[Federal Register Volume 70, Number 6 (Monday, January 10, 2005)]
[Notices]
[Pages 1721-1724]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-381]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2000P-1378]


Guidance for Industry: Labeling for Topically Applied Cosmetic 
Products Containing Alpha Hydroxy Acids as Ingredients; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance document entitled ``Guidance for Industry: 
Labeling for Topically Applied Cosmetic Products Containing Alpha 
Hydroxy Acids as Ingredients.'' The guidance recommends content for a 
labeling statement for cosmetic products containing alpha hydroxy acids 
(AHAs) as ingredients. This action was prompted by a citizen petition 
filed by the Cosmetic, Toiletry, and Fragrance Association, which 
requested that FDA issue a regulation establishing labeling 
requirements relating to sun protection with use of cosmetic products 
containing AHAs.

DATES: You may submit written or electronic comments on the guidance 
document at any time.

ADDRESSES: Submit written requests for single copies of the guidance 
document to the Office of Cosmetics and Colors, Center for Food Safety 
and Applied Nutrition (HFS-100), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740-3835. Include a self-
addressed adhesive label to assist that office in processing your 
request or include a fax number to which the guidance document may be 
sent.
    Submit written comments on the guidance document to the Division of 
Dockets Management (HFA-305), 5630 Fishers Lane, rm. 1061, Rockville, 
MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Julie N. Barrows, Center for Food 
Safety and Applied Nutrition (HFS-125), Food and

[[Page 1722]]

Drug Administration, 5100 Paint Branch Pkwy., College Park, MD 20740-
3835, 301-436-1344.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance document entitled 
``Guidance for Industry: Labeling for Topically Applied Cosmetic 
Products Containing Alpha Hydroxy Acids as Ingredients.''
    On December 2, 2002 (67 FR 71577), FDA announced the availability 
of the draft version of this guidance document in the Federal Register.

II. Comments on Draft Guidance

    FDA has evaluated the seven comments received in response to the 
draft guidance recommending ``Sunburn Alert'' labeling on cosmetic 
products that contain AHAs as ingredients.
    One comment from a nurse's association fully supported the AHA 
labeling statement. The comment stated that the inclusion of the 
``Sunburn Alert'' on skin care products containing AHAs is an important 
step in empowering health providers and consumers with valuable 
information about how to protect their skin while using these products.
    Three comments stated that the guidance should apply only to 
products intended to function as an exfoliant. For example, the 
comments suggested that the guidance should not apply to products 
containing citric acid when it is used for adjusting the hydrogen-ion 
concentration (pH) in shampoos and other products.
    Limiting the recommended labeling statement to products with 
exfoliation claims may leave out products that FDA believes should bear 
the labeling statement. FDA's surveys indicated that approximately half 
of the products on the market that contain an AHA as an ingredient have 
an intended use as an exfoliant, as determined by the presence of 
exfoliant claims in the product labeling. Even some salon products 
containing high levels of AHAs did not contain exfoliation claims in 
the labeling. FDA has no data suggesting that citric acid has less of 
an effect on the skin than glycolic acid or lactic acid, the 
predominant AHAs present in cosmetic products, regardless of its 
intended use. FDA has not modified the guidance in response to these 
comments.
    Two comments requested that FDA provide an exemption from the AHA 
labeling statement for products that exceed an appropriately high pH 
level.
    Percutaneous absorption studies suggest that topically applied AHAs 
in any cosmetic product may be absorbed by the skin to some extent, 
depending on product formulation, pH, and contact time (Refs. 1 and 2). 
The studies measured absorption of glycolic acid, lactic acid, and 
other AHAs by human skin at pH 3 and pH 7 using various product 
formulations. Although much greater absorption was observed at pH 3, 
substantial absorption was observed at pH 7. FDA has not modified the 
guidance in response to these comments.
    Three comments requested that FDA provide an exemption from the AHA 
labeling statement for cosmetic products containing low concentrations 
of AHAs. One comment suggested that products containing AHA ingredients 
at concentrations of 1 percent or less should be exempted. The comments 
did not provide any data to support their request.
    The evidence reviewed so far by FDA suggests that topical 
application of a cosmetic product containing an AHA as an ingredient at 
any concentration may increase skin sensitivity to the sun and the 
possibility of sunburn. FDA analyzed approximately 100 cosmetic 
products containing AHAs as ingredients and found concentrations of 
AHAs ranging from 0.01 percent to 67 percent (Ref. 3). Most of the 
analyzed products with very low levels of some AHAs also contained 
higher levels of other AHAs. One product for which FDA received five 
adverse experience reports (e.g., skin irritation, burning) contained 
only 0.3 percent [agr]-hydroxydecanoic acid and 0.4 percent [agr]-
hydroxyoctanoic acid, for a total of 0.7 percent AHAs, suggesting that 
AHAs may be associated with adverse reactions even at these low 
concentrations. FDA has not modified the guidance in response to these 
comments.
    FDA recognizes that an AHA can be present in a cosmetic product as 
an incidental ingredient. As defined in Sec.  701.3(l) (21 CFR 
701.3(l)), incidental ingredients are ingredients that are present in a 
cosmetic at insignificant levels and that have no technical or 
functional effect in the cosmetic. Incidental ingredients are not 
required to be declared in the ingredient lists on cosmetic labels. 
Therefore, if an AHA were used only as an incidental ingredient in a 
cosmetic product, its presence would not require declaration on the 
label. The agency finds that providing for a ``Sunburn Alert'' labeling 
statement on a cosmetic product in which the only use of an AHA was as 
an incidental ingredient would have very limited utility in protecting 
the consumer. Moreover, the presence of the ``Sunburn Alert'' labeling 
statement could be confusing to consumers because the ingredient label 
would not declare the presence of an AHA. Therefore, FDA has modified 
the guidance to state that the agency's recommendation for the AHA 
labeling statement does not apply to products in which an AHA is 
present as an incidental ingredient, as defined in Sec.  701.3(l).
    Three comments noted that AHA ingredients are used in a wide range 
of products as pH adjusters, chelating agents, fragrance ingredients, 
humectants, and skin conditioning agents and asserted that AHAs present 
in a product for these uses could not be reasonably anticipated to 
cause increased susceptibility to sunburn. An example given was citric 
acid. Two of the comments requested that the guidance apply only to 
AHA-containing cosmetic products used on areas of the body normally 
susceptible to sunburn.
    The comments addressed a range of intended uses for AHAs in 
cosmetic products, as well as identified many different types of 
products that contain AHAs as ingredients, but did not provide data to 
support their request. The percutaneous absorption studies discussed 
previously suggest that topically applied AHAs in any cosmetic product, 
regardless of intended use, may be absorbed by the skin, including the 
skin on the scalp or under the arms. The draft guidance did not address 
the possibility of unintentional topical application of AHAs to parts 
of the skin or mucous membrane that are exposed to the sun. Therefore, 
FDA has modified the guidance to state that FDA recommends ``Sunburn 
Alert'' labeling for cosmetic products that contain an AHA as an 
ingredient and that are intended for application to areas of the body 
that may result in unintentional application to the skin or mucous 
membrane that are exposed to the sun.
    FDA recognizes that AHAs can be present in cosmetic products that 
are applied to areas of the body that are not sun exposed. Such 
products include mouthwashes, breath fresheners, and douches. 
Therefore, FDA has modified the guidance to state that the guidance 
does not apply to cosmetic products that contain an AHA as an 
ingredient and that are intended for application to non-sun exposed 
areas of the body.
    Three comments recommended modified labeling statements for AHA-
containing products that also contain a sunscreen. The comments stated 
that the AHA labeling statement may not be appropriate for products 
containing sunscreens and may be confusing to consumers. One comment 
suggested

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that inclusion of a sunscreen at an appropriate level might serve as a 
basis for not recommending the AHA labeling statement. Two comments 
proposed that the AHA labeling statement for products containing a 
sunscreen should be shortened to address only the need to use a 
sunscreen for 7 days after use of the AHA product is discontinued.
    When an AHA is present in a product that is labeled to contain a 
sunscreen, that product meets the definition of a drug-cosmetic. Such 
products must comply with the requirements for drugs and cosmetics, 
including applicable over-the-counter sunscreen drug product 
regulations. FDA has modified the guidance to state that the 
recommended AHA labeling statement does not apply to drug-cosmetic 
products that contain an AHA as an ingredient and also are labeled to 
contain a sunscreen for sunburn protection. FDA intends to address 
labeling for such products in a future document.
    Three comments requested changes to FDA's recommended AHA labeling 
statement. Two comments urged FDA to reconsider identifying AHAs in the 
labeling statement because the presence of an AHA ingredient does not 
always result in increased sun sensitivity or likelihood of sunburn. 
Another comment stated that FDA's AHA labeling statement is quite long, 
especially for labeling cosmetic products packaged in small containers. 
The comment submitted a statement that is about three-fourths the 
length of FDA's recommended statement.
    In the AHA guidance, FDA discusses research on effective labeling 
statements. The research suggests that an effective labeling statement 
would begin with a signal phrase, identify the subject of the 
statement, identify the consequences of not heeding the statement, and 
provide instructions on what to do (or not do) to avoid these 
consequences. Removal of any of these elements may significantly 
decrease the effectiveness of the statement. Therefore, FDA finds that 
all of the recommendations in the ``Sunburn Alert'' are important 
components of information for an AHA labeling statement.
    FDA's current thinking on sun protection is that a total program to 
reduce harmful effects from the sun would include limiting sun 
exposure, wearing protective clothing, and using sunscreens. Therefore, 
in accordance with this current thinking on sun protection, the agency 
has modified the ``Sunburn Alert'' labeling statement that we 
recommended in our draft guidance to add the words ``wear protective 
clothing'' to the list of actions that may be taken to reduce the 
possibility of sunburn when using cosmetic products that contain an AHA 
as an ingredient.
    FDA recognizes that there is limited labeling space on cosmetic 
products packaged in small containers and has modified the guidance to 
clarify that it recommends that the AHA labeling statement appear 
prominently and conspicuously once in the labeling of a cosmetic 
product.
    One comment recommended that a ``Sunburn Alert'' labeling statement 
be extended to products containing poly hydroxy acid and/or beta 
hydroxy acid. The comment noted that these compounds are exfoliants 
with the same increased skin sensitivity concern as that for AHAs. The 
comment did not define the term ``poly hydroxy acid'' and did not 
provide data to support its recommendation to extend a ``Sunburn 
Alert'' labeling statement to products containing poly hydroxy acid 
and/or beta hydroxy acid. FDA does not have data on the effect of 
topical use of these compounds on the skin. Therefore, FDA finds that 
there is currently no basis to recommend that the ``Sunburn Alert'' 
statement appear in the labeling of cosmetics that contain the 
compounds discussed in this comment. FDA has not modified the guidance 
in response to this comment.
    Finally, two comments on the draft guidance requested that FDA 
provide an exemption from the AHA labeling statement for properly 
formulated cosmetic products when the manufacturer or distributor has 
competent and reliable scientific evidence demonstrating that the 
product containing an AHA at any level of concentration and pH does not 
increase sun sensitivity or the likelihood of sunburn. To support its 
contention, one comment provided documentation of a study of the 
effects of ultraviolet (UV) radiation on skin pre-treated with lactic 
acid.
    In its report (Ref. 4), published in 1998, the Cosmetic Ingredient 
Review (CIR) Expert Panel reported the following conclusion:
    Based on the available information included in this report, the 
CIR Expert Panel concludes that Glycolic and Lactic Acid, their 
common salts and their simple esters, are safe for use in cosmetic 
products at concentrations <=10 percent, at final formulation pH 
>=3.5, when formulated to avoid increasing sun sensitivity or when 
directions for use include the daily use of sun protection. These 
ingredients are safe for use in salon products at concentrations 
<=30 percent, at final formulation pH >=3.0, in products designed 
for brief, discontinuous use followed by thorough rinsing from the 
skin, when applied by trained professionals, and when application is 
accompanied by directions for the daily use of sun protection. * * *
    FDA reviewed the study submitted in the second comment and 
determined that the study used less sensitive methods than did the 
studies reviewed for the guidance (Ref. 5). For example, the study 
reported that exposure of control sites (i.e., sites without topical 
treatment with AHA-containing test samples) to 1 minimal erythema dose 
(MED) of UV radiation resulted in sunburn cell formation in only 4 out 
of 18 subjects. However, in the studies that FDA reviewed for the 
guidance and that used sunburn cell formation as an indicator of UV 
radiation-induced damage, exposure of control sites to 1 MED of UV 
radiation resulted in sunburn cell formation in 71 out of 72 subjects. 
(The MED is the minimum level of UV radiation needed to cause skin 
redness and has to be measured for each subject.)
    FDA has modified the guidance to state that it may be possible in 
the future to formulate a cosmetic product that contains an AHA as an 
ingredient and that does not increase the sensitivity of skin to the 
sun. However, FDA is not aware of the current existence of such a 
product.
    Based on evidence reviewed so far, FDA concludes that topically 
applied cosmetic products containing AHAs as ingredients may increase 
skin sensitivity to the sun while the products are used and for up to a 
week after use is stopped, and that this increased skin sensitivity to 
the sun may increase the possibility of sunburn. FDA does not know the 
extent of consumer awareness of the potential for increased skin 
sensitivity to the sun from the topical use of AHA-containing cosmetic 
products. The agency is publishing this guidance to help assure 
consumer awareness of this potential and to educate manufacturers to 
help ensure that their labeling is not false or misleading.
    Publication of this guidance is an interim measure while FDA 
continues to review the data on the effects of AHA-containing products 
on skin sensitivity to UV radiation, including a photocarcinogenicity 
study by the National Toxicology Program's Center for Phototoxicology 
and recent studies published in peer-reviewed journals. FDA invites 
comments to continue to inform FDA of new studies when they become 
available.
    FDA is issuing this guidance as a level 1 guidance consistent with 
FDA's good guidance practices regulation (21 CFR 10.115). This guidance 
represents the agency's current thinking on the

[[Page 1724]]

labeling of topically applied cosmetic products that contain an AHA as 
an ingredient. It does not create or confer any rights for or on any 
person and does not operate to bind FDA or the public. An alternative 
approach may be used if the approach satisfies the requirements of 
applicable statutes and regulations.

III. Comments on Guidance

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper copy. 
Comments are to be identified with the docket number found in brackets 
in the heading of this document. The guidance and received comments may 
be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday.

IV. Electronic Access

    Copies of this guidance also are available on the Internet at 
http://www/cfsan.fda.gov/dms/guidance.html.

V. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Sah, A., S. Mukherjee and R. R. Wickett, ``An In Vitro Study 
of the Effects of Formulation Variables and Product Structure on 
Percutaneous Absorption of Lactic Acid,'' Journal of Cosmetic 
Science, vol. 49, pp. 257-273, 1998.
    2. Kraeling, M. E. K. and R. L. Bronaugh, ``In Vitro 
Percutaneous Absorption of Alpha Hydroxy Acids in Human Skin,'' 
Journal of the Society of Cosmetic Chemists, vol. 48, pp. 187-197, 
1997.
    3. Yates, R. L. and D. C. Havery, ``Determination of Phenol, 
Resorcinol, Salicylic Acid and [agr]-Hydroxy Acids in Cosmetic 
Products and Salon Preparations,'' Journal of Cosmetic Science, vol. 
50, pp. 315-325, 1999.
    4. Andersen, F. A., ed., ``Final Report on the Safety Assessment 
of Glycolic Acid, Ammonium, Calcium, Potassium, and Sodium 
Glycolates, Methyl, Ethyl, Propyl, and Butyl Glycolates, and Lactic 
Acid, Ammonium, Calcium, Potassium, Sodium, and TEA-Lactates, 
Methyl, Ethyl, Isopropyl, and Butyl Lactates, and Lauryl, Myristyl, 
and Cetyl Lactates,'' International Journal of Toxicology, vol. 17, 
supplement 1, pp. 1-241, 1998.
    5. Wamer, W., Office of Cosmetics and Colors, CFSAN, Review of 
Documents from Access Business Group: Aupperlee, D., et al., ``The 
Effects of UV Light on Skin Pre-Treated With Alpha Hydroxy Acid 
Moisturizers,'' and Thomas J. Stevens and Associates, ``The Effects 
of Repetitive Cutaneous Application of Test Materials Containing 
Alpha Hydroxy Acid on the Sensitivity of Skin to Ultraviolet (UV) 
Light,'' July 1, 2003.

    Dated: December 29, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-381 Filed 1-7-05; 8:45 am]
BILLING CODE 4160-01-S