. Marks, ``Reduction of 
    Solar Keratoses by Regular Sunscreen Use,'' The New England Journal 
    of Medicine, 329:1147-1151, 1993.
        27. Marks, R. et al., ``Spontaneous Remission of Solar 
    Keratoses: The Case for Conservative Management,'' British Journal 
    of Dermatology, 115:649-654, 1986.
        28. Marks, R., and G. Rennie, ``Malignant Transformation of 
    Solar Keratoses to Squamous Cell Carcinoma,'' The Lancet, 795-796, 
    1988.
        29. Kornhauser, A., W. G. Wamer, and L. A. Lambert, ``Cellular 
    and Molecular Events Following Ultraviolet Irradiation of Skin,'' in 
    Dermatotoxicology, F. N. Marzulli and H. I. Maibach, eds., Taylor & 
    Francis, Washington, pp. 189-220, 1996.
        30. Kraemer, K. H., ``Sunlight and Skin Cancer: Another Link 
    Revealed,'' Proceeds of the National Academy of Sciences U. S. A., 
    94:11-14, 1997.
        31. Hurks, H. M. H. et al., ``In Situ Action Spectra Suggest 
    that DNA Damage Involved in Ultraviolet Radiation-Induced 
    Immunosuppression in Humans,'' Photochemistry and Photobiology, 
    66:76-81, 1997.
        32. Burren, R. et al., ``Sunlight and Carcinogenesis: Expression 
    of p53 and Pyrimidine Dimers in Human Skin Following UVA I, UVA I + 
    II and Solar Simulating Radiation,'' International Journal of 
    Cancer, 76:201-206, 1998.
    
    [[Page 27683]]
    
        33. Hersey, P. et al., ``Analysis of the Effect of a Sunscreen 
    Agent on the Suppression of Natural Killer Cell Activity Induced in 
    Human Subjects by Radiation from Solarium Lamps,'' The Journal of 
    Investigative Dermatology, 88:271-276, 1987.
        34. Van Prague, M. C. G. et al., ``Effect of Topical Sunscreens 
    on the UV-Radiation-Induced Suppression of the Alloactivating 
    Capacity in Human Skin In Vivo,'' The Journal of Investigative 
    Dermatology, 97:629-633, 1991.
        35. Miyagi, T., A. M. Bhutto, and S. Nonaka, ``The Effects of 
    Sunscreens on UVB Erythema and Langerhans Cell Depression,'' The 
    Journal of Investigative Dermatology, 21:645-651, 1994.
        36. Seite, S. et al., ``Effects of Repeated Suberythemal Doses 
    of UVA in Human Skin,'' European Journal of Dermatology, 7:204-209, 
    1997.
        37. Lavker, R. M. et al., ``Cumulative Effects from Repeated 
    Exposures to Suberythemal Doses of UVB and UVA in Human Skin,'' 
    Journal of the American Academy of Dermatology, 32:53-62, 1995.
        38. Baadsgaard, O., ``In Vivo Ultraviolet Irradiation of Human 
    Skin Results in Profound Perturbation of the Immune System,'' 
    Archives of Dermatology, 127:99-109, 1991.
        39. Marks, R., ``Reduction of Actinic Keratoses by Sunscreens,'' 
    in Sunscreens: Development, Evaluation, and Regulatory Aspects, 
    Lowe, N. J., N. A. Shaath, and M. A. Pathak, eds., Marcel Dekker, 
    Inc., New York, pp. 189-198, 1997.
        40. Dial, W. F., ``Mouse Study Creates Controversy Over the Use 
    of Sunscreens,'' Cosmetic Dermatology, 7:47-48, 1994.
        41. Goldsmith, L., et al., ``Proceedings from the National 
    Conference to Develop a National Skin Cancer Agenda,'' Journal of 
    the American Academy of Dermatology, 34:822-23, 1996.
        42. Standards Australia/Standards New Zealand, ``Sunscreen 
    Products--Evaluation and Classification,'' AS/NZS 2604, 1993.
        43. Beissart, S. and R. D. Granstein, ``UV-Induced Cutaneous 
    Photobiology,'' Critical Reviews in Biochemistry and Molecular 
    Biology, 31:381-404, 1995.
        44. Sayre, R. et al., ``Physical Sunscreens,'' Journal of the 
    Society of Cosmetic Chemists, 41:103-109, 1990.
        45. Comment No. CP8, Docket No. 78N-0038, Dockets Management 
    Branch.
        46. Comment No. LET166, Docket No. 78N-0038, Dockets Management 
    Branch.
        47. Food and Drug Administration, ``Supplement to the Economic 
    Impact Analysis of the Sunscreen Drug Products for Over-the-Counter 
    Human Use; Final Monograph,'' in OTC Vol. 06FR, Docket No. 78N-0038, 
    Dockets Management Branch.
        48. Eastern Research Group, Inc., ``Over-the-Counter Drug 
    Reformulation Changes,'' in OTC Vol. 06FR, Docket No. 78N-0038, 
    Dockets Management Branch.
    
    VII. Analysis of Impacts
    
        FDA has examined the impacts of this final rule under Executive 
    Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
    Unfunded Mandates Reform Act (2 U.S.C. 1501 et seq.). Executive Order 
    12866 directs agencies to assess all costs and benefits of available 
    regulatory alternatives and, when regulation is necessary, to select 
    regulatory approaches that maximize net benefits (including potential 
    economic, environmental, public health and safety, and other 
    advantages; distributive impacts; and equity). The agency believes that 
    this final rule is consistent with the principles identified in 
    Executive Order 12866. OMB has determined that the final rule is a 
    significant regulatory action as defined by the Executive Order and so 
    is subject to review. Under the Regulatory Flexibility Act, if a rule 
    has a significant economic impact on a substantial number of small 
    entities, an agency must analyze regulatory options that would minimize 
    any significant impact of the rule on small entities. Title II of the 
    Unfunded Mandates Reform Act requires that agencies prepare a written 
    assessment of anticipated costs and benefits before proposing any rule 
    that may result in an expenditure in any 1 year by State, local, and 
    tribal governments, in the aggregate, or by the private sector, of $100 
    million (adjusted annually for inflation) (2 U.S.C. 1532).
        Because the rule may have a significant economic impact on a 
    substantial number of small entities, this section of the preamble 
    constitutes the agency's Final Regulatory Flexibility Analysis. Because 
    the rule does not impose any mandates on State, local, or tribal 
    governments, or the private sector, that will result in an expenditure 
    in any 1 year of $100 million or more, FDA is not required to perform a 
    cost-benefit analysis according to the Unfunded Mandates Reform Act.
        An analysis of the costs and benefits of this regulation, conducted 
    under Executive Order 12291, was discussed in the tentative final 
    monograph for OTC sunscreen drug products (58 FR 28194 at 28294). The 
    agency received only one response to the specific request for data and 
    comment on the economic impact of this rulemaking. This comment 
    discussed the costs that would result from proposed changes in 
    sunscreen product labeling and testing methods. The agency's review of 
    this comment is included as follows.
    
    A. Background
    
        The purpose of this document is to establish conditions under which 
    OTC sunscreen drug products are generally recognized as safe, 
    effective, and not misbranded. The document sets specific requirements 
    for appropriate monograph ingredients, labeling format and content, and 
    SPF value and water resistant testing. Although the agency cannot 
    quantify the overall expected benefits, each provision of the rule will 
    support the ability of consumers to take desired protective actions. 
    Monograph ingredients have been proven safe and effective assuring the 
    quality of sunscreen products. This benefits consumers because it 
    ensures that the product will provide ingredients that safely protect 
    against sunburn. The new product labeling will better inform consumers 
    about the sunburn protection provided by the products; and if 
    manufacturers choose to include the optional ``Sun alert'' labeling 
    statement, the product labeling can reference that the use of 
    sunscreens may reduce the risk of skin aging, skin cancer, and other 
    harmful effects of the sun. These labeling requirements, in conjunction 
    with the format requirements of the OTC uniform labeling rule (64 FR 
    13254) will provide clearer and more concise information that will 
    benefit consumers in at least four ways: (1) They will increase 
    understanding regarding the selection of sunscreen drug products, (2) 
    they will make product comparison easier, (3) they will enhance the 
    ability to make informed decisions regarding product purchases and 
    proper use, and (4) they will make it easier to distinguish between 
    sunscreen drug products that contain sunscreens and suntanning products 
    that do not. Finally, the new requirements for product testing will 
    assure the accuracy of the SPF value on the product label. By improving 
    the accuracy of these ratings, this requirement will provide further 
    assurance that consumers receive adequate sunburn protection.
        The rule will require all manufacturers and distributors (or their 
    agents) to relabel their OTC sunscreen drug products to comply with the 
    monograph language. The labeling of certain suntanning products that do 
    not contain sunscreens will need to include the new required warning 
    statement. In some cases, the labeling of cosmetics containing 
    sunscreens for nontherapeutic, nonphysiologic uses (e.g., to protect 
    hair from sun damage) will need to describe the cosmetic role of the 
    sunscreen ingredient(s). The SPF of some OTC sunscreen drug products 
    may need to be retested using the method described in the final 
    monograph. In addition, only products containing the active ingredients 
    included in this final rule will be generally recognized as safe, 
    effective, and not misbranded. Of the 18 active ingredients under 
    consideration in the proposed rule, 16 currently have the required USP/
    N.F. compendial
    
    [[Page 27684]]
    
    monographs. The USP has not received applications for the remaining two 
    ingredients. If either of these active ingredients are not included in 
    the USP and added to the monograph by May 21, 2001, products containing 
    these ingredients would need to be reformulated to replace the 
    nonmonograph ingredient with a monograph ingredient, or the product 
    must be removed from the market.
    
    B. Number of Products Affected
    
        Based on data from FDA's Drug Listing System, the agency estimates 
    that there are approximately 2,800 OTC sunscreen drug products 
    (different formulations, not including products that differ only by 
    color) and about 12,000 individual stockkeeping units (SKU's) 
    (individual products, packages, and sizes). All of the SKU's will need 
    to be relabeled, some will require new SPF testing, and those products 
    lacking approved active ingredients will need to be reformulated to 
    stay on the market.
        In addition, certain suntanning products and certain cosmetic 
    products containing sunscreens will have to be relabeled. As FDA's Drug 
    Listing System does not include suntanning products, the agency used 
    1995 data from A. C. Nielsen, a recognized provider of market data, to 
    estimate that approximately 550 suntanning SKU's will be affected by 
    the labeling requirements of this rule. New labels will also be needed 
    for cosmetic products that contain a sunscreen for a nontherapeutic use 
    and that include the word ``sunscreen'' or similar terms in product 
    labeling. The agency is unable to identify the number of these cosmetic 
    products, but does not believe that there are a large number of SKU's 
    in this category.
    
    C. Cost to Relabel
    
        The relabeling costs for this rule will be moderated to the extent 
    that manufacturers coordinate labeling changes for the final sunscreen 
    monograph with labeling changes required by the recent rule 
    establishing uniform format and content for OTC drug product labeling 
    (64 FR 13254). These costs are not discussed in this analysis, however, 
    because they are already accounted for in the agency's analysis of its 
    OTC drug product labeling rule. That is, the agency's economic analysis 
    of that rule excluded redesign costs for all OTC drug products not 
    marketed under current NDA's or current final monographs, explaining 
    that the agency would attribute all redesign costs associated with 
    future final monographs to each final monograph rule as it published. 
    All redesign costs for this final sunscreen monograph therefore are 
    attributed to this rule alone.
        Approximately 12,000 sunscreen drug SKU's will have to be relabeled 
    within a 2-year implementation period to comply with the labeling 
    requirements of this final rule. In addition, approximately 550 
    suntanning SKU's will have to be relabeled within a 12-month 
    implementation period. (As noted previously, FDA could not estimate the 
    number of cosmetic products that contain a sunscreen for a 
    nontherapeutic use and that include the word ``sunscreen'' or similar 
    terms in product labeling. The agency believes, however, the relabeling 
    of this group of cosmetic products will impose a minimal economic 
    burden because some of these products already include the required 
    labeling, and most manufacturers revise these labels for marketing 
    considerations more frequently than the allowed 2-year phase-in period. 
    Therefore, the agency's estimates do not include a cost for relabeling 
    those products that contain sunscreens for a nontherapeutic, 
    nonphysiologic use.)
        Frequent labeling redesigns are a recognized cost of doing business 
    in the OTC drug industry, particularly for drug-cosmetic and seasonal 
    products. Thus, SKU's with labels that would normally be redesigned 
    within the implementation periods were assumed to incur no additional 
    costs. The cost for the remaining SKU's was calculated as the lost 
    value of the remaining life-years of the existing label design. FDA 
    estimates that labeling for the majority (90 percent) of the SKU's 
    affected by this final rule are redesigned at least every 2 years. Of 
    the remaining SKU's, the agency assumes that half would be redesigned 
    every 3 years and half every 6 years. Because the required labeling for 
    OTC sunscreen drug products now includes fewer words than the previous 
    language and the final rule contains a number of labeling modifications 
    for products used on small areas of the face (which are usually 
    marketed in small size packages), this rule is not expected to require 
    manufacturers to increase the package size or available labeling space. 
    (Although costs of redesigning labels for future final monographs were 
    excluded from FDA's analysis of its OTC drug product labeling rule, 
    costs for increased package sizes were considered in the analysis of 
    impacts for that regulation (64 FR 13254 at 13283)).
        FDA estimated the cost of redesign by counting only the value of 
    the label-years that would be lost, after adjusting for the length of 
    the traditional labeling cycle. The regulatory cost was calculated as 
    the product of the number of SKU's, the number of years of labeling 
    life lost, and the value of each year of labeling life lost (see 64 FR 
    13254 at 13278 through 13284).\2\
    ---------------------------------------------------------------------------
    
        \2\ Mathematically the following formula was used to calculate 
    the incremental relabeling costs:
        Costyx =  j NxAx(1/x), 
    where j = 1 to (x-y)
        Total Costy = Costy6 + Costy3 + 
    Costy2
        where:
        x = life of labeling in years (2, 3, or 6)
        y = phase-in period in years
        Nx = number of SKU's with labeling life of x years, 
    and
        Ax = amortized annual value of labeling with a life 
    of x years.
    ---------------------------------------------------------------------------
    
        Table 1 in section VIII.C of this document details FDA's estimates 
    of the distribution of relabeling costs resulting from the final rule. 
    A weighted average cost to redesign a label of $5,210 per SKU was used 
    to calculate the relabeling cost of sunscreen drug products, whereas a 
    weighted average cost of $6,620 per SKU was used to calculate the cost 
    of relabeling suntanning products. A detailed description of the cost 
    analysis is on file with the Docket Management Branch (Ref. 47). As 
    shown, the total incremental cost to relabel the approximately 12,000 
    sunscreen drug SKU's is about $1.5 million, while the cost to relabel 
    the approximately 550 suntanning SKU's was about $1.8 million. The 
    greater per SKU cost for relabeling suntanning products reflects the 
    shorter, 12-month, phase-in period. With a shorter phase-in period, 
    manufacturers are less able to incorporate labeling changes into 
    voluntary redesign cycles and, therefore, lose label inventory.
    
                          Table 1.--One-time Cost to Relabel Sunscreen and Suntanning SKU's ($)
    ----------------------------------------------------------------------------------------------------------------
                                                     Type of Product
    -----------------------------------------------------------------------------------------------------------------
               Size of Company                       Drug                  Suntanning               Total Cost
    ----------------------------------------------------------------------------------------------------------------
    Small\1\                                      649,283                1,128,700                1,777,983
    
    [[Page 27685]]
    
     
    Large                                         860,677                  691,800                1,552,477
    Total Cost                                  1,509,960                1,820,500                3,330,460
    ----------------------------------------------------------------------------------------------------------------
    \1\ See section VII.G of this document.
    
        The one comment that raised economic issues in response to the 
    tentative final monograph expressed concern about available labeling 
    space on small packages of sunscreen drug products. The comment stated 
    that all text needs to be concise. The agency considered this comment 
    in developing the final rule, which contains specific labeling 
    modifications for small packages and for sunscreen products used on 
    small areas of the face (e.g., lips, nose, ears, and/or around the 
    eyes).
    
    D. Cost to Retest SPF
    
         FDA is uncertain about the number of OTC sunscreen drug products 
    that have not been tested using the monograph SPF test method. However, 
    the SPF test method in this document is essentially the same as the 
    method described in the proposed rule. If manufacturers have added new 
    products, made formulation changes, or otherwise needed to test or 
    retest the SPF of their products since 1993, they would probably have 
    used the most current (i.e., the proposed) test method. Therefore, the 
    agency estimates that from 15 to 30 percent of the sunscreen drug 
    products will require retesting as a result of this document. The cost 
    of the SPF test varies, depending on the product claim (water resistant 
    or very water resistant) and SPF factor tested, and ranges from $2,500 
    to $6,500. On the assumption that 50 percent of the traditional 
    sunscreen drug products, and none of the make-up type sunscreen 
    products, make water resistant claims, and 50 percent of the products 
    that make water resistant claims make very water resistant claims, the 
    estimated weighted average cost of the SPF test is $3,514. FDA 
    estimates the total cost of this requirement, therefore, to range from 
    $3.1 million to $6.1 millions (see the following Table 2).
    
              Table 2.--One-time Cost to Retest SPF Assuming 15 Percent or 30 Percent Compliance Rates ($)
    ----------------------------------------------------------------------------------------------------------------
                                                                        15 Percent Non-          30 Percent Non-
                            Size of Company                                compliance               compliance
    ----------------------------------------------------------------------------------------------------------------
    Small                                                                1,300,000                2,600,000
    Large                                                                1,800,000                3,500,000
    Total Cost                                                           3,100,000                6,100,000
    ----------------------------------------------------------------------------------------------------------------
    
    E. Cost to Reformulate
    
        Reformulation costs will depend on the number of products, if any, 
    that will have no active ingredients with completed USP compendial 
    monographs by the end of the implementation period. At the present 
    time, only two of the active ingredients being considered do not have a 
    USP monograph. According to the agency's drug listing system, two 
    products, manufactured by one company contain one of these ingredients. 
    The agency is not currently aware of other products in the marketplace 
    that contain these two ingredients.
        The cost to reformulate a product varies by the nature of the 
    reformulation, the type of product, and the size and complexity of the 
    company. Because OTC sunscreen drug products are well characterized 
    topical formulations, FDA estimates the cost to reformulate at about 
    $350,000 per product. Thus, on the assumption that the manufacturer 
    reformulates rather than removes the products from the market, the one-
    time cost of reformulation for two products would be $700,000.
    
    F. Total Incremental Costs
    
        The estimated total one-time incremental cost of this rule, using 
    the midpoint of the cost range for retesting and reformulation is $8.6 
    million (see Table 3 of this document). These estimates are based on 16 
    of the 18 active sunscreen ingredients under consideration having USP 
    compendial monographs. If a USP monograph is completed for the one 
    ingredient in these two products or if the two products are removed 
    from the market, the cost of reformulation would be eliminated.
    
    G. Small Business Impact
    
        Based on the analysis of FDA's drug listing system and other data 
    described previously, there are about 180 domestic companies that 
    manufacture OTC sunscreen and suntanning products. Distributors were 
    not assigned costs because manufacturers of OTC drug products are 
    usually responsible for product labeling, testing, and formulation. 
    Approximately 78 percent of these firms meet the Small Business 
    Administration's definition of a small entity for this industry (less 
    than 750 employees).
    
                                    Table 3.--Total Incremental Cost to Industry ($)
    ----------------------------------------------------------------------------------------------------------------
                             Relabel Products
       Size of   ----------------------------------------    Retest SPF\1\     Reformulation\2\          Total
       Company           Drug             Suntanning
    ----------------------------------------------------------------------------------------------------------------
    Small             670,000           1,100,000           2,000,000                 n/a                 n/a
    Large             840,000             700,000           2,600,000                 n/a                 n/a
    
    [[Page 27686]]
    
     
    Total Cost      1,510,000           1,800,000           4,600,000             700,000           8,610,000
    ----------------------------------------------------------------------------------------------------------------
    \1\ Assumes 22.5 percent noncompliance (midpoint of range)
    \2\ Assumes 2 products would require reformulation
    
        The rule will require manufacturers of sunscreens to relabel their 
    products. Some firms will need to retest the SPF of these products, and 
    one firm may have to reformulate or remove two products from the 
    market. Because of the 2-year implementation period, most firms will be 
    able to relabel during a normal relabeling cycle, at no additional 
    cost. FDA cannot estimate with certainty the number of small firms that 
    will need to retest or reformulate their OTC sunscreen products, but 
    projects that from 15 to 30 percent of all products may need to be 
    retested and that 2 products may need to be reformulated. Costs will 
    vary by firm, depending on the type and number of products requiring 
    relabeling, retesting, and reformulation. The firm-specific impact may 
    vary inversely with the volume of product sales, however, because per 
    unit costs will be lower for products with high volume sales. Thus, the 
    relative economic impact of product retesting or relabeling may be 
    greater for small firms than for large firms.
        Because of the 2-year phase-in period allowed for sunscreen drug 
    and drug-cosmetic products, which allows manufacturers the flexibility 
    to incorporate regulatory changes with voluntary/market-driven changes, 
    the economic impact of the relabeling requirement is relatively low 
    (approximately $3.3 million). However, for those small companies that 
    may have to relabel a substantial number of products, the out-of-pocket 
    costs could be significant.
        Also, the cost to a small company needing to reformulate a product, 
    estimated at approximately $350,000 would be significant. This impact 
    may be moderated by other options available, which may be more cost 
    effective than reformulation. For example, a manufacturer may be able 
    to substitute other formulations, shift production to a contract 
    manufacturer with an approved formulation, or temporarily remove the 
    product from the market and await the completion of a USP compendial 
    monograph for the ingredient. Because the OTC drug industry is highly 
    regulated, all firms are expected to have access to the necessary 
    professional skills on staff or to make contractual arrangements to 
    comply with the paperwork and other requirements of this rule.
    
    H. Analysis of Alternatives
    
        The agency altered several proposed regulatory provisions to reduce 
    the economic burden of this rule on industry. For example, FDA 
    decreased the amount of required labeling and provided small package 
    accommodations for certain products. The labeling required by the 
    proposed rule would have increased the needed label and/or package size 
    for as many as 90 percent of the sunscreen products. Such size 
    adjustments could have imposed estimated additional one-time relabeling 
    costs of $18 million and annually recurring costs of $22 million (see 
    Eastern Research Group, ``Cost Impacts of the Over-the-Counter 
    Pharmaceutical Labeling Rule'' (Ref. 48)). Also, in response to the 
    comment (see section II.H, comment 32 of this document), the agency has 
    reconsidered its position on SPF testing of water resistant and very 
    water resistant products and eliminated the static test requirement for 
    these products. As the average cost of the static test is approximately 
    $2,800, the estimated savings to industry due to the elimination of 
    this test is about $750,000.
        The agency also considered a number of implementation alternatives 
    to this final rule. Generally, the agency allows only a 1-year 
    implementation period for final monographs. However, because most 
    sunscreen products are produced seasonally, the 2-year period will 
    substantially enhance the ability of the industry to relabel and 
    reformulate its products, if necessary, and sell its existing product 
    inventories. The 2-year period will also allow sunscreen manufacturers 
    to coordinate the required labeling changes with routine industry-
    initiated labeling changes and changes required by the new OTC drug 
    product labeling final rule (64 FR 13254).
        A 3-year implementation period for sunscreen drug products was 
    considered, but the agency determined that a 2-year period provides 
    sufficient time to allow the required relabeling and product retesting 
    to be completed. The agency found that the savings to industry of 
    delayed implementation (estimated to be about $845,000) were not great 
    enough to justify delaying appropriate use and safety information to 
    consumers of OTC sunscreen drug products.
        Finally, the agency is providing a 12-month implementation period 
    for certain suntanning preparations to add new warning information. For 
    this category, consumers may believe that these products are providing 
    sun protection when, in fact, they do not. They may forego using other 
    products that have been demonstrated to be effective in providing sun 
    protection, believing that their tanning product provides some measure 
    of protection. Because the new warning for suntanning preparations 
    presents an important safety issue that needs to be conveyed to 
    consumers at the earliest possible date, the agency considered 
    requiring a 6-month implementation period for these products. However, 
    given the seasonal nature of these products, the agency was concerned 
    that some manufacturers may not have sufficient time to incorporate the 
    labeling change without disrupting their production schedules. By 
    providing an additional 6 months to implement the change, compliance 
    costs were reduced by $1.8 million.
    
    VIII. Paperwork Reduction Act of 1995
    
        FDA concludes that the labeling requirements in this document are 
    not subject to review by the Office of Management and Budget because 
    they do not constitute a ``collection of information'' under the 
    Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). Rather, the 
    labeling statements are a ``public disclosure of information originally 
    supplied by the Federal government to the recipient for the purpose of 
    disclosure to the public'' (5 CFR 1320.3(c)(2)).
    
    IX. Environmental Impact
    
        The agency has determined that under 21 CFR 25.31(c) this action is 
    of a type that does not individually or cumulatively have a significant 
    effect on the human environment. Therefore,
    
    [[Page 27687]]
    
    neither an environmental assessment nor an environmental impact 
    statement is required.
    
    List of Subjects
    
    21 CFR Part 310
    
        Administrative practice and procedure, Drugs, Labeling, Medical 
    devices, Reporting and recordkeeping requirements.
    
    21 CFR Part 352
    
        Labeling, Over-the-counter drugs.
    
    21 CFR Part 700
    
        Cosmetics, Packaging and containers.
    
    21 CFR Part 740
    
        Cosmetics, Labeling.
        Therefore, under the Federal Food, Drug, and Cosmetic Act, and 
    under authority delegated to the Commissioner of Food and Drugs, 21 CFR 
    part 352 is added and 21 CFR parts 310, 700, and 740 are amended as 
    follows:
    
    PART 310--NEW DRUGS
    
        1. The authority citation for 21 CFR part 310 continues to read as 
    follows:
    
        Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
    360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262, 
    263b-263n.
    
        2. Section 310.545 is amended by adding paragraph (a)(29), by 
    revising paragraph (d) introductory text, by adding and reserving 
    paragraph (d)(30), and by adding paragraph (d)(31) to read as follows:
    
    Sec. 310.545  Drug products containing certain active ingredients 
    offered over-the-counter (OTC) for certain uses.
    
        (a) * * *
        (29) Sunscreen drug products.
    Diethanolamine methoxycinnamate
    Digalloyl trioleate
    Ethyl 4-[bis(hydroxypropyl)] aminobenzoate
    Glyceryl aminobenzoate
    Lawsone with dihydroxyacetone
    Red petrolatum
    * * * * *
        (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)(31) of this section.
    * * * * *
        (30) [Reserved]
        (31) May 21, 2001 for products subject to paragraph (a)(29) of this 
    section.
        3. Part 352 is added to read as follows:
    
    PART 352--SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE
    
    Subpart A--General Provisions
    
    Sec.
    352.1  Scope.
    352.3  Definitions.
    
    Subpart B--Active Ingredients
    
    352.10  Sunscreen active ingredients.
    352.20  Permitted combinations of active ingredients.
    
    Subpart C--Labeling
    
    352.50  Principal display panel of all sunscreen drug products.
    352.52  Labeling of sunscreen drug products.
    352.60  Labeling of permitted combinations of active ingredients.
    
    Subpart D--Testing Procedures
    
    352.70  Standard sunscreen.
    352.71  Light source (solar simulator).
    352.72  General testing procedures.
    352.73  Determination of SPF value.
    352.76  Determination if a product is water resistant or very water 
    resistant.
    352.77  Test modifications.
    
        Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.
    
    Subpart A--General Provisions
    
    
    Sec. 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 Sec. 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.
    
    
    Sec. 352.3  Definitions.
    
        As used in this part:
        (a) Minimal erythema dose (MED). The quantity of erythema-effective 
    energy (expressed as Joules per square meter) required to produce the 
    first perceptible, redness reaction with clearly defined borders.
        (b) Product category designation (PCD). A labeling designation for 
    sunscreen drug products to aid in selecting the type of product best 
    suited to an individual's complexion (pigmentation) and desired 
    response to ultraviolet (UV) radiation.
        (1) Minimal sun protection product. A sunscreen product that 
    provides a sun protection factor (SPF) value of 2 to under 12.
        (2) Moderate sun protection product. A sunscreen product that 
    provides an SPF value of 12 to under 30.
        (3) High sun protection product. A sunscreen product that provides 
    an SPF value of 30 or above.
        (c) Sunscreen active ingredient. An active ingredient listed in 
    Sec. 352.10 that absorbs, reflects, or scatters radiation in the UV 
    range at wavelengths from 290 to 400 nanometers.
        (d) Sun protection factor (SPF) value. The UV energy required to 
    produce an MED on protected skin divided by the UV energy required to 
    produce an MED on unprotected skin, which may also be defined by the 
    following ratio: SPF value = MED (protected skin (PS))/MED (unprotected 
    skin (US)), where MED (PS) is the minimal erythema dose for protected 
    skin after application of 2 milligrams per square centimeter of the 
    final formulation of the sunscreen product, and MED (US) is the minimal 
    erythema dose for unprotected skin, i.e., skin to which no sunscreen 
    product has been applied. In effect, the SPF value is the reciprocal of 
    the effective transmission of the product viewed as a UV radiation 
    filter.
    
    Subpart B--Active Ingredients
    
    
    Sec. 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.
    
    
    Sec. 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.
    
    [[Page 27688]]
    
        (a) Combinations of sunscreen active ingredients. (1) Two or more 
    sunscreen active ingredients identified in Sec. 352.10(a), (c), (e), 
    (f), and (h) through (r) may be combined with each other in a single 
    product when used in the concentrations established for each ingredient 
    in Sec. 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.
        (2) Two or more sunscreen active ingredients identified in 
    Sec. 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 Sec. 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) [Reserved].
        (c) [Reserved].
    
    Subpart C--Labeling
    
    
    Sec. 352.50  Principal display panel of all sunscreen drug products.
    
        In addition to the statement of identity required in Sec. 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 Sec. 352.76. 
    (1) For products with SPF values up to 30. ``SPF (insert tested SPF 
    value of the product up to 30).''
        (2) For products with SPF values over 30. ``SPF 30'' (select one of 
    the following: ``plus'' or ``+''). Any statement accompanying the 
    marketed product that states a specific SPF value above 30 or similar 
    language indicating a person can stay in the sun more than 30 times 
    longer than without sunscreen will cause the product to be misbranded 
    under section 502 of the Federal Food, Drug, and Cosmetic Act (the 
    act).
        (b) For products that satisfy the water resistant sunscreen product 
    testing procedures in Sec. 352.76. (1) (Select one of the following: 
    ``Water,'' ``Water/Sweat,'' or ``Water/Perspiration'') ``Resistant.''
        (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 Sec. 352.76).''
        (c) For products that satisfy the very water resistant sunscreen 
    product testing procedures in Sec. 352.76. (1) ``Very'' (select one of 
    the following: ``Water,'' ``Water/Sweat,'' or ``Water/Perspiration'') 
    ``Resistant.''
        (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 
    Sec. 352.76).''
    
    
    Sec. 352.52  Labeling of sunscreen drug products.
    
        (a) Statement of identity. The labeling of the product contains the 
    established name of the drug, if any, and identifies the product as a 
    ``sunscreen.''
        (b) Indications. The labeling of the product states, under the 
    heading ``Uses,'' all of the phrases listed in paragraph (b)(1) of this 
    section that are applicable to the product and may contain any of the 
    additional phrases listed in paragraph (b)(2) of this section, as 
    appropriate. Other truthful and nonmisleading statements, describing 
    only the uses that have been established and listed in this paragraph 
    (b), may also be used, as provided in Sec. 330.1(c)(2) of this chapter, 
    subject to the provisions of section 502 of the act relating to 
    misbranding and the prohibition in section 301(d) of the act against 
    the introduction or delivery for introduction into interstate commerce 
    of unapproved new drugs in violation of section 505(a) of the act.
        (1) For products containing any ingredient in Sec. 352.10. (i) 
    ``[bullet]\1\ helps prevent sunburn [bullet] higher SPF gives more 
    sunburn protection''.
    ---------------------------------------------------------------------------
    
        \1\ See Sec. 201.66(b)(4) of this chapter.
    ---------------------------------------------------------------------------
    
        (ii) For products that satisfy the water resistant testing 
    procedures identified in Sec. 352.76. ``[bullet] retains SPF after 40 
    minutes of'' (select one or more of the following: ``activity in the 
    water,'' ``sweating,'' or ``perspiring'').
        (iii) For products that satisfy the very water resistant testing 
    procedures identified in Sec. 352.76. ``[bullet] retains SPF after 80 
    minutes of'' (select one or more of the following: ``activity in the 
    water,'' ``sweating,'' or ``perspiring'').
        (2) Additional indications. In addition to the indications provided 
    in paragraph (b)(1) of this section, the following may be used for 
    products containing any ingredient in Sec. 352.10:
        (i) For products that provide an SPF of 2 to under 12. Select one 
    or both of the following: [``[bullet]'' (select one of the following: 
    ``provides minimal,'' ``provides minimum,'' ``minimal,'' or 
    ``minimum'') ``protection against'' (select one of the following: 
    ``sunburn'' or ``sunburn and tanning'')], or ``[bullet] for skin that 
    sunburns minimally''.
        (ii) For products that provide an SPF of 12 to under 30. Select one 
    or both of the following: [``[bullet]'' (select one of the following: 
    ``provides moderate'' or ``moderate'') ``protection against'' (select 
    one of the following: ``sunburn'' or ``sunburn and tanning'')], or 
    ``[bullet] for skin that sunburns easily''.
        (iii) For products that provide an SPF of 30 or above. Select one 
    or both of the following: [``[bullet]'' (select one of the following: 
    ``provides high'' or ``high'') ``protection against'' (select one of 
    the following: ``sunburn'' or ``sunburn and tanning'')], or ``[bullet] 
    for skin highly sensitive to sunburn''.
        (c) Warnings. The labeling of the product contains the following 
    warnings under the heading ``Warnings:''
        (1) For products containing any ingredient in Sec. 352.10. (i) 
    ``When using this product [bullet] keep out of eyes. Rinse with water 
    to remove.''
        (ii) ``Stop use and ask a doctor if [bullet] rash or irritation 
    develops and lasts''.
        (2) For products containing any ingredient identified in 
    Sec. 352.10 marketed as a lipstick. The external use only warning in 
    Sec. 201.66(c)(5)(i) of this chapter and the warning in paragraph 
    (c)(1)(i) of this section are not required.
        (d) Directions. The labeling of the product contains the following 
    statements, as appropriate, under the heading ``Directions.'' More 
    detailed directions applicable to a particular product formulation 
    (e.g., cream, gel, lotion, oil, spray, etc.) may also be included.
        (1) For products containing any ingredient in Sec. 352.10. (i) 
    ``[bullet] apply'' (select one or more of the following, as applicable: 
    ``liberally,'' ``generously,'' ``smoothly,'' or ``evenly'') ``(insert 
    appropriate time interval, if a waiting period is needed) before sun 
    exposure and as needed''.
        (ii) ``[bullet] children under 6 months of age: ask a doctor''.
        (2) In addition to the directions provided in Sec. 352.52(d)(1), 
    the following may be used for products containing any ingredient in 
    Sec. 352.10. ``[bullet] reapply as needed or after towel drying, 
    swimming, or'' (select one of the following: ``sweating'' or 
    ``perspiring'').
        (3) If the additional directions provided in Sec. 352.52(d)(2) are 
    used, the phrase ``and as needed'' in Sec. 352.52(d)(1) is not 
    required.
        (4) For products marketed as a lipstick. The directions in 
    paragraphs (d)(1) and (d)(2) of this section are not required.
    
    [[Page 27689]]
    
        (e) Statement on product performance--(1) For products containing 
    any ingredient identified in Sec. 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. (Select one of the following: ``minimal'' 
    or ``minimum'') ``sun protection product.''
        (ii) For products containing active ingredient(s) that provide an 
    SPF value of 12 to under 30. ``moderate sun protection product.''
        (iii) For products containing active ingredient(s) that provide an 
    SPF value of 30 or above. ``high sun protection product.''
        (2) For products containing any ingredient identified in 
    Sec. 352.10, the following labeling statement may be used under the 
    heading ``Other information'' or anywhere outside of the ``Drug Facts'' 
    box or enclosure. ``Sun alert: Limiting sun exposure, wearing 
    protective clothing, and using sunscreens may reduce the risks of skin 
    aging, skin cancer, and other harmful effects of the sun.'' Any 
    variation of this statement will cause the product to be misbranded 
    under section 502 of the act.
        (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 Sec. 201.66(d)(10) of this chapter. The title, 
    headings, subheadings, and information described in Sec. 201.66(c) of 
    this chapter shall be printed in accordance with the following 
    specifications:
        (1) The labeling shall meet the requirements of Sec. 201.66(c) of 
    this chapter except that the title, headings, and information described 
    in Sec. 201.66(c)(1), (c)(3), and (c)(7) may be omitted, and the 
    headings, subheadings, and information described in Sec. 201.66(c)(2), 
    (c)(4), (c)(5), and (c)(6) may be presented as follows:
        (i) The active ingredients (Sec. 201.66(c)(2) of this chapter) 
    shall be listed in alphabetical order.
        (ii) The heading and the indication required by Sec. 201.66(c)(4) 
    may be limited to: ``Use [in bold type] helps prevent sunburn.''
        (iii) The ``external use only'' warning in Sec. 201.66(c)(5)(i) of 
    this chapter may be omitted.
        (iv) The subheadings in Sec. 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 Sec. 201.66(c)(5)(x) of this chapter may be 
    limited to the following: ``Keep out of reach of children.''
        (vi) For a lipstick, the warnings ``Keep out of eyes'' in 
    Sec. 352.52(f)(1)(iv) and ``Keep out of reach of children'' in 
    Sec. 352.52(f)(1)(v) and the directions in Sec. 352.52(d) may be 
    omitted.
        (2) The labeling shall be printed in accordance with the 
    requirements of Sec. 201.66(d) of this chapter except that any 
    requirements related to Sec. 201.66(c)(1), (c)(3), and (c)(7), and the 
    horizontal barlines and hairlines described in Sec. 201.66(d)(8), may 
    be omitted.
    
    
    Sec. 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. For a combination drug product that has 
    an established name, the labeling of the product states the established 
    name of the combination drug product, followed by the statement of 
    identity for each ingredient in the combination, as established in the 
    statement of identity sections of the applicable OTC drug monographs. 
    For a combination drug product that does not have an established name, 
    the labeling of the product states the statement of identity for each 
    ingredient in the combination, as established in the statement of 
    identity sections of the applicable OTC drug monographs.
        (b) Indications. The labeling of the product states, under the 
    heading ``Uses,'' the indication(s) for each ingredient in the 
    combination as established in the indications sections of the 
    applicable OTC drug monographs, unless otherwise stated in this 
    paragraph. Other truthful and nonmisleading statements, describing only 
    the indications for use that have been established in the applicable 
    OTC drug monographs or listed in this paragraph (b), may also be used, 
    as provided by Sec. 330.1(c)(2) of this chapter, subject to the 
    provisions of section 502 of the Federal Food, Drug, and Cosmetic Act 
    (the act) relating to misbranding and the prohibition in section 301(d) 
    of the act against the introduction or delivery for introduction into 
    interstate commerce of unapproved new drugs in violation of section 
    505(a) of the act.
        (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 Sec. 352.20(b).
        (c) Warnings. The labeling of the product states, under the heading 
    ``Warnings,'' the warning(s) for each ingredient in the combination, as 
    established in the warnings section of the applicable OTC drug 
    monographs. For permitted combinations containing a sunscreen and a 
    skin protectant identified in Sec. 352.20(b).
        (d) Directions. The labeling of the product states, under the 
    heading ``Directions,'' directions that conform to the directions 
    established for each ingredient in the directions sections of the 
    applicable OTC drug monographs, unless otherwise stated in this 
    paragraph. When the time intervals or age limitations for 
    administration of the individual ingredients differ, the directions for 
    the combination product may not contain any dosage that exceeds those 
    established for any individual ingredient in the applicable OTC drug 
    monograph(s), and may not provide for use by any age group lower than 
    the highest minimum age limit established for any individual 
    ingredient. For permitted combinations containing a sunscreen and a 
    skin protectant identified in Sec. 352.20(b).
    
    Subpart D--Testing Procedures
    
    
    Sec. 352.70  Standard sunscreen.
    
        (a) Laboratory validation. A standard sunscreen shall be used 
    concomitantly in the testing procedures for determining the SPF value 
    of a sunscreen drug product to ensure the uniform evaluation of 
    sunscreen drug products. The standard sunscreen shall be an 8-percent 
    homosalate preparation with a mean SPF value of 4.47 (standard 
    deviation = 1.279). In order for the SPF determination of a test 
    product to be considered valid, the SPF of the standard sunscreen must 
    fall within the standard deviation range of the expected SPF (i.e., 
    4.47  1.279) and the 95-percent confidence interval for the 
    mean SPF must contain the value 4.
        (b) Preparation of the standard homosalate sunscreen. (1) The 
    standard homosalate sunscreen is prepared from two different 
    preparations (preparation A and preparation B) with the following 
    compositions:
    
    [[Page 27690]]
    
    
    
                        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  deg.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  deg.C). Add sufficient purified water to obtain 
    100 grams of standard sunscreen preparation.
        (c) Assay of the standard homosalate sunscreen. Assay the standard 
    homosalate sunscreen preparation by the following method to ensure 
    proper concentration:
        (1) Preparation of the assay solvent. The solvent consists of 1 
    percent glacial acetic acid (V/V) in denatured ethanol. The denatured 
    ethanol should not contain a UV radiation absorbing denaturant.
        (2) Preparation of a 1-percent solution of the standard homosalate 
    sunscreen preparation. Accurately weigh 1 gram of the standard 
    homosalate sunscreen preparation into a 100-milliliter volumetric 
    flask. Add 50 milliliters of the assay solvent. Heat on a steam bath 
    and mix well. Cool the solution to room temperature (15 to 30  deg.C). 
    Then dilute the solution to volume with the assay solvent and mix well 
    to make a 1-percent solution.
        (3) Preparation of the test solution (1:50 dilution of the 1-
    percent solution). Filter a portion of the 1-percent solution through 
    number 1 filter paper. Discard the first 10 to 15 milliliters of the 
    filtrate. Collect the next 20 milliliters of the filtrate (second 
    collection). Add 1 milliliter of the second collection of the filtrate 
    to a 50-milliliter volumetric flask. Dilute this solution to volume 
    with assay solvent and mix well. This is the test solution (1:50 
    dilution of the 1-percent solution).
        (4) Spectrophotometric determination. The absorbance of the test 
    solution is measured in a suitable double beam spectrophotometer with 
    the assay solvent and reference beam at a wavelength near 306 
    nanometers.
        (5) Calculation of the concentration of homosalate. The 
    concentration of homosalate is determined by the following formula 
    which takes into consideration the absorbance of the sample of the test 
    solution, the dilution of the 1-percent solution (1:50), the weight of 
    the sample of the standard homosalate sunscreen preparation (1 gram), 
    and the standard absorbance value (172) of homosalate as determined by 
    averaging the absorbance of a large number of batches of raw 
    homosalate:
    Concentration of homosalate = absorbance x 50 x 100 x 172 = percent 
    concentration by weight.
    
    
    Sec. 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  deg.; 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.
    
    
    Sec. 352.72  General testing procedures.
    
        (a) Selection of test subjects (male and female). (1) Only fair-
    skin subjects with skin types I, II, and III using the following 
    guidelines shall be selected:
    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. The physical examination shall determine 
    the presence of sunburn, suntan, scars, active dermal lesions, and 
    uneven skin tones on the areas of the back to be tested. The presence 
    of nevi, blemishes, or moles will be acceptable if in the physician's 
    judgment they will not interfere with the study results. Excess hair on 
    the back is acceptable if the hair is clipped or shaved.
        (c) Informed consent. Legally effective written informed consent 
    must be obtained from all individuals.
        (d) Test site delineation--(1) Test site area. A test site area 
    serves as an area for determining the subject's MED after application 
    of either the sunscreen standard or the test sunscreen product, or for 
    determining the subject's MED when the skin is unprotected (control 
    site). The area to be tested shall be the back between the beltline and 
    the shoulder blade (scapulae) and lateral to the midline. Each test 
    site area for applying a product or the standard
    
    [[Page 27691]]
    
    sunscreen shall be a minimum of 50-square centimeters, e.g., 5 x 10 
    centimeters. The test site areas are outlined with ink. If the person 
    is to be tested in an upright position, the lines shall be drawn on the 
    skin with the subject upright. If the subject is to be tested while 
    prone, the markings shall be made with the subject prone.
        (2) Test subsite area. Each test site area shall be divided into at 
    least three test subsite areas that are at least 1 square centimeter. 
    Usually four or five subsites are employed. Each test subsite within a 
    test site area is subjected to a specified dosage of UV radiation, in a 
    series of UV radiation exposures, in which the test site area is 
    exposed for the determination of the MED.
        (e) Application of test materials. To ensure standardized reporting 
    and to define a product's SPF value, the application of the product 
    shall be expressed on a weight basis per unit area which establishes a 
    standard film. Both the test sunscreen product and the standard 
    sunscreen application shall be 2 milligrams per square centimeter. For 
    oils and most lotions, the viscosity is such that the material can be 
    applied with a volumetric syringe. For creams, heavy gels, and butters, 
    the product shall be warmed slightly so that it can be applied 
    volumetrically. On heating, care shall be taken not to alter the 
    product's physical characteristics, especially separation of the 
    formulations. Pastes and ointments shall be weighed, then applied by 
    spreading on the test site area. A product shall be spread by using a 
    finger cot. If two or more sunscreen drug products are being evaluated 
    at the same time, the test products and the standard sunscreen, as 
    specified in Sec. 352.70, should be applied in a blinded, randomized 
    manner. If only one sunscreen drug product is being tested, the testing 
    subsites should be exposed to the varying doses of UV radiation in a 
    randomized manner.
        (f) Waiting period. Before exposing the test site areas after 
    applying a product, a waiting period of at least 15 minutes is 
    required.
        (g) Number of subjects. A test panel shall consist of not more than 
    25 subjects with the number fixed in advance by the investigator. From 
    this panel, at least 20 subjects must produce valid data for analysis.
        (h) Response criteria. In order that the person who evaluates the 
    MED responses does not know which sunscreen formulation was applied to 
    which site or what doses of UV radiation were administered, he/she must 
    not be the same person who applied the sunscreen drug product to the 
    test site or administered the doses of UV radiation. After UV radiation 
    exposure from the solar simulator is completed, all immediate responses 
    shall be recorded. These include several types of typical responses 
    such as the following: An immediate darkening or tanning, typically 
    greyish or purplish in color, fading in 30 to 60 minutes, and 
    attributed to photo-oxidation of existing melanin granules; immediate 
    reddening, fading rapidly, and viewed as a normal response of 
    capillaries and venules to heat, visible and infrared radiation; and an 
    immediate generalized heat response, resembling prickly heat rash, 
    fading in 30 to 60 minutes, and apparently caused by heat and moisture 
    generally irritating to the skin's surface. After the immediate 
    responses are noted, each subject shall shield the exposed area from 
    further UV radiation for the remainder of the test day. The MED is 
    determined 22 to 24 hours after exposure. The erythema responses of the 
    test subject should be evaluated under the following conditions: The 
    source of illumination should be either a tungsten light bulb or a warm 
    white fluorescent light bulb that provides a level of illumination at 
    the test site within the range of 450 to 550 lux, and the test subject 
    should be in the same position used when the test site was irradiated. 
    Testing depends upon determining the smallest dose of energy that 
    produces redness reaching the borders of the exposure site at 22 to 24 
    hours postexposure for each series of exposures. To determine the MED, 
    somewhat more intense erythemas must also be produced. The goal is to 
    have some exposures that produce absolutely no effect, and of those 
    exposures that produce an effect, the maximal exposure should be no 
    more than twice the total energy of the minimal exposure.
        (i) Rejection of test data. Test data shall be rejected if the 
    exposure series fails to elicit an MED response on either the treated 
    or unprotected skin sites, or if the responses on the treated sites are 
    randomly absent (which indicates the product was not spread evenly), or 
    if the subject was noncompliant (e.g., subject withdraws from the test 
    due to illness or work conflicts, subject does not shield the exposed 
    testing sites from further UV radiation until the MED is read, etc.).
    
    
    Sec. 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:
        Vi () = 1.0 (250 <> < 298="" nm)="">i () = 1.00.094 (298 - ) 
    (298 <> < 328="" nanometers)="">i () = 1.00.015 (139 - ) 
    (328 <> < 400="" nanometers)="" (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:="" billing="" code="" 4160-01-f="" [[page="" 27692]]="" [graphic]="" [tiff="" omitted]="" tr21my99.000="" billing="" code="" 4160-01-c="" (b)="" determination="" of="" med="" of="" the="" unprotected="" skin.="" a="" series="" of="" uv="" radiation="" exposures="" expressed="" as="" joules="" per="" square="" meter="" (adjusted="" to="" the="" erythema="" action="" spectrum="" calculated="" according="" to="" sec.="" 352.73(a))="" is="" administered="" to="" the="" subsite="" areas="" on="" each="" subject="" with="" an="" accurately="" calibrated="" solar="" simulator.="" a="" series="" of="" five="" exposures="" shall="" be="" administered="" to="" the="" untreated,="" unprotected="" skin="" to="" determine="" the="" subject's="" inherent="" med.="" the="" doses="" selected="" shall="" be="" a="" geometric="" series="" represented="" by="">n), wherein each exposure time interval 
    is 25 percent greater than the previous time to maintain the same 
    relative uncertainty (expressed as a constant percentage), independent 
    of the subject's sensitivity to UV radiation, regardless of whether the 
    subject has a high or low MED. Usually, the MED of a person's 
    unprotected skin is determined the day prior to testing a product. This 
    MED(US) shall be used in the determination of the series of UV 
    radiation exposures to be administered to the protected site in 
    subsequent testing. The MED(US) should be determined again on the same 
    day as the standard and test sunscreens and this MED(US) should be used 
    in calculating the SPF.
        (c) Determination of individual SPF values. A series of UV 
    radiation exposures expressed as Joules per square meter (adjusted to 
    the erythema action spectrum calculated according to Sec. 352.73(a)) is 
    administered to the subsite areas on each subject with an accurately-
    calibrated solar simulator. A series of seven exposures shall be 
    administered to the protected test sites to determine the MED of the 
    protected skin (MED(PS)). The doses selected shall consist of a 
    geometric series of five exposures, where the middle exposure is placed 
    to yield the expected SPF plus two other exposures placed symmetrically 
    around the middle exposure. The exact series of exposures to be given 
    to the protected skin shall be determined by the previously established 
    MED(US) and the expected SPF of the test sunscreen. For products with 
    an expected SPF less than 8, the exposures shall be the MED(US) times 
    0.64X, 0.80X, 0.90X, 1.00X, 1.10X, 1.25X, and 1.56X, where X equals the 
    expected SPF of the test product. For products with an expected SPF 
    between 8 and 15, the exposures shall be the MED(US) times 0.69X, 
    0.83X, 0.91X, 1.00X, 1.09X, 1.20X, and 1.44X, where X equals the 
    expected SPF of the test product. For products with an expected SPF 
    greater that 15, the exposures shall be the MED(US) times 0.76X, 0.87X, 
    0.93X, 1.00X, 1.07X, 1.15X, and 1.32X, where X equals the expected SPF 
    of the test product. The MED is the quantity of erythema-effective 
    energy required to produce the first perceptible, unambiguous redness 
    reaction with clearly defined borders at 22 to 24 hours postexposure. 
    The SPF value of the test sunscreen is then calculated from the dose of 
    UV radiation required to produce the MED of the protected skin and from 
    the dose of UV radiation required to produce the MED of the unprotected 
    skin (control site) as follows:
        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. Use data 
    from at least 20 test subjects with n representing the number of 
    subjects used. First, for each subject, compute the SPF value as stated 
    in Sec. 352.73(b) and (c). Second, compute the mean SPF value, x, and 
    the standard deviation, s, for these subjects. Third, obtain the upper 
    5-percent point from the t distribution table with n-1 degrees of 
    freedom. Denote this value by t. Fourth, compute ts/ n. Denote 
    this quantity by A (i.e., A = ts/ n). Fifth, calculate the SPF 
    value to be used in labeling as follows: the label SPF equals the 
    largest whole number less than x - A. Sixth and last, the drug product 
    is classified into a PCD as follows: if 30 + A < x,="" the="" pcd="" is="" high;="" if="" 12="" +="" a="">< x="">< 30="" +="" a,="" the="" pcd="" is="" moderate;="" if="" 2="" +="" a="">< x="">< 12="" +="" a,="" the="" pcd="" is="" minimal;="" if="" x="">< 2="" +="" a,="" the="" product="" shall="" not="" be="" labeled="" as="" a="" sunscreen="" drug="" product="" and="" shall="" not="" display="" an="" spf="" value.="" sec.="" 352.76="" determination="" if="" a="" product="" is="" water="" resistant="" or="" very="" water="" resistant.="" the="" general="" testing="" procedures="" in="" sec.="" 352.72="" shall="" be="" used="" as="" part="" of="" the="" following="" tests,="" except="" where="" modified="" in="" this="" section.="" an="" indoor="" fresh="" water="" [[page="" 27693]]="" pool,="" whirlpool,="" and/or="" jacuzzi="" maintained="" at="" 23="" to="" 32="" deg.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.="" for="" sunscreen="" products="" making="" the="" claim="" of="" ``water="" resistant,''="" the="" label="" spf="" shall="" be="" the="" label="" spf="" value="" determined="" after="" 40="" minutes="" of="" water="" immersion="" using="" the="" following="" procedure="" for="" the="" water="" resistance="" test:="" (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="" sec.="" 352.73.="" (b)="" procedure="" for="" testing="" a="" very="" water="" resistant="" sunscreen="" product.="" for="" sunscreen="" products="" making="" the="" claim="" of="" ``very="" water="" resistant,''="" the="" label="" spf="" shall="" be="" the="" label="" spf="" value="" determined="" after="" 80="" minutes="" of="" water="" immersion="" using="" the="" following="" procedure="" for="" the="" very="" water="" resistant="" test:="" (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="" sec.="" 352.73.="" sec.="" 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="" sec.="" 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.="" part="" 700--general="" 4.="" the="" authority="" citation="" for="" 21="" cfr="" part="" 700="" continues="" to="" read="" as="" follows:="" authority:="" 21="" u.s.c.="" 321,="" 331,="" 352,="" 355,="" 361,="" 362,="" 371,="" 374.="" 5.="" section="" 700.35="" is="" added="" to="" subpart="" b="" to="" read="" as="" follows:="" sec.="" 700.35="" cosmetics="" containing="" sunscreen="" ingredients.="" (a)="" a="" product="" that="" includes="" the="" term="" ``sunscreen''="" in="" its="" labeling="" or="" in="" any="" other="" way="" represents="" or="" suggests="" that="" it="" is="" intended="" to="" prevent,="" cure,="" treat,="" or="" mitigate="" disease="" or="" to="" affect="" a="" structure="" or="" function="" of="" the="" body="" comes="" within="" the="" definition="" of="" a="" drug="" in="" section="" 201(g)(1)="" of="" the="" act.="" sunscreen="" active="" ingredients="" affect="" the="" structure="" or="" function="" of="" the="" body="" by="" absorbing,="" reflecting,="" or="" scattering="" the="" harmful,="" burning="" rays="" of="" the="" sun,="" thereby="" altering="" the="" normal="" physiological="" response="" to="" solar="" radiation.="" these="" ingredients="" also="" help="" to="" prevent="" diseases="" such="" as="" sunburn="" and="" may="" reduce="" the="" chance="" of="" premature="" skin="" aging,="" skin="" cancer,="" and="" other="" harmful="" effects="" due="" to="" the="" sun="" when="" used="" in="" conjunction="" with="" limiting="" sun="" exposure="" and="" wearing="" protective="" clothing.="" when="" consumers="" see="" the="" term="" ``sunscreen''="" or="" similar="" sun="" protection="" terminology="" in="" the="" labeling="" of="" a="" product,="" they="" expect="" the="" product="" to="" protect="" them="" in="" some="" way="" from="" the="" harmful="" effects="" of="" the="" sun,="" irrespective="" of="" other="" labeling="" statements.="" consequently,="" the="" use="" of="" the="" term="" ``sunscreen''="" or="" similar="" sun="" protection="" terminology="" in="" a="" product's="" labeling="" generally="" causes="" the="" product="" to="" be="" subject="" to="" regulation="" as="" a="" drug.="" however,="" sunscreen="" ingredients="" may="" also="" be="" used="" in="" some="" products="" for="" nontherapeutic,="" nonphysiologic="" uses="" (e.g.,="" as="" a="" color="" additive="" or="" to="" protect="" the="" color="" of="" the="" product).="" to="" avoid="" consumer="" misunderstanding,="" if="" a="" cosmetic="" product="" contains="" a="" sunscreen="" ingredient="" and="" uses="" the="" term="" ``sunscreen''="" or="" similar="" sun="" protection="" terminology="" anywhere="" in="" its="" labeling,="" the="" term="" must="" be="" qualified="" by="" describing="" the="" cosmetic="" benefit="" provided="" by="" the="" sunscreen="" ingredient.="" (b)="" the="" qualifying="" information="" required="" under="" paragraph="" (a)="" of="" this="" section="" shall="" appear="" prominently="" and="" conspicuously="" at="" least="" once="" in="" the="" labeling="" in="" conjunction="" with="" the="" term="" ``sunscreen''="" or="" other="" similar="" sun="" protection="" terminology="" used="" in="" the="" labeling.="" for="" example:="" ``contains="" a="" sunscreen--to="" protect="" product="" color.''="" part="" 740--cosmetic="" product="" warning="" statements="" 6.="" the="" authority="" citation="" for="" 21="" cfr="" part="" 740="" continues="" to="" read="" as="" follows:="" authority:="" 21="" u.s.c.="" 321,="" 331,="" 352,="" 355,="" 361,="" 362,="" 371,="" 374.="" 7.="" section="" 740.19="" is="" added="" to="" subpart="" b="" to="" read="" as="" follows:="" sec.="" 740.19="" suntanning="" preparations.="" the="" labeling="" of="" suntanning="" preparations="" that="" do="" not="" contain="" a="" sunscreen="" ingredient="" must="" display="" the="" following="" warning:="" ``warning--="" this="" product="" does="" not="" contain="" a="" sunscreen="" and="" does="" not="" protect="" against="" sunburn.="" repeated="" exposure="" of="" unprotected="" skin="" while="" tanning="" may="" increase="" the="" risk="" of="" skin="" aging,="" skin="" cancer,="" and="" other="" harmful="" effects="" to="" the="" skin="" even="" if="" you="" do="" not="" burn.''="" for="" purposes="" of="" this="" section,="" the="" term="" ``suntanning="" preparations''="" includes="" gels,="" creams,="" liquids,="" and="" other="" topical="" products="" that="" are="" intended="" to="" provide="" cosmetic="" effects="" on="" the="" skin="" while="" tanning="" through="" exposure="" to="" uv="" radiation="" (e.g.,="" moisturizing="" or="" conditioning="" products),="" or="" to="" give="" the="" appearance="" of="" a="" tan="" by="" imparting="" color="" to="" the="" skin="" through="" the="" application="" of="" approved="" color="" additives="" (e.g.,="" dihydroxyacetone)="" without="" the="" need="" for="" exposure="" to="" uv="" radiation.="" the="" term="" ``suntanning="" preparations''="" does="" not="" include="" products="" intended="" to="" provide="" sun="" protection="" or="" otherwise="" intended="" to="" affect="" the="" structure="" or="" any="" function="" of="" the="" body.="" dated:="" april="" 22,="" 1999.="" william="" k.="" hubbard,="" associate="" commissioner="" for="" policy="" coordination.="" [fr="" doc.="" 99-12853="" filed="" 5-20-99;="" 8:45="" am]="" billing="" code="" 4160-01-f="">

Document Information

Effective Date:
5/21/2001
Published:
05/21/1999
Department:
Food and Drug Administration
Entry Type:
Rule
Action:
Final rule.
Document Number:
99-12853
Dates:
This regulation is effective May 21, 2001 for parts 310, 352, and 700 and is effective May 22, 2000 for part 740.
Pages:
27666-27693 (28 pages)
Docket Numbers:
Docket No. 78N-0038
RINs:
0910-AA01: Over-the-Counter (OTC) Drug Review
RIN Links:
https://www.federalregister.gov/regulations/0910-AA01/over-the-counter-otc-drug-review
PDF File:
99-12853.pdf
Supporting Documents:
» Request for Extension from Personal Care Products Council and Consumer Healthcare Products Association
» Reference 210 - Yiin_2015_Assessment of Dermal Absorption of DEET-Containing Insect Repellent and Oxybenzone-Containing Sunscreen
» Reference 190 - EPA_Using Insect Repellents Safely and Effectively
» Reference 185 - Kong_2015_Assessment of Consumer Knowledge of New Sunscreen Labels
» Reference 180 - TGA_2016_Australian regulatory guidelines for sunscreens
» Reference 179 - Fourtanier_2008_Sunscreens containing the BS UVA absorber prevent cutaneous detrimental effects of UV exposure
» Reference 169 - Damian_2011_An action spectrum for UV radiation-induced immunosuppression in humans
» Reference 154 - Liu_2018_Particle Size Distribution Analysis of OTC Aerosol or Powder Drug Products with Potential for Inhalation Exposure
» Reference 153 - Liu_2017_Particle Size Distribution Analysis of OTC Drug Products with Unintended Inhalation Exposure to Consumers
» Reference 152 - Brown_2013_Thoracic and Respirable Particle Definitions for Human Health Risk Assessment
CFR: (25)
21 CFR 352.76).''
21 CFR 352.10(b)
21 CFR 201.66(c)(5)(i)
21 CFR 352.52(f)(1)(v)
21 CFR 352.52(f)(1)(iv)
More ...