[Federal Register Volume 76, Number 117 (Friday, June 17, 2011)]
[Rules and Regulations]
[Pages 35619-35665]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-14766]



[[Page 35619]]

Vol. 76

Friday,

No. 117

June 17, 2011

Part IV





Department of Health and Human Services





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Food and Drug Administration





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21 CFR Parts 201, 310, and 352





Sunscreen Drug Products for Over-the-Counter Human Use; Final Rules and 
Proposed Rules

Federal Register / Vol. 76 , No. 117 / Friday, June 17, 2011 / Rules 
and Regulations

[[Page 35620]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201 and 310

[Docket No. FDA-1978-N-0018] (Formerly Docket No. 1978N-0038)
RIN 0910-AF43


Labeling and Effectiveness Testing; Sunscreen Drug Products for 
Over-the-Counter Human Use

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing this 
document to address labeling and effectiveness testing for certain 
over-the counter (OTC) sunscreen products containing specified active 
ingredients and marketed without approved applications. This document 
addresses labeling and effectiveness testing issues raised by the 
nearly 2,900 submissions that we received in response to the sunscreen 
proposed rule of August 27, 2007 (2007 proposed rule). The document 
also identifies specific claims that render a product that is subject 
to this rule misbranded or would not be allowed on any OTC sunscreen 
product marketed without an approved application. The document does not 
address issues related to sunscreen active ingredients or certain other 
issues regarding the GRASE determination for sunscreen products. The 
document requires OTC sunscreen products to comply with the content and 
format requirements for OTC drug labeling contained in the 1999 Drug 
Facts final rule (published in the Federal Register of March 17, 1999, 
by lifting the delay of implementation date for that rule that we 
published on September 3, 2004).

DATES: Effective Date: This final rule is effective June 18, 2012. For 
additional information concerning this effective date, see section X in 
the preamble of this document. The incorporation by reference of a 
certain publication listed in this rule is approved by the Director of 
the Federal Register as of June 18, 2012.
    Compliance Date: The compliance date for all products subject to 
this final rule with annual sales less than $25,000 is June 17, 2013. 
The compliance date for all other products subject to this final rule 
is June 18, 2012.
    Implementation date: FDA is lifting the delay of implementation 
date for Sec.  201.66 as published at 69 FR 53801, September 3, 2004.

FOR FURTHER INFORMATION CONTACT: Reynold Tan, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 5411, Silver Spring, MD 20993, 301-796-
2090.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Overview of Document
    A. Rulemaking History
    B. Scope of This Document
    C. Issues Outside the Scope of This Document
    D. Enforcement Policy
    E. Summary of Major Revisions to the Labeling and Testing 
Requirements Included in the 2007 Proposed Rule
II. Administrative and Other Issues
III. Principal Display Panel (PDP) Labeling
    A. SPF Statement
    B. Broad Spectrum Statement
    C. Water Resistance Statement
    D. UVB and UVA Educational Statement
IV. Drug Facts Labeling
    A. Active Ingredients/Purpose
    B. Uses
    C. Warnings
    D. Directions
    E. Constitutionality of Labeling Statements Regarding Skin 
Cancer and Skin Aging
    F. Other Information
    G. Reduced Labeling
V. Miscellaneous Labeling Outside Drug Facts
VI. SPF Test Parameters
    A. Solar Simulator
    B. Sunscreen Standards
    C. Test Subjects
    D. Test Sites and Subsites
    E. Finger Cot
    F. Application Amount
    G. Water Resistance
VII. SPF Test Issues (Other Than Test Parameters)
    A. Pass/Fail (Binomial) SPF Test
    B. Photostability
    C. In Vitro SPF Test
    D. Anti-Inflammatory Ingredients
VIII. Broad Spectrum Test
    A. In Vivo Test Method: Not Required
    B. In Vitro Test Method: Critical Wavelength
    C. Critical Wavelength Test Parameters
IX. Analysis of Impacts
    A. Final Regulatory Impact Analysis
    B. Small Business Impact (Final Regulatory Flexibility Analysis)
X. Paperwork Reduction Act of 1995
XI. Environmental Impact
XII. Federalism
XIII. References

I. Overview of Document

A. Rulemaking History

    This section of the document does not discuss every regulatory 
action associated with OTC sunscreen products. It highlights the major 
regulatory actions that are related to the regulatory actions being 
taken in this document. For a complete list of all regulatory actions 
associated with OTC sunscreen products, please refer to our Web site: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm072134.htm.
    In the Federal Register of May 12, 1993 (58 FR 28194), we published 
a proposed rule for OTC sunscreen products that identified active 
ingredients we tentatively considered to be generally recognized as 
safe and effective (GRASE), as well as associated labeling and sun 
protection factor (SPF) testing to be required for these OTC sunscreen 
products (the 1993 proposed rule). The SPF test and corresponding 
labeling reflect the level of protection against sunburn, which is 
caused primarily by UVB radiation. The 1993 proposed rule also 
explained the importance of protection against UVA radiation (58 FR 
28194 at 28232 and 28233). The proposed rule referenced published UVA 
test methods but did not propose a specific method (58 FR 28194 at 
28248 to 28250). Rather, the proposed rule stated that a sunscreen 
product could be labeled as ``broad spectrum,'' or labeled with a 
similar statement, if it protected against UVA radiation as 
demonstrated by one of the published UVA tests or a similar test.
    In April 1994, we reopened the administrative record to allow 
additional submissions concerning UVA-related issues. We also announced 
a public meeting to be held in May 1994 to discuss UVA testing 
procedures (59 FR 16042, April 5, 1994). We held the public meeting to 
gather more information to help us determine the most appropriate UVA 
test method and labeling.
    In November 1997, Congress enacted the Food and Drug Administration 
Modernization Act of 1997 (FDAMA), which addressed OTC sunscreen 
products among other FDA issues. Section 129 of FDAMA stated that ``not 
later than 18 months after the date of enactment of this Act, the 
Secretary of Health and Human Services shall issue regulations for 
over-the-counter sunscreen products for the prevention or treatment of 
sunburn.'' We then determined that the GRASE active ingredients, SPF 
testing requirements, and related labeling were issues that we could 
finalize within the timeframe set by FDAMA. Because we had not 
previously proposed specific UVA testing and labeling requirements, we 
did not have sufficient time to finalize these UVA requirements within 
the FDAMA timeframe.
    In the Federal Register of May 21, 1999, we published a final rule 
for OTC

[[Page 35621]]

sunscreen products (64 FR 27666). The 1999 sunscreen final rule added 
the sunscreen monograph (regulations) in part 352 (21 CFR part 352) and 
included an effective date of May 2001. The 1999 sunscreen final rule 
stated that we would publish a proposed rule outlining UVA testing and 
labeling requirements at a future date. In 2000, we extended the 
effective date for the 1999 sunscreen final rule to December 2002 (65 
FR 36319, June 8, 2000).
    In December 2001, we stayed the December 2002 effective date of the 
1999 sunscreen final rule indefinitely. We took this action because we 
planned to revise part 352 to add UVA testing and labeling requirements 
so that OTC sunscreen products would be tested and labeled for both UVB 
and UVA radiation protection. We included these revisions in a proposed 
rule that published in the Federal Register of August 27, 2007 (72 FR 
49070). The 2007 proposed rule identified UVA testing and labeling that 
we proposed should be required for all OTC sunscreen products. The 
proposed rule also revised SPF testing and corresponding labeling from 
the 1999 final rule. The proposed rule did not lift the existing stay 
of the effective date for part 352.
    On September 3, 2004 (69 FR 53801), we delayed until further notice 
the implementation date for the Drug Facts final rule (64 FR 13254, 
March 17, 1999) (21 CFR 201.66) for OTC sunscreen products. The Drug 
Facts final rule (21 CFR 201.66) establishes general labeling format 
and content requirements for all OTC drugs. We explained that we 
postponed the implementation date for general Drug Facts labeling 
requirements for sunscreens because we did not expect to issue the 
sunscreen final rule containing UVA testing and product-specific 
labeling requirements (i.e., this document) by the Drug Facts 
implementation date of May 2005. Therefore, we delayed the 
implementation date until further notice to prevent sunscreen product 
manufacturers from having to relabel their products at two closely 
related time intervals, as initially required by the 1999 Drug Facts 
final rule and the 1999 sunscreen final rule.

B. Scope of This Document

    This final rule establishes the labeling and testing requirements 
for OTC sunscreen products containing specific ingredients or 
combinations of ingredients and marketed without an approved 
application under section 505 of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 355) (the FD&C Act). The requirements in this final rule 
will help ensure that these currently marketed sunscreen products are 
appropriately labeled and tested for both UVA and UVB protection. In 
addition, the requirements in this final rule will help ensure the 
proper use of these sunscreens and greater consumer protection from the 
damaging effects of UV radiation. This final rule also identifies 
claims that render a product that is subject to this rule misbranded or 
are not allowed on any OTC sunscreen drug product marketed without an 
approved application.
    As described in the previous section of this document, we issued 
the 2007 proposed rule as a proposed amendment to the sunscreen 
monograph requirements in 21 CFR part 352 primarily to establish UVA 
testing and labeling requirements so that all OTC sunscreen products 
marketed under the sunscreen monograph would be tested and labeled for 
both UVB and UVA radiation protection. Sunscreen active ingredients, 
UVB testing, UVB labeling, and other conditions under which sunscreens 
would be considered GRASE and not misbranded had been addressed in the 
1999 (stayed) final rule. In response to the 2007 proposed rule, 
however, we received submissions from the public concerning all aspects 
of the sunscreen monograph (i.e., the conditions specified in the 1999 
final rule and the 2007 proposed rule). As discussed further in this 
section, some of the issues regarding the monograph conditions raised 
in the public submissions will require further evaluation by us. 
Therefore, we are not issuing a final monograph with GRASE conditions 
for sunscreens in this document. Instead, we are publishing this final 
rule establishing labeling and the effectiveness testing upon which it 
relies, which applies to the same sunscreens that were the subject of 
the 2007 proposed rule to amend the monograph, because it is in the 
best interest of public health to publish this final rule while we work 
on remaining issues that need to be addressed in order to publish a 
final monograph. This labeling will help ensure that these products are 
not misbranded by providing specific indications, directions, warnings, 
and other important information to help consumers select and use them 
appropriately.
    In this final rule, then, we are codifying in 21 CFR part 201 
requirements for OTC sunscreen products containing specified active 
ingredients and marketed without approved applications under section 
505 of the FD&C Act (21 U.S.C. 355) (hereafter referred to as 
``covered'' products). With respect to these covered products, this new 
section 21 CFR 201.327 includes requirements for labeling and the 
effectiveness testing upon which it relies. Because we have not yet 
resolved all of the issues regarding conditions under which sunscreens 
are GRASE and not misbranded, the stay of 21 CFR part 352 remains in 
effect. Although we are not yet codifying these labeling and related 
effectiveness testing provisions in the monograph regulation, they do 
embody the agency's current determination on appropriate regulation of 
these aspects of sunscreens that were previously identified as falling 
within the monograph in part 352, and supersede the prior approach 
embodied in the never-effective provisions of 21 CFR part 352 subparts 
C and D. While this rule does not lift the stay of part 352, we are 
lifting the delay of implementation date for the Drug Facts labeling 
requirements of 21 CFR 201.66. In addition, this rule codifies certain 
specific claims that render a covered product misbranded or are not 
allowed on any OTC sunscreen drug product marketed in the United States 
without an approved application.
    We note that all provisions of new 21 CFR 201.327 and the 
amendments to 310.545 included in this rule apply only to the 
aforementioned covered products, and references in this document to 
``covered'' products recognize this limitation. Manufacturers of 
sunscreen products that are already being marketed pursuant to an 
approved application can contact FDA's Center for Drug Evaluation and 
Research to discuss supplemental submissions that would enable them to 
include labeling on their products like that specified in this final 
rule.

C. Issues Outside the Scope of This Document

    There are a number of issues that were raised in public submissions 
responding to the 2007 proposed rule that are outside the scope of this 
document. The issues fall into two categories:
     GRASE determination for sunscreen products and active 
ingredients
     Issues affecting multiple OTC drug monographs

As explained below, in this document, we are not addressing these 
issues related to determining the GRASE status of sunscreen products or 
sunscreen active ingredients and are not addressing the issues 
described below affecting multiple OTC drug monographs.

[[Page 35622]]

1. Issues Regarding GRASE Determination for Sunscreen Products and 
Active Ingredients
    A large number of submissions on the 2007 proposed rule raised 
issues related to the conditions that define what constitutes a GRASE 
finished OTC sunscreen product, irrespective of its active ingredients. 
These included over 1000 submissions requesting that we limit the 
monograph to sunscreens that offer broad spectrum protection and have 
SPF values of 15 or higher. Because this final rule is a labeling rule, 
and not a monograph, we do not address these issues here but plan to 
address them in future rulemakings regarding the monograph and 
conditions for general recognition of safety and effectiveness.
    This rule also does not address issues related to the GRASE status 
of sunscreen active ingredients that are included in the 2007 proposed 
rule (proposed 21 CFR 352.10 and 352.20). We received 20 submissions 
raising questions about the safety of ingredients in sunscreens (Ref. 
1). Ten of the submissions specifically asked that we ensure that none 
of the ingredients are carcinogenic. Others asked that we ensure that 
all ingredients in sunscreens are safe without citing a specific 
concern. We intend to address carcinogenicity and other safety 
considerations related to sunscreen active ingredients in a future 
rulemaking.
    We also received submissions requesting that we increase the GRASE 
concentration of avobenzone from 3 percent to 5 percent (Ref. 1). 
Another submission points out that there are two USP \1\ monographs for 
zinc oxide:
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    \1\ United States Pharmacopeia.
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     Zinc oxide (Ref. 2)
     Zinc oxide neutral (Ref. 3)

The submission would like us to clarify that zinc oxide in OTC 
sunscreen products can meet the specifications of either USP monograph 
(Ref. 1). We intend to address all of these issues regarding GRASE 
determination for sunscreen active ingredients in future rulemakings.
    In addition, we received two submissions requesting that we 
classify three new ingredients not previously marketed in the United 
States as GRASE: bemotrizinol, bisoctrizole, and octyl triazone (Ref. 
1). We found these active ingredients eligible for review under the OTC 
drug monograph system in 2003 (octyl triazone) and 2005 (bemotrizinol 
and bisoctrizole) (68 FR 41386, July 11, 2003, and 70 FR 72449, 
December 5, 2005). We are currently reviewing the safety and 
effectiveness data submitted for these and other sunscreen active 
ingredients found eligible for potential addition to the monograph. 
When we complete our review, we will issue proposed rules stating our 
tentative conclusions on the safety and effectiveness of all of these 
ingredients.
2. Issues Affecting Multiple OTC Drug Monographs
    This final rule also does not address three issues raised in 
response to the 2007 sunscreen proposed rule that are not specific to 
sunscreen products. Because these issues apply more generally to 
multiple categories of OTC drug products, we are not addressing these 
issues in this final rule, which is limited to OTC sunscreen products.
    The first issue concerns the inclusion of expiration dates on 
sunscreen labels. We received 12 submissions requesting that we require 
OTC sunscreen products to be labeled with an expiration date (Ref. 1). 
Currently, regulations in 21 CFR 211.137(h) do not require that an 
expiration date be included in labeling if an OTC drug product does not 
have any dosage limitations and is stable for at least 3 years. This 
regulation applies to many OTC drug products, including sunscreen 
products. Any modification of the existing regulations would require 
publication of a proposed rule addressing all OTC drug products 
affected by the expiration date regulations.
    The second issue concerns the term ``final monograph.'' One 
submission argued that we should not use this term because it is 
inaccurate (Ref. 1). As the submission states, ``FDA is to continually 
evaluate products, so nothing is ever finalized.'' This issue applies 
to monographs representing all categories of OTC drug products. 
Therefore, we are not addressing the issue in this document.
    The third issue concerns the country of origin listing for all 
ingredients (i.e., both active and inactive ingredients) on a sunscreen 
drug product. We received a submission requesting that we provide the 
country of origin for each ingredient. The submission also requested 
that manufacturers be required to provide specific details about what 
each ingredient does in the product. This issue applies to all OTC drug 
products and, therefore, we are not addressing it in this document.

D. Enforcement Policy

    As noted, no final monograph is currently in effect for OTC 
sunscreen drug products, and in its absence, questions may arise 
regarding FDA's enforcement policy for OTC sunscreen products marketed 
without approved applications. To clarify expectations for industry, 
elsewhere in this issue of the Federal Register, we are announcing the 
availability of a draft guidance document, explaining the agency's 
intended enforcement policy for these products until a final sunscreen 
monograph becomes effective.

E. Summary of Major Revisions to the Labeling and Effectiveness Testing 
Included in the 2007 Proposed Rule

    In response to the 2007 proposed rule, we received almost 2,900 
submissions from the public. Of these submissions, over 2,500 expressed 
general support for the proposed rule and urged us to finalize and 
implement the new rule quickly. Three hundred twenty-five of the 
submissions raised approximately 90 specific issues related to the 
proposed rule. We have addressed the issues specifically relating to 
labeling and effectiveness testing in this final rule. Based on the 
submissions received, and the information and data included in those 
submissions or otherwise available to us, we have re-evaluated our 
position on several issues in the 2007 proposed rule and made several 
changes to our proposed labeling and testing requirements. Tables 1, 2, 
4, and 5 in this document summarize the labeling and effectiveness 
testing requirements included in the 2007 proposed rule as well as the 
labeling and effectiveness testing required by this final rule:
     Table 1: PDP Labeling (discussed in section III)
     Table 2: Drug Facts Labeling (discussed in section IV)
     Table 4: SPF Test (discussed in section VI)
     Table 5: Broad Spectrum Test (discussed in section VIII)

Rather than summarizing all of the revisions to the labeling and 
testing included in the 2007 proposed rule, we are highlighting what we 
consider to be the most important revisions in this section of the 
document.

    We made the following changes to the proposed labeling:
    1. The proposed UVA ``star rating'' is not required on the PDP.
    2. A combined ``Broad Spectrum SPF'' statement is required on the 
PDP for sunscreen products that pass the broad spectrum test 
established in new 21 CFR 201.327(j). To pass the broad spectrum test, 
the amount of UVA protection must increase as the SPF value increases.
    3. For sunscreen products that pass the broad spectrum test 
established in new 21 CFR 201.327(j) and have SPF

[[Page 35623]]

values of 15 or higher in accordance with the SPF test in 21 CFR 
201.327(i):
    a. The ``Sun Alert'' warning proposed as the first warning in 2007 
is not required (Warning proposed located in 21 CFR 352.52(c)(1)).
    b. A new indication statement may be included to inform consumers 
that using the product ``as directed with other sun protection measures 
(see Directions [in bold italic font]) decreases the risk of skin 
cancer and early skin aging caused by the sun.''
    c. A new direction statement has been added informing consumers 
that exposure to the sun increases the risk of skin cancer and early 
skin aging and providing a list of specific sun protection measures 
that can decrease this risk.
    4. For any OTC sunscreen product that does not pass the broad 
spectrum test in 21 CFR 201.327(j), or that are broad spectrum with an 
SPF value less than 15, this final rule, like the 2007 proposed rule, 
requires that the first warning indicate the adverse consequences of 
spending time in the sun. The wording of this warning has been revised 
to state, ``Skin Cancer/Skin Aging Alert [in bold font]: Spending time 
in the sun increases your risk of skin cancer and early skin aging. 
This product has been shown only to help prevent sunburn, not [in bold 
font] skin cancer or early skin aging.''
    We also made the following changes to the effectiveness testing 
proposed in 2007:
    1. The number of subjects required in the SPF test has been reduced 
from 20 subjects to 10 subjects.
    2. One in vitro test is required to demonstrate broad spectrum 
protection rather than the two previously proposed tests (an in vitro 
test and an in vivo test).
    3. The broad spectrum test is a pass/fail test based on the 
critical wavelength value of 370 nm \2\.
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    \2\ Nanometers.
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II. Administrative and Other Issues

    Some of the submissions that we received following publication of 
the 2007 proposed rule made the following requests involving 
administrative issues (Ref. 1):
     Extend the comment period of the 2007 proposed rule.
     Lift the stay on 21 CFR part 352, imposed in 2001 (66 FR 
67485).
     Allow interim marketing of products containing avobenzone 
with ensulizole and avobenzone with zinc oxide.
     Set an effective date for this final rule other than the 
18 months proposed in the 2007 proposed rule.
     Revise the preemption language included in the 2007 
proposed rule by deleting any references regarding the rule's potential 
preemption of State tort law.

Our positions on these issues are discussed in the remainder of this 
section of the document.
    All of the requests to extend the comment period were submitted 
before the November 28, 2007 Federal Register notice in which we 
extended the comment period of the 2007 proposed rule (72 FR 67264). In 
that notice, we extended the close of the comment period from November 
26, 2007, to December 26, 2007. We have not received any more requests 
to extend the comment period since December 2007.
    With regard to requests to lift the stay of 21 CFR part 352 (the 
OTC sunscreen monograph), as already discussed, our 2007 proposed rule 
anticipated amending the testing and labeling provisions of that 
monograph and subsequently lifting the stay. However, comments received 
on the 2007 proposed rule not only addressed labeling and effectiveness 
testing for final sunscreen formulations, but also raised other issues 
about the monograph conditions for OTC sunscreen products that require 
further consideration. As a result, we are not finalizing amendments to 
part 352 at this time nor lifting the stay placed on that section as 
enacted in 1999 (66 FR 67485). Rather, this final rule establishes in 
21 CFR 201.327 labeling requirements and the effectiveness testing upon 
which it relies for covered OTC sunscreen drug products. We intend to 
lift the stay on part 352 when we reach our final conclusions on the 
conditions under which sunscreen products are GRASE and not misbranded, 
including a determination regarding sunscreen active ingredients, and 
publish a revised final monograph. In the interim, the labeling and 
effectiveness testing provisions of this rule apply to covered OTC 
sunscreen products.
    We received a request that we allow interim marketing of avobenzone 
combinations in proposed Sec.  352.20(a)(2) prior to issuing a final 
rule for part 352. Subject to our enforcement discretion, we will 
continue to allow the marketing of avobenzone combinations provided for 
in the 1999 sunscreen final rule. However, we are not allowing 
marketing of the additional avobenzone combinations discussed in the 
2007 proposed rule until we reach a final conclusion on the GRASE 
determination for sunscreen active ingredients and combinations of 
those ingredients.
    We are requiring that this final rule become effective in 1 year, 
even though we considered 18 months in the 2007 proposed rule (72 FR 
49070 at 49110). We are allowing products with annual sales less than 
$25,000 to comply with this rule in 2 years, as stated in the 2007 
proposed rule. In response to the proposed rule, we received one 
submission arguing that we should require this final rule to become 
effective in 1 year (Ref. 1). The submission stated that a later 
effective date would have a negative public health impact. We received 
eight submissions arguing that we should extend the effective date from 
the proposed 18 months to 3 years (Ref. 1). The submissions listed the 
following reasons for allowing more than 18 months:
     Repackaging
     Relabeling
     Testing/retesting
     Removing products from market
     Impact on small businesses

The most common argument was that more time would be needed to test/
retest OTC sunscreen products for broad spectrum protection in 
accordance with both the in vitro and in vivo UVA test methods included 
in the proposed rule.

    We agree with the submission which stated that it would be 
beneficial for consumers to have this rule become effective within 1 
year. As explained in section VIII.A of this document, we are not 
requiring manufacturers to demonstrate broad spectrum protection by 
conducting in vivo and in vitro tests. This final rule requires that 
manufacturers conduct only the simpler and less expensive nonclinical 
in vitro test to demonstrate broad spectrum protection. In vitro tests 
are substantially shorter than in vivo tests. Therefore, we are setting 
an effective date for this rule 1 year from the date of publication in 
the Federal Register. However, we are providing two years for all 
products with annual sales less than $25,000 to comply with this rule. 
In addition, in order to ensure that limited testing laboratory 
capacity does not result in sunscreen shortages during the transition 
to the new rule, we intend to exercise enforcement discretion for a 
period of time with regard to the SPF test for certain OTC sunscreen 
products on the market by June 17, 2011 (see our draft guidance 
entitled ``Guidance for Industry: Enforcement Policy--OTC Sunscreen 
Drug Products Marketed Without An Approved Application'' announced 
elsewhere in this issue of the Federal Register).
    The submissions stating that additional time is necessary for

[[Page 35624]]

repackaging and relabeling did not submit any information or data to 
support these arguments (Ref. 1). The argument that more than 18 months 
is needed to remove non-compliant products from the market is not 
valid. In the 2007 proposed rule, we indicated that sunscreen products 
which are already distributed by the effective date of the final rule 
would not be expected to be relabeled or retested in conformity with 
the final rule conditions unless these products were subsequently 
relabeled or repackaged after the effective date (72 FR 49070 at 
49109). Consistent with this statement, we do not expect non-compliant 
products introduced or delivered for introduction into interstate 
commerce prior to the compliance dates specified for this final rule to 
be removed from the market.
    We received a submission that expressed concern about the agency's 
preemption discussion in the 2007 proposed rule (72 FR 49070 at 49109 
and 49110) and requested that we delete any discussion regarding the 
rule's potential preemption of State tort law (Ref. 1). The submission 
claimed that we exceeded our authority when we stated that section 
751(a) of the FD&C Act displaces both State legislative requirements 
and State common law duties. The submission argued that Congress 
intended to preserve State common law claims by including section 
51(e), which exempts State product liability claims from express 
preemption under section 751(a) of the FD&C Act. The commenter appears 
to have construed our statement in a way that would nullify section 
751(e) of the FD&C Act. We did not intend to suggest that section 
751(a) of the FD&C Act preempts State product liability claims, whether 
based on State legislative enactments or common law, because section 
751(e) exempts such actions from the express preemption provision in 
section 751(a). However, it is important to note that section 751(e) of 
the FD&C Act exempts only those common law claims that are based on 
State product liability law. Our revised preemption discussion in 
section XII remains consistent with applicable law.
    The submission also requested that we delete any references to 
implied preemption. In this final rule, we have omitted any statement 
regarding implied preemption because, although implied preemption may 
arise, such scenarios are necessarily case-specific. Section XII of 
this document makes clear that the sole statutory provision giving 
preemptive effect to the final rule is section 751 of the FD&C Act.

III. Principal Display Panel (PDP) Labeling

    In response to the 2007 sunscreen proposed rule, we received 45 
submissions requesting that we revise the proposed principal display 
panel (PDP) labeling (Ref. 1). We are revising the PDP labeling based, 
in part, on these submissions (see table 1 of this document). We have 
decided that the PDP labeling included in this document will simplify 
the purchase decision for consumers by allowing them to more easily 
find important information included on the PDP.

  Table 1--Summary of PDP Labeling in the 2007 Proposed Rule and This Final Rule Using a Broad Spectrum SPF 30
 Water Resistant Sunscreen Product as Example A and an SPF 6 Sunscreen That Is Not Broad Spectrum and Not Water
                                             Resistant as Example B
----------------------------------------------------------------------------------------------------------------
         Labeled information                       2007 Proposed rule                     This final rule
----------------------------------------------------------------------------------------------------------------
Effectiveness Rating \1\.............  Example A:                                  Example A:
                                       ``UVB SPF 30 High''                         ``Broad Spectrum SPF 30''
                                       ``UVA [starf][starf][starf][star14] High''
                                       Example B:                                  Example B:
                                       ``UVB SPF 6 Low''                           ``SPF 6''
                                       ``No UVA Protection''
Water Resistance.....................  Example A:                                  Example A:
                                       ``Water Resistant''                         ``Water Resistant (40
                                                                                    minutes)''
                                       Example B:                                  Example B:
                                       No statement on water resistance            No statement on water
                                                                                    resistance
Educational Statement................  Examples A & B:                             Examples A & B:
                                       ``UV rays from the sun are made of UVB and  No educational statement
                                        UVA. It is important to protect against
                                        both UVA and UVB rays.''
----------------------------------------------------------------------------------------------------------------
\1\ The UVA rating in the 2007 proposed rule is a four-tier rating (low, medium, high, highest). The UVA testing
  in this final rule is pass/fail--a product is either allowed or not allowed to include a broad spectrum
  statement depending on results of the test described in new 21 CFR 201.327(j) (see section VIII of this
  document).

A. SPF Statement

    In the 2007 sunscreen proposed rule, we proposed redefining the 
acronym ``SPF'' as the ``sunburn protection factor.'' We also proposed 
that the term ``UVB SPF'' would be required on the PDP of all OTC 
sunscreen products (proposed 21 CFR 352.50(a)). This term would be 
followed by the numerical value determined from SPF testing and one of 
the following descriptors: ``low,'' ``medium,'' ``high,'' or 
``highest.'' For example, a sunscreen product could have contained the 
statement ``UVB SPF 40 High'' on the PDP.
    We received 12 submissions regarding the SPF statement in response 
to the 2007 sunscreen proposed rule (Ref. 1). Collectively, the 
submissions made the following requests:
    1. Do not change the definition of SPF to ``sunburn protection 
factor''
    2. Remove UVB from ``UVB SPF''
    3. Redefine the ``highest'' product category descriptor to include 
SPF 50
    4. Require SPF values expressed in multiples of 5
    5. Label SPF as the percent of UVB radiation screened

As discussed in the remainder of this section, we agree with the first 
and second requests, but are not granting the other three requests.

    In this final rule, unlike the 2007 proposed rule, we have no 
express definitional section. However, we identify ``SPF'' as an 
abbreviation for ``sun protection factor'' in new 21 CFR 201.327(a)(1), 
and use it consistently in this way throughout the rule. This use of 
the term SPF is identical to the definition in the 1999 stayed 
sunscreen final rule (64 FR 27666). For products that are not broad 
spectrum, the term ``SPF'' will appear on the PDP with the numerical 
SPF value calculated according to the test method in new 21

[[Page 35625]]

CFR 201.327(i). For broad spectrum sunscreen products, the term ``Broad 
Spectrum SPF'' will appear on the PDP along with the numerical SPF 
value calculated according to the test method in new 21 CFR 201.327(i).
    The term ``UVB'' will not be required as part of the SPF statement. 
We are also not requiring the descriptor (e.g., ``high'' or ``low''). 
We included these two requirements in the 2007 proposed rule because we 
had concluded that the requirements would help consumers understand the 
side-by-side SPF numerical rating in conjunction with the UVA star 
rating, which included the term ``UVA'' and the same descriptors (72 FR 
49070 at 49084). As discussed in section III.B of this document, the 
UVA star rating is not being included in this final rule, and as 
discussed below, we have concluded that neither the term ``UVB'' nor 
the descriptor is necessary for consumers to understand the 
effectiveness statement.
    Neither the term ``UVB'' nor a descriptor (e.g. ``low'' or 
``high'') had been included on sunscreen labels prior to our 2007 
proposal, and consumers had been able to make purchase and use 
decisions based on SPF values alone. Under this final rule, the SPF 
value will be expressed on the PDP by including the term ``SPF,'' 
followed by the numerical value determined from the SPF test, similar 
to how it has appeared on the labels of OTC sunscreen products for more 
than 30 years. As described in section III.B of this document, for 
products passing the critical wavelength test in new 21 CFR 201.327(j), 
the SPF value statement will be expressed as ``Broad Spectrum SPF'' 
followed by the numerical SPF value calculated according to the test 
method in 21 CFR 201.327(i).
    We received five submissions objecting to the definition of SPF as 
``sunburn protection factor'' and only one submission supporting the 
definition (Ref. 1). The submissions objecting to the definition argued 
that, if the term ``sunburn protection factor'' is used, consumers may 
mistakenly assume that a higher SPF value means a higher probability of 
sunburn. Additionally, they argued that sunscreen products protect 
against various harmful effects of sun exposure, such as early skin 
aging and skin cancer, in addition to protecting against sunburn. Some 
submissions suggested that the term ``sunburn protection factor'' will 
lead consumers with darker skin to assume that they do not need 
sunscreen products because they do not burn easily (Ref. 1).
    We agree with the arguments provided by the submissions suggesting 
that the term ``sunburn protection factor'' may be misleading. In the 
2007 sunscreen proposed rule, we revised the definition of SPF from 
``sun protection factor'' to ``sunburn protection factor'' because we 
thought that the new definition was more descriptive of what an SPF 
value represents (72 FR 49070 at 49077). The SPF value is determined 
from a clinical test with sunburn as the endpoint. However, for broad 
spectrum sunscreen products, the SPF statement also serves as a 
relative measure of the magnitude of broad spectrum protection (Ref. 
4). In this final rule, while we do not codify a separate definitional 
section, we continue to use the term ``SPF'' to mean ``sun protection 
factor,'' as we had done in the 1999 final rule (21 CFR 201.327(a)(1)).
    In this final rule, we are also revising the effectiveness 
statement so that the term ``UVB'' is not required before the term 
``SPF,'' as proposed in the 2007 proposed rule (proposed 21 CFR 
352.50(a)). We received six submissions requesting this revision (Ref. 
1). These submissions argued that ``UVB SPF'' is an incorrect 
representation of the SPF value determined from a test using a solar 
stimulator that emits both UVA and UVB radiation. The submissions point 
out that sunburn is not caused solely by UVB radiation. It is well 
known that UVA radiation contributes up to 20 percent of the skin's 
sunburn response (Refs. 5 and 6). One submission points out that if a 
sunscreen product blocked 100 percent of the incident UVB radiation and 
none of the erythemally effective UVA radiation, the sunscreen product 
would have SPF values no higher than 11 (if only 9 percent or 1/11 of 
UV radiation reaches the skin) (Ref. 4).
    We agree that UVA radiation contributes to the development of 
sunburn. Although the contribution of UVA to sunburn is less than UVB, 
it is still significant (Ref. 5). Further, as stated in the 
submissions, protection against UVA radiation is necessary to achieve 
higher SPF values (Ref. 5). We proposed including the term ``UVB'' in 
the SPF statement in the 2007 proposed rule to help consumers 
understand that the SPF effectiveness rating is different from the UVA 
effectiveness (star) rating being proposed (72 FR 49070 at 49084). 
However, as discussed elsewhere in this final rule we are not requiring 
a UVA effectiveness rating on the PDP (see section III.B.). Therefore, 
the term ``UVB'' is not necessary as part of the SPF statement. In this 
final rule, we are not requiring the term ``UVB'' be placed before the 
term ``SPF.''
    In the 2007 sunscreen proposed rule, we stated that the SPF value 
should be followed by one of the descriptors ``low,'' ``medium,'' 
``high,'' or ``highest'' (proposed 21 CFR 352.50(a)). The proposed 
descriptors were included to help consumers understand the SPF value 
because the label would have included identical descriptors for the UVA 
star rating. As discussed in section III.B. of this document, we are 
not requiring a UVA effectiveness rating on the PDP. Therefore, 
descriptors are no longer required to distinguish the SPF value from 
the UVA rating on a sunscreen label. Because we are not requiring a 
descriptor after the SPF value on the PDP in this document, the request 
to include SPF 50 sunscreen products in the ``highest'' category is no 
longer relevant.
    We received two other requests for revision to the SPF statement 
with which we do not agree. First, a submission stated that SPF values 
should only be labeled in multiples of five to be consistent with SPF 
labeling recommendations by the European Commission (Ref. 7). Second, 
one request from a submission suggested that SPF values should be 
expressed as the percent of UV absorption. The submission argued that 
the current SPF values are misleading because consumers believe an SPF 
15 sunscreen product is not very protective even though it screens 93 
percent of UV radiation.
    We do not agree with either submission. Based on SPF test data we 
have reviewed, we find that SPF values for sunscreen products generally 
can be determined with a precision that allows the products to be 
labeled with SPF values in intervals of less than 5 units (Ref. 1). 
Therefore, there is no mathematical or statistical basis for 
restricting SPF values to multiples of five. Contrary to the second 
request, consumers have relied on SPF values for over 30 years and are 
familiar with this format. Therefore, expressing SPF values as 
percentages may be confusing. It would imply that the stated percentage 
of the entire UV spectrum is absorbed by a sunscreen. However, the SPF 
values only reflect protection against the portion of the UV spectrum 
that causes sunburn. Additionally, the percentages of UV radiation 
screened that the submission notes are theoretical. The percentages are 
determined in a laboratory setting and not under actual use conditions. 
For example, laboratory tests may show that an SPF 15 sunscreen absorbs 
93 percent of UV rays, but, under actual use conditions, the level of 
protection provided by an SPF 15 sunscreen product may be significantly 
below 93 percent. There are a number of factors

[[Page 35626]]

that lead to this decreased protection, the most important being under-
application of the sunscreen product (72 FR 49070 at 49092). Therefore, 
if SPF values were expressed as percentages, consumers might mistakenly 
believe that the sunscreen products they are using provide more 
protection than they really do provide under actual use conditions.

B. Broad Spectrum Statement

    In response to the 2007 proposed rule, we received over 50 
submissions collectively making the following four requests regarding 
the UVA effectiveness rating (Ref. 1):
    1. Do not require UVA 4-star rating system.
    2. Do not require ``no UVA protection'' statement if a product does 
not protect against UVA radiation.
    3. Do not require the UVA statement to be the same size as the SPF 
statement.
    4. Perform label comprehension studies prior to implementing 
proposed PDP labeling.

The submissions included arguments, but no data, to support these 
requests.

    We agree with the first and second requests. However, we are not 
granting the third and fourth requests. Our reasons for these decisions 
are explained below, but we first summarize the related provisions of 
this final rule. We are not requiring a star rating or descriptors to 
indicate the level of UVA protection as proposed. Instead, to indicate 
the level of UVA and UVB protection, we are establishing a pass/fail 
broad spectrum test and a broad spectrum labeling statement. If a 
sunscreen product passes the broad spectrum test (see section VIII.B. 
of this document), under this final rule, the PDP of the product must 
include the statement ``Broad Spectrum SPF [insert numerical SPF value 
resulting from testing under paragraph (i) of this section],'' without 
any ``UVA'' reference (Sec.  201.327(a)(1)(i)). We are requiring the 
Broad Spectrum SPF statement to appear as continuous text with no 
intervening text or graphics. We are also requiring that the entire 
text be the same font style, size and color on the same background 
color. (Sec.  201.327(a)(1)(ii)).
    With regard to the submissions received, nearly all of the 50+ 
submissions argued against requiring the 4-star rating system to 
display the level of UVA protection on the PDP of OTC sunscreen 
products (Ref. 1). Many submissions stated that the presence of stars 
and a number (SPF) on the PDP will lead to consumer confusion. Some 
submissions argued that consumers may be confused when determining 
whether a star is filled or empty, thereby not knowing the UVA 
protection level. Other submissions argued that consumers are familiar 
with star ratings, but that the star rating for items such as movies 
and hotels are based on recommendations and not rigorous data. They 
suggested several options for labeling UVA protection, such as a 
numerical rating or another symbol other than stars.
    Some submissions suggested that the UVA rating should be 
proportional to the SPF value but requested that there not be two 
ratings on the PDP. The submissions cited the European Commission's 
recommendation that UVA protection increase as the SPF value increases 
(Ref. 7). The European Commission recommends a minimum UVA protection 
factor equal to at least one-third of the labeled SPF or a critical 
wavelength of at least 370 nm, but does not recommend that the actual 
value of the UVA protection factor or critical wavelength be displayed. 
The European Commission recommends that the main indicator of sun 
protection be the SPF value. Broad spectrum protection is indicated by 
a symbol on sunscreen labels--the acronym ``UVA'' enclosed within a 
circle the diameter of which should not exceed the height of the SPF 
value.
    We agree with the submissions that the UVA star rating would likely 
be confusing in conjunction with the numerical SPF rating. We also 
agree with the submissions requesting that UVA protection should be 
proportional to the SPF value. We are requiring such proportionality in 
the broad spectrum test described in this document. Because of this 
proportionality, there is no longer a need for a separate UVA rating. 
Instead of a rating, we are requiring a ``broad spectrum'' statement on 
the PDP if a product has a critical wavelength equal to or greater than 
370 nm. This pass/fail ``broad spectrum'' statement is consistent with 
the recommendations in the submissions citing the recommendations of 
the European Commission.
    As noted, several submissions responding to our proposal for a 
separate UVA rating with stars suggested that consumer comprehension 
testing should be performed before the proposed labeling is 
implemented. We agree with the submissions that consumer comprehension 
data can be very helpful in formulating labeling changes. In fact, in 
conjunction with our 1993 proposal to allow products to be labeled as 
``broad spectrum'' if they contained sunscreen active ingredients that 
absorbed UVA radiation (58 FR 28194 at 28233), we requested label 
comprehension study data to allow us to determine consumer 
understanding of the terms ``broad spectrum,'' ``UVA,'' and ``UVB'' (58 
FR 28194 at 28243). Unfortunately, the data we received were not 
sufficient to allow us to determine the level of consumer understanding 
of these terms (72 FR 49070 at 49081 through 49085), and we received no 
further consumer comprehension data in response to the 2007 proposal to 
require the UVA star rating. While we acknowledge the value of consumer 
comprehension data, for reasons explained below, we conclude that 
conducting consumer comprehension testing is not necessary in this case 
in light of the labeling we have selected for the final rule.
    First, submissions suggesting consumer testing were responding to 
the UVA star rating in the proposed rule, the value of which would have 
been based on the results of two tests (72 FR 49070 at 49081 through 
49085). As noted, we agree with the submissions suggesting that the 
2007 UVA labeling proposal was likely to be confusing. Elsewhere in the 
document, we also discuss our final choice of a pass-fail test for 
establishing UV protection (section VIII.B). As a result of these 
changes in the underlying test method and the submissions on the 
proposed labeling, we have incorporated a much simpler labeling 
statement in this final rule. This statement designates as ``broad 
spectrum'' those products that are demonstrated to have a critical 
wavelength of at least 370 nm, using the test in new 21 CFR 201.327(j).
    Second, unlike in 1993 when we first sought consumer data on the 
term ``broad spectrum'', and unlike the UVA star rating that we 
proposed in 2007, consumers are now likely to be familiar with the term 
``broad spectrum'' as included in this document because some sunscreen 
manufacturers have labeled sunscreen products as ``broad spectrum'' for 
over 20 years. For example, the Johnson and Johnson ``Sundown Broad 
Spectrum'' line of sunscreens was on the market in 1988 (Ref. 8). As 
already noted, in our 1993 proposed rule, we not only sought consumer 
data, but in fact proposed that products be permitted to be labeled as 
``broad spectrum'' if they contained sunscreen active ingredients that 
absorbed UVA radiation, although we did not at that time propose to 
require a specific test to demonstrate UVA protection (58 FR 28194 at 
28233). We continued to allow this statement in the 1999 sunscreen 
final rule (64 FR 27666 at 27666 through 27667).
    Many consumers may also be familiar with the term ``broad 
spectrum'' because

[[Page 35627]]

of public health campaigns and news articles about the importance of 
broad spectrum UV protection over the last two decades. For example, an 
article appearing in Working Woman magazine in 1990 urged women to 
``make sure to look for the term `broad spectrum' on the label of a 
sunscreen'' because ``it means you're getting protection from both 
types of radiation'' (Ref. 9).
    For consumers not already familiar with the term ``broad 
spectrum,'' the additional indication statement allowed in this 
document for certain broad spectrum sunscreen products should help 
consumers recognize the benefit of these products. Under ``Uses'' in 
Drug Facts, broad spectrum sunscreen products with an SPF value of 15 
or higher are allowed the following indication statement: ``if used as 
directed with other sun protection measures (see Directions [in bold 
italic font]), decreases the risk of skin cancer and early skin aging 
caused by the sun'' (new 21 CFR 201.327(c)(2)).
    In addition, educational campaigns about sun protection will 
further inform consumers about the benefits of using sunscreens that 
include the term ``broad spectrum'' on their labels and have an SPF 
value of 15 or higher. We expect consumers to learn that a sunscreen 
labeled with the statement ``Broad Spectrum SPF'' 15 or higher, when 
used as directed with other sun protection measures, offers more 
comprehensive protection against sun-induced skin damage than that 
provided by a sunscreen that is not broad spectrum or that are broad 
spectrum with an SPF value less than 15.
    It is important to note that the broad spectrum test required in 
this document captures both UVB and UVA protection for the 
effectiveness of a sunscreen product. The broad spectrum test is not 
limited to UVA wavelengths as was the case with the proposed test (see 
section VIII.B of this document). By requiring that a broad spectrum 
sunscreen provide both UVB and UVA protection in a pass/fail test, the 
amount of UVA protection for a sunscreen product that passes the test 
must increase as the SPF increases. For example, a Broad Spectrum SPF 
40 sunscreen product provides greater protection against both UVB and 
UVA than a Broad Spectrum SPF 20 sunscreen product. In contrast, an SPF 
40 sunscreen product that is not broad spectrum provides more UVB 
protection than a SPF 20 sunscreen product that is not broad spectrum, 
but may not provide more UVA protection.
    This proportionality between UVB and UVA protection is important 
because consumers have been accustomed to basing their purchase 
decision concerning protection level primarily on the SPF value, and 
only secondarily on indications of whether or not the sunscreen 
provides broad spectrum protection. For example, a consumer seeking 
lower protection may have chosen an SPF 15 sunscreen product, whereas a 
consumer seeking higher protection may have chosen an SPF 40 sunscreen 
product. By creating a clear and standardized ``yes/no'' indicator 
regarding broad spectrum protection, these final labeling requirements 
will enable consumers to make better and more informed purchase 
decisions by looking to see if a product has a ``Broad Spectrum SPF'' 
value on the label. Thus, the ultimate purchase decision would be based 
on the numerical value associated with the Broad Spectrum SPF 
statement. For products offering broad spectrum protection, the Broad 
Spectrum SPF value on the PDP will not only indicate the relative level 
of protection against UVB radiation but will also reflect the level of 
UVA protection, with increasing SPF values indicating greater 
protection against both UVA and UVB radiation. For broad spectrum 
products, linking the amount of UVA protection to the SPF value, is 
consistent with the approach taken in Europe (Ref. 7).
    For broad spectrum products, we are requiring the broad spectrum 
statement on the PDP to appear in combination with the SPF statement. 
For example, an SPF 40 sunscreen product which passes the broad 
spectrum test will be labeled ``Broad Spectrum SPF 40'' in a uniform 
font style, size, and color and with the same background color. This 
placement will help consumers recognize that the particular sunscreen 
product is broad spectrum in conjunction with the SPF value. As 
previously explained, the broad spectrum statement and SPF value 
together will provide a relative measure of both UVB and UVA 
protection. Combining the broad spectrum and SPF statements will help 
consumers become more aware of the importance of broad spectrum 
protection.
    Under the 2007 proposed rule, if an OTC sunscreen product was not 
tested for or did not protect against UVA radiation, the statement ``No 
UVA protection'' would have been required on the PDP (proposed 21 CFR 
352.50(b)(1)). Ten submissions argued against requiring this statement 
(Ref. 1). Some submissions argued that this statement is misleading 
because all sunscreen products provide some UVA protection. Submissions 
also stated that a negative statement is inconsistent with the OTC Drug 
Review because a drug should only describe the indications for which it 
is effective. Other submissions suggested that we should require all 
sunscreen products to provide UVA and UVB protection, making this 
statement unnecessary.
    We have concluded that the ``No UVA Protection'' statement is not 
necessary and could be misleading. Under this final rule, the labeling 
on the PDP of sunscreens no longer refers the type of UV radiation (UVA 
or UVB) protection offered; rather, products that pass the critical 
wavelength test in 201.327(j) are labeled with ``Broad Spectrum SPF'' 
values. Under this labeling, consumers who see ``UVA'' on the PDP, even 
if it is part of the statement ``No UVA Protection,'' may mistakenly 
believe that the product offers UVA protection. To eliminate this 
potential misunderstanding, we are not including the ``No UVA 
Protection'' statement on the PDP.
    In contrast to four submissions requesting that we make the UVA 
statement less prominent than the SPF statement, we are requiring the 
SPF and broad spectrum statements to be equally prominent on the PDP by 
appearing as a combined statement. The four submissions stated that 
they believe UVB radiation contributes more to skin cancer and 
photodamage than UVA radiation and argued that more prominence should 
be given to the SPF statement. However, none of the submissions 
included data to support this argument. Some submissions suggested that 
consumers are familiar with SPF ratings and that providing another 
rating with similar prominence may mislead and confuse consumers.
    It is well known that both UVA and UVB radiation contribute to 
photodamage and skin cancer (Refs. 6-7 and 10-12). Therefore, in our 
view, providing consumers with information about the effectiveness of a 
sunscreen product for UVA and UVB radiation protection is equally 
important. We are requiring that the broad spectrum statement be 
displayed in combination with the SPF statement. The two statements 
must not be interrupted with any graphics or text. In addition, the 
broad spectrum statement must be the same font style, size, and color 
as the SPF statement with the same background color. It is important 
for consumers to evaluate both statements when making a purchase 
decision. By requiring this information to be presented with identical 
prominence on the PDP, consumers should be able to quickly and easily 
identify sunscreen products that provide broad spectrum protection, as 
well as the SPF of all sunscreen products. While we are not requiring a 
negative statement on the

[[Page 35628]]

PDP of products that do not pass the critical wavelength test in new 
301.327(j), we caution that such products may be misbranded if they 
include statements regarding UVA protection; such statements may 
misleadingly imply that the product provides benefits that are similar 
or superior to those of products labeled with Broad Spectrum SPF 
values.

C. Water Resistance Statement

    In the 2007 sunscreen proposed rule (proposed 21 CFR 352.52), we 
allowed the PDP of OTC sunscreen products to contain the statement 
``water resistant'' if a sunscreen product was shown to retain the 
labeled SPF value after 40 minutes of water immersion, or ``very water 
resistant'' if a sunscreen product was shown to retain the labeled SPF 
value after 80 minutes of water immersion, according to the test in 
proposed 21 CFR 352.76. We simultaneously proposed that the ``Uses'' 
section of labeling (not the PDP) indicate specifically whether the 
product had been established to be water resistant for 40 minutes or 80 
minutes, and included specific directions addressing times for 
reapplication of each product, dependent on its level of water 
resistance (proposed 21 CFR 352.52(b)(1)(vii), (b)(1)(viii), (d)(2), 
and (d)(3); 72 FR 49070 at 49113). In this document, we are revising 
the PDP to contain the statement ``water resistant (40 minutes)'' or 
``water resistant (80 minutes)'' as determined by the water resistance 
test in new 21 CFR 201.327(i)(7). We are removing this information from 
the indications section of Drug Facts (section IV.B of this document). 
We continue to include directions based on the duration of water 
resistance established under the new water resistance test (section 
IV.D of this document).
    One submission stated that including information about water 
resistance in the indications section as well as in the directions 
section is ``redundant and confusing'' (Ref. 1). The submission 
recommended that we delete the indications statement. We agree with the 
submission. To eliminate redundancy and simplify the labeling for 
consumers, we are relocating the information formerly contained within 
the indication statement to the PDP.
    The content of the labeling as a whole is the same as that included 
in the 2007 proposed rule. However the proposed statement on the PDP 
did not clearly and accurately convey to consumers the difference 
between ``water resistant'' and ``very water resistant'' sunscreen 
products. For example, knowing that a sunscreen product is ``very water 
resistant'' does not give any indication of how much time a consumer 
can safely spend in the water. Under the 2007 proposed rule, a consumer 
would have had to read either the ``Uses'' or the ``Directions'' 
section of the Drug Facts label to determine the duration of water 
resistance for a sunscreen product (proposed 21 CFR 352.52(b)(1)(vii) 
and (b)(1)(viii) and proposed 21 CFR 352.52(d)(2) and (d)(3), 
respectively; 72 FR 49070 at 49113).
    Providing, on the PDP, specific information about the actual time 
(40 or 80 minutes) a consumer can expect a sunscreen product to retain 
its labeled SPF value is likely to be more helpful to consumers because 
the information is displayed in one place--on the PDP and not on 
different parts of the labeling. The revised statements ``water 
resistant (40 minutes)'' or ``water resistant (80 minutes)'' should 
make it clearer and easier for consumers to understand water resistance 
as part of their purchase decision. This water resistance information 
continues to be reinforced by information in the directions regarding 
reapplication.

D. UVB and UVA Educational Statement

    In the 2007 sunscreen proposed rule, we proposed that the following 
educational statement be included on the PDP of all OTC sunscreen 
products (proposed 21 CFR 352.50(c)): ``UV rays from the sun are made 
of UVB and UVA. It is important to protect against both UVB and UVA 
rays to prevent sunburn and other skin damage.''
    We received four submissions regarding the UVB and UVA educational 
statement in response to the 2007 sunscreen proposed rule (Ref. 1). The 
submissions made the following requests:
     Do not require the educational statement on the PDP or
     Combine the educational statement with the sun alert 
statement and include the combined statement in the ``Other 
Information'' section of the Drug Facts label.
    We considered including the proposed educational statement on the 
PDP. We concluded that this information is not critical for effective 
use of sunscreen products, particularly since we are no longer 
requiring other PDP statements to refer separately to UVA and UVB 
protection. An understanding that the sun produces ultraviolet (UV) 
rays or that there are two types of UV rays that reach the earth's 
surface is not necessary to ensure the safe and effective use of 
sunscreen products. The explanation of these concepts on sunscreen 
labeling is potentially confusing and could raise additional questions 
about their meaning. We could not determine a succinct educational 
statement that would not also be potentially misleading. Therefore, we 
have concluded that an educational statement should not be required on 
the PDP.
    As noted, submissions also requested that the proposed educational 
statement be combined with proposed sun alert, included in the proposed 
rule as a warning. In section IV.C of this document, we address 
submissions on the sun alert warning, and explain our decision to 
incorporate the information regarding the role of certain sunscreens in 
reducing the risk of skin cancer and early skin aging into a new 
indication and accompanying directions for sunscreens with Broad 
Spectrum SPF values of 15 or higher. We are retaining a modified 
warning to be included as the first warning on sunscreen products that 
are either not broad spectrum or that are broad spectrum with an SPF 
value less than 15. Because we are not requiring an educational 
statement on the PDP and are either eliminating or modifying the 
proposed sun alert warning, the request to combine these two statements 
is no longer relevant.

IV. Drug Facts Labeling

    In September 2004 (69 FR 53801), we delayed the May 16, 2005, 
implementation date for the Drug Facts final rule (21 CFR 201.66) for 
OTC sunscreen products until further notice). The Drug Facts final rule 
(21 CFR 201.66) establishes general labeling format and content 
requirements for all OTC drugs. With the additional exception of 
certain OTC drug products in ``convenience size'' packages (see 67 FR 
16304 at 16306 (April 5, 2002), other OTC drug products are already 
required to comply with 201.66. We delayed implementation of 201.66 for 
sunscreens so as to avoid the potential that sunscreen manufacturers 
would have to relabel their products twice within a short time period 
if a final rule specifying labeling for sunscreens published shortly 
after the original May 2005 implementation date for the general content 
and format requirements of the Drug Facts final rule. We published the 
notice of delay for OTC sunscreens' implementation of the Drug Facts 
final rule so that such products could simultaneously implement both 
the general labeling provisions of that rule and the specific labeling 
provisions for sunscreens when we published a sunscreen labeling final 
rule. We are now lifting the stay on the implementation of the Drug 
Facts final

[[Page 35629]]

rule for OTC sunscreen products. In this document, we are requiring the 
same implementation date for the regulations set forth in this labeling 
and testing final rule (21 CFR 201.327) and in the Drug Facts final 
rule (21 CFR 201.66) as applied to these sunscreen products.
    This action will benefit both consumers and manufacturers. 
Consumers will benefit by having sunscreen labeling presented in the 
Drug Facts format that they are familiar with. Manufacturers benefit 
because they will achieve compliance with two rules through one 
labeling revision (rather than following the more expensive course of 
making two labeling changes at two different times).
    In 2003 (68 FR 33362, June 4, 2003), we also stayed the part of the 
skin protectant monograph that describes GRASE combinations of skin 
protectant and sunscreen active ingredients (21 CFR 347.20(d)). Because 
this document addresses the labeling and testing of sunscreen products 
and not the GRASE status of individual sunscreen active ingredients, we 
are not lifting the stay of 21 CFR 347.20(d).
    This document requires much of the Drug Facts labeling included in 
the 2007 proposed rule. However, we have made several revisions to the 
proposed labeling. These revisions are discussed in detail throughout 
the remainder of this section. In addition, table 2 of this document 
summarizes these revisions as follows:

                             Table 2--Summary of Drug Facts Labeling Included in the 2007 Proposed Rule and This Final Rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
         Drug facts section                              2007 Proposed rule                                          This final rule
--------------------------------------------------------------------------------------------------------------------------------------------------------
Active Ingredients/Purpose.........  Name and amount of ingredient(s) followed by               Name and amount of ingredient(s) followed by
                                      ``sunscreen''                                              ``sunscreen.''
Uses...............................   [low, medium, high, or highest] UVB sunburn        for all sunscreen products: ``helps prevent
                                      protection                                                 sunburn.''
                                      [low, medium, high, or highest] UVA protection     Optional, for sunscreen products with Broad
                                      retains SPF after 80 minutes of activity in the    Spectrum SPF values of 15 or higher, ``if used as
                                      water                                                      directed with other sun protection measures (see
                                                                                                 Directions), decreases the risk of skin cancer and
                                                                                                 early skin aging caused by the sun.''
 
Warnings...........................  UV exposure from the sun increases the risk of skin        For sunscreen products that are not broad spectrum or
                                      cancer, premature skin aging, and other skin damage. It    for products that are broad spectrum with an SPF value
                                      is important to decrease UV exposure by limiting time in   less than 15, Skin Cancer/Skin Aging Alert [in bold
                                      the sun, wearing protective clothing, and using a          font]: Spending time in the sun increases your risk of
                                      sunscreen.                                                 skin cancer and early skin aging. This product has been
                                                                                                 shown only to help prevent sunburn, not [in bold font]
                                                                                                 skin cancer or early skin aging.
                                                                                                For all sunscreens:
                                     For external use only                                      For external use only
                                                                                                Do not use on damaged or broken skin
                                     Stop use and ask a doctor if skin rash occurs              Stop use and ask a doctor if rash occurs
                                     When using this product keep out of eyes. Rinse with       When using this product keep out of eyes. Rinse with
                                      water to remove.                                           water to remove.
                                     Keep out of reach of children. If swallowed, get medical   Keep out of reach of children. If swallowed, get medical
                                      help or contact a Poison Control Center right away.        help or contact a Poison Control Center right away.
Directions.........................  Non-Water Resistant Product                                Non-Water Resistant Product
                                      apply liberally [ minutes] before sun     apply liberally 15 minutes before sun exposure
                                      exposure                                                   use a water resistant sunscreen if swimming or
                                      reapply at least every 2 hours and after towel     sweating
                                      drying, swimming, or sweating                              reapply at least every 2 hours
                                      apply and reapply as directed to avoid lowering    children under 6 months: Ask a doctor
                                      protection
                                      children under 6 months: Ask a doctor
                                     Water Resistant Product                                    Water Resistant Product
                                      apply liberally [ minutes] before sun     apply liberally 15 minutes before sun exposure
                                      exposure
                                      reapply after 40 [or 80] minutes of swimming or    reapply:
                                      sweating and after towel drying. Otherwise, reapply at     after 40 [or 80] minutes of swimming or
                                      least every 2 hours.                                       sweating
                                      apply and reapply as directed to avoid lowering    immediately after towel drying
                                      protection                                                 at least every 2 hours
                                      children under 6 months: Ask a doctor              children under 6 months: Ask a doctor
                                     Water Resistant and Non-Water Resistant Products           Water Resistant and Non-Water Resistant Products
                                     No statement                                               For sunscreens with Broad Spectrum SPF values of 15 or
                                                                                                 higher:
                                                                                                 Sun Protection Measures [in bold font].
                                                                                                 Spending time in the sun increases your risk of skin
                                                                                                 cancer and early skin aging. To decrease this risk,
                                                                                                 regularly use a sunscreen with a Broad Spectrum SPF
                                                                                                 value of 15 or higher and other sun protection measures
                                                                                                 including:
                                                                                                 limit time in the sun, especially from 10 a.m.-
                                                                                                 2 p.m.
                                                                                                 wear long-sleeved shirts, pants, hats, and
                                                                                                 sunglasses.
Inactive Ingredients...............  List inactive ingredients in alphabetical order            List inactive ingredients in alphabetical order.
Other Information..................  No required statements                                      protect this product from excessive heat and
                                                                                                 direct sun.
Questions?.........................  No required statements                                     No required statements.
--------------------------------------------------------------------------------------------------------------------------------------------------------


[[Page 35630]]

A. Active Ingredients/Purpose

    We received one submission regarding the listing of active 
ingredients and one submission requesting that we provide specific 
details about what each ingredient does in the product (Ref. 1). One of 
these submission also requested that we require listing of the 
percentage of each active ingredient next to the ingredient name.
    We are not making any changes to the ``Active ingredients/Purpose'' 
section of the Drug Facts label. The general OTC labeling regulations 
specify that the ``quantity of each active ingredient per dosage unit'' 
be listed with the established name of each active ingredient (21 CFR 
201.66(c)(2)). Therefore, every sunscreen product is already required 
to include the active ingredient names followed by the percentage 
(weight per volume) in the ``Active ingredients/Purpose'' section, as 
requested by the first submission.
    We are not requiring specific details about what each ingredient 
does in the product. The function of each active ingredient in an OTC 
drug product is already required to be listed by 21 CFR 201.66(c)(3), 
which specifies that the ``Active ingredients/Purpose'' section of the 
label list the ``general pharmacologic categories or principal intended 
actions of each active ingredient.'' There is not currently a 
requirement to list the purpose of inactive ingredients on OTC drug 
labels. This information is not needed to safely and effectively use 
sunscreen products. Therefore, in this document, we are not requiring 
the purpose of inactive ingredients to be listed on sunscreen labels.

B. Uses

1. Indications Statements Proposed in the 2007 Proposed Rule
    The 2007 proposed rule included three indication statements under 
``Uses'' in Drug Facts:
    1. Level of UVB sunburn protection (proposed 21 CFR 
352.52(b)(1)(i)-(b)(1)(iv))
    2. Level of UVA protection (proposed 21 CFR 352.52(b)(1)(v) and 
(b)(1)(vi))
    3. Extent of water resistance (proposed 21 CFR 352.52(b)(1)(vii) 
and (b)(1)(viii))

The first statement would have appeared on all monograph sunscreen 
products. The second statement would only have appeared on monograph 
sunscreen products providing UVA protection. The third statement would 
only have appeared on monograph sunscreen products that are water 
resistant for either 40 or 80 minutes. We received numerous submissions 
from the public concerning these statements following publication of 
the 2007 proposed rule (Ref. 1).

    We are not requiring these indication statements in this final 
rule. Instead, all sunscreen products covered by this rule will be 
required to include the indication statement ``helps prevent sunburn,'' 
as required in the 1999 sunscreen final rule (64 FR 27666; new 21 CFR 
201.327(c)(1)). We are requiring this statement instead of the first 
proposed statement (level of UVB sunburn protection) because we agree 
with submissions arguing that sunburn is not caused solely by UVB 
radiation (Ref. 1). We also agree with submissions arguing that the SPF 
value by itself on the PDP informs consumers of the level of sunburn 
protection, so a separate description of the level of sunburn 
protection does not need to be included as an indication.
    In addition, sunscreen products covered by this rule that provide 
broad spectrum protection according to the test in new 21 CFR 
201.327(j) and have SPF values of 15 or higher, may include the 
following indication statement (new 21 CFR 201.327(c)(2)(i)): ``if used 
as directed with other sun protection measures (see Directions), 
decreases the risk of skin cancer and early skin aging caused by the 
sun.'' This statement replaces the second proposed indication 
statement. We are allowing this statement for certain sunscreens 
covered by this rule based on available clinical studies, the fact that 
UV radiation from the sun is harmful, and the scientific understanding 
that substantially limiting overall UVB and UVA exposure reduces the 
risk of skin cancer and early skin aging.
    As discussed in the remainder of this section of the document, it 
is critical that the indication statement regarding skin cancer and 
early skin aging includes information about using the products as 
directed and following other sun protection measures (listed under the 
heading Directions). We have concluded that the reference to other sun 
protection measures is necessary to ensure that the consumer's overall 
UV exposure is substantially decreased. A consumer who relies on the 
use of a sunscreen with Broad Spectrum SPF value of 15 or higher alone 
may not obtain a meaningful net decrease from the risk of skin cancer 
or early skin aging if, because he or she is wearing the sunscreen, the 
consumer spends more time in the sun and/or wears less protective 
clothing. In fact, reliance on sunscreen use alone, without also 
employing other sun protection measures, could actually result in an 
increase in the consumer's overall UV exposure. Therefore, if the 
indication statement regarding decreasing risk of skin cancer and early 
skin aging does not include the information about using the product as 
directed, which includes following other sun protection measures, the 
statement will be considered misleading (and thus make a sunscreen 
product misbranded) (new 21 CFR 201.327(c)(3)). Similarly, sunscreen 
products covered by the rule that provide broad spectrum with SPF 
values between 2 and 15 or do not provide broad spectrum protection 
should not state or imply that the use of a sunscreen product alone 
will reduce the risk of skin cancer or early skin aging. Doing so would 
cause the product to be misbranded.
    We are not including the third proposed indication statement 
(regarding water resistance) in this document. As already discussed, 
under this final rule, information about water resistance is included 
on the PDP, as well as under ``Directions'' in Drug Facts (see sections 
III.C and IV.D of this document). We conclude that information about 
the water resistance of a sunscreen product is more effectively and 
accurately presented on the PDP and as a direction than as an 
indication statement. The extent of water resistance informs a consumer 
about how long the SPF value is retained following water exposure and, 
therefore, how long an interval can elapse before reapplying the 
sunscreen product (40 or 80 minutes). In addition, the PDP requirements 
in this document include the time interval as part of the water 
resistance statement, so that consumers can readily distinguish between 
products on this basis when making purchasing decisions. Because we 
include water resistance on the PDP and under ``Directions,'' we are 
not including a separate indication statement about water resistance in 
this document.
2. Statement Regarding Skin Cancer and Early Skin Aging
a. Submissions Arguing For a Skin Cancer and Early Skin Aging 
Indication
    As already stated, in this final rule we have adopted, for the 
first time, an indication for skin cancer and early skin aging for 
sunscreen products covered by the rule that have Broad Spectrum SPF 
values of 15 or higher. In our 2007 proposed rule, we had included 
indication statements that indicated the degree of protection against 
both UVB and UVA radiation but that linked UVB protection only to 
sunburn prevention and did not expressly link UVA

[[Page 35631]]

protection to any specific health benefit (proposed 21 CFR 352.52(a)). 
At the same time, however, we had proposed both an educational 
statement on the PDP stating that UV rays from the sun are made of both 
UVB and UVA and that it is important to protect against both types of 
radiation to prevent sunburn and other skin damage (proposed 21 CFR 
352.50 (c)). We also proposed a ``sun alert'' statement as the first 
warning. This first warning read, ``UV exposure from the sun increases 
the risk of skin cancer, premature skin aging, and other skin damage. 
It is important to decrease UV exposure by limiting time in the sun, 
wearing protective clothing, and using a sunscreen.'' (proposed 21 CFR 
352.52(c)(1)).
    In response to our proposed rule, we received a total of 12 
submissions asking that we include a specific statement regarding 
reduction in risk of skin cancer and early skin aging as an indication 
for covered sunscreens (Ref. 1). The submissions asked that we allow an 
indication statement informing consumers that the regular, consistent, 
or continued use of a sunscreen product reduces or helps reduce the 
risk or chance of developing skin damage, early skin aging, and some 
types of skin cancer (Ref. 1). These submissions also supported our 
proposed requirement of a ``sun alert'' on the labeling to inform 
consumers of the need to limit time in the sun and wear protective 
clothing. The submissions came from sunscreen manufacturers and public 
health organizations including the American Academy of Dermatology, the 
American Cancer Society, and the Skin Cancer Foundation. Many of the 
submissions provided references to studies that they argued support the 
inclusion of this indication statement. One submission specifically 
requested that we allow an anti-aging claim (without mention of skin 
cancer), and one other submission argued that no sunscreen can claim to 
prevent cancer (Ref. 1). We received no new data to accompany these 
requests for a separate indication that the regular use of sunscreen 
decreases the risk of skin cancer and early skin aging. However, on 
reconsideration of the data reviewed prior to the 2007 proposed rule, 
we agree with the argument that the data underpinning our proposed 
education statement and warning are sufficient to support an 
appropriately qualified skin cancer and premature skin aging indication 
for one subset of sunscreens covered by this rule--those that have 
Broad Spectrum SPF values of 15 or higher. As a result, our final rule 
provides different labeling for these sunscreens than for sunscreens 
covered by the rule that are not broad spectrum or that provide broad 
spectrum with SPF values less than 15. In addition, we conclude that 
such an indication should not be included in the Warnings section of 
Drug Facts. We have concluded that, as proposed in 2007, the second 
sentence of the first warning (i.e., the ``Sun Alert'' warning) is an 
implied indication: ``It is important to decrease UV exposure by 
limiting time in the sun, wearing protective clothing, and using a 
sunscreen.'' Because it follows a warning that ``UV exposure from the 
sun increases the risk of skin cancer, premature skin aging, and other 
forms of skin damage,'' the second sentence implies that using any 
sunscreen, regardless of SPF value or broad spectrum protection, and 
following other sun protection measures will decrease the risks of skin 
cancer, early skin aging, and other consequences of UV exposure to the 
sun. We have concluded, based on a reconsideration of data previously 
reviewed in the 2007 proposed rule, that, if consumers use broad 
spectrum sunscreens with SPF values of 15 or higher and follow other 
sun protection measures, they can reduce their risk of skin cancer and 
early skin aging. For these products, we agree with the public 
submissions that this information is most appropriately placed as an 
indication (i.e., under Uses) with a reference to the need to use the 
product as directed with other sun protection measures. For these 
products, we include under the heading Directions, specific reference 
not only to regularly use sunscreens with Broad Spectrum SPF values of 
15 or higher (the subset of sunscreens for which the indication is 
allowed) but also to employ the other listed sun protection measures 
listed under Directions. For sunscreen products covered by this rule 
that are not Broad Spectrum or that are broad spectrum with an SPF 
value less than 15, however, we conclude that existing data are 
insufficient to support an indication for reducing risk of skin cancer 
or early skin aging. In the sections that follow, we explain the 
specific scientific basis for our conclusion, as well as explain our 
rationale for the specific framing of the labeling, as included in the 
final rule, for both subsets of the sunscreens covered by the final 
rule--those that have Broad Spectrum SPF values of 15 or higher and 
those that do not have Broad Spectrum or that are Broad spectrum with 
SPF values less than 15.
b. Limiting Overall UV Exposure Reduces Risk of Skin Cancer and Early 
Skin Aging
    For drugs subject to OTC monographs, like sunscreen products, 
indication statements about the effectiveness of the drug products must 
be supported with scientific data (21 CFR 330.10(a)(4)(ii)). In order 
for an OTC drug to be considered generally recognized as effective 
(GRAE), there must be a reasonable expectation that, in a given 
proportion of the target population, the drug will provide clinically 
significant relief of the type claimed (21 CFR 330.14(a)(4)(ii)). Based 
on the available data concerning the harmful effects of UV radiation 
and sunscreen UV protection, we have concluded that sunscreens, in 
conjunction with the critical behavioral steps of limiting time in the 
sun particularly during the midday hours and wearing protective 
clothing (long sleeve shirt, pants, hat, and sunglasses), provide 
``clinically significant relief'' in reducing the risk of skin cancer 
and early skin aging. Based on the available data, we have limited this 
claim to broad spectrum sunscreen products with an SPF value of 15 or 
higher.
    UV radiation from the sun has been associated with nonmelanoma skin 
cancers since 1927 and with melanomas since 1952 (Ref. 13). It is 
estimated that as much as 90 percent of melanomas and nonmelanomas are 
caused by sun exposure (Ref. 5). In 1992, the International Agency for 
Research on Cancer (IARC), under the auspices of the World Health 
Organization, identified UV radiation as a human carcinogen \3\ (Ref. 
14). More recently, broad spectrum UV radiation was listed as a human 
carcinogen in the National Toxicology Program's 11th Report on 
Carcinogens issued in 2005 (Ref. 15). It is important to note that this 
report indicates that UVB and UVA radiation across the spectrum are 
known human carcinogens, but that either UVB radiation alone or UVA 
radiation alone is ``reasonably anticipated to be a human carcinogen.'' 
This classification is due to the fact that the exact wavelengths of UV 
radiation that cause different harmful effects (e.g., DNA damage or 
loss of skin elasticity) have not yet been identified. It is clear, 
though, that broad spectrum UV radiation causes skin cancer. Broad 
spectrum UV radiation has also been shown to cause other types of skin 
damage, including early skin aging (Refs. 6 and 16). Therefore, we 
agree

[[Page 35632]]

with the principle that a reduction, of sufficient magnitude, in broad 
spectrum UV exposure should reduce the risk of harmful effects to the 
skin, including skin cancer and early skin aging.
---------------------------------------------------------------------------

    \3\ A carcinogen is anything that is known to cause the 
development of cancer. UV radiation is known to cause skin cancer.
---------------------------------------------------------------------------

    Broad spectrum sunscreens, by absorbing UVA and UVB radiation, 
decrease consumer exposure to both types of UV radiation from the sun 
that reach the earth's surface. Other critical behavioral steps, such 
as limiting time in the sun and wearing protective clothing, also 
decrease consumer exposure to UVA and UVB radiation. After considering 
the submissions and other available data, we have concluded that a 
claim for the reduction in risk of skin cancer and early skin aging is 
appropriate for certain sunscreen products, when the claim also 
includes the requirement that consumers use the product as directed and 
the Directions specify other sun protection measures be followed (see 
section IV.D of this document). We are basing this claim on the 
scientific understanding of the harm from UVA and UVB radiation and the 
absorption and/or reflection of that UV radiation by broad spectrum 
sunscreens, as well as data from studies concerning sunscreen use and 
the development of skin cancer or precursors of skin cancer (section 
IV.B.2.c of this document).
    For a sunscreen to be effective (i.e., provide ``clinically 
significant relief'') in reducing the risk of skin cancer and early 
skin aging, consumers must not increase their overall exposure to UV 
radiation by overreliance on sunscreen use. Other behavioral factors 
could account for such an increase, such as the amount of time spent in 
the sun and the use of protective clothing. If consumers rely on 
sunscreen use to spend more time in the sun and/or to wear less 
protective clothing, then consumers could actually increase their 
overall UV exposure, which would eliminate the effectiveness of 
sunscreen use in reducing the risk of skin cancer and early skin aging.
    To illustrate this point, it is helpful to consider what has been 
termed the ``compensation hypothesis.'' As we noted in the 2007 
proposed rule, the compensation hypothesis states that consumers who 
wear high SPF sunscreens generally spend more time in the sun and/or 
wear less protective clothing (72 FR 49070 at 49086). If the hypothesis 
is true, consumers would not reduce their risk of skin cancer or early 
skin aging because their overall UV exposure increases, even though a 
properly applied (and reapplied) sunscreen absorbs UV radiation and 
helps prevent sunburn. We cited two retrospective studies which support 
the compensation hypothesis in the 2007 proposed rule (72 FR 49070 at 
49086). Reynolds et al. published a study in 1996 finding, in a study 
of 509 sixth-graders, that adolescents who used sunscreen on both 
Saturday and Sunday of a Labor Day weekend spent significantly more 
time in the sun than those who used sunscreen only one day or not at 
all (Ref. 17). In the second study, parents of 503 children, aged less 
than 2 to 12 years, were surveyed as to parental attitudes about their 
children's sun exposure (Ref. 18). The authors reported that 
``sunscreen use in children was significantly associated with longer 
duration of sun exposure'' (Ref. 18).
    Increased overall UV exposure might, in fact, increase the risk of 
skin cancer and early skin aging, despite the proper use of sunscreens. 
Likewise, if consumers limit time in the sun, especially during midday, 
and wear more protective clothing (such as broad brimmed hats, long 
pants, and long sleeve shirts) while outside, but do not use sunscreens 
for areas of the skin exposed to the sun (such as parts of face and 
neck), then the consumer may not decrease the risk of skin cancer and 
early skin aging for sun-exposed areas. For these reasons, for products 
that are entitled to include an indication for reducing the risk of 
skin cancer and early skin aging, we continue to direct consumers to 
follow a comprehensive sun protection program that includes use of 
sunscreens with Broad Spectrum SPF values of 15 or higher, limiting 
time in the sun, and wearing protective clothing, similar to the sun 
protection measures discussed in the 2007 proposed rule (72 FR 49070 at 
49089). Nearly identical multi-step behavioral sun protection programs 
are advocated by a number of medical and public health organizations, 
including the American Academy of Dermatology, the Skin Cancer 
Foundation, and the American Cancer Society.
    We have concluded that a comprehensive sun protection approach is 
critical to ensure that consumers who are seeking to obtain a reduction 
in the risk of skin cancer and early skin aging limit their overall sun 
exposure. Without the reduction in consumers' overall UV exposure, even 
a sunscreen with Broad Spectrum SPF value of 15 or higher may not be 
effective in decreasing the risk of skin cancer and early skin aging. 
As discussed below, the available clinical studies do not control for 
these behavioral factors and, therefore, do not demonstrate that even 
this subset of sunscreens alone reduce the risk of skin cancer and 
early skin aging. However, based on the scientific understanding of the 
harm from UV exposure and our assessment of the study data, we have 
concluded that if consumers use sunscreens with Broad Spectrum SPF 
values of 15 or higher, limit time in the sun especially during the 
midday hours, and wear protective clothing when exposed to the sun, the 
resulting reduction in overall UV exposure will reduce the risk of skin 
cancer and early skin aging. Therefore, there is sufficient evidence of 
``clinically significant relief'' to justify the indication and related 
directions for this subset of products, as set forth in the rule. 
However, we conclude that the omission of prominent information in the 
indication regarding the need for other sun protection measures would 
misbrand the product, as would the omission of the associated direction 
specifying these measures. Indeed, it would suggest a different 
indication than that which available evidence supports. Consequently, 
we have included in this final rule a new provision indicating that 
``Any labeling or promotional materials that suggest or imply that the 
use, alone, of any sunscreen reduces the risk of or prevents skin 
cancer or early skin aging will cause the product to be misbranded 
under section 502 of the FD&C Act (21 U.S.C. 352).'' (new 21 CFR 
201.327(c)(3)).
c. Available Scientific Data
    We are not aware of any data other than what we reviewed in the 
2007 proposed rule that evaluate the effectiveness of sunscreens in 
reducing the risk of skin cancer or early skin aging for healthy 
subjects. One more recent study, published in 2009, found that regular 
use of Broad Spectrum SPF 50+ sunscreen ``may prevent'' the development 
of actinic keratoses and non-melanoma skin cancer in immune-compromised 
organ transplant recipients (Ref. 19). We have not relied on this study 
in reaching our conclusions regarding OTC sunscreens, because we do not 
consider the immune-compromised study population to be representative 
of the general population.
    We have re-evaluated the data originally reviewed in preparing the 
2007 proposed rule to determine whether those data support allowing the 
indication for all sunscreen products or only for certain sunscreen 
products. Based on our re-evaluation, we have concluded that the data 
is supportive of an indication for broad spectrum sunscreens having SPF 
values of at least 15. Further, we have determined that, while the 
existing evidence does not support a claim for the use of any sunscreen 
alone, it does support an indication that the combination of using

[[Page 35633]]

a sunscreen with Broad Spectrum SPF value of 15 or higher along with 
other sun protection measures, reduces the risk of skin cancer and 
early skin aging, consistent with other positions in the 2007 proposed 
rule (72 FR 49070 at 49087 through 49090).
    To date, there are no clinical studies demonstrating that use of 
any sunscreen alone can prevent skin cancer. There are two prospective 
\4\ studies that directly examine the role of sunscreen products in 
preventing skin cancer. Although it did not show any difference in 
primary endpoints, a large 1999 study conducted in Australia 
demonstrated that people who applied a Broad Spectrum SPF 15 sunscreen 
product on a daily basis over a 4.5 year period had a lower overall 
incidence of one type of skin cancer, squamous cell carcinoma, on the 
head, neck, arms, and forearms than study participants who did not 
apply sunscreen (28 cases in the broad spectrum sunscreen group vs. 46 
cases in the group not using broad spectrum sunscreen) (Ref. 20). In an 
extension of that study, van der Pols et al. evaluated the same 
population of subjects over an additional 8 years, and found that the 
sunscreen users continued to have a statistically significant lower 
incidence of squamous cell carcinoma over the entire 12.5 year period 
(Ref. 21). Neither study found that daily sunscreen use had any 
measurable effect on the most common form of skin cancer, basal cell 
carcinoma. Further, we are not aware of any studies examining the 
effect of sunscreen use on the development of melanoma, which is the 
deadliest form of skin cancer.
---------------------------------------------------------------------------

    \4\ A prospective study is designed to study subjects under pre-
specified conditions. These studies differ from retrospective 
studies that try to prove hypotheses by assessing past experiences. 
Generally, prospective studies are superior to retrospective studies 
in demonstrating drug effectiveness.
---------------------------------------------------------------------------

    Although data from clinical studies addressing the specific end 
points of cancer is limited, some prospective studies have evaluated 
the effects of regular sunscreen use on the development of surrogate 
skin lesions that can be precursors to cancer: actinic keratoses and 
melanocytic nevi. A small percentage of actinic keratoses progress to 
squamous cell carcinomas (Ref. 22). At least four studies have 
demonstrated that the number of actinic keratoses is lower for 
individuals regularly using sunscreens with Broad Spectrum SPF values 
of 15 or higher (Refs. 23 through 26). We are not aware of any studies 
examining the potential effects on surrogate skin lesions of sunscreens 
that either are not broad spectrum or are broad spectrum with SPF 
values less than 15.
    Two prospective studies have shown that regular use of a Broad 
Spectrum SPF 30 sunscreen reduces the risk of developing melanocytic 
nevi, which can progress into melanomas (Ref. 22). In a 2000 study, 
Gallagher et al. examined the formation of new melanocytic nevi in 393 
Canadian school children. The group of children given Broad Spectrum 
SPF 30 sunscreen product had fewer new nevi over the course of the 
three year study than did children not given sunscreen products or 
advice on sunscreen use (Ref. 27). The difference was small (24 v. 28 
nevi, respectively), but statistically significant (p = 0.048). In a 
follow-up study published in 2005, Lee et al. evaluated the same group 
of children for differences in melanocytic nevi by location on the body 
and demographic factors (Ref. 28). These investigators found that the 
sunscreen group had significantly fewer new nevi on the trunk than the 
control group (p = 0.05).
    With respect to the role of sunscreen products in decreasing the 
risk of early skin aging, we are aware of only indirect evidence that 
sunscreen use decreases early skin aging. One recent study demonstrated 
that a broad spectrum sunscreen product can reduce the extent of solar 
UV-induced damage to factors associated with early skin aging even when 
the SPF value is less than 10 (Ref. 29). Although this study was small, 
evaluating only 12 Caucasian subjects, it shows the importance of broad 
spectrum protection. These findings have been corroborated in a large 
number of studies using broad spectrum sunscreens with SPF values 
ranging from 19 to 50, as reported by Fourtanier et al. in two recent 
reviews (Refs. 10 and 30).
    Neither those studies evaluating the long term effect of regular 
sunscreen use on the development of skin cancer and early skin aging 
nor those evaluating the long term effect of sunscreen use on surrogate 
markers for these conditions were adequately controlled. Such studies, 
which must take place over many years, make adequate controls extremely 
difficult, if not impossible to implement. For example, one cannot 
control for time and duration of exposure, application and re-
application amounts, or use of supplemental behavioral measures such as 
wearing protective clothing for a study which takes place over several 
years.
    Despite their limitation, the results of the short-term 
effectiveness studies are consistent with our understanding that 
measures which significantly reduce UV exposure decrease the risk of 
skin cancer and early skin aging. UVA and UVB radiation is the only 
known external risk factor for skin cancer and early skin aging. 
Therefore, measures that significantly reduce both UVA and UVB exposure 
should decrease the risk of skin cancer and early skin aging. Based on 
this understanding, limiting time in the sun, wearing protective 
clothing and using a broad spectrum sunscreen with an SPF value of 15 
or higher should decrease the risk of skin cancer and early skin aging. 
Using a broad spectrum sunscreen with an SPF value of 15 or higher 
ensures adequate breadth and magnitude of UVA and UVB protection. For 
these products, the broad spectrum test measures breadth and SPF test 
measures magnitude of UV protection. Consistent with this scientific 
principle, the short-term effectiveness studies demonstrate a decrease 
in the development of surrogates for skin cancer and early skin aging. 
Thus, we have concluded that the available evidence supports our 
finding that sunscreen products, in conjunction with limiting time in 
the sun and wearing protective clothing, reduce the risk of developing 
skin cancer or early skin aging.
d. Indication Limited to Covered Sunscreens With Broad Spectrum SPF 
Values of 15 or Higher
    In light of the submissions requesting that we reframe our labeling 
information regarding sunscreen use and reduced risk of skin cancer and 
premature skin aging as an indication, we re-evaluated skin cancer and 
aging studies discussed in the 2007 proposed rule to determine whether 
the skin cancer and early skin aging indication should apply to all 
sunscreen products or be limited to certain sunscreen products. 
Available data support this indication only for broad spectrum 
sunscreens with SPF values of 15 or higher. Several reports have 
indicated that UV-induced skin damage associated with both skin cancer 
and early skin aging can be reduced by the use of broad spectrum 
sunscreens (Refs. 10 and 29 through 31). In a direct comparison of a 
broad spectrum sunscreen and a non-broad spectrum sunscreen with the 
same SPF, Moyal and Fourtanier found that the broad spectrum sunscreen 
provided significantly better protection from UV radiation-induced 
immunosuppression, a factor associated with both skin cancer and early 
skin aging (Ref. 32). Furthermore, the National Toxicology Program 
classified broad spectrum UV radiation as a known human carcinogen 
because it is not clear which UVB and/or UVA wavelengths contribute to 
the development of cancer (Ref. 15).

[[Page 35634]]

Therefore, available data indicate that a broad spectrum sunscreen is 
necessary to reduce the risk of skin cancer. Likewise, we do not know 
which UVB and/or UVA wavelengths contribute to early skin aging. 
Therefore, it is reasonable to conclude that reducing the risk of early 
skin aging also requires a broad spectrum sunscreen (in conjunction 
with limiting time in the sun and wearing protective clothing).
    With regard to SPF value, the available study data concerning the 
use of sunscreens in reducing the risk of skin cancer is based on 
products with SPF values of 15 or higher. The sunscreen product used in 
the 1999 Australian study on skin cancer (squamous cell and basal cell 
carcinomas) had a Broad Spectrum SPF value of 16, and those that were 
found to reduce actinic keratoses and nevi had SPF values ranging from 
16 to 46. The studies on early skin aging make it difficult to know for 
certain whether Broad Spectrum SPF values of 15 or higher are necessary 
to reduce the risk of early skin aging. However, we conclude that the 
data regarding the minimum sunscreen protection necessary to reduce the 
risk of skin cancer can be extrapolated to early skin aging. In many 
ways, the biological processes that take place in response to UV 
radiation are similar for both conditions. For both skin cancer and 
early skin aging, UV radiation causes damage in the skin that is not 
completely repaired and leads to cancer, fine lines, wrinkles, etc. 
Because the supporting data for a skin cancer claim are based on 
products with SPF values of 15 or higher, we are only allowing the skin 
cancer and early skin aging claim for covered sunscreen products that 
are broad spectrum and have SPF values of at least 15. This rule does 
not preclude approval of a new drug application including an indication 
for reduction in risk of skin cancer and early skin aging for any 
sunscreen product. To be approved, such an application must be 
supported by the submission of adequate data. This rule also does not 
preclude future amendment of the sunscreen monograph in 21 CFR part 
352, if additional data are provided to support a similar indication 
for other types of sunscreens.
e. Precedent for an Indication Statement That Includes Behavior 
Modification
    There is at least one other OTC drug product with an indication 
statement that describes not only the drug's intended effect but also 
one or more behavioral measures to ensure the effect. The indication 
statement on the weight loss aid orlistat states that the product is to 
be used ``for weight loss in overweight adults, 18 years and older, 
when used along with a reduced-calorie and low-fat diet'' (Ref. 33). 
The behavioral measure of reduced caloric intake is necessary for 
consumers to experience weight loss. A low-fat diet is necessary for 
consumers to avoid the undesirable side effect of diarrhea caused by 
consuming a high-fat diet while taking orlistat.
    The need to include reduced caloric intake as part of the 
indication statement for orlistat is similar to the need for including 
the use of other sun protection measures as part of the indication 
statement for sunscreens. Orlistat increases the likelihood of weight 
loss by preventing fat from being absorbed as food is digested in the 
stomach and intestines. If consumers take orlistat and decrease their 
caloric intake, they increase the likelihood of losing weight. However, 
if consumers increase their caloric intake while taking orlistat, they 
are less likely to lose weight. Orlistat's effect of preventing fat 
absorption could be offset by the high number of calories being eaten. 
Similarly, the reduction in UV exposure afforded by use of broad 
spectrum sunscreens with SPF values of 15 or higher can be offset if 
consumers increase their UV exposure by spending more time in the sun 
and/or wearing less protective clothing. This increased overall 
exposure could eliminate the effectiveness of sunscreen use in reducing 
the risk of skin cancer and early skin aging.
    The labeling of prescription cholesterol-lowering drug products 
(i.e., statins) follows a similar principle by emphasizing that 
reduction of cholesterol levels requires not only use of the drug 
product but also a healthy diet. The National Institutes of Health 
(NIH) specifies therapeutic lifestyle changes that can be followed to 
lower levels of cholesterol in the blood (Ref. 34). These changes 
include following a diet restricted in saturated fat and cholesterol, 
exercising regularly, and managing weight. Used in conjunction with 
cholesterol reducing drugs (currently available only by prescription), 
these lifestyle changes improve the chance of effectively treating high 
cholesterol levels.
    Prescription cholesterol-lowering drug products include the 
behavioral step of following a low fat diet in the indication statement 
(Ref. 35). The body produces cholesterol, which the drug product 
inhibits to produce the desired drug effect of lowering cholesterol 
being made by the body. However, the total cholesterol circulating in 
the blood reflects cholesterol made by the body plus cholesterol 
absorbed from foods containing fats. Therefore, if consumers use a 
statin and minimize the amounts of food containing fats in their diet, 
then they will reduce the total cholesterol level in the blood. 
However, if consumers do not minimize the amounts of food containing 
fats in their diet, they may not reduce the total cholesterol in the 
blood. The decreased cholesterol production in the body caused by the 
statin may not be significant compared to the high amount of 
cholesterol derived from food eaten by consumers.
    In the same way that regularly taking an OTC weight loss aid or a 
prescription cholesterol-lowering drug product without also following a 
healthy diet may not result in the intended health effect, use of a 
sunscreen with Broad Spectrum SPF value of 15 or higher without also 
limiting time in the sun and covering sun-exposed areas may not result 
in a net reduction in the risk of developing skin cancer or early skin 
aging. For this reason, we are requiring that the indication statement 
allowed on sunscreens with Broad Spectrum SPF values of 15 or higher 
include all parts of the sun protection program and not suggest or 
imply that use of a sunscreen alone reduces the risk of skin cancer or 
early skin aging.

C. Warnings

    We received submissions requesting that we revise warnings included 
in the 2007 proposed rule and that we add new warnings not included in 
the 2007 proposed rule (Ref. 1). In section IV.C.1 of this document, we 
discuss one new and one revised warning included in this final rule. We 
are adding the new warning ``Do not use on damaged or broken skin'' 
(new 21 CFR 201.327(d)(1)). We are revising the warning about skin rash 
(proposed 21 CFR 352.52(c)(3)): ``Stop use and ask a doctor if skin 
rash occurs'' to read ``Stop use and ask a doctor if rash occurs.''
    In section IV.C.2 of this document, we discuss our revision to the 
proposed ``Sun Alert'' warning. Under this final rule, the warning 
proposed for all monograph sunscreens is replaced with an optional 
indication and required direction on covered sunscreens with Broad 
Spectrum SPF values of 15 or higher, while covered sunscreens that are 
broad spectrum with SPF values less than 15 or that do not provide 
broad spectrum protection will bear a revised warning, called the 
``Skin Cancer/Skin Aging Alert.'' (new 21 CFR 201.327(d)(2)).
    In section IV.C.3 of this document, we discuss three new warnings 
that were requested in submissions, but are not

[[Page 35635]]

being included in this document. Submissions argued that we should add 
warnings that the regular use of sunscreen products may cause vitamin D 
deficiency and may reduce the photoprotective effects of tanning. We 
also considered adding a warning concerning sunscreen products 
containing alpha hydroxy acids (AHAs). We are not adding any of these 
warnings because the available data do not support the need for these 
warnings.
    In summary, this document requires the following warnings on all 
covered OTC sunscreen products (new 21 CFR 201.327(d)):
     ``Do not use on damaged or broken skin''
     ``Stop use and ask a doctor if rash occurs''
     ``When using this product keep out of eyes. Rinse with 
water to remove.''

For all covered sunscreen products that either are not broad spectrum 
or are broad spectrum with SPF values less than 15, this final rule 
also requires a ``Skin Cancer/Skin Aging Alert'' as the first statement 
under the heading Warnings. In addition to these warnings, all 
sunscreen products are required to include the ``external use'' and 
``keep out of reach of children'' warning statements required on all 
topical OTC drug products (21 CFR 201.66(c)(5)(i) and (c)(5)(x)).
1. New and Revised Warnings for Damaged or Broken Skin and Rash
    The new warning that we are requiring on all covered sunscreen drug 
products reads, ``do not use on damaged or broken skin.'' We require 
this warning or a similar warning for other topical OTC drug products:
     Acne treatments (21 CFR 333.350(c)(3))
     Skin protectants (21 CFR 347.50(c)(6))
     Antiperspirants (21 CFR 350.50(c)(1))

The safety data for these ingredients are based on application to 
intact (i.e., unbroken or undamaged) skin. We do not have data of the 
safe use of these ingredients if the skin is not intact. For the same 
reason, the warning appears on sunscreen products marketed under new 
drug applications (NDAs).\5\ Therefore, in this document, we are 
requiring this warning for all covered OTC sunscreen products, which 
are marketed without approved applications (new 21 CFR 
201.327(d)(1)(i)).
---------------------------------------------------------------------------

    \5\ NDAs 21-501, 21-502, 21-471, and 22-009.
---------------------------------------------------------------------------

    In addition to the new warning, we are revising the warning in 
proposed 21 CFR 352.52(c)(3): ``Stop use and ask a doctor if skin rash 
occurs.'' We are deleting the word ``skin'' so that the new warning 
reads: ``Stop use and ask a doctor if rash occurs'' (new 21 CFR 
201.327(d)(1)(iii)). We received two submissions arguing that the word 
''skin'' is unnecessary in this warning because every rash is a skin 
rash (Ref. 1). We agree and are removing the word to make the warning 
more concise. Consumers will likely understand the warning without the 
word ``skin.''
2. Revision of the Proposed ``Sun Alert'' Warning
    In 2007, we proposed a warning, based on the ``Sun Alert'' 
statement cited in the 1999 stayed sunscreen final rule (64 FR 27666 at 
27679), as the first statement under the heading Warnings for all 
monograph sunscreen products regardless of SPF value or broad spectrum 
protection (proposed 21 CFR 352.52(c)(1)). As proposed, this warning 
would have stated, ``UV exposure from the sun increases the risk of 
skin cancer, premature skin aging, and other skin damage. It is 
important to decrease UV exposure by limiting time in the sun, wearing 
protective clothing, and using a sunscreen.'' Submissions regarding 
this proposed warning are discussed in section IV.B.2 of this document. 
As noted there, we agree that, as proposed, this warning included an 
implied indication that all sunscreens reduce the risk of skin cancer 
and skin aging. Under this final rule, we are no longer requiring a 
``Sun Alert'' or similar warning on broad spectrum sunscreens with SPF 
values of 15 or higher covered by the rule. This decision is based on 
our re-evaluation of the available scientific data. We are now 
permitting an indication stating that, used as directed with other sun 
protection measures, these sunscreens reduce the risk of skin cancer 
and premature skin aging (new 21 CFR 201.327 (c)(2)).
    For these products we are also requiring a new direction statement 
(new 21 CFR 201.327(e)(1)(iv)). The direction states:

    Sun Protection Measures. [in bold font] Spending time in the sun 
increases your risk of skin cancer and early skin aging. To decrease 
this risk, regularly use a sunscreen with a Broad Spectrum SPF of 15 
or higher and other sun protection measures including: [bullet] 
limit time in the sun, especially from 10 a.m.-2 p.m. [bullet] wear 
long-sleeved shirts, pants, hats, and sunglasses

    We have concluded that information about decreasing sun exposure 
and wearing protective clothing is more appropriate in ``Directions'' 
than in ``Warnings.'' These measures, in addition to use of a sunscreen 
with Broad Spectrum SPF value of 15 or higher, are necessary for the 
consumers' sun protection as part of a comprehensive program.
    For covered sunscreen products that do not provide broad spectrum 
protection or those that do provide broad spectrum protection with SPF 
values less than 15, we conclude that a warning regarding the risks of 
skin cancer and skin aging remains necessary. In light of comments 
received on the ``Sun Alert'' warning proposed in 2007, however, we are 
revising the text to read as follows: ``Skin Cancer/Skin Aging Alert 
[in bold font]: Spending time in the sun increases your risk of skin 
cancer and early skin aging. This product has been shown only to help 
prevent sunburn, not [in bold font] skin cancer or early skin aging.'' 
(new 21 CFR 201.327(d)(2). The title ``Skin Cancer/Skin Aging Alert'' 
more accurately and specifically conveys the nature of the warning that 
follows than the proposed ``Sun Alert'' warning, particularly since the 
products that will bear this statement are indicated to help prevent 
sunburn, one consequence of sun exposure. The first sentence of this 
warning is a factual statement similar in content to the opening 
statement of the warning proposed in 2007. Like the proposed ``Sun 
Alert'' warning, this statement alerts consumers to risks they continue 
to incur from sun exposure, the conditions under which they will make 
use of the product. The second sentence clarifies for users the limits 
on the benefits that the product in hand has been established to 
provide, specifying that these products have been shown to help prevent 
sunburn but have not been shown to reduce the risk of skin cancer or 
early skin aging. Inclusion of this warning is critical to help ensure 
that consumers do not mistakenly conclude that all sunscreens have been 
demonstrated to provide the same benefits. It will reinforce the 
distinction between sunscreens indicated only for preventing sunburn 
(those that have broad spectrum with SPF values below 15 or that are 
not broad spectrum) and sunscreens that have also been shown to reduce 
the risk of skin cancer and early skin aging when used as directed with 
other sun protection measures (those with Broad Spectrum SPF values of 
15 or higher). This warning serves a similar purpose to one required on 
cosmetic suntanning preparations that do not contain a sunscreen 
ingredient, which likewise is intended to assist consumers in 
distinguishing among products that they might otherwise confuse. (See 
21 CFR 740.19).

[[Page 35636]]

3. Warnings Requested in Submissions But Not Included in This Final 
Rule
    We considered adding the following three warnings:
     Sunscreens may reduce the photoprotective effects of 
tanning
     Increased sun sensitivity caused by alpha hydroxy acids 
(AHAs) in sunscreen products
     Regular use of sunscreen products may cause vitamin D 
deficiency

However, as discussed in this section of the document, we conclude that 
these warnings are not needed for the safe and effective use of 
sunscreen products.

    We received a submission arguing that we should require the 
following warning on all OTC sunscreen products containing UVA-
protective active ingredients (Ref. 1): ``The use of this product will 
prevent the development of photo-protective facultative pigmentation, 
a.k.a., a tan.'' The submission implies that UVA protection is not only 
unnecessary but harmful to consumers. No data were included in the 
submission.
    We agree that tanning caused by UVA radiation offers some 
protection against sunburn. However, tanning, particularly when 
attributable to prolonged exposure to UVA radiation in tanning beds or 
booths, may also have harmful effects on the skin (Refs. 36 and 37). In 
addition, one study suggests that the protective effects of tanning are 
small, as a tan only appears to provide an SPF value of approximately 4 
(Ref. 36). As stated in the 2007 proposed rule (72 FR 49070 at 49083), 
we do not know which UVA wavelengths cause specific types of damage 
(e.g., skin cancer or early skin aging). We continue to assert, 
however, that protection against UVA radiation is important for 
consumers' health (72 FR 49070 at 49083). We have concluded that the 
warning suggested in the submission is not in the best interest of 
public health because the warning discourages consumers from using 
broad spectrum sunscreen products. Therefore, we are not requiring any 
warning related to tanning.
    We are not adding any additional warnings to sunscreen products 
containing AHAs. In the 2007 proposed rule, we requested comment on the 
need for additional warnings or directions on sunscreen products 
combined with AHAs (72 FR 49070 at 49110). We made this request in 
response to a 2005 guidance that we issued for cosmetic products 
containing alpha hydroxy acids (70 FR 1721, January 10, 2005). The 
guidance recommends the following warning be included on cosmetic 
products containing alpha hydroxy acids: ``Sunburn Alert: This product 
contains an alpha hydroxy acid (AHA) that may increase your skin's 
sensitivity to the sun and particularly the possibility of sunburn. Use 
a sunscreen and limit sun exposure while using this product and for a 
week afterwards.''
    Many cosmetic products containing alpha hydroxy acids also contain 
sunscreens because the sunscreen helps protect the skin made sensitive 
to the sun by the alpha hydroxy acids. The guidance does not address 
products combining alpha hydroxy acids and sunscreens.
    Two submissions stated that additional warnings are not necessary 
on these products (Ref. 1). We agree with these submissions. We 
considered added a warning or other labeling to inform consumers that 
AHAs contained in some sunscreen products may make the consumer more 
likely to sunburn. However, the sunscreen component of such products 
would, in fact, protect consumers from sunburn. Furthermore, we have 
concluded that the addition of sunscreen active ingredients to AHA-
containing cosmetic products provides valuable UV protection for 
consumers. Therefore, at this time, we have concluded that a warning 
about AHA is not necessary on OTC sunscreen products.
    The other new warning requested in submissions relates to vitamin D 
deficiency. We received six submissions arguing that consumers should 
be warned that frequent sunscreen use may result in vitamin D 
deficiency (Ref. 1). The submissions cite articles discussing the 
negative effects of vitamin D deficiency, such as growth retardation, 
rickets, and osteoporosis (Ref. 38). The submissions include numerous 
published articles concerning vitamin D, but only four clinical studies 
that directly examine the effect of sunscreen use on vitamin D levels. 
In the remainder of this section, we discuss the four studies included 
in submissions, as well as three additional studies that we located 
through a literature search. Collectively, the studies do not 
demonstrate that the use of sunscreen causes vitamin D deficiency.
    The term ``vitamin D'' refers to several forms of the vitamin, but 
the two forms important to humans are vitamin D2 
(ergocalciferol) and vitamin D3 (cholecalciferol) (Ref. 39). 
Vitamin D2 is obtained by eating vitamin D-rich foods such 
as fish or food fortified with vitamin D. The skin makes vitamin 
D3 when it is exposed to sunlight (Ref. 40) and, therefore, 
vitamin D production may vary depending on the following factors: (1) 
Skin pigmentation, (2) age, (3) clothing, (4) season, (5) latitude, (6) 
time of day, (7) weather conditions, and (8) sunscreen application 
(Refs. 40-43). Vitamin D deficiency has long been associated with 
Ricketts, but recent research suggests that vitamin D deficiency may 
also be associated with other diseases (Ref. 38). However, the 
threshold of vitamin D blood levels that constitutes a deficiency is 
currently being re-evaluated by scientific experts (Refs. 40, 44, and 
45).
    To determine whether sunscreen use causes vitamin D deficiency, we 
reviewed four clinical studies included in the submissions that 
explored the effect of sunscreen use on vitamin D levels as well as 
three studies that we identified in a literature search:
     Matsuoka et al 1987 (Ref. 46)
     Matsuoka et al 1988 (Ref. 47)
     Marks et al. 1995 (Ref. 48)
     Farrerons et al. 1998 (Ref. 49)
     Kimlin et al., 2007 (Ref. 50)
     Cusack et al., 2008 (ref. 51)
     Hoesl et al., 2010 (Ref. 52).

All but one of these studies assessed 25-hydroxyvitamin D levels 
because 25-hydroxyvitamin D is typically used as the biological marker 
for vitamin D (in the D2 or D3 form) (Ref. 53). 
Much of the data available in the literature involves nonclinical 
studies, which can be difficult to extrapolate to consumer (human) 
actual use conditions. Studies with clinical data provide more 
meaningful results because, if adequately designed, they can be more 
easily extrapolated to consumer actual use conditions. Therefore, we 
are focusing discussion in this document on the clinical studies.

    In the 1987 study by Matsuoka et al., four subjects applied a 
sunscreen product with an unknown SPF to the entire body, while four 
control subjects did not apply any topical product (Ref. 46). All of 
the subjects were exposed to 1 MED \6\ of UV radiation (260-330 nm \7\) 
and then vitamin D3 levels were monitored for 15 days. The 
subjects using sunscreen product applied the sunscreen product 1 hour 
before UV exposure. The level of vitamin D3 was determined 
one day before UV exposure to serve as the baseline measure.
---------------------------------------------------------------------------

    \6\ MED refers to the lowest dose of UV radiation that produces 
perceptible reddening of the skin.
    \7\ Nanometers.
---------------------------------------------------------------------------

    The level of vitamin D3 in the control group (no 
sunscreen) increased significantly over baseline 1 day after UV 
exposure (from ~2 ng/ml \8\ to 25 ng/ml) and then decreased gradually, 
returning to baseline 15 days after UV exposure. In contrast, the 
levels of vitamin D3 in the sunscreen group did

[[Page 35637]]

not change significantly from the baseline level (5 ng/ml) at each time 
point.
---------------------------------------------------------------------------

    \8\ Nanograms per milliliter.
---------------------------------------------------------------------------

    Based on this preliminary study, Matsuoka et al. conducted another 
study in 1988 (Ref. 47). This study enrolled 40 subjects from Illinois 
and Pennsylvania with 20 subjects in the control group and 20 subjects 
in the sunscreen group. Each time they went outdoors for 1 year, the 
subjects in the sunscreen group, who had a history of skin cancer, 
applied a sunscreen product with an unknown SPF to all sun-exposed 
areas of the body.
    Serum 25-hydroxyvitamin D levels were measured in each group at the 
conclusion of the study and were significantly lower in the sunscreen 
group than the control group: 40.2 and 91.3 nmol/L,\9\ respectively. 
The difference in 25-hydroxyvitamin D levels between the two groups was 
statistically significant (p < 0.001).
---------------------------------------------------------------------------

    \9\ Nanomoles per liter.
---------------------------------------------------------------------------

    Marks et al. conducted a randomized, double-blind controlled 
clinical study over a summer period in Australia (Ref. 48). In this 
study, 113 subjects over 40 years old who exhibited at least one solar 
keratosis (a precursor of carcinoma of the skin) were recruited and 
divided into two groups. The first group of 56 subjects applied an SPF 
17 sunscreen cream. Fifty-five subjects in the control group applied a 
placebo cream. Subjects in both groups were asked to apply their cream 
on the head, neck, forearm and dorsal side of each hand once a day in 
the morning and more frequently if sweating, swimming, or involved in 
activities that might rub off the cream.
    The mean levels of 25-hydroxyvitamin D rose significantly by almost 
the same amount in both groups over the period of the study. The mean 
level in the placebo group increased by 12.8 mmol/L, whereas the mean 
level in the sunscreen group increased by 11.8 mmol/L. The difference 
between these increases from baseline values was not statistically 
significant.
    In 1998, Farrerons et al. carried out a study to examine the 
effects of sunscreen use on vitamin D levels in elderly individuals 
(Ref. 49). In this 2-year study, 24 subjects (10 men and 14 women with 
a mean age of 71 years) were enrolled in the sunscreen group. The 
subjects had actinic keratosis, basal cell carcinoma, or squamous cell 
carcinoma. None of the subjects had previously used sunscreen products, 
but were instructed to apply an SPF 15 sunscreen product to sun-exposed 
areas of the body each morning, avoid mid-day sun, and wear UV-
protective clothing during the spring and autumn. The control group of 
19 subjects did not use sunscreen product, but had the same skin 
characteristics. Mean serum levels of 25-hydroxyvitamin D were measured 
at eight different time points (four in the autumn and four in the 
spring) over the two-year study period.
    The mean serum levels of 25-hydroxyvitamin D were statistically 
lower in the sunscreen group as compared to the control group at one 
spring and one autumn time point (p < 0.05). However, the mean serum 
levels of 25-hydroxyvitamin D were not statistically different between 
the groups at the other 6 spring and autumn time points.
    In 2007, Kimlin et al. reported that there was ``no association'' 
between use of sunscreens with SPF values higher than 15 and blood 
levels of 25-hydroxyvitamin D in a study of 126 Australian adults 18-87 
years of age (Ref. 50). However, the authors stated that mean levels of 
25-hydroxy vitamin D increased with increasing frequency of sunscreen 
use. Interestingly, study ``participants who `usually' or `almost 
always' wore a hat when outdoors'' were significantly more likely to 
have higher serum 25-hydroxy vitamin D levels than those who wore hats 
less often (Ref. 50). On the other hand, study participants who usually 
or almost always wore long sleeve shirts or pants while outside were 
statistically more likely to have lower serum 25-hydroxyvitamin D 
levels than those who wore these types of protective clothing less 
often (Ref. 50).
    In 2008, Cusack et al. reported that decreased levels of 25-
hydroxyvitamin D levels were only ``weakly correlated'' with sunscreen 
usage in 52 Irish patients with cutaneous lupus erythematosus (Ref. 
51). This study population was specifically selected because patients 
with lupus are particularly sensitive to exposure to the sun. While an 
analysis of the effects of daily sunscreen use on serum levels of 25-
hydroxyvitamin D showed the relationship between these two parameters 
to be significant, a multivariate analysis of the same data was not 
significant (Ref. 51).
    Most recently, in 2010, Hoesl et al. reported ``no statistically 
significant association'' between serum levels of 25-hydroxyvitamin D 
and use of the sunscreen drometrizole trisiloxane in a cohort of 15 
patients with Xeroderma pigmentosum (Ref. 52). Like those with lupus 
ertythematosus, patients with Xeroderma pigmentosum are extremely 
sensitive to the sun. The authors reported that reductions in serum 
levels of 25-hydroxyvitamin D are ``not associated with any type or 
duration of sun protection applied by these patients'' (Ref. 52).
    These seven clinical studies are inconclusive because the results 
were contradictory. Two studies suggest that sunscreens decrease 
vitamin D levels and the other five studies suggest that sunscreens do 
not decrease vitamin D levels. In addition, the studies were relatively 
small, only enrolling 8 to 126 subjects. The study with the greatest 
number of participants was inconclusive showing that people who 
regularly used sunscreens and wore hats had increased levels of vitamin 
D, whereas people who regularly wore pants outside had decreased levels 
(Ref. 50).
    Because the preponderance of currently available data suggests that 
sunscreen use does not cause clinically meaningful decreases in vitamin 
D levels (i.e., decreases that lead to vitamin D deficiency and/or 
disease caused by low levels of vitamin D), we are not including a 
warning regarding vitamin D deficiency on OTC sunscreen products. In 
addition, determining whether decreases in vitamin D levels result in 
vitamin D deficiency is especially difficult because the threshold of 
vitamin D blood levels that constitutes a deficiency is currently being 
re-evaluated by scientific experts (Refs. 38, 44, and 45). We recognize 
that certain subpopulations may be at increased risk of vitamin D 
deficiency, as pointed out in one submission. However, there are many 
factors that determine the amount of sun exposure necessary to ensure 
adequate vitamin D levels (e.g., geographical location, season, skin 
pigmentation, dietary vitamin D intake). Because of these many other 
factors, it is difficult for us to determine a meaningful message in 
sunscreen product labeling for consumers, especially in the absence of 
conclusive data. If we become aware of data from adequate and well-
controlled studies demonstrating that regular use of sunscreen causes 
vitamin D deficiency, we will re-evaluate this issue.

D. Directions

    We received numerous submissions requesting that we revise 
directions included in the 2007 proposed rule (Ref. 1). In response to 
those requests and our reevaluation of OTC sunscreen labeling, we are 
revising the following directions:
     ``Reapply after [select one of the following: `40 minutes 
of' or `80 minutes of' '' for products that satisfy either the water 
resistant or very water resistant test procedures in proposed 
paragraphs 352.76(a) and (b), respectively] swimming or [select one of 
the

[[Page 35638]]

following: `sweating' or `perspiring'] and after towel drying. 
Otherwise, reapply at least every 2 hours'' (proposed 21 CFR 
352.52(d)(2)).
     ``Reapply at least every 2 hours after towel drying, 
swimming, or sweating'' (proposed 21 CFR 352.52(d)(3)).

These two directions are the reapplication instructions for water 
resistant and non-water resistant products, respectively. We also 
received five submissions requesting that we revise the direction: 
``Apply [select one of the following: `liberally' or `generously'] 
[and, as an option: `and evenly'] [insert appropriate time interval, if 
a waiting period is needed] before sun exposure'' (proposed 21 CFR 
352.52(d)(1)(i)). As discussed in this section, we are not revising 
this direction statement.

    In addition to the revisions to these provisions (described in more 
detail in this section of the document), we are no longer requiring the 
following proposed direction: ``Apply and reapply as directed to avoid 
lowering protection'' (proposed 21 CFR 352.52(d)(1)(ii)).
    As already discussed, for covered sunscreen products with Broad 
Spectrum SPF values of 15 or higher, we are requiring the following 
direction:

    ``Sun Protection Measures. [in bold font] Spending time in the 
sun increases your risk of skin cancer and early skin aging. To 
decrease this risk, regularly use a sunscreen with a Broad Spectrum 
SPF of 15 or higher and other sun protection measures including: 
[bullet] limit time in the sun, especially from 10 a.m.-2 p.m. 
[bullet] wear long-sleeved shirts, pants, hats, and sunglasses''

(new 21 CFR 201.327(e)(1)(iv)). For these products, this direction most 
appropriately conveys the information proposed in the ``Sun Alert'' 
warning included in the 2007 proposed rule, and provides the necessary 
directions to complement the new indication permitted for these 
products.

    In addition to the required directions, we will allow the optional 
direction heading ``for sunscreen use'' (new 21 CFR 201.327(e)(1)(i)).
1. Revised Directions
    We are revising the directions for water resistant sunscreen 
products (new 21 CFR 201.327(e)(2)) to read:
     Reapply:
     After 40 [or 80] minutes of swimming or sweating
     Immediately after towel drying
     At least every 2 hours

We are also revising the directions for non-water resistant sunscreen 
products (new 21 CFR 201.327(e)(3)) to read: ``[Bullet] reapply at 
least every 2 hours [bullet] use a water resistant sunscreen if 
swimming or sweating.'' These revisions should clarify the directions. 
We are removing reapplication directions concerning swimming and 
sweating from non-water resistant products because these products 
should not be used when swimming or sweating. Instead, we are requiring 
more accurate directions instructing consumers to use a different 
sunscreen product--a water resistant sunscreen product--if swimming or 
sweating.
    We considered revising the 2-hour reapplication timeframe because 
some of the submissions objected to this specific timeframe (Ref. 1). 
The submissions argued that we should require the word ``often'' 
instead of a 2-hour reapplication timeframe because there are no data 
supporting this timeframe. The submissions also point out that the 
American Academy of Dermatology (AAD) no longer supports a 2-hour 
timeframe, even though we cited AAD as supporting the 2-hour timeframe 
in the 2007 proposed rule (72 FR 49070 at 49093).
    In its submission following the 2007 proposed rule, the AAD does 
not state its support for the 2-hour timeframe. However, all of the 
public education materials from AAD instruct consumers to reapply 
sunscreen at least every 2 hours (Refs. 54 through 58). In addition, 
other public health organizations such as the Centers for Disease 
Control and Prevention (CDC) and the U.S. Environmental Protection 
Agency (EPA) recommend reapplication at least every 2 hours (Refs. 59 
and 60).
    We disagree with the submissions stating that data do not support 
this timeframe. In the 2007 proposed rule, we described two studies 
demonstrating a significantly decreased sunburn risk if sunscreen 
product were applied at least every 2 hours (72 FR 49070 at 49092 
through 49093). Wright et al. found that subjects who reapplied 
sunscreen every 1 to 2 hours and after swimming were not sunburned 
(Ref. 61). Similarly, Rigel et al. reported that people who reapplied 
sunscreen every two hours or sooner were five times less likely to 
sunburn compared to those who reapplied sunscreen only after 2.5 hours 
or longer (Ref. 62).
    One of the submissions following the 2007 proposed rule included 
results from a computer-simulation of sunscreen product reapplication 
based on a mathematical model (Ref. 1). The results of this simulation 
suggested that sunscreen products should be reapplied 15 to 30 minutes 
after sun exposure begins. The results also suggested that further 
reapplication of sunscreen product is necessary after vigorous activity 
that could remove sunscreen product, such as swimming, toweling, 
excessive sweating, or rubbing. No other reapplication time is 
suggested. The usefulness of this study in determining whether to 
revise the directions is limited. In particular, we do not know whether 
this simulation was validated, because it has not been confirmed with 
clinical studies. Until we receive clinical studies demonstrating that 
consumers do not experience skin damage when sunscreen is reapplied at 
longer timeframes, we will continue to require the 2-hour reapplication 
timeframe. As discussed in the 1999 final rule, manufacturers may seek 
approval of different reapplication directions by submitting specific 
and substantive supporting data to us under an NDA deviation (described 
in 21 CFR 330.11).
2. Proposed Directions Not Being Revised
    We are not revising proposed 21 CFR 352.52(d)(1)(i): ``Apply 
[select one of the following: `Liberally' or `generously'] [and, as an 
option: `And evenly'] [insert appropriate time interval, if a waiting 
period is needed] before sun exposure.'' Several submissions requested 
that we allow ``smoothly'' to be included in this statement (Ref. 1). 
However, we continue to consider this word to be vague (72 FR 49070 at 
49072 and 49092). Some submissions also requested that we include a 
specific application amount in place of the terms ``generously'' and 
``liberally'' (Ref. 1). For example, the submissions suggested that the 
statement could read ``apply 2 tablespoonsful.'' The submissions argued 
that more specific directions would lead to consumers applying more 
sunscreen product, reflecting the 2 milligrams per square centimeter 
(mg/cm\2\) used during the SPF test. However, specifying a certain 
amount in the directions will not accomplish this goal. The amount of 
sunscreen product that needs to be applied to reach 2 mg/cm\2\ varies 
for each sunscreen product and depends on the amount of skin surface 
area being covered. For example, the volume of sunscreen oil applied to 
the neck and face will differ greatly from the amount needed to apply a 
sunscreen lotion to every sun-exposed area of the body. Therefore, we 
are continuing to require the terms ``generously'' and ``liberally.''
3. Proposed Directions Not Being Required
    We are not requiring the proposed statement ``apply and reapply as 
directed to avoid lowering protection'' (proposed 21 CFR 
352.52(d)(1)(ii)). We included this statement in the 2007

[[Page 35639]]

proposed rule because reapplication time appears to be critical to 
achieve proper sun protection (72 FR 49070 at 49093). However, we have 
concluded that this statement is redundant with more specific 
reapplication directions and may confuse consumers. It is not clear 
that consumers will understand the intent of this statement to 
emphasize the need to follow reapplication instructions. Therefore, we 
are not requiring the statement in this document.
4. New Directions Resulting From Submissions on the Proposed Rule
    For covered sunscreens with Broad Spectrum SPF values of 15 or 
higher, we are requiring a new Directions statement that emphasizes the 
need not only to regularly use such a sunscreen, but also to follow 
other sun protection measures. For these sunscreens, the statement will 
read, ``[bullet] Sun Protection Measures. [in bold font] Spending time 
in the sun increases your risk of skin cancer and early skin aging. To 
decrease this risk, regularly use a sunscreen with a Broad Spectrum SPF 
of 15 or higher and other sun protection measures including: [Bullet] 
limit time in the sun, especially from 10 a.m.-2 p.m. [bullet] wear 
long-sleeved shirts, pants, hats, and sunglasses (new 21 CFR 
201.327(e)(1)(iv)). This statement is taken from the proposed warning 
``UV exposure from the sun increases the risk of skin cancer, premature 
skin aging, and other skin damage. It is important to decrease UV 
exposure by limiting time in the sun, wearing protective clothing, and 
using a sunscreen.'' (proposed 21 CFR 352.52(c)(1)). As discussed in 
section IV.C. of this document, this warning is no longer being 
required for sunscreens with Broad Spectrum SPF values of 15 or higher. 
Rather, as discussed in section IV.B of this document, submissions 
suggested that the information proposed as a warning is better 
understood as an indication, with the supporting conditions for 
achieving effectiveness. As described in section IV.B, on reexamination 
of the scientific data, we agree that an appropriately limited 
indication for reduction in risk of skin cancer and early skin aging is 
supported for sunscreens with Broad Spectrum SPF values of 15 or 
higher. For these products, the direction instructs users how to use 
the product in a manner that supports that indication.
    In this final rule, we are being more specific about the need to 
limit time in the sun especially during the midday hours of 10 a.m. to 
2 p.m. when the intensity of solar radiation is greatest because the 
sun is at its zenith (i.e., directly overhead). In our 1993 proposed 
rule, we stated that, ``on any day of the year, the intensity of the UV 
energy of sunlight is greatest between 10 a.m. and 2 p.m.'' (58 FR 
28194 at 28199). We have concluded that this information is important 
to consumers trying to protect themselves from the sun and are 
including the information in the new direction statement. This change 
is also responsive to the concerns of two submissions on the portion of 
the proposed sun alert that referred to ``limiting time in the sun,'' 
both of which suggested alternatives intended to provide more concrete 
information for consumers to act on (Ref. 1).
    Several submissions argued that we should allow different Drug 
Facts labeling for cosmetics containing sunscreens so that consumers 
will apply the product appropriately for its intended cosmetic use 
(Ref. 1). For example, the submissions argued that reapplication every 
2 hours may not be appropriate for cosmetic-sunscreen products. We 
disagree with these submissions. Cosmetic-sunscreen combinations that 
are intended for use as drugs require adequate labeling for their drug 
use. (See 21 CFR 700.35). The Drug Facts label communicates information 
to the consumer so that the cosmetic-sunscreen product can be used 
safely and effectively. To help consumers understand that the sunscreen 
directions apply to the use of the product as a drug, for sun 
protection, we are allowing the optional statement ``for sunscreen 
use:'' to appear as the first line under ``Directions.'' Consumers who 
are using these products primarily for cosmetic use will be more likely 
to understand that they might not receive the intended sun protection 
if they do not follow the directions in the Drug Facts label.

E. Constitutionality of Labeling Statements Regarding Skin Cancer and 
Skin Aging

    Two submissions questioned the constitutionality of the labeling 
provisions in the 2007 sunscreen proposed rule. Specifically, the 
submissions contended that our proposed restriction on any claims about 
the prevention of skin cancer, early skin aging, and related skin 
damage would violate the sunscreen manufacturers' commercial speech 
rights under the First Amendment to the U.S. Constitution.
    In the 2007 proposed rule preamble, we had concluded that our 
proposed restriction on claims about the prevention of skin cancer, 
early skin aging, and related skin damage would be permissible under 
the First Amendment, in part, because, at that time, we tentatively 
concluded that there were insufficient scientific data to support 
inclusion of such claims in the sunscreen monograph. As described 
elsewhere in this document, we received numerous submissions in 
response to the 2007 proposed rule, some of which contained references 
to clinical studies we had reviewed in preparing the 2007 proposed rule 
about the effectiveness of sunscreens in protecting against the harmful 
effects of UV radiation. As already described in section IV.B.2, based 
in part on our re-evaluation of the data from these studies, as well as 
the scientific fact that reducing exposure to both UVB and UVA 
radiation by a substantial amount (i.e., equivalent to that provided by 
a broad spectrum sunscreen with an SPF value of 15 or higher) decreases 
the risk of damaging the skin, we find that the science supports the 
conclusion that one subset of sunscreens covered by this rule, broad 
spectrum sunscreen products with an SPF value of 15 or higher, in 
conjunction with limiting time in the sun and wearing protective 
clothing, reduce the risk of developing skin cancer and early skin 
aging. Our conclusion is reflected in the permissible indication 
described in this final rule for covered products with Broad Spectrum 
SPF values of 15 or higher. Although we have decided to permit a claim 
about the prevention of skin cancer and early skin aging for certain 
covered sunscreens, as requested in the submissions, we have 
nevertheless conducted a First Amendment analysis of our requirements 
concerning the skin cancer/early skin aging claim in this final rule 
(hereinafter ``skin cancer/early aging indication''), as well as the 
``Skin Cancer/Skin Aging Alert'' required as a warning for covered 
products that do not provide broad spectrum protection with an SPF 
value of 15 or higher. For the following reasons, we have concluded 
that these requirements do not violate the First Amendment.
    This rule establishes effectiveness testing methods and labeling 
that are appropriate for the safe and effective use of OTC sunscreen 
products covered by this rule. Any covered sunscreen product that 
deviates from the requirements set forth in this labeling regulation 
and any other applicable labeling regulation would be considered 
misbranded under section 502 of the FD&C Act. In particular, sunscreen 
products covered by this rule would be misbranded if they are labeled 
with a skin cancer/early aging indication but

[[Page 35640]]

do not provide broad spectrum protection with an SPF value of 15 or 
higher. Such products would also be misbranded if they do not include 
the ``Skin Cancer/Skin Aging Alert'' described in this rule (see 21 CFR 
201.327(d)(2)). Covered sunscreen products that do provide broad 
spectrum protection with an SPF value of 15 or higher would be 
misbranded if they are labeled with the permissible skin cancer/early 
aging indication but do not include reference to the need to use the 
product as directed with other sun protection measures (21 CFR 
201.327(c)(3)). Manufacturers of covered sunscreen products that comply 
with the labeling requirements in this document would not be subject to 
enforcement actions on the basis that the products are misbranded, 
provided they comply with all other requirements under section 502 of 
the FD&C Act. Because this rule applies only to products marketed 
without approved applications, manufacturers who wish to deviate from 
the testing or labeling requirements in this document may do so by 
means of a new drug application (NDA) under section 505 of the FD&C 
Act.
    We have concluded that the labeling requirements in this rule 
satisfy the applicable tests governing commercial speech, as set forth 
by the Supreme Court. The requirements for the ``Skin Cancer/Skin Aging 
Alert'' and the information in the skin cancer/early aging indication 
about using the product as directed with other sun protection measures, 
are permissible under the First Amendment because they are reasonably 
related to the Government's interest in protecting public health (see 
Zauderer v. Office of Disciplinary Counsel, 471, U.S. 626, 651 (1985)).
    We are requiring covered sunscreen products that do not provide 
broad spectrum protection with an SPF value of 15 or higher to include 
the ``Skin Cancer/Skin Aging Alert'' under the ``Warnings'' heading on 
the label to ensure that consumers are aware of the continued risks of 
skin cancer and early skin aging that occur from sun exposure, the 
conditions under which they will be using the product, and that they 
understand that the product has been shown only to help protect against 
sunburn. Without this warning, consumers could fail to distinguish 
between these sunscreen products and other sunscreen products that have 
been proven to help provide protection against skin cancer and early 
skin aging. Providing this information is important for consumers to be 
able to make informed choices about the selection and use of 
sunscreens.
    For covered sunscreen products that do provide broad spectrum 
protection with an SPF value of 15 or higher, we are requiring that the 
additional information about using the product as directed with other 
sun protection measures be included in the indication so that consumers 
are not misled about how to use these sunscreens effectively or about 
the conditions under which these sunscreens are effective. Use of a 
sunscreen alone--even a broad spectrum sunscreen with an SPF value of 
15 or higher--has not been shown to reduce the risk of skin cancer or 
early skin aging if a consumer increases overall UV exposure by 
spending greater time in the sun and/or wearing less protective 
clothing. The additional information required in the skin cancer/early 
aging indication about using the product as directed with additional 
sun protection measures clarifies how the use of sunscreens is part of 
a comprehensive sun protection program. Displaying this information 
elsewhere would underemphasize its importance in relation to the use of 
these sunscreens for protection against skin cancer and early skin 
aging (see N.Y. State Rest. Ass'n v. N.Y. City Bd. of Health, 556 F.3d 
114 (2d Cir. 2009); see also 21 U.S.C. 352(c)). Thus, these disclosure 
requirements will promote the proper use of covered sunscreens and are, 
therefore, reasonably related to the Government's interest in 
protecting public health.
    Our requirements concerning the skin cancer/early aging indication 
would also be permissible under the First Amendment using the 
analytical framework provided in Central Hudson Gas & Electric 
Corporation v. Public Service Commission, 447 U.S. 557 (1980). Under 
Central Hudson, commercial speech that is false, misleading, or 
concerns unlawful activity is not entitled to protection under the 
First Amendment. While commercial speech that concerns lawful activity 
and is not misleading receives some protection under the First 
Amendment, it may nonetheless be regulated by the Government if the 
following conditions are met: (1) The asserted governmental interest is 
substantial; (2) the regulation directly advances the asserted 
governmental interest; and (3) the regulation is not more restrictive 
than necessary to serve that interest (Id. at 566). The Supreme Court 
has explained that the last element of the Central Hudson test is not a 
``least restrictive means'' requirement but, rather, requires narrow 
tailoring (i.e., ``a fit that is not necessarily perfect, but 
reasonable'' between means and ends) (Board of Trustees of the State 
Univ. of N.Y. v. Fox, 492 U.S. 469, 480 (1989)). In subsequent 
decisions, the Court has also clarified that ``misleading'' in the 
first element of the test refers to speech that is inherently or 
actually misleading.
    Based on the data currently available, we have concluded that the 
following statements or omissions would be false or inherently 
misleading: (1) Use of the skin cancer/early aging indication on the 
labeling of a sunscreen product that does not provide broad spectrum 
protection with an SPF value of 15 or higher, (2) the omission of the 
``Skin Cancer/Skin Aging Alert'' under the ``Warnings'' heading of the 
labeling for sunscreen products that do not provide broad spectrum 
protection with an SPF value of 15 or higher, and (3) use of the skin 
cancer/early aging indication that omits the required information about 
using the product as directed with other sun protection measures.
    Use of the skin cancer/premature aging indication on the labeling 
of covered sunscreen products that do not provide broad spectrum 
protection with an SPF value of 15 or higher would be false or 
inherently misleading for several reasons. As discussed elsewhere in 
this document, only broad spectrum UV radiation is classified as a 
known human carcinogen, according to the National Toxicology Program. 
Therefore, covered sunscreen products that do not provide broad 
spectrum UV protection may not reduce the risk of skin cancer. 
Furthermore, since the precise wavelengths of UV radiation that cause 
skin cancer and early skin aging are unknown, a covered sunscreen 
product that only provides protection against part of the UV spectrum 
may not ensure a reduction in the risk of developing skin cancer or 
early skin aging. In addition, all of the scientific data that support 
the skin cancer/early aging indication for certain covered sunscreens 
were derived from studies that used sunscreen products with an SPF 
value of 15 or higher. Therefore, the skin cancer/early aging 
indication would be false or inherently misleading on covered sunscreen 
products that do not provide this level of protection, because there is 
a lack of any evidence demonstrating that these products would reduce 
the risk of skin cancer or early skin aging. Similarly, omitting the 
``Skin Cancer/Skin Aging Alert'' on these products, which are 
identified on their labels as ``sunscreens,'' would be inherently 
misleading because consumers who are using these products for sun 
protection would not be sufficiently alerted to the fact that these 
products have been shown only to

[[Page 35641]]

protect against sunburn, while sun exposure also increases the risks of 
skin cancer and early skin aging.
    A skin cancer/early aging indication on a covered product with 
Broad Spectrum SPF value of 15 or higher that omits the required 
information about using the product as directed with other sun 
protection measures would also be false or inherently misleading 
because sunscreen use alone has not been shown to reduce the risk of 
skin cancer or early skin aging if a consumer increases overall UV 
exposure by spending greater time in the sun and/or wearing less 
protective clothing. As discussed above in this section and elsewhere 
in this document, without the reduction in consumers' overall UV 
exposure, a covered sunscreen product may not be effective in reducing 
consumers' risk of skin cancer and early skin aging.
    We also conclude that the labeling claims and omissions described 
above would cause the product to be misbranded and, therefore, relate 
to an unlawful activity. As described earlier in this section and 
elsewhere in this document, labeling regulations establish certain 
requirements that help ensure the safe and effective use of OTC drug 
products. The false or misleading labeling described above would cause 
covered products to be misbranded under section 502 of the act. 
Therefore, such labeling would concern the illegal sale of misbranded 
drugs. Under the Central Hudson test, then, we have not violated the 
First Amendment with these requirements, which simply prohibit false or 
inherently misleading labeling.
    Although we conclude that the labeling described above would not be 
entitled to First Amendment protection under the threshold inquiry of 
the Central Hudson test, we conclude that our regulation directly 
advances a substantial Government interest and is no more extensive 
than necessary, and therefore would also pass muster under the test's 
three remaining steps. Under the first remaining step, we have a 
substantial interest in protecting public health (see Pearson v. 
Shalala, 164 F.3d 650, 656 (DC Cir. 1999) (citing Rubin v. Coors 
Brewing Co., 514 U.S. 476, 484-485 (1995)).
    Under the second remaining step of the Central Hudson test, our 
labeling requirements discussed in this section directly advance the 
Government's interests in protecting public health because they help 
ensure that covered sunscreen products are adequately labeled for safe 
and effective use by consumers.
    As stated previously in this document, scientific evidence only 
supports the skin cancer/premature aging indication for sunscreen 
products that provide broad spectrum protection with an SPF value of 15 
or higher. Allowing the skin cancer/early aging indication on sunscreen 
products for which it is not scientifically supported would lead to 
consumers unjustifiably relying on such products for protection against 
skin cancer and early skin aging. Furthermore, the ``Skin Cancer/Skin 
Aging Alert'' allows consumers to be aware that spending time in the 
sun increases their risk of skin cancer and early skin aging, and that 
products on which this alert appears have not been shown to provide 
this type of protection. The requirement for information in the skin 
cancer/early aging indication about using sunscreens as directed with 
sun protection measures also directly advances our interest in 
protecting public health because these elements are essential for 
consumers to reduce their overall UV exposure and, consequently, their 
risk of developing skin cancer and early skin aging. Thus, these 
requirements directly advance the Government's interest in protecting 
public health through the safe and effective use of sunscreens.
    Under the final remaining step of the Central Hudson test, our 
requirements concerning the skin cancer/early aging indication are not 
more restrictive than necessary, because there are not numerous and 
obvious alternatives (Cincinnati v. Discovery Network, 507 U.S. 410, 
418 n. 13 (1993)) to achieve the Government's substantial interests. By 
permitting the skin cancer/early aging indication only for covered 
sunscreen products with Broad Spectrum SPF values of 15 or higher, and 
requiring the ``Skin Cancer/Skin Aging Alert'' for products that do not 
offer this level of protection, we are ensuring that consumers do not 
mistakenly rely on sunscreen products that have not been demonstrated 
to be effective for protection against skin cancer and early skin 
aging. In addition, labeling that omits a statement regarding the use 
of other sun protection measures as directed from the skin cancer/early 
aging indication could lead to consumers foregoing other sun protection 
measures, thereby negating the protective effect of the sunscreen. 
Including a statement in the skin cancer/early aging indication 
regarding the need to follow other sun protection measures as well as 
the related directions ensures that consumers understand how to use 
sunscreens to reduce their risk of skin cancer and early skin aging.
    It is important to note that manufacturers of OTC sunscreens 
covered by this rule have several alternatives for adding labeling 
information that is not included in this labeling regulation. For 
example, such manufacturers can file an NDA under section 505 of the 
FD&C Act or submit a petition under 21 CFR 10.30 to amend the labeling 
regulation. In either case, the manufacturer need only submit the 
requisite evidence to support the indication or other labeling for the 
product that differs from that addressed by the regulation. Therefore, 
we are not being more restrictive than necessary when these viable 
alternatives are available for manufacturers.
    Reacting to the fact that our proposed rule did not permit any 
indication statement for any sunscreen regarding prevention of skin 
cancer and early skin aging, one submission asserted that we must 
consider use of a disclaimer as an alternative means of addressing the 
limits of the product's effectiveness. As noted previously in this 
document, this final labeling regulation permits an appropriately 
limited indication for broad spectrum sunscreens with SPF values of 15 
or higher--one stating that when used as directed with other sun 
protection measures, such products decrease the risk of skin cancer and 
early skin aging caused by the sun. The claim is authorized for this 
subset of covered sunscreen products because available scientific data 
discussed elsewhere in this document are sufficient to substantiate the 
claim for these products. Because we have included a skin cancer/early 
skin aging claim in these labeling regulations, we no longer view the 
submission's request as being applicable.
    In any event, we note that the use of disclaimers on drug labeling 
to qualify inadequately supported or unapproved indications is not an 
effective, less restrictive means of achieving FDA's substantial 
interests in protecting public health and preserving the integrity of 
its premarket approval systems. Indeed, disclaimers on drug labeling 
would severely undermine the Government's interests here. For over 100 
years, Congress has charged FDA with enforcing misbranding laws to 
protect public health. In 1962, Congress amended the FD&C Act to 
require that all new drugs be approved as both safe and effective prior 
to marketing. Congress found that a premarket approval system, 
requiring specific types of supporting evidence (see 21 U.S.C. 355(d)), 
and misbranding provisions, among other requirements, were necessary to 
avoid further tragedies involving unsafe and ineffective drugs. Using 
disclaimers for drugs would completely undermine the

[[Page 35642]]

regulatory framework established by Congress for the protection of 
public health. FDA's labeling regulations help ensure the safety and 
effectiveness of OTC drugs and establish the conditions under which a 
drug is not misbranded under the FD&C Act. If a manufacturer of a 
covered sunscreen would like to label its sunscreen product in a way 
that does not conform to this labeling regulation, it cannot circumvent 
the premarket NDA process.
    In summary, we conclude that the labeling requirements provided in 
this document do not violate the First Amendment.

F. Other Information

    We received submissions requesting that we add a new statement 
about storage conditions under ``Other information'' in the Drug Facts 
label (Ref. 1). The submissions argued that sunscreen products in 
containers are often exposed to heat when used at the beach, swimming 
pools, etc. The concern expressed in the submissions was that heat 
could cause sunscreen formulations inside containers to change, 
resulting in less sun protection. We agree with the submissions. 
Sunscreen products within containers should not be exposed to direct 
sun and can be protected by wrapping them in towels and/or keeping them 
in shaded environments (e.g., under an umbrella and/or in a purse or 
bag). Consumers could also store sunscreen product containers in 
coolers while outside during hot periods. In this final rule we are 
requiring the following statement in the ``Other information'' section 
of the Drug Facts label: ``[Bullet] protect the product in this 
container from excessive heat and direct sun'' (new 21 CFR 201.327(f)).
    In addition to the statement about storage conditions, we received 
numerous submissions requesting that we relocate the proposed ``sun 
alert'' warning to the ``Other information'' section of the Drug Facts 
label. The submissions argued that the ``sun alert'' is an educational 
statement and not a warning: ``UV exposure from the sun increases the 
risk of skin cancer, premature skin aging, and other skin damage. It is 
important to decrease UV exposure by limiting time in the sun, wearing 
protective clothing, and using a sunscreen.''
    As already discussed, in light of our re-evaluation of the evidence 
supporting the indications for sunscreens, we have made changes to the 
labeling to more accurately convey appropriate information to consumers 
about the benefits, directions, and limitations of two different groups 
of products covered by the rule--those that provide broad spectrum 
protection with an SPF value of 15 or higher, and those that do not. We 
do not agree that this information belongs under the heading ``Other 
information'' but have included it in modified form under the headings 
Uses and Directions for products with Broad Spectrum SPF values of 15 
or higher (new 201.327(c)(2) and (e)(2), and under a revised ``Skin 
Cancer/Skin Aging Alert'' under the heading Warnings for other 
sunscreens (new 201.327(d)(2)).
    In this document, we are also removing the optional ``Other 
information'' statements in proposed 21 CFR 352.52(e):
    1. ``Low,'' ``medium,'' ``high'' or ``highest'' ``sunburn 
protection product''
    2. ``Higher SPF products give more sun protection, but are not 
intended to extend the time spent in the sun.''

According to the 2007 proposed rule, these statements could appear in 
``Other information'' or anywhere outside Drug Facts. However, in this 
rule, we have revised the labeling and are no longer requiring the 
principal display panel to characterize the level the sunburn 
protection. Rather, for broad spectrum products, the rule requires only 
the statement ``Broad Spectrum SPF [fill in tested SPF value]'' to 
appear on the principal display panel. In light of this revised 
approach to labeling, we are concerned that including the 
characterizations of the product as providing ``low,'' ``medium,'' 
``high'' or ``highest'' ``sunburn protection would be confusing or 
misleading, and are no longer including it as an option.

    We have concluded that the second statement, although truthful, is 
not necessary. Consumers likely understand the first part of this 
statement (higher SPF values represent more sun protection) based on 
the long-standing inclusion on SPF values on OTC sunscreen products. 
The second part of the statement (higher SPF products are not intended 
to extend time spent in the sun) is redundant with the information 
already provided under ``Uses'' and ``Directions,'' particularly 
concerning the need for limiting time in the sun (see sections IV.B and 
IV.D). Although we are not requiring inclusion of the second statement 
under ``Other information,'' the statement may appear outside the Drug 
Facts label because it is truthful and nonmisleading.

G. Reduced Labeling

    Five submissions requested changes to our proposed regulations 
allowing reduced labeling for sunscreen products sold in small packages 
(i.e., packages which meet the requirements in 21 CFR 201.66(d)(10)) 
that are labeled for use only on small areas of the face. One 
submission stated that all cosmetic products labeled with sunscreen 
indications should be required to include all sunscreen product 
labeling.
    After reassessing the criteria for reduced labeling, we are not 
allowing the reduced labeling included in the 2007 proposed rule. OTC 
drug labeling regulations (21 CFR 201.66(d)(10)) allow reduced labeling 
for any OTC drug product sold in a small package, including sunscreen 
products. In the 2007 proposed rule, we proposed additional reductions 
in labeling for three types of sunscreen products sold in small 
packages and intended for use on small areas of the face:
     Proposed 21 CFR 352.52(f)(1)(i)-(f)(1)(iv): Sunscreen 
products sold in small packages and labeled for use specifically on the 
lips, nose, ears, and/or around the eyes (i.e., small areas of the 
face)
     Proposed 21 CFR 352.52(f)(1)(v): Sunscreen-lip protectant 
combination products sold in small packages
     Proposed 21 CFR 352.52(f)(1)(vi): Sunscreen products 
formulated as lipsticks, lip products that prolong wear of lipstick, 
lip gloss, and lip balms
    Three submissions argued that we should not restrict labeling 
exemptions only to sunscreen products sold in small packages and 
labeled for use on small areas of the face. The submissions stated that 
reduced labeling provisions should apply to all sunscreen products sold 
in small packages whether or not they are labeled for use on small 
parts of the face. Two of the submissions argued that such a 
restriction violates the Administrative Procedures Act (APA). The 
submissions cite Bracco Diagnostics, Inc., v. Shalala 963 F. Supp. 20, 
27-28 (D.D.C. 1997) as evidence that the courts oppose regulations 
requiring ``two sets of similar products to run down two sets of 
separate [regulatory] tracks * * * for no apparent reason.''
    In this document, we continue to allow the reduced labeling 
specified in 21 CFR 201.66(d)(10). Therefore, if the information listed 
under Drug Facts requires more than 60 percent of the total available 
surface area, the Drug Facts labeling can be reduced by making the 
formatting changes specified in 21 CFR 201.66(d)(10)(i)-(d)(10)(v). 
However, in contrast to the 2007 proposed rule, we are not allowing 
additional reductions in labeling for any sunscreen products.
    When we proposed the additional reduced labeling, we recognized 
that many of the sunscreen products sold in

[[Page 35643]]

small packages and labeled for use on small areas of the face could not 
accommodate full Drug Facts labeling. However, in the last several 
years, manufacturers have introduced new label designs that permit full 
Drug Facts labeling on very small packages. For example, some stick 
products, including lip protectant-external analgesic combinations 
marketed in 0.15 oz. amounts, have been labeled with wrap-around labels 
that contain full Drug Facts labeling. If these products can be labeled 
to accommodate full Drug Facts labeling, then all sunscreen products 
should be able to accommodate full Drug Facts labeling. Requiring full 
Drug Facts labeling should not discourage manufacturers from including 
sunscreen ingredients because of limited labeling space, as stated in 
the 2007 proposed rule (72 FR 49070 at 49075 through 49077). Therefore, 
in this document, we are eliminating all of the allowances for reduced 
labeling in proposed 21 CFR 352.52(f). Sunscreen products can only have 
reduced labeling for formatting if they meet the criteria in 21 CFR 
201.66(d)(10).

V. Miscellaneous Labeling Outside Drug Facts

    We received several submissions regarding various performance 
claims, including comments asking us to allow claims for protection 
immediately upon application (instant protection) and for extended 
duration between applications (extended wear) and comments asking us 
not to allow terms such as ``sunblock,'' ``waterproof,'' and 
``sweatproof'' (Ref. 1). These kinds of claims were not included in the 
2007 proposed rule (Ref. 1).
    We are not including labeling in 21 CFR 201.327 permitting these 
claims on OTC sunscreen products covered by the rule. The current 
record does not contain support for any of these kinds of claims. To 
clarify the status of these kinds of claims, we are finalizing two 
provisions. We include instant protection and extended wear claims, 
which are claims that we think may be capable of substantiation, in 21 
CFR 310.545(a)(29)(ii). While these claims may not be included on 
products marketed without approved applications, including them in this 
provision makes it clear that these claims may be substantiated for an 
individual product by the submission of adequate data in an NDA.
    We agree with the submissions that argue that ``sunblock,'' 
``waterproof,'' and ``sweatproof'' claims are false or misleading, as 
we have stated in previous sunscreen rulemakings (58 FR 28194 at 28228; 
64 FR 27666 at 27676 through 27680). These terms are essentially 
exaggerations of performance that FDA does not think can be 
substantiated. Accordingly, in this final rule, we codify these as 
terms or phrases that would be false or misleading on covered products, 
and are therefore prohibited (21 CFR 201.327(g)).
    In addition to submissions requesting that we allow certain 
labeling outside Drug Facts, we also received a submission requesting 
that we require information about the UV index (UVI). A stated in the 
2007 proposed rule, we have determined that the usage information 
provided on OTC sunscreen products applies regardless of the UVI value 
(72 FR 49070 at 49073). Therefore, we will allow but do not require 
information about the UV index to be included on sunscreen products 
outside the Drug Facts label.
    A submission requested that we require that the UV index appear on 
sunscreen product labels because this information would help consumers 
understand and use the UV index to determine their risk of sunburn. The 
UV index was developed in 1995 by the National Weather Service, 
Environmental Protection Agency, and Centers for Disease Control and 
Prevention to provide a forecast of the expected risk of overexposure 
to UV rays. The UV index is calculated using ozone data, atmospheric 
pressure, temperature, and cloudiness. As stated in the 2007 proposed 
rule, we are not requiring labeling of UV index information because it 
is not necessary for consumers to understand this index in order to 
safely and effectively use OTC sunscreen products (72 FR 49070 at 
49073). However, manufacturers may include truthful and nonmisleading 
information about the UV index in the labeling outside of Drug Facts if 
they choose.
    We also received a submission requesting that we allow a claim of 
``instant protection'' and to allow claims for extended periods of 
protection between applications (i.e., longer than the 2 hours 
specified in ``Directions'' in the 2007 proposed rule). The submission 
argued that several marketed products provide sunburn protection 
immediately upon application, as demonstrated by test results included 
in the submissions. In this document, SPF testing requires a 15-minute 
waiting period between sunscreen application and UV exposure of the 
test site. It appears that the submitted test method included the same 
15-minute waiting period. Therefore, the assertion that this product 
provides ``instant protection'' does not appear to be substantiated. We 
also did not receive any data regarding claims for extended periods of 
use, so it is not clear whether these claims are truthful. Claims that 
a product provides for an extended period of protection between 
applications or immediately upon application would have to be supported 
by data. Therefore, these claims could be made only under approved new 
drug applications (NDAs) with the required data.
    In this document, we are specifically identifying these claims as 
not allowed on any OTC sunscreen product, regardless of SPF value or 
broad spectrum protection, without an approved application containing 
sufficient substantiation to support the claim. (new 21 CFR 
310.545(a)(29)(ii)):
     Instant protection or protection immediately upon 
application
     Claims for ``all-day'' protection or extended wear claims 
citing a specific number of hours of protection that are inconsistent 
with the directions for application in 21 CFR 201.327.
    In addition, we are identifying the terms ``sunblock'' 
``waterproof,'' and ``sweatproof'' as false and misleading, as we have 
stated in previous sunscreen rulemakings:
     Sunblock (64 FR 27666 at 27679 and 27680)
     Sweatproof (58 FR 28194 at 28227 through 28228)
     Waterproof (58 FR 28194 at 28227 through 28228).
    We have previously identified these claims as ones that would 
render a product misbranded but are addressing them again in this 
document because OTC sunscreen products currently marketed without 
approved applications continue to contain the claims. In this final 
rule, we are listing these false and misleading terms in 21 CFR 
201.327(g). These terms may not be included on any OTC sunscreen 
products covered by the rule.
    Finally, in the 2007 proposed rule, we proposed to specify other 
optional statements that could be included outside of Drug Facts in 
proposed 21 CFR 352.52(e)(3):
     ``Broad spectrum sunscreen''
     ``Provides [select one of the following: `UVA and UVB' or 
`broad spectrum'] protection''
     ``Protects from UVA and UVB [select one of the following: 
`rays' or `radiation']''
     ``[Select one of the following: `absorbs' or `protects'] 
within the UVA spectrum.''
    This final rule is not a monograph, and we do not consider it 
necessary in this rule to codify optional statements for use outside of 
``Drug Facts.'' The labeling required in this document

[[Page 35644]]

should provide consumers with the information that they need to safely 
and effectively use the sunscreen products that it addresses. Under 
this final rule, products marketed without approved applications that 
provide broad spectrum protection according to the test in new 21 CFR 
201.327(j) of this document will be identified on the PDP by use of the 
term ``Broad
    Spectrum SPF.'' In light of this requirement in the rule for use of 
the term ``broad spectrum'' on these particular products, including a 
statement anywhere in the labeling of a product that does not pass the 
broad spectrum test in 21 CFR 201.327(j) that suggests or implies that 
the product provides broad spectrum protection would misbrand that 
product. We likewise caution against references to ``UVA'' (or ``UVA/
UVB'') protection on products that do not provide broad spectrum 
protection as demonstrated by the test in 21 CFR 201.327(j). Such 
labeling would misbrand the products if it misleadingly suggests that 
the products provide protection that is equivalent or greater to that 
provided by products labeled with ``Broad Spectrum SPF'' values or is 
otherwise false or misleading.

VI. SPF Test Parameters

    The 2007 proposed rule included the SPF test from the 1999 final 
rule with revisions to a few test parameters. In response to the 2007 
proposed rule, we received numerous submissions requesting that we 
revise additional test parameters (Ref. 1). In this document, we have 
rewritten the regulations describing the SPF test in an effort to make 
it easier to read and understand and to more closely follow the order 
in which steps of the SPF testing procedure are conducted. We have also 
made several revisions to the test parameters. However, we did not make 
all of the revisions requested in the submissions. Table 4 of this 
document summarizes test parameters that we considered revising. The 
table identifies the parameters that we are changing in this document 
as well as those that we are not changing. Detailed discussion of each 
test parameter appears throughout the remainder of this section.

  Table 4--Summary of SPF Test Parameters Included in the 2007 Proposed
                        Rule and This Final Rule
------------------------------------------------------------------------
            2007 Proposed rule                     This final rule
------------------------------------------------------------------------
   21 CFR 352.70(a). Standard sunscreens      21 CFR 201.327(i)(2). SPF
                                                       standard
 
Two standards:                              One standard:
    8% homosalate (SPF 2-- <= 15)              7% padimate, 3%
                                                oxybenzone (all SPFs)
    7% padimate, 3% oxybenzone (SPF > 15)
HPLC reference standard:                    HPLC reference standard:
    no limits set for accuracy of              limit set to within 5% of
     oxybenzone & padimate O                    theoretical for accuracy
                                                of oxybenzone & padimate
                                                O
 
   21 CFR 352.70(b). Light source (solar       21 CFR 201.327(i)(1). UV
                simulator)                      source (solar simulator)
 
Emission spectrum specifications:           Emission spectrum
                                             specifications:
    (1) COLIPA \1\ 1994 (Ref. 63)              (1) COLIPA \1\ 2006 (Ref.
                                                64)
    (2) no specifications for UVA              (2) specifications for
                                                UVA I and UVA II
                                                percentages of total UV
Calibration:                                Calibration:
    every 6 months                             at least annually
Total irradiance:                           Total irradiance:
    1500 Watts/square meter (W/m\2\)           1500 Watts/square meter
                                                (W/m\2\)
Beam uniformity:                            Beam uniformity:
    within 20 percent                          within 20 percent
 
  21 CFR 352.70(c)(7). Number of subjects    21 CFR 201.327(i)(3). Test
                                                       subjects
 
SPF < 30:                                   All SPFs:
    20-25 subjects; >= 20 valid results         10-13 subjects;
                                                >= 10 valid results
SPF >= 30:
    25-30 subjects; >= 25 valid results
 
21 CFR 352.70(c)(4). Test site delineation/  21 CFR 201.327(i)(4)(i) and
                  subsite                      (ii). Test site/subsite
 
test site area:                             test site area:
    >= 50 cm\2\                                >= 30 cm\2\
test subsite area:                          test subsite area:
    >= 1 cm\2\                                 >= 0.5 cm\2\
Distance between subsites:                  Distance between subsites:
    >= 1 cm                                    >= 0.8 cm
 
 21 CFR 352.70(c)(5). Application of test    21 CFR 201.327(i)(4)(iii).
                 materials                     Applying test materials
 
Application amount:                         Application amount:
    2 milligrams per square centimeter (mg/    2 milligrams per square
     cm\2\)                                     centimeter (mg/cm\2\)
Presaturation of finger cot:                Presaturation of finger cot:
    Required                                   not required
Water-resistant statement requirements:     Water-resistant statement
                                             requirements:
    20 minute water immersion times            20 minute water immersion
                                                times
    20 minute drying times                     15 minute drying times
 
   21 CFR 352.70(d)(3). Determination of      21 CFR 201.327(i)(5). UV
           individual SPF values                       exposure
 
Definitions of MED:                         Definitions of MED:
    (1) MED(PS) = MED for protected skin       (1) ssMEDp = MED for skin
                                                protected by sunscreen
                                                standard
    (2) MED(US) = MED for unprotected skin     (2) tpMEDp = MED for skin
                                                protected by test
                                                product
                                               (3) initial MEDu = MED
                                                for unprotected skin
                                                prior to testing test
                                                product
                                               (4) final MEDu = MED for
                                                unprotected skin
                                                determined when testing
                                                test product
UV doses for MED(US):                       UV doses for initial MEDu:

[[Page 35645]]

 
    five doses                                 number of doses not
                                                specified
   21 CFR 352.70(c)(8) Response criteria      21 CFR 201.327(i)(5). UV
                                                       exposure
Maximal UV exposure:                        Maximal UV exposure:
    ``no more than twice the total energy      not specified
     of the minimal exposure''
------------------------------------------------------------------------
\1\ Draft test method entitled ``International Sun Protection Factor
  (SPF) Test Method'' developed by the European Cosmetic, Toiletry and
  Perfumery Association (COLIPA).

    We are not making some of the requested changes to certain test 
parameters because we lack adequate data to determine whether these 
changes would change the accuracy or reproducibility of the SPF test. 
We are making changes to some test parameters based on the following 
developments since the 2007 proposed rule published:
     New data (submitted by the public or published in the 
scientific literature)
     Technical improvement of SPF testing equipment
     Accumulating experience in the performance of SPF testing
     Efforts towards international harmonization of SPF testing 
procedures
    In support of the requested changes, several submissions (Ref. 1) 
cited differences between the SPF test in the 2007 proposed rule and 
the COLIPA SPF test (Ref. 64). The COLIPA SPF test is a joint effort by 
the cosmetic industry trade associations in Europe, Japan, South 
Africa, and the United States to harmonize SPF test procedures. The 
International Organization for Standardization (ISO) is currently 
developing an SPF test method. Because harmonization of testing methods 
is important, we are actively involved in the ISO working group 
responsible for developing methods for assessing the efficacy of sun 
protection products.
    We are revising our proposed SPF test method to be as consistent as 
possible with the COLIPA SPF test. We acknowledge the merits of 
harmonizing test methods and are an active participant in ongoing 
harmonization efforts. However, some of the test parameters in this 
document differ from comparable parameters in the COLIPA SPF test 
because we have concluded that the data do not support using the COLIPA 
SPF test parameters. Throughout the remainder of this section, we 
discuss whether test parameters in this document match or do not match 
those in the COLIPA SPF methods.

A. Solar Simulator

    Several submissions recommended adopting the solar simulator 
specifications in the COLIPA SPF test (Ref. 1). We are revising solar 
simulator specifications to:
     Allow the use of smaller beam, multiport simulators
     Adjust the relative cumulative erythemal effectiveness 
(RCEE) range specifications for each wavelength band
     Specify that UVA II (320-340 nm) and UVA I (340-400 nm) 
irradiance should equal or exceed 20 percent and 60 percent, 
respectively, of the total UV (290-400 nm) irradiance
     Change the regular calibration period from every 6 months 
to at least once a year

These changes are consistent with the COLIPA SPF test. More 
importantly, these revisions will allow the SPF test to continue to be 
accurate and reproducible. For example, we received calibration data 
demonstrating that solar simulators and their UV lamps are stable for 
periods longer than 1 year. Therefore, the requirement in the 2007 
proposed rule to calibrate every 6 months is unnecessary. The test 
results should be the same whether calibration is done annually or 
every 6 months.

    In contrast, we are not changing the following solar simulator 
specifications because changes to these specifications could reduce 
test accuracy and/or reproducibility:
     Total irradiance limit of 1500 W/m\2\
     Total irradiance range of 250-1400 nm
     20 percent beam uniformity requirement.

These test specifications differ from the COLIPA SPF test, which 
recommends a 1600 W/m\2\ limit and a 10 percent beam uniformity 
requirement.

    Two submissions (Ref. 1) objected to limiting total solar simulator 
irradiance to 1500 W/m\2\ for all wavelengths between 250 and 1400 nm 
(proposed 21 CFR 352.70(b)(1)). We proposed the 1500 W/m\2\ limit 
because we were concerned that solar simulators operating above this 
limit could cause excessive heat. Excessive heat could harm test 
subjects and/or cause loss of dose reciprocity, the correlation between 
UV dose and resulting erythema. One submission argued that no data 
indicate that exceeding 1500 W/m\2\ causes excessive heat or affects 
SPF test results. The submission argued that higher intensities should 
be allowed as long as they are thermally tolerated by test subjects, 
because allowing higher intensities enables faster SPF testing.
    We are not changing the 1500 W/m\2\ total irradiance limit. We do 
not have data demonstrating that exceeding 1500 W/m\2\ leads to loss of 
dose reciprocity. However, we conclude that the limit should be 
retained to protect test subjects. The COLIPA SPF test cites a study 
showing that total irradiance of 1600 W/m\2\ induces heat and pain in a 
majority of test subsites, and recommends keeping total irradiance 
below 1600 W/m\2\ (Ref. 64). Therefore, we are keeping the 1500 W/m\2\ 
total irradiance limit (new 21 CFR 201.327(i)(1)(i)).
    One submission also objected to the 250-1400 nm range over which 
total irradiation should be monitored (Ref. 1). The submission argued 
that portable spectroradiometers are typically incapable of measuring 
wavelengths out to 1400 nm. According to the submission, emissions from 
longer wavelengths have not been shown to affect SPF testing.
    We are not changing the requirement that total irradiation be 
monitored over a range of 250-1400 nm. We have concluded that 
monitoring over this range of wavelengths helps protect SPF test 
subjects from being exposed to undesirable, unnecessary radiation. The 
requirement should not impose undue hardship, because longer 
wavelengths can be monitored using a thermopile, pyroelectric, or 
similar detectors.
    We received two submissions addressing the requirement in proposed 
21 CFR 352.70(b)(2) that a solar simulator have ``good beam uniformity 
(within 20 percent) in the exposure plane'' (Ref. 1). One submission 
argued that advances in equipment and monitoring allow for a stricter 
beam uniformity requirement (<20 percent), which would result in less 
variability in SPF test results. Another submission argued that the 
beam uniformity

[[Page 35646]]

requirement is only important for large diameter beams and has no 
impact on SPF testing using small beams.
    We are not changing the 20 percent beam uniformity requirement 
because accurate determination of SPF values relies upon good beam 
uniformity for all beam sizes. In the 2007 proposed rule, we described 
how small diameter beams can be tested for beam uniformity (see 72 FR 
49070 at 49098). The submission requesting stricter requirements did 
not include data showing that current solar simulators can reasonably 
be expected to have beam uniformity less than 20 percent. We conclude 
that a 20 percent beam uniformity requirement is adequate to produce 
reliable SPF results. Therefore, we are keeping the requirement that 
solar simulators demonstrate good beam uniformity (within 20 percent) 
in new 21 CFR 201.327(i)(1) (iii).

B. Sunscreen Standards

    The 2007 proposed rule include two sunscreen standards for use in 
SPF testing. The two proposed sunscreen standards were a 7 percent 
padimate O/3 percent oxybenzone standard (mean SPF value of 16.3) and 
an 8 percent homosalate standard (mean SPF value of 4.47). For SPF 
testing of sunscreen products with SPF values of 2 to 15, either the 
padimate O/oxybenzone standard or the homosalate standard would have 
been required to be tested along with the test sunscreen product. Tests 
for sunscreen products with SPF values over 15 would have required use 
of the padimate O/oxybenzone standard.
    We received two requests to include an additional sunscreen 
standard with an SPF value of 30 or higher to test sunscreen products 
with SPF values of 30 or more (Ref. 1). Neither request specified any 
particular sunscreen standard formulation with an SPF in this range. If 
a particular sunscreen standard formulation were specified, we would 
also need validation data to support including the additional sunscreen 
standard in the monograph. Therefore, we are not including a sunscreen 
standard with an SPF value of 30 or more in this document.
    We also received a request to include the JCIA SPF 15 `P3' 
sunscreen standard containing 0.5-percent avobenzone, 3-percent octyl 
methoxycinnamate, and 2.78-percent phenylbenzimidazole sulfonic acid. 
To support including the ``P3'' standard, the request included a table 
showing mean, maximum, and minimum SPF values from tests conducted in 
labs in Europe, Japan, Australia, and South Africa. We recognize that 
the ``P3'' standard has been widely used and is included in the COLIPA 
SPF test, but we are not including the ``P3'' standard in this 
document. In the 2007 proposed rule (72 FR 49070 at 49095 to 49095), we 
requested further data to show that testing using the ``P3'' standard 
could be performed with:
     Low level interlaboratory variation
     Sufficient sensitivity to detect experimental error
     A reasonable degree of accuracy

The submitted data (i.e. the table of SPF values) fail to show that the 
``P3'' standard meets these performance requirements because they do 
not show:

     Individual lab results
     The number of tests conducted in each lab
     The number of test subjects used in each test
     Calculated standard errors for each test

Without these data, we cannot assess interlaboratory variability, 
sensitivity to experimental error, or test result accuracy. In 
addition, the advantage of using the ``P3'' standard instead of the 
padimate O/oxybenzone standard is unclear, because both these standards 
have approximately the same SPF value of 16. Therefore, we are not 
including the ``P3'' standard in this document.

    We are also eliminating the proposed homosalate standard with an 
SPF value of 4.47 because the padimate O/oxybenzone standard with an 
SPF value of 16.3 is adequate for validating all test methodologies. In 
the 2007 proposed rule, we stated that the sunscreen standards were 
``method controls rather than calibration tools.'' As a method control, 
the purpose of the sunscreen standard is verifying proper and 
consistent performance of test equipment and procedures, rather than 
verifying the accuracy of the SPF value determined for sunscreen test 
products. Therefore, we conclude that it is not critical for the SPF 
value of the sunscreen standard to be close to the SPF value of the 
sunscreen test product. It is more important that the sunscreen 
standard demonstrate consistency of test performance. Consequently, we 
have concluded that including multiple sunscreen standards is 
unnecessary, and that the padimate O/oxybenzone standard is a suitable 
sunscreen standard for all sunscreen products. We favor including the 
padimate O/oxybenzone standard over the homosalate standard because the 
homosalate standard was only proposed for use for SPF testing of 
sunscreen products with SPF values lower than 15. Because most 
currently marketed sunscreen products have SPF values of 15 or higher, 
the padimate O/oxybenzone standard is used much more frequently than 
the homosalate standard.
    We received one submission identifying errors in the ``Composition 
of the Padimate O/Oxybenzone Standard Sunscreen'' table that appears in 
the 2007 proposed rule. As suggested by the submission, we are moving 
the inactive ingredient ``propylparaben'' from ``Part A'' to ``Part 
B,'' as it appears in the COLIPA SPF test. We are not revising the 
listing of the inactive ingredient ``glyceryl monostearate'' to read 
``glyceryl monostearate (Glyceryl Stearate SE),'' as suggested. The 
United States Pharmacopeia defines ``glyceryl monostearate'' as an 
``emulsifying and/or solubilizing agent,'' which adequately describes 
the ingredient that is appropriate for use in the formulation.

C. Test Subjects

    In the 2007 proposed rule, we proposed requiring the following 
numbers of test subjects providing valid results:
     20 to 25 subjects for sunscreen products with SPF less 
than 30
     25 to 30 subjects for sunscreen products with SPF value of 
30 or more

We explained that a minimum of 20 subjects would be required to provide 
an acceptably accurate SPF result (i.e., low standard error of the 
mean). We had concluded that sunscreen products with SPF values of 30 
or more required a greater number of test subjects because we suspected 
higher test result variability for these sunscreen products. However, 
the data used for determining appropriate test subject numbers were 
limited and dated. Therefore, we invited submission of additional data 
demonstrating what subject numbers would be adequate.
    Several submissions recommend requiring 10 to 25 test subjects as 
in the COLIPA SPF test (Ref. 1). These submissions include data 
demonstrating that SPF testing can be performed with suitable accuracy 
and precision with as few as 10 test subjects. The submissions further 
argued that SPF testing using a minimum of 10 test subjects has been 
practiced globally for many years, even for sunscreen products with 
high SPF values.
    We agree with the submissions and are lowering the number of test 
subjects required for SPF testing. We are requiring that a test panel 
produce a minimum of 10 valid test results. A maximum of three subjects 
may be rejected from the panel. Therefore, if 3 subjects would be 
rejected, a test panel would have had to include 13 subjects.
    We are reducing the number of test subjects in this document 
because the

[[Page 35647]]

data we received demonstrate that SPF testing can be conducted with 
adequate accuracy and precision using as few as 10 test subjects, even 
when testing high SPF products. The submissions include SPF test 
results for several sunscreen formulations using panels of 20 to 25 
test subjects. We randomly selected 10 subjects within each of these 
panels to determine if using fewer subjects significantly decreased 
test accuracy and precision. For each of these panels, the mean SPF 
value and standard error calculated from a randomly selected subset of 
10 subjects were not significantly different from those calculated from 
all 20 to 25 subjects in the panel. Therefore, these data indicate that 
using as few as 10 test subjects will not compromise SPF test accuracy 
or precision. Consequently, fewer test sites and subsites need to be 
tested and fewer test results need to be rejected, thereby decreasing 
the number of test subjects needed. Our revised SPF test subject number 
requirement is similar to the COLIPA SPF test requirement. The only 
significant difference related to test subject number is that we are 
not including a statistical requirement or allowing individual subjects 
to be added incrementally to a test panel as allowed under the COLIPA 
SPF test.

D. Test Sites and Subsites

    Several submissions requested the following revisions of the 
minimum size specifications for test sites and subsites proposed in the 
2007 proposed rule (Ref. 1):
     Test site: proposed 50 cm\2\ revised to 30 cm\2\
     Test subsite: proposed 1 cm\2\ revised to 0.5 cm\2\
     Subsite separation: proposed 1 cm revised to 0.8 cm

According to the submissions, these smaller revised minimum sizes would 
allow multiport solar simulators to be used, while the larger proposed 
sizes would not. These revised specifications have also been adopted in 
the COLIPA SPF test (Ref. 64).
    We are revising the test site and subsite size specifications as 
requested by these submissions. Our previously proposed specifications 
were based on single port solar simulators. Some new multiport solar 
simulators cannot meet these proposed specifications. In the 2007 
proposed rule, we stated that reducing test site/subsite size 
specifications would be considered if data were submitted showing that 
these reductions would not compromise testing accuracy (72 FR 49070 at 
49100). New data show that SPF testing can still be accurately 
performed using the recommended reduced test site/subsite size 
specifications (Ref. 1). Therefore, we are revising the test site/
subsite size specifications to accommodate new equipment and to 
harmonize our specifications with global SPF test methods.

E. Finger Cot

    In the 2007 proposed rule, we proposed that a finger cot, 
presaturated with sunscreen, be used to apply the sunscreen in the SPF 
test (proposed 21 CFR 352.70(c)(5)):

    Use a finger cot compatible with the sunscreen to spread the 
product as evenly as possible. Pretreat the finger cot by saturating 
with the sunscreen and then wiping off material before application. 
Preteatment is meant to ensure that sunscreen is applied at the 
correct density of 2 mg/cm \2\.

    We received one submission that objected to the use of finger cots 
because consumers do not typically use finger cots when applying 
sunscreens (Ref. 1). Other submissions argued that the presaturation 
requirement for finger cots is unnecessary and introduces variability 
in applied amounts (Ref. 1). Other submissions requested the optional 
use of sponge applicators for testing powder formulations, because they 
argued that sponge applicators distribute powder formulations more 
evenly than finger cots (Ref. 1). We are not addressing issues 
regarding the use of sponge applicators for the testing of powders in 
this rule. Elsewhere in this issue of the Federal Register, we publish 
an advance notice of proposed rulemaking that discusses sunscreen 
dosage forms, including powders. We may address this issue in a future 
rulemaking..
    While we acknowledge that consumers do not use finger cots to apply 
sunscreens, we are continuing to require the use of finger cots in the 
SPF test. The use of finger cots seems to increase reproducibility of 
test results, which was why we originally proposed requiring use of 
finger cots (72 FR 49070 at 49100 through 49101). We agree with the 
submissions that the presaturation requirement is unnecessary and are 
removing this requirement. We proposed requiring finger cot 
presaturation to prevent sunscreen product from adhering to the finger 
cot instead of being transferred to the test subject's skin, resulting 
in sunscreen product being applied at less than the intended 2 mg/cm 
\2\. We received study results showing that a residual amount of 
sunscreen product may adhere to non-presaturated finger cots, but the 
amount was small (approximately 2 percent) (Ref. 1). In this study, 
each of 100 finger cots (without presaturation) was weighed before and 
after sunscreen product application at 2 mg/cm \2\ (100 mg sunscreen 
product applied over 50 cm \2\). However, the study did not include a 
comparison to presaturated finger cots. Therefore, it is difficult to 
determine the effect of presaturation on residual sunscreen amounts.
    In addition, we reassessed the basis for presaturation. We are now 
concerned that performing the presaturation step may lead to 
overestimation of SPF values, because the residual amount normally left 
on a finger cot with presaturation may increase the amount of sunscreen 
applied to the skin This could lead to overestimation of SPF values. 
Overestimation of SPF may, in turn, lead to increased incidence of 
sunburn because consumers may anticipate greater protection than a 
sunscreen product actually provides. This overestimation risk is a 
sufficient basis to remove the presaturation step from the proposed SPF 
test method.
    We also received data showing that testing without the 
presaturation step can produce highly reproducible results (Ref. 1). In 
a test of 20 subjects without the presaturation step, a control 
sunscreen product yielded a mean SPF value of 4.19 with a standard 
error of 0.06 (i.e., 1.4 percent error), while a test sunscreen product 
yielded a mean SPF value of 15.54 with a standard error of 0.22 (i.e., 
1.4 percent error). These errors are small, suggesting that the 
calculated SPF values did not vary significantly between test subjects. 
If lack of presaturation increased variability, then the errors would 
be expected to be larger. Therefore, we are removing the presaturation 
requirement because of the risk of overestimation of SPF values and our 
conclusion that the removal of the presaturation step will not affect 
the reproducibility of SPF test results.

F. Application Amount

    We are continuing to require that 2 mg/cm\2\ sunscreen product be 
applied for the SPF test (proposed 21 CFR 352.70(c)(5); new 21 CFR 
201.327(i)(4)(iii)). Several submissions argued for a lower application 
amount that better reflects the actual amount used by consumers, which 
they argued is commonly 1 mg/cm\2\ or less (Ref. 1). These submissions 
argued that the unrealistically high 2 mg/cm\2\ application amount 
results in SPF values that overstate the actual sun protection provided 
by the amounts consumers typically apply. Other submissions supported 
the 2 mg/cm\2\ application amount (Ref. 1). These submissions argued 
that SPF values are relative, not absolute, values that allow 
comparison of sun protection provided

[[Page 35648]]

by different sunscreen products. According to the submissions, changing 
the application amount will affect the ability of consumers to make 
this comparison.
    We are not changing the sunscreen product application amount 
because we have concluded that the advantages of continuing to require 
2 mg/cm\2\ exceed the disadvantages of lowering the amount. Requiring 
the 2 mg/cm\2\ sunscreen product application amount is consistent with 
SPF test methods used in other countries. The 2 mg/cm\2\ application 
amount is being used in Europe, Australia, Canada, Korea, and Japan 
(Refs. 65-67). If we lower the application amount, sunscreen products 
available in the United States will have significantly lower SPF values 
than similar products available in other countries. This discrepancy in 
SPF values is counterproductive to our global harmonization efforts and 
would likely mislead consumers traveling to other countries about the 
SPF protection of foreign sunscreen products.
    Another advantage of continuing to require a 2 mg/cm\2\ sunscreen 
product application amount is greater reproducibility of SPF test 
results. Bimczok et al. compared the SPF values determined using 
sunscreen product application amounts of 0.5, 1, and 2 mg/cm\2\ (Ref. 
68). The SPF values determined using 2 mg/cm\2\ sunscreen product were 
more reliable and reproducible than SPF values determined using the 
lower application amounts. A sunscreen product application amount of 2 
mg/cm\2\ is a large enough amount to allow visualization of the 
distribution of sunscreen product as it is applied. This allows for 
more consistent and uniform application of the sunscreen used in 
testing. Therefore, the 2 mg/cm\2\ sunscreen product application amount 
is more likely to generate reproducible results.

G. Water Resistance

    In the 2007 proposed rule, sunscreen products tested with two 20-
minute immersion periods (i.e., 40 minutes total) would be allowed to 
include a ``water resistant'' statement and sunscreen products tested 
with four 20-minute immersion periods (i.e., 80 minutes total) would be 
allowed to include a ``very water resistant'' statement. There is a 20-
minute drying period between each immersion period. For example, a 
``water resistant'' sunscreen product would be tested by having test 
subjects in the water for 20 minutes, out of the water for 20 minutes, 
and in the water for 20 minutes.
    We received various requests to revise the test (Ref. 1). One 
submission recommended longer water immersion times equal to those in 
water resistance tests used in Australia and New Zealand. Another 
submission included data from an in vitro water resistance test to 
support removing the in vivo water resistance test. A third submission 
stated the test should be eliminated because it is not validated and 
requires too much time. Further, the submission argued that directions 
for frequent reapplication make the test unnecessary.
    We are continuing to include a water resistance test because water 
resistance is an important property of sunscreen products that can 
benefit consumers. The water resistance test indicates that a sunscreen 
product's labeled SPF protection is retained for a certain period of 
time after immersion in water. This is useful information to consumers. 
Therefore, we conclude that a water resistance statement based on the 
test should be allowed (see section III.C of this document).
    We are not changing the 20-minute water immersion periods or the 
number of immersion periods required. We based these time periods on 
marketing data indicating that individuals at the beach or the pool 
spend an average of 21 minutes in the water and go into the water an 
average of 3.6 times (43 FR 38206 at 38263, August 25, 1978). We have 
not received any other data supporting different time periods. We have 
concluded that more or longer water immersion periods are not needed.
    We are, however, reducing the drying period from 20 minutes to 15 
minutes. We are making this change to decrease the time required for 
testing. Shorter testing time may increase test accuracy and 
reproducibility, especially for high SPF sunscreens that retain their 
water resistance for 80 minutes. In addition, 15 minutes is adequate 
time to allow for drying. It is possible that sunscreens may lose water 
resistance with repeated wetting and drying. However, we have concluded 
that a 15-minute drying period mimics consumer behavior and ensures 
that the water resistant properties of a sunscreen do not change with 
multiple cycles of water immersion and drying.

VII. SPF Test Issues (Other than Test Parameters)

A. Pass/Fail (Binomial) SPF Test

    Several submissions requested the optional use of a pass/fail 
(binomial) test to determine the SPF value of a sunscreen product (Ref. 
1). These submissions promote the pass/fail test because it would 
expose fewer subjects to UV irradiation, cost less, and save time. The 
pass/fail test is based on the hypothesis that a sunscreen product of a 
certain SPF has a 50:50 probability of preventing the MED response when 
irradiated with a UV dose correlated with that SPF. For example, a 
sunscreen product with an expected SPF value of 30 or more should 
prevent the MED response in greater than 50 percent of test subsites 
irradiated with a UV dose equivalent to 30 times the UV dose that 
causes the MED response on unprotected skin. If a test sunscreen 
product prevents the MED response in a significant number of the 
subsites (i.e., significantly more subsites that ``pass'' versus 
``fail''), then the test sunscreen product would be allowed to be 
labeled with the SPF correlated to the UV dose.
    We are not including the optional use of a pass/fail test for SPF 
testing. We considered a pass/fail SPF test in the 2007 proposed rule 
(72 FR 49070 at 49094 to 49095). We stated that a pass/fail test could 
be a reasonable substitute for our proposed SPF test for sunscreen 
products with SPF values of 30 or more if certain modifications were 
made and validation data demonstrated that the test could be performed 
similarly between labs.
    In response to our invitation for public comment, one submission 
included two studies comparing a pass/fail SPF test to the proposed SPF 
test: (1) A single center study of four sunscreen products with 
different SPF values and (2) a multicenter (four laboratories) study of 
two high SPF sunscreen products. After reviewing these data, we have 
determined that the pass/fail test has the following drawbacks:
     Each test subsite evaluation is biased towards ``pass'' 
because the evaluator expects that no skin reaction should occur on 
subsites protected by the test sunscreen product.
     The test fails to reject test sites where all of the 
subsites show positive responses or all of the subsites show negative 
responses.
     The validity of treating each subsite as an independent 
variable is questionable.
     The test endpoint (any observed reaction) differs from the 
endpoint in the proposed SPF test (clearly defined erythema).
     A passing test result for the sunscreen standard does not 
demonstrate that the test is being performed correctly.
     Test results do not include data for water resistant 
sunscreen products.
     Allowing this test as an option would yield products with 
different UV

[[Page 35649]]

protection levels labeled with the same SPF.
     SPF test methods developed by various standards-setting 
organizations do not include a pass/fail test.
     The study report includes statistical errors that 
overstate the statistical power of the test to distinguish whether a 
test sunscreen product provides significant UV protection.

Therefore, we are not including a pass/fail test in the SPF test 
procedure, because including a pass/fail test would present numerous 
complications and the available data indicate that a pass/fail test has 
disadvantages compared to the SPF test included in this document.

B. Photostability

    Several submissions expressed concern about the loss of UV 
protection by sunscreen products due to breakdown of ingredients from 
exposure to sunlight (Ref. 1). These submissions recommended a test to 
ensure that sunscreen products exposed to sunlight retain sufficient UV 
protection. Submitted data show that the composition of sunscreen 
products can change from exposure to UV radiation. The submissions 
argue that the published photostability studies are inconclusive 
because the studies employ artificial test conditions that may not be 
appropriately extrapolated to actual use of sunscreens:
     Tested sunscreen active ingredients were contained in 
solutions rather than in typical sunscreen product formulations
     Tested sunscreen products contained active ingredients 
that are not representative of the active ingredients included in 
typical sunscreen products
     Products were tested over a limited range of the UV 
spectrum

The submissions argue that understanding the photostability of 
sunscreen active ingredients alone is not useful. Rather, the 
submissions argue that it is critical to understand the photostability 
of sunscreen active ingredients as part of an overall sunscreen 
product.

    We agree that the available data have limitations. Although the 
submissions argue that the inconclusive data support including a test 
for photostability, we have concluded that the data do not justify 
requiring a photostability test at this time. We are not able to 
establish specific photostability test procedures or specifications 
based on the available data. We have not received data validating the 
performance of a photostability test, nor have we received data 
demonstrating that the effectiveness of any particular sunscreen 
product is significantly diminished because of photodegradation. We 
maintain that the proposed SPF test procedure does account for 
photostability to some extent, because the SPF test exposes sunscreen 
products to UV radiation before an SPF value is determined. 
Consequently, sunscreen products susceptible to photodegradation have 
correspondingly lower SPF values. One submission argued that the SPF 
test does not fully account for photostability because the solar 
simulator emission spectrum is different than natural sunlight. 
However, this difference is an unavoidable limitation in testing 
because solar simulators cannot perfectly replicate natural sunlight.
    We acknowledge that UV radiation can change the composition of 
sunscreen products if the products are not photostable, as demonstrated 
by the submitted data. However, we are not certain that these data are 
applicable under actual use conditions. The data regarding the effects 
of UV radiation on the protection provided by sunscreen active 
ingredients are limited and inconclusive. Therefore, we are not 
creating a photostability test as part of the SPF test procedure in 
this document.

C. In Vitro SPF Test

    One submission suggested replacing the proposed in vivo SPF test 
with an in vitro SPF test (Ref. 1). An in vitro SPF test would have 
advantages of faster performance, lower expense, and no exposure of 
subjects to UV radiation.
    We agree that an in vitro SPF test has these advantages. However, 
we are not replacing the in vivo SPF test with an in vitro SPF test for 
the same reasons we stated in the 2007 proposed rule (72 FR 49070 at 
49095). One shortcoming of an in vitro test is the lack of data on the 
performance characteristics of in vitro test substrates, such as quartz 
or artificial skin. In the 2007 proposed rule, we stated that data 
failed to show that a substrate adequately mimicked the physiological 
characteristics of human skin. We stated that we would consider an in 
vitro test if validating data demonstrated that the performance of the 
in vitro test was equivalent to the in vivo test. We have not received 
adequate data to validate an in vitro SPF test. Therefore, we are not 
including an in vitro test in this document.

D. Anti-Inflammatory Ingredients

    One submission recommended requiring a test to verify that 
sunscreen products do not contain anti-inflammatory ingredients that 
significantly decrease erythemic response to UV radiation (Ref. 1). The 
submission did not identify specific anti-inflammatory ingredients. The 
submission argued that, by decreasing the erythemal response, these 
ingredients could falsely inflate SPF values determined in SPF testing. 
In addition, these anti-inflammatory ingredients may increase the 
likelihood of unwanted harmful effects from sun exposure because 
sunburn, a cue to avoid sun exposure, would be less evident.
    Although the submission raises a serious concern, we are not aware 
of any data confirming that this problem exists. Therefore, a test to 
show that anti-inflammatory ingredients may be decreasing erythemic 
response to UV radiation is not required at this time. It seems 
unlikely that anti-inflammatory ingredients will affect SPF values 
because their anti-erythemic effect is relatively short-lived compared 
to the 16-24 hour interval between UV exposure and erythema observation 
in the SPF test.

VIII. Broad Spectrum Test

    In this document, we are referring to testing involving the UVA 
part of the spectrum as ``broad spectrum testing.'' The term ``broad 
spectrum'' more accurately describes the test as covering the full 
extent of the terrestrial solar UV spectrum (i.e., UVA and UVB 
radiation). Section VIII.A. of this document provides our rationale for 
no longer requiring an in vivo test assessing the persistent pigment 
darkening associated with UVA radiation. Section VIII.B. of this 
document explains why the in vitro test should be changed from a 
modified Diffey-Robson ratio to the critical wavelength test. Section 
VIII.C. defines the testing parameters to be employed in evaluating the 
critical wavelength of an OTC sunscreen product.

A. In Vivo Test Method: Not Required

    We stated in the 2007 proposed rule that an assessment of UVA 
protection should include determination of both the magnitude and 
breadth of absorption in the UVA part of the spectrum (72 FR 49070 at 
49102 through 49106). We proposed that an in vivo Persistent Pigment 
Darkening (PPD) test be used to evaluate the magnitude of absorption 
and an in vitro test be used to evaluate the breadth of absorption. The 
PPD test, a modification of the PPD test accepted by JCIA \10\ since 
1996, is almost identical to the SPF test. It is recognized as a 
standard for the in vivo assessment of UVA protection by the JCIA and 
the European Commission

[[Page 35650]]

(Ref. 7). The most significant differences in the PPD test compared to 
the SPF test are (1) the light source emits only UVA radiation (320-400 
nm) and (2) the endpoint is darkening of the skin (tanning) rather than 
reddening of the skin (erythema).
---------------------------------------------------------------------------

    \10\ Japanese Cosmetic Industry Association.
---------------------------------------------------------------------------

    We have concluded that the PPD test is not necessary to establish 
that a sunscreen product provides protection against UVA radiation. The 
magnitude of absorption over the solar terrestrial UV portion of the 
spectrum (both UVA and UVB) can be effectively assessed based on the 
SPF test in combination with a pass/fail broad spectrum in vitro test 
(see Section VIII.B of this document). If sunscreen products pass the 
in vitro broad spectrum test, then the amount of UVA radiation 
protection, as well as UVB radiation protection, must increase as the 
SPF value increases. For example, a Broad Spectrum SPF 40 sunscreen 
product must provide more UVB and UVA radiation protection than a Broad 
Spectrum SPF 20 sunscreen product.
    For sunscreen products that pass the in vitro broad spectrum test, 
we have concluded that the SPF and PPD tests are redundant of each 
other, but we have reasons to prefer the SPF test. The SPF and PPD 
tests are both clinical and indicative of the magnitude of absorbance 
of UV radiation. Furthermore, both tests depend on the skin type of the 
individual. The SPF test measures skin reddening, which is due 
primarily to UV radiation in the UVB and UVA II regions (290-340 nm). 
The PPD test measures skin darkening, which is due primarily to UV 
radiation in the UVA II part of the spectrum (320-340 nm). Therefore, 
the UV radiation range covered by the PPD test is also covered by the 
SPF test. In both tests, the endpoint is indicative of how much UV 
radiation is absorbed. As the magnitude of UV radiation absorbance 
increases for a sunscreen product, both the SPF and PPD ratings 
increase.
    We have identified several disadvantages of the PPD test as 
described in the proposed rule (72 FR 49070 at 49103):
     Human subjects are exposed to high doses of UVA radiation 
with unknown health consequences.
     Exposure to UVA radiation alone (i.e., in the absence of 
UVB radiation) is never encountered in nature, and the biological 
effects of such exposure may differ greatly from those due to exposure 
to natural sunlight.
     Because it is unclear how tanning relates to the harmful 
effects of sunlight, it is unclear whether persistent pigment darkening 
represents a clinically meaningful endpoint.

Other disadvantages are pointed out by Nash et al. (Ref. 4):

     The physical properties of sunscreen products may differ 
when sunscreen products are exposed to UVA radiation alone.
     The PPD test is expensive, time consuming, and labor 
intensive.
     The ability to identify small differences in pigmentation 
requires a high degree of expertise and interpretation of pigmentation 
changes will be dependent on the examiner.
     There may be a high degree of variability in test results 
between subjects in the same test panel as well as between different 
test panels for the same sunscreen product.
     The test results may not be reproducible between labs.
    Because of these disadvantages of conducting the PPD test, and the 
fact that information obtained from such tests is already provided by 
SPF testing for sunscreen products that pass the in vitro broad 
spectrum test, we are eliminating the requirement to conduct a PPD or 
any other in vivo UVA test in this final rule.

B. In Vitro Test Method: Critical Wavelength

    Many submissions objected to our proposal to use a modification of 
the Boots adaptation of the Diffey/Robson ratio as an in vitro measure 
of UVA protection (Ref. 1). The Diffey/Robson ratio evaluates UVA 
protection relative to UVB protection. The ratio is calculated as the 
area under the absorbance curve in the UVA region (320-400 nm) divided 
by the area under the absorbance curve in the UVB region (290-320 nm). 
As the degree of protection against UVA radiation increases, the ratio 
increases.
    We proposed a modification of this ratio to be calculated as the 
area under the absorbance curve in the UVA I region (340-400 nm) 
divided by the area under the absorbance curve over total UVB and UVA 
range (290-400 nm). We indicated that this modification was necessary 
because we were concerned that a sunscreen product absorbing strongly 
in the UVA II region (320-340 nm), but not absorbing strongly in the 
UVA I region, might produce a disproportionately high ratio value (72 
FR 49070 at 49105). We would not consider this sunscreen product to be 
a good broad spectrum sunscreen product even though it has a high ratio 
value. We noted the importance of ensuring that protection extends well 
into the UVA I region (340-400 nm), because neither SPF nor PPD 
measurements provide much information about the longer wavelengths of 
UVA radiation. Therefore, we modified the ratio to give more emphasis 
to the UVA I area under the absorbance curve.
    Many submissions argued that we should require a determination of 
critical wavelength rather than the proposed ratio to determine broad 
spectrum protection (Ref. 1). We agree with the arguments made in the 
submissions. Therefore, in this document, we are requiring that broad 
spectrum protection be assessed by determining the critical wavelength 
of a sunscreen formulation. The submissions noted the following 
disadvantages with the proposed ratio:
     The proposed ratio places too much emphasis on the UVA I 
region, which is not generally considered to contribute significantly 
to the harmful effects of exposure to UV radiation.
     A large ratio could result if one or more ingredients 
absorb radiation in the shorter wavelength UVA II region but not at all 
or only minimally in the longer wavelength UVA I region. For example, 
oxybenzone absorbs radiation at 340-360 nm, and inclusion of this 
ingredient at higher concentrations might result in a high ratio even 
though it does not provide true broad spectrum protection.
     The proposed ratio is not a validated measure of UVA 
protection and is not used anywhere else in the world.
     To achieve high ratios with existing GRASE active 
ingredients, the concentrations of ingredients that absorb in the UVB 
and UVA II parts of the spectrum have to be reduced, lowering 
protection in these parts of the spectrum (i.e., the SPF has to be 
lowered to increase the ratio).
    We agree that our proposed ratio is not the most appropriate in 
vitro measure of broad spectrum protection. In agreement with many of 
the submissions, we have concluded that the ratio places too much 
emphasis on absorption in the UVA I part of the spectrum. Although 
there is some evidence that UVA I radiation contributes to immune 
suppression and an increase in p53-positive cells, the effects of UVA I 
radiation on these processes are 100 to 1000 times less than the 
effects attributed to UVB and UVA II radiation (Ref. 4). We also 
acknowledge that there is no experience using the proposed ratio. 
Further, we received some data in the submissions that demonstrate the 
need to reduce SPF values in order to achieve high ratio values. We are 
concerned that, in an effort to gain UVA protection, consumers may be 
more susceptible to

[[Page 35651]]

sunburn because SPF values could be lower in products with higher 
ratios.
    In agreement with many of the submissions, we have concluded that 
the critical wavelength method provides a better measure of broad 
spectrum protection. The critical wavelength ([lambda]c) is 
derived from the same data as the modified ratio. The critical 
wavelength is the wavelength at which the area under the absorbance 
curve represents 90 percent of the total area under the curve in the UV 
region. This is expressed mathematically as:
[GRAPHIC] [TIFF OMITTED] TR17JN11.001

In this expression, A([lambda]) is the mean absorbance at each 
wavelength, and d[lambda] is the wavelength interval between 
measurements.
    Like the proposed ratio, the critical wavelength measures the 
breadth of the UV absorbance curve. Unlike the proposed ratio, the 
critical wavelength does not emphasize certain parts of the UV 
spectrum, but is a measure of absorbance across the entire solar 
terrestrial UV spectrum (UVB and UVA radiation). Sunscreen products 
offering primarily UVB protection would have a critical wavelength less 
than 320 nm, whereas those providing both UVB and UVA protection would 
have critical wavelengths between 320 and 400 nm.
    The critical wavelength method is simple, reproducible, and 
inexpensive. It has been used by sunscreen manufacturers to evaluate 
UVA protection for over a decade and is one of the most commonly used 
UVA tests. This is evidenced by the organizations that recommend its 
use for determining broad spectrum protection, including the European 
Commission, the American Academy of Dermatology, the American Society 
for Dermatologic Surgery, and the Skin Cancer Foundation (Ref. 1).
    In this document, we are requiring that sunscreen products have a 
critical wavelength of at least 370 nm (the mean value must be equal to 
or greater than 370 nm) to be labeled as providing broad spectrum 
protection (see section VIII.B.). This differs from the tiered rating 
(low, medium, high, and highest) that we included in the 2007 proposed 
rule (proposed 21 CFR 352.50(b)(2)). We have concluded that the 
threshold critical wavelength for a broad spectrum statement should be 
370 nm. This wavelength is sufficiently difficult to achieve and will 
ensure that sunscreen products meeting this threshold provide a 
significant amount of broad spectrum protection. On the other hand, it 
is not so difficult to formulate sunscreen products to achieve this 
critical wavelength that manufacturers cannot develop broad spectrum 
sunscreen products. We have concluded that UV radiation in the range of 
370--400 nm is not very harmful based on the available action spectra 
for sunburn and skin cancer. We conclude that most of the harmful 
effects from the sun are caused by UV radiation in the range of 290--
370 nm. Further, we conclude that critical wavelength (breadth of UVB 
and UVA protection) coupled with the SPF value (magnitude of UVB and 
UVA protection) provides a complete measure of broad spectrum 
protection provided by a sunscreen product.

C. Critical Wavelength Test Parameters

    Although the proposed ratio and critical wavelength calculations 
are different, both tests are based on the construction of a 
transmittance curve over the range of UV wavelengths from 290 to 400 
nm. We received several submissions requesting that we change or, in 
some cases, better define aspects of the methodology used to measure 
transmittance over these wavelengths (Ref. 1). Although the 
submissions, in most cases, referred specifically to the proposed ratio 
test, the points made regarding methodology apply equally to the 
critical wavelength test.
    We are making several revisions to the section we referred to as 
the ``UVA in vitro testing procedure'' in the 2007 proposed rule 
(proposed 21 CFR 352.71). To more accurately describe the test as 
covering both the UVB and UVA regions of the spectrum, we now refer to 
the test as the ``broad spectrum test.'' The revisions are listed in 
Table 5 in the order in which they appear in this section of the 
document.

     Table 5--Summary of Revisions to the Proposed in Vitro Broad Spectrum Test Included in This Final Rule
----------------------------------------------------------------------------------------------------------------
       Revised test  parameter                     2007 proposed rule                     This final rule
----------------------------------------------------------------------------------------------------------------
Plate................................  Quartz plate (21 CFR 352.71(b))             PMMA\1\ plate (21 CFR
                                                                                    201.327(j)(1)(i))
Term ``spectroradiometer''...........  Spectroradiometer                           Spectrometer
                                       (21 CFR 352.71(c) and (d))                  (21 CFR 201.327(j)(1)(ii),
                                                                                    (iv), and (v))
Light source for transmittance         Solar simulator                             Produce a continuous spectral
 measurements.                         (21 CFR 352.71(a))                           distribution of UV radiation
                                                                                    from 290 to 400 nanometers
                                                                                   (21 CFR 201.327(j)(1)(iii)
Input optics: Bandwidth..............  5 nanometers                                1 nanometer
                                       (21 CFR 352.71(d))                          (21 CFR 201.327(j)(1)(iv))
Dynamic range of the spectrometer....  Not specified                               Sufficient to measure
                                                                                    transmittance accurately
                                                                                    through highly absorbing
                                                                                    sunscreen (21 CFR
                                                                                    201.327(j)(1)(v))
Application of sunscreen drug product  2.0 mg/cm\2\ with single-phase spreading    0.75 mg/cm\2\ with 2-phase
 to plate.                              (21 CFR 352.71(e))                          spreading (21 CFR
                                                                                    201.327(j)(2))
Pre-Irradiation dose.................  Proportional to SPF value (21 CFR           Fixed at 800 J/m\2\-eff (21
                                        352.71(f))                                  CFR 201.327(j)(3))
Number of transmittance measurements.  12 measurements of mean transmittance on 5  5 measurements of mean
                                        different plates (21 CFR 352.71(g) and      transmittance on 3 different
                                        (i))                                        plates (21 CFR 201.327(j)(4)
                                                                                    and (6))
Calculation of critical wavelength...  Not applicable                              21 CFR 201.327(j)(7))
----------------------------------------------------------------------------------------------------------------
\1\ Polymethylmethacrylate


[[Page 35652]]

    We re-organized the broad spectrum test parameters in this final 
rule so that they are listed in the order that the test is done. This 
section of the document begins with a description of the plates to be 
used and the requirements for UV spectrometry. The next section 
addresses application of the sunscreen product to the plate, and the 
following section addresses the pre-irradiation procedure. The last 
sections included under broad spectrum test parameters address 
measuring the amount of radiation transmitted through the sunscreen 
product, converting these measurements to absorbance values, and 
calculating the critical wavelength of a sunscreen product.
    All of the proposed test parameters were re-evaluated in the 
preparation of this document. Some of the parameters did not require 
revision. Test parameters not revised include:
     Sample holder
     Input optics (other than slit width)
     Light source for pre-irradiation
     Calculation of mean transmittance values
     Calculation of mean absorbance values
    The parameters defined in this section are based on our review of 
submitted data (Ref. 1) and peer-reviewed literature. Wherever possible 
and consistent with sound science, we have attempted to harmonize the 
parameters with existing standards, including those of the European 
Commission (Ref. 7) and COLIPA (Ref. 69). As stated earlier in this 
document, we are also actively involved in the ISO working group 
responsible for developing methodologies for assessing sun protection 
(both UVB and UVA protection).
1. Plate
    Many submissions argued that we should specify that roughened PMMA 
(polymethylmethacrylate) plates be used as a substrate rather than 
roughened quartz included in the 2007 proposed rule (Ref. 1). The 
submissions stated that they prefer PMMA plates because these plates 
are:
     Less expensive than quartz
     Disposable--no need to clean or re-roughen
     Readily available with roughened surface
     Validated in COLIPA ring tests and in widespread use for 
more than a decade
     Recommended by the European Commission and COLIPA
    We agree with these submissions and are specifying, in this 
document, that PMMA plates be used as the substrate in this document. 
We are specifying the use of PMMA plates primarily because the vast 
majority of validation data we have reviewed was collected using PMMA 
rather than quartz plates. Further, we agree with the submissions 
noting that PMMA plates are less expensive than quartz and, therefore, 
can be disposable. The disposability of the PMMA plates will eliminate 
the requirements for cleaning and re-roughening the surface 
characteristic of quartz plates.
    Consistent with COLIPA, we are also specifying the degree of 
roughness and size of the application area on these plates. Plates 
should be roughened on one side to a three-dimensional surface 
topography measure (Sa) between 2 and 7 micrometers. These Sa values 
are supported by validation studies (Ref. 70) and are comparable to 
those recommended by COLIPA (Ref. 69). The application area must be at 
least 16 square centimeters with no side shorter than 4 centimeters. We 
are also replacing the word ``substrate'' with the simpler and more 
widely used term ``plate.''
    These changes are included in 21 CFR 201.327(j)(1)(i) of this 
document. Specifying standardized roughness and size parameters will 
result in more accurate and reproducible intra- and inter-laboratory 
measurements of broad spectrum photoprotection. Because these PMMA 
plates of specified roughness and size are already being used in many 
parts of the world and are recommended by COLIPA, we have concluded 
that they can be employed in broad spectrum testing in this country 
with minimal expense or training of personnel.
2. ``Spectroradiometer'' vs. ``Spectrometer''
    Four submissions asked us to replace the term ``spectroradiometer'' 
with the more generally used term ``spectrophotometer'' (Ref. 1). We 
originally chose the term ``spectroradiometer'' because UV radiation is 
not detectable by the human eye and, therefore, is not gauged by 
photometry (which measures visible light). However, the term 
``spectrophotometer'' is often used interchangeably with the term 
``spectroradiometer.'' In this document, we are replacing the term 
``spectroradiometer'' with the more inclusive term ``spectrometer.'' 
Use of the term ``spectrometer'' allows the use of either a 
spectroradiometer or spectrophotometer and will make the language more 
consistent with current COLIPA guidelines (Ref. 69).
3. Light Source for Transmittance Measurements
    Four submissions (Ref. 1) asserted that it is inappropriate to 
specify a solar simulator as the light source for measuring 
transmittance (proposed 21 CFR 352.71(a)). Three of the submissions 
argued that radiation emitted from a solar simulator is filtered such 
that there is very low energy output in the UV region below 300 nm 
(Ref. 1). One submission noted that a light source filtered in this way 
cannot provide sufficient energy to measure transmittance through 
highly absorbing sunscreen products. The same submission suggested that 
there may not be enough transmittance at wavelengths less than 300 nm 
to exceed the noise level of the system even in the absence of a 
sunscreen product (when transmittance should be maximal).
    We agree with the submissions and, in 21 CFR 201.327(j)(1)(iii) of 
this document, are specifying that the light source for transmittance 
measurements provide continuous, full spectrum radiation from 290 to 
400 nanometers. The use of such a light source should maximize 
instrument transmission properties while retaining full sensitivity. We 
note that this type of light source is recommended by COLIPA (Ref. 69).
4. Wavelength Interval Between Transmittance Measurements
    Two submissions argued that we should reduce the wavelength 
intervals between transmittance measurements from the proposed 5 nm to 
1 nm (Ref. 1). The submissions stated that specifying a smaller 
interval would produce more accurate results and noted that current 
spectrometers are capable of making measurements at 1 nm intervals. We 
agree with the submissions. Additionally, we are aware that the COLIPA 
guideline (Ref. 69) specifies that transmittance measurements are to be 
taken at 1 nm intervals. Therefore, we are revising the required input 
slit bandwidth in this document to specify that it be less than or 
equal to 1 nm (new 21 CFR 201.327(j)(1)(iv)). We are also revising the 
measurement interval (new 21 CFR 201.327(j)(4)) to state that 
transmittance values should be measured at 1 nm intervals.
5. Dynamic Range of the Spectrometer
    We are adding new 21 CFR 201.327(j)(1)(v) to specify that the 
dynamic range of the spectrometer be ``sufficient to measure 
transmittance accurately through a highly absorbing sunscreen product 
at all UV

[[Page 35653]]

wavelengths (between 290 and 400 nm).'' The information in this section 
had been included in the section entitled ``Calculation of the spectral 
transmittance at each wavelength interval'' in the proposed rule 
(proposed 21 CFR 352.71(g)). We considered requiring a minimum dynamic 
range of 2.2 absorbance units, as specified in the COLIPA guidelines 
(Ref. 69). However, we have concluded that it is not necessary to 
include this requirement because nearly all current spectrometers are 
capable of measuring a dynamic range of 2.2 absorbance units or better.
6. Application of Sunscreen Product to PMMA Plate
    Thirteen submissions (Ref. 1) expressed one or more concerns over 
the method by which we proposed applying sunscreen product to the plate 
(proposed 21 CFR 352.71(e)). Eleven of the thirteen submissions 
recommended we reduce the amount applied from 2 milligrams per square 
centimeter (mg/cm\2\) to between 0.75 and 1.2 mg/cm\2\. Three 
submissions suggested we specify that the sunscreen product be applied 
with a better defined spreading action. Two submissions requested we 
consider requiring that a saturated fingertip be used to apply the 
product rather than a gloved finger.
    We are reducing the application amount in this document because 
transmittance of UV radiation through a film of 2 mg/cm\2\ thickness is 
low and, therefore, can result in inaccurate and/or irreproducible 
measures of UVA protection. UV detectors have a range of UV radiation 
that they can accurately measure referred to as the dynamic range. If 
UV radiation is outside the dynamic range (either lower or higher), 
measurements from the detector become less accurate and often less 
reproducible. We received validation data demonstrating that 
application amounts lower than 2 mg/cm\2\ are more accurate and 
reproducible than an application of 2 mg/cm\2\ (Ref. 1). The 2007 
proposed rule required an application amount of 2 mg/cm\2\ because this 
is the amount specified in the proposed in vivo SPF and PPD tests. We 
are not including the PPD test in this document and we have concluded 
that consistency with the SPF test is not warranted given the concerns 
about inaccurate and/or irreproducible results with an application 
amount of 2 mg/cm\2\ in the in vitro UVA method. A reduced application 
amount is consistent with the COLIPA guidelines (Ref. 69). Both of 
these documents specify an application amount of 0.75 mg/cm\2\. Data we 
have reviewed from the Personal Care Product Council demonstrate that 
application of 0.75 to 1.0 mg/cm\2\ results in good transmission within 
the dynamic range of UV detectors (Ref. 1). Therefore, in this 
document, we are reducing the application amount to 0.75 mg/cm\2\ to 
ensure the UV radiation transmitted through sunscreens is within the 
dynamic range of UV detectors (21 CFR 201.327(j)(2)).
    We are also specifying the type of spreading action to be employed 
when applying sunscreen product to a plate. One submission noted that 
the type of spreading action employed would depend on the type of 
product being applied. The submission argued that it might take 30 
seconds to evenly spread thicker water resistant creams, but only 10 
seconds to evenly spread lotions or oils. We recognize that the very 
light spreading action for 10 seconds we proposed may not be sufficient 
to evenly distribute all dosage forms on a plate (proposed 21 CFR 
352.71(e)). One submission provided data from a ring test involving 7 
different laboratories showing that the UVAI/UV absorbance ratio is 
affected by the amount of pressure applied during application. A second 
submission referenced a paper by Ferrero et al. which shows that light 
pressure applied to some sunscreen products results in different ratios 
than application with greater pressure (Ref. 70). Both submissions 
recommended adopting a two-phase application process like that 
recommended by COLIPA (Ref. 69).
    We agree that a two-phase spreading action is a more effective 
means of achieving a film of uniform thickness and distribution for a 
variety of sunscreen dosage forms than is the proposed 10 seconds of 
light spreading. This type of spreading action is more reflective of 
actual use than the method we proposed. Therefore, we are harmonizing 
the standard with the COLIPA guidelines by specifying that a two-phase 
process be used. Section 201.327(j)(2) in this document specifies that 
``spreading should be done with a very light spreading action for 
approximately 30 seconds followed by spreading with greater pressure 
for approximately 30 seconds.''
    Two submissions argued that we should specify a saturated fingertip 
be used rather than a gloved finger. We do not agree for the reasons 
specified in section VI.E of this document.
7. Pre-Irradiation Dose
    Several submissions expressed concern that the pre-irradiation dose 
we proposed to account for differences in photostability is too high, 
particularly if we reduce the application amount (Ref. 1). We proposed 
that the pre-irradiation dose be proportional to the SPF value of a 
sunscreen product (proposed 21 CFR 352.71(f)). This was to account for 
the possibility that consumers may spend more time in the sun with 
higher SPF products. Proportional pre-irradiation dosing is also 
recommended in the testing procedure published by COLIPA (Ref. 69). In 
these documents, the pre-irradiation dose is determined relative to the 
UVA protection factor. Pre-irradiation dose increases as the UVA 
protection factor increases.
    Two submissions suggested that we use a fixed or absolute dose 
rather than a relative dose proportional to the SPF value of a 
sunscreen product (Ref. 1). The submissions noted that, at the same 
time and location on the earth's surface, all sunscreen products are 
exposed to the same intensity of sunlight. Therefore, sunscreen 
products with higher SPF values or UVA protection factors should not be 
exposed to higher pre-irradiation doses.
    We agree with these two submissions. It is appropriate to evaluate 
sunscreen product photostability using a fixed exposure intensity. We 
have data demonstrating that avobenzone-containing sunscreen products 
undergo almost complete photodegradation when exposed to doses between 
2 and 3 MEDs \11\ (Ref. 71). At a dose of 4 MEDs, there were no further 
decreases in UVB and UVA absorption of five different sunscreen 
products containing 2.5- to 3- percent avobenzone. These data reflect 
the worst case scenario for photodegradation because avobenzone appears 
to be the least photostable active ingredient in the sunscreen 
monograph. Therefore, all sunscreen products marketed under the 
monograph are likely to be completely degraded after 4 MEDs. Based on 
this data, we are specifying a fixed pre-irradiation dose equivalent to 
4 MEDs. As we noted in the 2007 proposed rule, one MED for a skin type 
II individual is 200 J/m\2\-eff (72 FR 49070 at 49107). Therefore, in 
this document, we are specifying a pre-irradiation dose of 4 times 200 
J/m\2\-eff (800 J/m\2\-eff).
---------------------------------------------------------------------------

    \11\ Minimal erythema dose--the lowest UV dose that produces 
skin reddening (erythema).
---------------------------------------------------------------------------

8. Number of Transmittance Measurements
    Two submissions (Ref. 1) stated that requiring 12 transmittance 
measurements on each plate as proposed is excessive and not 
statistically warranted (proposed 21 CFR 352.71(g)). One submission 
provided data showing that there are no significant differences in 
UVAI/UV ratios calculated based on 3, 5, 8, or 12

[[Page 35654]]

sub-sites per plate. The submission argued that we should reduce the 
number of required test sites per sample to 6. The other submission 
proposed that we require only one transmittance measurement per plate. 
The submission suggested that, rather than taking multiple measurements 
from several small areas on the plate, one measurement could be made 
over a relatively broad area.
    One of the submissions also argued that it is not necessary to 
evaluate transmittance on five different plates (proposed 21 CFR 
352.71(j)). The submission provided data showing that the UVAI/UV ratio 
for an SPF 15 sunscreen product is not significantly different whether 
it is measured on 1, 2, 3, or 5 plates (with 12 measurements per 
plate). We note that the COLIPA guidelines (Ref. 69) recommend that 3 
separate plates be used.
    We agree with the submissions that requiring 12 discrete 
measurements on each plate is not necessary to obtain an accurate 
transmittance spectrum. The submitted data demonstrate that there are 
no significant differences in UVAI/UV ratios based on 3, 5, 8, or 12 
test sites. Similarly, we agree with the submissions that requiring 
measurements for five plates is not necessary to obtain an accurate 
transmittance spectrum. Determining 12 transmittance measurements on 
five plates, as proposed, results in a total of 60 transmittance 
measurements. Based on the submitted data, a total of 15 transmittance 
measurements should produce an accurate transmittance spectrum. 
Therefore, we are requiring 5 or more measurements on at least 3 
different plates (21 CFR 201.327(j)(6) in this document.
9. Determination of Critical Wavelength
    Critical wavelength is to be determined as described in section 
VIII.B of this document.

IX. Analysis of Impacts

A. Final Regulatory Impact Analysis

    We have examined the impacts of the final rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct 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). OMB has determined that this final rule is a significant 
regulatory action under Executive Order 12866. Consistent with 
Executive Order 13563, the approach taken here maintains ``flexibility 
and freedom of choice for the public,'' above all by providing 
``information for the public in a form that is clear and intelligible.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because we lack information characterizing the 
number of products by firm-size and because most affected entities are 
considered small, we conclude that this final rule will have a 
significant economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $136 million, using the most current (2010) Implicit 
Price Deflator for the Gross Domestic Product. We do not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.
1. Background
    The purpose of this rule is to finalize labeling and testing 
conditions under which OTC sunscreen drug products marketed without 
approved applications are not misbranded. This rule addresses labeling 
and testing requirements for both UVB and UVA radiation protection. The 
rule modifies the existing SPF test, specifies a test for broad 
spectrum protection, and requires changes to the product label that 
affect both the front of the package (the principal display panel or 
PDP) and the Drug Facts section. In addition, the rule lifts the stay 
of effective date applied to the 1999 Drug Facts labeling final rule 
(64 FR 13254) specifically for sunscreen products (66 FR 67485). All 
manufacturers of sunscreens will incur some labeling costs due to 
revisions to both the PDP and the Drug Facts section of the product 
label (see section IX.A.4 of this document). In addition, many 
manufacturers will incur additional broad spectrum testing costs unless 
they have already tested their products according to the broad spectrum 
test required in this rule. Manufacturers of sunscreens will also incur 
SPF testing costs (see section IX.A.5 of this document). Some 
manufactures will also have to relabel products that are currently 
labeled with claims that are not allowed under this final rule (Sec.  
201.327(g) and Sec.  310.545(a)(29)(ii)).
2. Benefits
    As discussed in section IV.B of this document, the regular use of a 
Broad Spectrum SPF 15 or higher sunscreen product, when combined with 
limiting time in the sun and wearing clothing to protect sun-exposed 
areas, reduces the risk of skin cancer and early skin aging. The 
National Cancer Institute estimates that there are more than one 
million new cases of non-melanoma skin cancer and more than 68,000 new 
cases of melanoma per year in the United States (Refs. 72 and 73). 
According to the National Cancer Institute, about 8,700 persons will 
die of melanoma in 2010. Fatal cases of non-melanoma skin cancer are 
less common but nonetheless number several hundred per year. The 
labeling requirements in this rule, in conjunction with implementing 
the format and content requirements in 21 CFR 201.66, which were stayed 
for sunscreens but are being lifted in this rule, will provide 
consumers with clear and concise information about sunscreen use and 
protection, and about the role of sun exposure in increasing the risk 
of skin cancer and early skin aging. Consumers will be able to more 
easily identify products that reduce the risks of skin cancer and early 
skin aging, when used as directed. The new requirements for product 
testing will ensure the accuracy of the SPF value and broad spectrum 
claim on the product label.
    Although we are unable to quantify the effects of clear and concise 
information, the final rule will provide clearer and more consistent 
information on the benefits of certain sunscreens in regard to skin 
cancer risk reduction than is available on current labels. By requiring 
better information on levels of protection, the rule should contribute 
to reduced exposure to UVB and UVA radiation and thereby reduce the 
incidence of skin cancer.
    The benefits from reduced incidence of skin cancer will equal the 
value of the illnesses averted. The most appropriate measure of that 
value is based on the average willingness to pay to reduce the 
probability of skin cancer. We would then multiply the value per 
illness averted by the likely number of illnesses averted to determine 
the benefits of this final rule. Because we lack estimates of the 
likely numbers of illnesses averted, we present estimates of the value 
per

[[Page 35655]]

illness averted to illustrate the gains per averted case.
    We estimated the value per case of preventing skin cancer for fatal 
and non-fatal cases of melanoma and non-melanoma skin cancer. The 
estimated average medical cost of treatment, lost productivity, and 
willingness to pay to avoid some symptoms and other effects represents 
a plausible lower bound on willingness to pay to avoid a non-fatal case 
of skin cancer. For melanoma, the estimated total cost is about $2,860 
per non-fatal case; for non-melanoma skin cancer, the total cost is 
about $1,400 per non-fatal case; (Refs. 74 and 75).
    The largest potential public health gains from this final rule 
would likely come from averted deaths. We can calculate the monetary 
value of averted fatal cases as either the value of statistical lives 
saved or the value of statistical life-years saved. Although skin 
cancers occur at all ages, most cases occur at older ages. For that 
reason, we estimate the benefit from preventing fatal cases using the 
value of life years saved. According to the National Cancer Institute, 
the average age of death from melanoma is 68 (Ref. 73); life expectancy 
for a person between the ages of 68 and 69 is about 16 years (Ref. 76). 
If we discount the average years of life saved for averted fatal 
melanoma with rates of 3 and 7 percent, we get discounted statistical 
life-years saved equal to 12.6 and 9.4 years. The various studies of 
fatal cases of non-melanoma skin cancer find mean or median ages of 
death in the 77 to 82 range (Refs. 77-79). The life expectancy for 
someone between the ages of 79 and 80 is about 9 years (Ref. 76). If we 
discount the average years of life saved for fatal non-melanoma skin 
cancers with discount rates of 3 and 7 percent, we get discounted years 
saved equal to 7.9 and 6.5 years.
    In other analyses of life-years saved, we have used values for a 
statistical life-year in the $107,000 to $322,000 range (74 FR 33030, 
July 9, 2009; updated to current prices). For this illustrative 
analysis, we use a medium value of $214,000 per statistical life-year. 
We multiply the value of a statistical life-year by the discounted 
life-years saved per fatal case of melanoma, which yields $2.69 million 
using a 3 percent rate of discount and $2.02 million using a 7 percent 
rate of discount. If we multiply the value of a statistical life-year 
by discounted life-years saved per fatal case of non-melanoma skin 
cancer, we get $1.67 million using a 3 percent rate of discount and 
$1.39 million using a 7 percent rate of discount.
    The development of melanoma and non-melanoma skin cancer from 
chronic exposure to sunlight, as well as any preventative effects of 
sunscreen (or any other intervention), occur with a long lag. To 
estimate the monetary value of an averted case of melanoma or non-
melanoma skin cancer through combining other protective measures with 
increased broad spectrum and at least SPF 15 protection, we adjust for 
the lag between increased protection and a decrease in the incidence of 
non-melanoma skin cancer. The only available long-term study finds a 
minimum lag of 5 years before any significant risk reduction would 
occur (Refs. 20 and 21). Substantial reductions occur with a much 
longer lag, probably 15 to 25 years; we use a 20-year lag in this 
illustrative analysis. With a 20-year lag discounted at 3 percent, the 
value per averted statistical case of non-fatal melanoma is $1,586; if 
we discount for at 7 percent, the value per averted case is $740. With 
a 20-year lag discounted at 3 percent per year, the monetary value per 
averted statistical case of non-melanoma skin cancer is $773; if we 
discount at 7 percent, the value per averted case is $361.
    For fatal cases, with the 20-year lag discounted at 3 percent per 
year, the monetary value per averted statistical case of fatal melanoma 
is $1.49 million; discounted at 7 percent, the value per averted fatal 
case is $520,000. With a 20-year lag and a 3 percent rate of discount, 
the discounted value per averted case of non-melanoma skin cancer is 
$920,000 million; with a 7 percent rate of discount, value per averted 
fatal case is $360,000.
    We have four estimates of the discounted value per averted cases of 
melanoma and non-melanoma skin cancer, with values corresponded to non-
fatal and fatal cases. The annual benefits of this final rule will be 
the numbers of cases of each type averted multiplied by the value of 
each type. We do not, however, have estimates of the numbers of actual 
or statistical cases that will be averted. Although there is wide 
agreement among experts that the use of more effective sunscreens 
reduces the risk of sun-related skin cancer, we are unaware of any 
studies that quantify the reduced risk. Without quantitative estimates 
of the risk reduction associated with broad spectrum protection, we are 
unable to quantity the overall effects of this final rule on public 
health.
3. Number of Products Affected
    Estimating the number of products affected by this rule is 
difficult because we do not have complete data on the number of OTC 
sunscreen products currently marketed. Our Drug Listing System does not 
have accurate information on the number of marketed OTC sunscreen 
products. In the 2007 proposed rule (72 FR 49070 at 49108), we 
estimated that there were about 3,000 OTC sunscreen drug products, 
including cosmetic products containing sunscreen, with about 12,000 
SKUs.\12\
---------------------------------------------------------------------------

    \12\ SKUs refers to ``stock keeping units,'' which are 
individual products, packages, and sizes.
---------------------------------------------------------------------------

    In response to the 2007 proposed rule, we received a submission 
arguing that our estimates of the number of products and SKUs were low 
but the submission did not suggest a corrected value. We contracted 
with the consulting firm Eastern Research Group (ERG) to profile the 
sunscreen market and assess the cost to reformulate a sunscreen 
product. ERG's full report can be found in Docket No. FDA-1978-N-0018 
(Ref. 80). ERG did an extensive search using the internet and other 
sources and found fewer dosage forms and SKUs than we had estimated. 
ERG estimates that there are about 3,065 to 3,600 SKUs. More recently, 
the new FDA labeling cost model estimates that about 3,591 sunscreen 
SKUs are marketed, with up to 2,348 different formulations. Because 
these data are based on a recent survey of the market, we conclude that 
they are more representative of the number of products affected than 
the estimates in the proposed rule. For this analysis, we therefore use 
3,591 SKUs to represent the number of affected sunscreen labels and 
2,348 for the number of formulations.
    To comply with the rule, sunscreen products currently marketed as 
providing broad spectrum protection that were already tested using the 
test method in this rule will have to be re-labeled but will not have 
to be retested for broad spectrum protection. Other products will be 
tested for broad spectrum protection and, if they pass and, will be 
relabeled with the broad spectrum protection claim. Manufacturers may 
also choose to reformulate their products to pass the test or 
discontinue production of the products.
    We have not attributed any reformulation costs to this final rule 
but realize that some manufacturers may choose to reformulate their 
product if it does not pass the broad spectrum test.
4. Cost To Relabel Sunscreen Products
    The cost to relabel varies greatly depending on the printing method 
and number of colors used. In the 2007 proposed rule, we stated that 
the majority of sunscreen products are packaged in plastic bottles or 
tubes with the label printed directly on the

[[Page 35656]]

container or applied as a decal or paper label during the packaging 
process.
    The labeling requirements in this rule will change both the PDP and 
the Drug Facts section of the package and are considered a major 
redesign. Frequent label redesigns are typical for OTC sunscreen 
products, with redesigns generally implemented every 1 to 2 years. If a 
scheduled redesign coincides with relabeling required by this rule, the 
incremental labeling cost will be lower than if the labeling change 
takes place before scheduled changes. To estimate the cost to relabel, 
we are assuming that all products will be relabeled and none are 
discontinued.
    In the 2007 proposed rule, we used a model developed for us by the 
consulting firm RTI International to derive an estimate of the cost to 
relabel sunscreen products (Ref. 81). The model was developed to 
estimate the cost of food labels, which are similar to the labels on 
the products affected by this final rule. In response to the 2007 
proposed rule, we received a submission disagreeing with our estimates 
of how sunscreens are packaged and the cost to relabel these products 
(Ref. 1). The submission argued that many sunscreen products, 
particularly sunscreen-cosmetic combinations, have a secondary 
container and, therefore, an additional label. The submission also 
argued that some sunscreen products would require a fold-out label or 
new secondary carton to accommodate the labeling required in this rule. 
Furthermore, the submission argued that relabeling these products would 
cost $15,000 to $17,000 per SKU. The submission did not include any 
data or information to support its estimate.
    We agree that cosmetic packaging and labeling is generally more 
costly than OTC drug labeling. We also agree that manufacturers of 
sunscreen-cosmetic products would use the packaging norm of the 
cosmetic industry because those are the products they are competing 
with. The cost estimates we are using now demonstrate a large variation 
in the price per SKU to account for the differences in packaging. If 
the standard content and format changes required by the OTC labeling 
final rule (64 FR 13254) are being implemented for the first time, 
there could be increases in the size of container and carton labels. 
Since we are allowing, in this rule, for a compliance period of 1 year 
for most products but 2 years for products with low sales volume 
($25,000 annually), inventory losses for unused packaging and labels 
are minimized and accounted for in this analysis.
    For this final rule, we use the new FDA labeling cost model 
developed by RTI International, which includes estimates for changing 
sunscreen labels. The one-time costs for a major labeling change to 
sunscreen labels are $7,454 to $18,785, depending on the type of 
labeling and packaging. The medium estimate is $11,572 per major 
labeling changes. These costs include mostly labor and materials, with 
some cost for lost inventory.
    We estimate that the timing of scheduled relabeling will coincide 
with the relabeling required by this rule for 50 percent of the 3,591 
SKUs . We estimate the total labeling cost for the SKUs with coinciding 
scheduled redesign would be minimal administrative costs or about $550 
($310 to $790). Therefore, the total one-time cost for relabeling would 
be about $13.9 million to $35.1 million, with a medium estimate of 
$21.8 million (1,796 x $11,572 + 1,796 x $550).
5. Cost To Test or Retest Products To Determine SPF Values
    Manufacturers will incur SPF testing costs because the rule 
requires labeling for OTC sunscreen products to include SPF values 
determined in accordance with the specific test method that it 
describes. We will publish draft guidance entitled ``Guidance for 
Industry: Enforcement Policy--OTC Sunscreen Drug Products Marketed 
Without An Approved Application'' that describes our intended 
enforcement policy regarding these OTC sunscreen products. In the draft 
guidance, we propose to exercise enforcement discretion for a period of 
2 years after the publication of this final rule with regard to the SPF 
testing requirements for certain OTC sunscreen products on the market 
prior to June 17, 2011. We estimate that 65 to 75 percent of sunscreen 
reformulations, or 1,526 to 1,761 will require SPF retesting. The cost 
of an SPF test depends on whether the product is also making water 
resistance claims and the SPF value being tested; the cost of water 
resistant testing is much higher than static testing (see Table 6). In 
their analysis of the sunscreen market ERG found that about 5 percent 
of products claimed water resistance and SPF values less than 30, 3 
percent of products claimed water resistance with SPF greater than 30, 
while the remaining 92 percent could use the static SPF test. We use 
those percentages to estimate total SPF testing costs of $3.2 to $5.9 
million (see Table 6). The midpoint of estimated SPF testing costs is 
$4.6 million.

                                                              Table 6--Cost of SPF Testing
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                Estimated number of                Cost of test                     Total cost
                                                                   formulations          ---------------------------------------------------------------
                      Type of test                       --------------------------------
                                                                Low            High             Low            High             Low            High
--------------------------------------------------------------------------------------------------------------------------------------------------------
Water resistant, SPF < 30...............................              76              88          $4,500          $4,860        $343,395        $427,923
Water resistant, > 30...................................              46              53           4,500           5,130         260,037         271,018
SPF static test.........................................           1,404           1,620           1,900           3,240       2,667,798       5,249,189
                                                         -----------------------------------------------------------------------------------------------
    Total Cost for SPF testing..........................  ..............  ..............  ..............  ..............       3,217,230       5,948,130
--------------------------------------------------------------------------------------------------------------------------------------------------------

6. Cost to Test or Retest Products for Broad Spectrum Protection
    In the proposed rule, we estimated that about 75 percent of 
sunscreen products would need to be tested for broad spectrum 
protection. We received a submission arguing that our estimate was too 
low and that at least 90 percent of products would need to be tested 
(Ref. 1). The argument in the submission was based on the four-tier UVA 
star rating in the proposed rule. The submission stated that sunscreen 
products with ``low,'' one-star protection would need to be tested. We 
have now changed the rating criteria to pass-fail, where a critical 
wavelength of at least 370 nm is necessary to make the broad spectrum 
statement. Over the years, there has been a steady increase in the 
number of products with claims of broad spectrum protection. A recent 
survey of marketed products found that 65 percent of the products 
surveyed met the criteria for the broad spectrum statement (Ref. 82). 
Products that were tested in accordance with the broad

[[Page 35657]]

spectrum test in this rule would not need to be re-tested.
    Because the broad spectrum test in this rule is different than the 
proposed test, we assume that all affected products would need to be 
tested. In the 2007 proposed rule, we estimated a one-time testing cost 
of approximately $5.4 million for products that have broad spectrum 
protection claims. This estimate was based on 2,250 sunscreen products 
(75 percent of marketed products) being tested with a test cost of 
$2,400. The test costs were estimated as $2,200 for the proposed in 
vivo test and $200 for the proposed in vitro test. In this rule, we are 
not requiring the in vivo test.
    In response to the proposed rule, we received two submissions 
arguing that our estimate of $200 for the cost of the in vitro test was 
too low (Ref. 1). The first submission states that the cost of an in 
vitro test is $500, and the second states that the cost is $800. The 
first submission, from a sunscreen manufacturer, states that $500 is 
the price charged by an independent testing laboratory to test its 
product. The second submission does not provide any basis for its 
estimate. Although the in vitro test in this rule is different than the 
in vitro test in the 2007 proposed rule, the cost to conduct the tests 
is the same. ERG found that the cost of the test ranges from $300 to 
$800 (Ref. 80). Assuming all affected marketed product formulations 
(1,526 to 1,761 formulations) will be tested for broad spectrum 
protection at a cost ranging from $300 to $800, the total cost to test 
sunscreen products for broad spectrum protection is estimated to be 
$457,860 to $1,408,800 [(1,526 x $300) to (1,761 x $800)].
7. Total Incremental Costs
    Because we took steps earlier to mitigate the impact of labeling 
changes on the sunscreen industry by staying the requirements in 
earlier rules, the labeling costs in this rule incorporate the labeling 
costs from three final rules:
    1. 1999 OTC drug labeling final rule (64 FR 13254)
    2. 1999 Sunscreen final rule (64 FR 27666)
    3. This rule.

Manufacturers were able to postpone compliance costs when we chose to 
stay the labeling requirements for the 1999 final rule that 
standardized the format and content requirements for labeling OTC drug 
products (21 CFR part 201), which would have become effective for all 
sunscreens by 2005 (69 FR 53801). We include, as part of labeling 
costs, the cost of increased container labels and package size to 
accommodate the Drug Facts format.

    The estimated total one-time incremental cost of this rule range 
$17.6 to 42.5 million [($13.9 million labeling cost + $3.2 million SPF 
testing cost + $0.5 million broad spectrum testing cost) to ($35.1 
million labeling cost + $5.9 million SPF testing cost + $1.4 million 
broad spectrum testing cost)]. The medium estimated one-time 
incremental costs are $27.3 million. Annualized over 10 years, the 
costs are $2.1 to $5 million using a 3 percent rate of discount and 
$2.5 to $6.1 million using a 7 percent rate of discount. Annualized 
medium costs are $3.2 million using a 3 percent rate of discount and 
$3.9 million using a 7 percent rate of discount. If some manufacturers 
of sunscreen products have already complied with the 1999 final rule 
and would not otherwise have to relabel products as a result of this 
final rule, then these estimates may overstate actual total costs.
8. Analysis of Alternatives
    The principal alternatives we identified were the inclusion of 
several provisions from the 2007 proposed rule. In the 2007 proposed 
rule, we required in vivo and in vitro tests for determining UVA 
protection. In this rule, we have eliminated the in vivo test 
requirement, reducing compliance costs by about $5 million. We also 
proposed labeling on the PDP that would indicate the level of UVA 
protection. In this rule, we changed the in vitro test to one that 
measures both UVB and UVA protection (i.e., broad spectrum protection). 
We also established a pass/fail broad spectrum protection statement on 
the PDP in place of a UVA rating.
    We considered requiring a negative statement on the PDP indicating 
that a product did not have broad spectrum protection if it failed the 
in vitro test. Numerous submissions from manufacturers opposed this 
requirement, and we are concerned that the statement could be 
misinterpreted by consumers. Moreover, as noted previously, this 
alternative is beyond the scope of this final rule, which applies only 
to products that do provide broad spectrum protection.

B. Small Business Impact (Final Regulatory Flexibility Analysis)

    We estimate that about 78 percent of the approximately 100 domestic 
companies that manufacture OTC sunscreen products would be considered 
small business entities (defined by the Small Business Administration 
as having fewer than 750 employees). Because most affected entities are 
considered small, we conclude that this final rule will have a 
significant economic impact on a substantial number of small entities. 
Consequently, this analysis, together with other relevant sections of 
this document, serves as the Final Regulatory Flexibility Analysis, as 
required under the Regulatory Flexibility Act.
    The average one-time incremental cost per firm will be about 
$185,000 to $445,000, with a medium of about $285,000. This burden, 
described in more detail in section IX.A of this document, includes 
labeling costs, SPF testing costs, and broad spectrum testing costs. 
The economic impact will vary by firm, depending on the number of 
products requiring testing and the number of SKUs requiring labeling. 
Also, firm-specific impact will vary inversely with the product sales; 
the per firm burden will be lower for firms with products with high 
sales volumes. Because the relative economic impact of product 
retesting is greater for products with lower sales volume, which could 
disproportionately affect smaller firms, we are providing a longer 
implementation period (2 years) for products with annual sales of less 
than $25,000. Because the OTC drug industry is highly regulated, all 
firms are expected to have access to the necessary professional skills 
on staff or to have contractual arrangements to comply with the testing 
requirements of this rule.

X. Paperwork Reduction Act of 1995

    This final rule contains certain information collection provisions 
that are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). 
Specifically, the final rule establishes requirements for SPF labeling 
based on specified testing of covered products, (21 CFR 201.327(a)(1) 
and (i)). This rule also lifts the delay of implementation date for 
Sec.  201.66 (21 CFR 201.66), the general OTC Drug Facts labeling 
format regulation, which has applied to all OTC sunscreen products (69 
FR 53801). The information collections associated with Sec.  201.66 
have been approved in accordance with the PRA under OMB Control Number 
0910-0340, but this approval does not currently include application of 
these provisions to OTC sunscreens. (76 FR 9022, February 16, 2011). 
The lifting of the stay of effective date of Sec.  201.66 for OTC 
sunscreens will modify this information collection.
    Elsewhere in this issue of the Federal Register, in accordance with 
section 3506(c)(2)(A) of the PRA (44 U.S.C.

[[Page 35658]]

3506(c)(2)(A)), we are publishing a 60-day notice soliciting public 
comment on the collections of information resulting from this final 
rule and will then submit these information collection provisions to 
OMB for approval. These requirements will not be effective until we 
obtain OMB approval. We will publish a notice concerning OMB approval 
of these requirements in the Federal Register prior to the effective 
date of this final rule.
    With the exceptions noted above, we conclude that the other 
provisions of this rule are not subject to OMB review under the PRA. 
Section 201.327 contains specific labeling information, including 
directions and warnings, which 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)) and, 
therefore, are not collections of information. The requirements for 
obtaining certain medical history information and informed consent from 
test subjects (21 CFR 201.327(i)(3)(ii) and (i)(3)(iv)) are not 
collections of information because information collected from subjects 
of clinical testing does not constitute information under 5 CFR 
1320.3(h)(5). There are no recordkeeping provisions associated with the 
SPF and broad spectrum testing (i.e., effectiveness testing) described 
in this rule. The burdens of SPF testing as relevant to labeling (third 
party disclosures) are addressed in the notice published elsewhere in 
this issue of the Federal Register.

XI. Environmental Impact

    FDA has determined under 21 CFR 25.31(a) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

XII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. Section 4(a) of the Executive order 
requires agencies to ``construe * * * a Federal statute to preempt 
State law only where the statute contains an express preemption 
provision or there is some other clear evidence that the Congress 
intended preemption of State law, or where the exercise of State 
authority conflicts with the exercise of Federal authority under the 
Federal statute.'' The sole statutory provision giving preemptive 
effect to the final rule is section 751 of the FD&C Act (21 U.S.C. 
379r). We have complied with all of the applicable requirements under 
the Executive order and have determined that the preemptive effects of 
this rule are consistent with Executive Order 13132.

XIII. References

    The following references are on display in the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20857, under Docket No. FDA-1978-N-0018 
(formerly 1978N-0038) and may be seen by interested persons between 9 
a.m. and 4 p.m., Monday through Friday. (FDA has verified all Web site 
addresses, but FDA is not responsible for any subsequent changes to the 
Web sites after this document publishes in the Federal Register.
    1. FDA List of Docket Submissions Addressed in This Rule; Organized 
by Issue.
    2. The United States Pharmacopeia 31-National Formulary 26, The 
United States Pharmacopeial Convention, Inc., MD, p., 3547, 2009.
    3. The United States Pharmacopeia 31-National Formulary 26, The 
United States Pharmacopeial Convention, Inc., MD, p., 3548, 2009.
    4. Nash, J. F. et al., ``Ultraviolet A Radiation: Testing and 
Labeling for Sunscreen Products,'' Dermatologic Clinics, 24:63-74, 
2006.
    5. Sayre, R. M. et al., ``Commentary on `UVB-SPF': the SPF Labels 
of Sunscreen Products Convey More Than Just UVB Protection,'' 
Photodermatology Photoimmunology Photomedicine, 24:218-220, 2008.
    6. Vainio, H. and F. Bianchini, ``Cancer-Preventive Effects of 
Sunscreens'' in IARC Handbooks of Cancer Prevention: Volume 5 
Sunscreens, IARC, Lyon, FR, 69-124, 2001.
    7. ``Commission Recommendation of 22 September 2006 on the Efficacy 
of Sunscreen Products and the Claims Made Relating Thereto,'' Official 
Journal of the European Union, L265, 49:39-43, 2006.
    8. Document No. FDA-1978-N-0018-0692 in Docket No. FDA-1978-N-0018.
    9. Calvacca, L., ``Screening the New Sunscreens,'' Working Woman, 
15:120-123, 1990.
    10. Fourtanier, A. et al., ``Sunscreens Containing the Broad-
Spectrum UVA absorber, Mexoryl SX, Prevent the Cutaneous Detrimental 
Effects of UV Exposure: A Review of Clinical Study Results,'' 
Photodermatology, Photoimmunology, and Photomedicine, 24:164-174, 2008.
    11. De Gruijl, F., ``UV Radiation, DNA Damage, Mutations, and Skin 
Cancer'' in Environmental UV Radiation: Impact on Ecosystems and Human 
Health and Predictive Models, Springer, Netherlands, 249-258, 2006.
    12. Lucas, R. et al., ``Solar Ultraviolet Radiation. Global Burden 
of Disease from Solar Ultraviolet Radiation'', Environmental Burden of 
Disease Series No. 13, World Health Organization, 2006.
    13. Armstrong, B. K. et al., ``Sun Exposure and Skin Cancer,'' 
Australasian Journal of Dermatology, 38:S1-S6, 1997.
    14. World Health Organization, IARC, ``IARC Monographs on the 
Evaluation of Carcinogenic Risks to Humans. Vol. 55. Solar and 
Ultraviolet Radiation,'' http://monographs.iarc.fr/ENG/Monographs/vol55/volume55.pdf, September 1, 2009.
    15. ``Report on Carcinogens, Eleventh Edition,'' http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932, October 13, 2009.
    16. Rabe, J. et al., ``Photoaging: Mechanisms and Repair,'' Journal 
of the American Academy of Dermatology, 55:1-19, 2006.
    17. Reynolds, K.D., et al., ``Predictors of Sun Exposure in 
Adolescents in a Southeastern U.S. Population,'' Journal of Adolescent 
Health, 19:409-415, 1996.
    18. Robinson, J.K., D.S. Rigel, and R.A. Amonette, ``Summertime Sun 
Protection Used by Adults for Their Children,'' Journal of the American 
Academy of Dermatology, 42:746-753, 2000.
    19. Ulrich, C., et al., ``Prevention of Non-Melanoma Skin Cancer in 
Organ Transplant Patients by Regular Use of a Sunscreen: A 24 Months, 
Prospective, Case-Control Study,'' British Journal of Dermatology, 
161:78-84, 2009.
    20. Green, A. et al., ``Daily Sunscreen Application and 
Betacarotene Supplementation in Prevention of Basal-Cell and Squamous-
Cell Carcinomas of the Skin: A Randomized Controlled Trial,'' The 
Lancet, 354:723-729, 1999.
    21. van der Pols, J. C. et al., ``Prolonged Prevention of Squamous 
Cell Carcinoma of the Skin by Regular Sunscreen Use,'' Cancer 
Epidemiology, Biomarkers, and Prevention, 15:2546-2548, 2006.
    22. Habif, T. P. et al., ``Premalignant and Malignant Nonmelanoma 
Skin Tumors'' in Skin Disease Diagnosis and Treatment, Mosby, St. 
Louis, MO, 360-395, 2001.
    23. Araki, K. et al., ``Incidence of Skin Cancers and Precancerous 
Lesions in Japanese. Risk Factors and Prevention,'' Journal of 
Epidemiology, 9:S14-S21, 1999.
    24. Darlington, S. et al., ``A Randomized Controlled Trial to 
Assess

[[Page 35659]]

Sunscreen Application and Beta Carotene Supplementation in the 
Prevention of Solar Keratoses,'' Archives of Dermatology, 139:451-455, 
2003.
    25. Naylor, M. F. et al., ``High Sun Protection Factor Sunscreens 
in the Suppression of Actinic Neoplasia,'' Archives of Dermatology, 
131:170-175, 1995.
    26. Thompson, S. C. et al., ``Reduction of Solar Keratoses by 
Regular Sunscreen Use,'' New England Journal of Medicine, 329:1147-
1151, 1993.
    27. Gallagher, R. P. et al., ``Broad-Spectrum Sunscreen Use and the 
Development of New Nevi in White Children: A Randomized Controlled 
Trial,'' The Journal of the American Medical Association, 283:2955-
2960, 2000.
    28. Lee, T. K. et al., ``Site-Specific Protective Effect of Broad-
Spectrum Sunscreen on Nevus Development Among White Schoolchildren in a 
Randomized Trial,'' Journal of the American Academy of Dermatology, 
52:786-792, 2005.
    29. Seite, S. and A. Fourtanier, ``The Benefit of Daily 
Photoprotection,'' Journal of the American Academy of Dermatology, 
58:S160-S166, 2008.
    30. Fourtanier, A. et al., ``Protection of Skin Biological Targets 
by Different Types of Sunscreens,'' Photodematology, Photoimmunology, 
and Photomedicine, 22:22-32, 2006.
    31. Young, A. R. et al., ``The Detrimental Effects of Daily Sub-
Erythemal Exposure on Human Skin In Vivo Can Be Prevented by a Daily-
Care Broad-Spectrum Sunscreen,'' Journal of Investigative Dermatology, 
127:975-978, 2007.
    32. Moyal, D. D. and A. M. Fourtanier, ``Broad-Spectrum Sunscreens 
Provide Better Protection From Solar Ultraviolet-Simulated Radiation 
and Natural Sunlight-Induced Immunosuppression In Human Beings,'' 
Journal of the American Academy Dermatology, 58:S149-54, 2008.
    33. ``Label Information for Alli\TM\ Weight Loss Aid,'' http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021887lbl.pdf, 
November 23, 2009.
    34. ``Your Guide to Lowering Your Cholesterol with TLC. Therapeutic 
Lifestyle Changes,'' NIH Publication No. 06-5235, 2005.
    35. ``Lipitor'' in Physicians' Desk Reference, ed., Thomson 
Healthcare Inc., Montvale, NJ, 2457-2462, 2008.
    36. ``The Risks of Tanning,'' http://www.fda.gov/Radiation-EmittingProducts/RadiationEmittingProductsandProcedures/Tanning/ucm116432.htm, October 21, 2009.
    37. Dowdy, J. C. et al., ``Indoor Tanning Injuries: An Evaluation 
of FDA Adverse Event Reporting Data,'' Photodermatology Photoimmunology 
Photomedicine, 25:216-220, 2009.
    38. Holick, M. F. and T. C. Chen, ``Vitamin D Deficiency: A 
Worldwide Problem with Health Consequences,'' The American Journal of 
Clinical Nutrition, 87:1080S-1086S, 2008.
    39. Cable News Network, ``Vitamin D is Hot! Here's How to Get it,'' 
http://www.cnn.com/2008/HEALTH/diet.fitness/05/20/cl.vitamin.d/index.html, October 31, 2008.
    40. Holick, M. F., ``Sunlight, UV-Radiation, Vitamin D and Skin 
Cancer: How Much Sunlight do We Need?,'' Advances in Experimental 
Medicine and Biology, 624:1-15, 2008.
    41. Maxwell, J. D., ``Seasonal Variation in Vitamin D,'' 
Proceedings of the Nutrition Society, 53:533-543, 1994.
    42. Salih, F. M., ``Effect of Clothing Varieties on Solar 
Photosynthesis of Previtamin D3: An in Vitro Study,'' Photodermatology, 
Photoimmunology, and Photomedicine, 20:53-58, 2004.
    43. Webb, A. R., ``Who, What, Where and When-Influences on 
Cutaneous Vitamin D Synthesis,'' Progress in Biophysics and Molecular 
Biology, 92:17-25, 2006.
    44. Institute of Medicine, ``Vitamin D'' in Dietary Reference 
Intakes For Calcium, Phosphorus, Magnesium, Vitamin D, And Flouride, 
National Academies Press, Washington, DC, 250-287, 1997.
    45. Wolpowitz, D. and B. A. Gilchrest, ``The Vitamin D Questions: 
How Much Do You Need And How Should You Get It?,'' Journal of the 
American Academy of Dermatology, 54:301-17, 2006.
    46. Matsuoka, L. Y. et al., ``Sunscreens Suppress Cutaneous Vitamin 
D3 Synthesis,'' Journal of Clinical Endocrinology and Metabolism, 
64:1165-1168, 1987.
    47. Matsuoka, L. Y. et al., ``Chronic Sunscreen Use Decreases 
Circlulating Concentrations of 25-hydroxyvitamin D. A preliminary 
Study,'' Archives of Dermatology, 124:1802-1804, 1988.
    48. Marks, R. et al., ``The Effect of Regular Sunscreen Use on 
Vitamin D Levels in an Australian Population. Results of a Randomized 
Controlled Trial,'' Archives of Dermatology, 131:415-421, 1995.
    49. Farrerons, J. et al., ``Clinically Prescribed Sunscreen (Sun 
Protection Factor 15) Does not Decrease Serum Vitamin D Concentration 
Sufficiently Either to Induce Changes in Parathyroid Function or in 
Metabolic Markers,'' British Journal of Dermatology, 139:422-427, 1998.
    50. Kimlin, M. et al., ``Does a High UV Environment Ensure Adequate 
Vitamin D Status?'' Journal of Photochemistry and Photobiology B. 
Biology, 89:139-147, 2007.
    51. Cusack, C et al., ``Photoprotective Behavior and Sunscreen Use: 
Impact on Vitamin D Levels in Cutaneous Lupus Erythematosus,'' 
Photodermatology, Photoimmunology, and Photomedicine, 24:260-267, 2008.
    52. Hoesl, M. et al., ``Vitamin D Levels of XP-Patients Under 
Stringent Sun Protection,'' European Journal of Dermatology, 20:457-
460, 2010.
    53. Zerwekh, J. E., ``Blood Biomarkers of Vitamin D Status,'' 
American Journal of Clinical Nutrition, 87:1087S-1091S, 2008.
    54. The American Academy of Dermatology, ``Sun Protection for 
Children,'' http://www.aad.org/public/publications/pamphlets/sun_sunprotection.html, February 1, 2009.
    55. The American Academy of Dermatology, ``Actinic Keratoses,'' 
http://www.aad.org/public/publications/pamphlets/sun_actinic.html, 
February 1, 2009.
    56. The American Academy of Dermatology, ``The Sun and Your Skin,'' 
http://www.aad.org/public/publications/pamphlets/sun_sun.html, 
February 1, 2009.
    57. The American Academy of Dermatology, ``The Darker Side of 
Tanning,'' http://www.aad.org/public/publications/pamphlets/sun_darker.html, February 1, 2009.
    58. The American Academy of Dermatology, ``Skin Cancer,'' http://www.aad.org/public/publications/pamphlets/sun_skin.html, February 1, 
2009.
    59. Centers for Disease Control and Prevention, ``Sunscreen for 
Your Sun Day,'' http://www.cdc.gov/cancer/skin/chooseyourcover/index.htm, October 23, 2009.
    60. ``Sunwise Program: Action Steps for Sun Safety,'' http://www.epa.gov/sunwise/actionsteps.html, February 1, 2009.
    61. Wright, M.W. et al., ``Mechanisms of Sunscreen Failure,'' 
Journal of the American Academy of Dermatology, 44:781-784, 2001
    62. Rigel, D., ``American Academy of Dermatology's Melanoma/Skin 
Cancer Detection and Prevention Month Press Release,'' April 25, 2001.
    63. European Cosmetic, Toiletry and Perfumery Association (COLIPA); 
JCIA; CTFA-SA; CTFA, ``Sun Protection Factor Test Method,'' 1994.
    64. European Cosmetic, Toiletry and Perfumery Association (COLIPA); 
JCIA; CTFA-SA; CTFA, ``International Sun

[[Page 35660]]

Protection Factor (SPF) Test Method,'' 2006.
    65. Standards Australia and Standards New Zealand, ``Australian/New 
Zealand Standard Sunscreen Products Evaluation and Classification,'' 
AS/NZS 2604:1998,'' 1998.
    66. Health Canada, ``Category IV Monograph Sunburn Protectants. 
Procedure for Determining an SPF,'' 2002.
    67. Korea Food and Drug Administration, ``Korean Measurement 
Standards for UV Protection Efficacy,'' 2001.
    68. Bimczok, R. et al., ``Influence of Applied Quantity of 
Sunscreen Products on the Sun Protection Factor--A Multicenter Study 
Organized by the DGK Task Force Sun Protection,'' Skin Pharmacology and 
Physiology, 20:57-64, 2007.
    69. COLIPA (The European Cosmetics Association), ``Method for the 
In Vitro Determination of UVA Protection Provided by Sunscreen 
Products,'' COLIPA Guidelines, 2007a.
    70. Ferrero, L. et al., ``Importance of Substrate Roughness for In 
Vitro Sun Protection Assessment,'' IFSCC Magazine, 9:97-108, 2006.
    71. Sayre, R. M. and J. C. Dowdy, ``Photostability Testing of 
Avobenzone,'' Cosmetics and Toiletries, 114:85-91, 1999.
    72. National Cancer Institute, ``Skin Cancer,'' http://www.cancer.gov/cancertopics/types/skin, April 17, 2009.
    73. National Cancer Institute, ``Surveillance Epidemiology and End 
Results: Melanoma of the Skin,'' http://seer.cancer.gov/statfacts/html/melan.html, November 10, 2010.
    74. Bickers, D.R. et al., ``The Burden of Skin Diseases: 2004,'' 
Journal of the American Academy of Dermatology, 55:490-500, 2006.
    75. Freedberg, K.A. et al., ``Screening for Mealignant Melanoma: A 
Cost-Effective Analysis,'' Journal of the American Academy of 
Dermatology, 41:738-745, 1999.
    76. Arias, E., B.L. Rostron, and B. Tejada-Vera, ``United States 
Life tables, 2005,'' National Vital Statistics Reports, 58:1-132, 2010.
    77. Lewis, K.G. and M.A. Weinstock, ``Nonmelanoma Skin Cancer 
Mortality (1988-2000),'' Archives of Dermatology, 140:837-842, 2004.
    78. Nolan, R.C., M. T.-L. Chan, and P.J. Heenan, ``A 
Clinicopathologic Review of Lethal Nonmelanoma Skin Cancers in Western 
Australia,'' Journal of the American Academy of Dermatology, 52:101-
108, 2005.
    79. Girschik, J. et al., ``Deaths from Non-Melanoma Skin Cancer in 
Western Australia,'' Cancer Causes & Control, 19:879-885, 2008.
    80. Eastern Research Group (2010) ``Sunscreen Drug Formulations for 
Over-the-Counter Human Use,'' Task Order No. 21, Contract No. 223-03-
8500.
    81. RTI International, ``FDA Labeling Cost Model, Final Report,'' 
prepared by Mary Muth, Erica Gledhill, and Shawn Karns, RTI. Prepared 
for Amber Jessup, FDA Center for Food Safety and Applied Nutrition, 
Revised January 2003.
    82. ``Sunscreen Market Analysis: The Evolution and Use of UVA-1 
Actives,'' The Proctor and Gamble Company, Sharon Woods Technical 
Center, Cincinatti, OH, 2004.

List of Subjects

21 CFR Part 201

    Drugs, Incorporation by reference, Labeling, Reporting and 
recordkeeping requirements.

21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
201 is amended as follows:

PART 201--LABELING

0
1. The authority citation for 21 CFR part 201 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

0
2. Section 201.327 is added to subpart G to read as follows:


Sec.  201.327  Over-the-counter sunscreen drug products; required 
labeling based on effectiveness testing.

    The following provisions apply to sunscreen products containing 
aminobenzoic acid, avobenzone, cinoxate, dioxybenzone, ensulizole, 
homosalate, meradimate, octinoxate, octisalate, octocrylene, 
oxybenzone, padimate O, sulisobenzone, titanium dioxide, trolamine 
salicylate, or zinc oxide, alone or in combination. The provisions do 
not apply to sunscreen products marketed under approved new drug 
applications or abbreviated new drug applications.
    (a) Principal display panel. In addition to the statement of 
identity in paragraph (b) of this section, the following labeling shall 
be prominently placed on the principal display panel:
    (1) Effectiveness claim. (i) For products that pass the broad 
spectrum test in paragraph (j) of this section. (A) The labeling states 
``Broad Spectrum SPF [insert numerical SPF value resulting from testing 
under paragraph (i) of this section]''.
    (B) Prominence. The Broad Spectrum SPF statement shall appear as 
continuous text with no intervening text or graphic. The entire text 
shall appear in the same font style, size, and color with the same 
background color.
    (ii) For sunscreen products that do not pass the broad spectrum 
test in paragraph (j) of this section. The labeling states ``SPF 
[insert numerical SPF value resulting from testing under paragraph (i) 
of this section]''. The entire text shall appear in the same font 
style, size, and color with the same background color.
    (2) Water resistance statements. (i) For products that provide 40 
minutes of water resistance according to the test in paragraph 
(i)(7)(i) of this section. The labeling states ``Water Resistant (40 
minutes)''.
    (ii) For products that provide 80 minutes of water resistance 
according to the test in paragraph (i)(7)(ii) of this section. The 
labeling states ``Water Resistant (80 minutes)''.
    (b) Statement of identity. The labeling of the product contains the 
established name of the drug, if any, and identifies the drug as a 
``sunscreen.''
    (c) Indications. The labeling of the product states, under the 
heading ``Uses,'' the phrases listed in this paragraph (c), as 
appropriate. Other truthful and nonmisleading statements, describing 
only the uses that have been established and listed in this paragraph 
(c), may also be used, as provided in Sec.  330.1(c)(2) of this 
chapter, subject to the provisions of section 502 of the Federal Food, 
Drug, and Cosmetic Act (the FD&C Act) relating to misbranding and the 
prohibition in section 301(d) of the FD&C Act against the introduction 
or delivery for introduction into interstate commerce of unapproved new 
drugs in violation of section 505(a) of the FD&C Act.
    (1) For all sunscreen products, the following indication statement 
must be included under the heading ``Uses'': ``[Bullet] helps prevent 
sunburn''. See Sec.  201.66(b)(4) of this chapter for definition of 
bullet.
    (2) For sunscreen products with a Broad Spectrum SPF value of 15 or 
higher according to the tests in paragraphs (i) and (j) of this 
section, the labeling may include the following statement in addition 
to the indication in Sec.  201.327(c)(1): ``[Bullet] if used as 
directed with other sun protection measures (see Directions [in bold 
italic

[[Page 35661]]

font]), decreases the risk of skin cancer and early skin aging caused 
by the sun''.
    (3) Any labeling or promotional materials that suggest or imply 
that the use, alone, of any sunscreen reduces the risk of or prevents 
skin cancer or early skin aging will cause the product to be misbranded 
under section 502 of the FD&C Act (21 U.S.C. 352).
    (d) Warnings. The labeling of the product contains the following 
warnings under the heading ``Warnings''.
    (1) For all sunscreen products. (i) The labeling states ``Do not 
use [bullet] on damaged or broken skin''.
    (ii) The labeling states ``When using this product [bullet] keep 
out of eyes. Rinse with water to remove.''
    (iii) The labeling states ``Stop use and ask a doctor if [bullet] 
rash occurs''.
    (2) For sunscreen products that are broad spectrum with SPF values 
of at least 2 but less than 15 according to the SPF test in paragraph 
(i) of this section or that do not pass the broad spectrum test in 
paragraph (j) of this section. The first statement under the heading 
``Warnings'' states ``Skin Cancer/Skin Aging Alert [in bold font]; 
Spending time in the sun increases your risk of skin cancer and early 
skin aging. This product has been shown only to help prevent sunburn, 
not [in bold font] skin cancer or early skin aging.''
    (e) 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 may 
also be included.
    (1) For all sunscreen products. (i) As an option, the labeling may 
state ``For sunscreen use:''.
    (ii) The labeling states ``[bullet] apply [select one of the 
following: `Liberally' or `generously'] [and, as an option: `And 
evenly'] 15 minutes before sun exposure''.
    (iii) As an option, the labeling may state ``[bullet] apply to all 
skin exposed to the sun''.
    (iv) The labeling states ``[bullet] children under 6 months of age: 
Ask a doctor''.
    (2) For sunscreen products with a Broad Spectrum SPF value of 15 or 
higher according to the tests in paragraphs (i) and (j) of this 
section. The labeling states ``[bullet] Sun Protection Measures. [in 
bold font] Spending time in the sun increases your risk of skin cancer 
and early skin aging. To decrease this risk, regularly use a sunscreen 
with a Broad Spectrum SPF value of 15 or higher and other sun 
protection measures including: [Bullet] limit time in the sun, 
especially from 10 a.m.-2 p.m. [bullet] wear long-sleeved shirts, 
pants, hats, and sunglasses''.
    (3) For products that satisfy the water resistance test in 
paragraph (i)(7) of this section. The labeling states ``[bullet] 
reapply: [Bullet] after [select one of the following determined by 
water resistance test: `40 minutes of' or `80 minutes of'] swimming or 
sweating [bullet] immediately after towel drying [bullet] at least 
every 2 hours''.
    (4) For products that do not satisfy the water resistance test in 
paragraph (i)(7) of this section. The labeling states ``[bullet] 
reapply at least every 2 hours [bullet] use a water resistant sunscreen 
if swimming or sweating''.
    (f) Other information. The labeling of the product contains the 
following statement under the heading ``Other information:'' ``[bullet] 
protect the product in this container from excessive heat and direct 
sun''.
    (g) False and misleading claims. There are claims that would be 
false and/or misleading on sunscreen products. These claims include but 
are not limited to the following: ``Sunblock,'' ``sweatproof,'' and 
``waterproof.'' These or similar claims will cause the product to be 
misbranded under section 502 of the FD&C Act (21 U.S.C. 352).
    (h) Labeling of products containing a combination of sunscreen and 
skin protectant 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. Labeling provisions in Sec.  347.50(e) of this 
chapter shall not apply to these products.
    (i) SPF test procedure. (1) UV source (solar simulator). (i) 
Emission spectrum. A single port or multiport solar simulator should be 
filtered so that it provides a continuous emission spectrum from 290 to 
400 nanometers (nm) with a limit of 1,500 Watts per square meter (W/
m\2\) on total irradiance for all wavelengths between 250 and 1,400 nm.
    (A) The solar simulator should have the following percentage of 
erythema-effective radiation in each specified range of wavelengths:

                    Solar Simulator Emission Spectrum
------------------------------------------------------------------------
                                                       Percent erythemal
                Wavelength range (nm)                   contribution \1\
------------------------------------------------------------------------
< 290................................................              < 0.1
290-300..............................................            1.0-8.0
290-310..............................................          49.0-65.0
290-320..............................................          85.0-90.0
290-330..............................................          91.5-95.5
290-340..............................................          94.0-97.0
290-400..............................................         99.9-100.0
------------------------------------------------------------------------
\1\ Calculation of erythema action spectrum described in Sec.
  201.327(i)(1)(ii) of this section.

     (B) In addition, UVA II (320-340 nm) irradiance should equal or 
exceed 20 percent of the total UV (290-400 nm) irradiance. UVA I (340-
400 nm) irradiance should equal or exceed 60 percent of the total UV 
irradiance.
    (ii) Erythema action spectrum. (A) Calculate the erythema action 
spectrum weighting factor (Vi) at each wavelength [lambda]:
    (1) Vi ([lambda]) = 1.0 (250 < [lambda] <= 298 nm)
    (2) Vi ([lambda]) = 10\0.094 * (298-[lambda])\ (298 < 
[lambda] <= 328 nm)
    (3) Vi ([lambda]) = 10\0.015 * (140-[lambda])\ (328 < 
[lambda] 400 nm)
    (B) Calculate the erythema-effective UV dose (E) delivered by a 
solar simulator as follows:
[GRAPHIC] [TIFF OMITTED] TR17JN11.002


Where Vi([lambda]) = erythema action spectrum weighting 
factor at each wavelength [lambda]
    I([lambda]) = irradiance (Watts per square meter) at each 
wavelength [lambda]
    t = exposure time (seconds)


Erythema-effective dose (E) is expressed as effective Joules per square 
meter (J/m\2\-eff).

    (C) The emission spectrum must be determined using a handheld 
radiometer with a response weighted to match the spectrum in ISO 17166 
CIE S 007/E entitled ``Erythemal reference action spectrum and standard 
erythema dose,'' dated 1999 (First edition, 1999-12-15; corrected and 
reprinted 2000-11-15), which is incorporated by reference in accordance 
with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain a copy from the 
ISO Copyright Office, Case Postale 56, CH-1211, Geneva 20, Switzerland, 
telephone +41-22-749-01-11 or fax +41-22-74 -09-47. http://www.iso.org. 
You may inspect a copy at the Center for Drug Evaluation and Research, 
10903 New Hampshire Ave., Bldg. 22, Silver Spring, MD 20993, call 301-
796-2090, or at the National Archives and Records Administration 
(NARA). For information on the availability of this material at NARA, 
call 202-741-6030, or go to: http://

[[Page 35662]]

www/archives.gov/federal_register/code_offederal_regulations/ibr_locations.html. The solar simulator output should be measured before 
and after each phototest or, at a minimum, at the beginning and end of 
each test day. This radiometer should be calibrated using side-by-side 
comparison with the spectroradiometer (using the weighting factors 
determined according to paragraph (i)(1)(ii)(A) of this section) at the 
time of the annual spectroradiometric measurement of the solar 
simulator as described in paragraph (i)(1)(iv) of this section.
    (iii) Operation. A solar simulator should have no significant time-
related fluctuations (within 20 percent) in radiation emissions after 
an appropriate warm-up time and demonstrate good beam uniformity 
(within 20 percent) in the exposure plane. The delivered dose to the UV 
exposure site must be within 10 percent of the expected dose.
    (iv) Periodic measurement. To ensure that the solar simulator 
delivers the appropriate spectrum of UV radiation, the emission 
spectrum of the solar simulator should be measured at least annually 
with an appropriate and accurately calibrated spectroradiometer system 
(results should be traceable to the National Institute for Standards 
and Technology). In addition, the solar simulator must be recalibrated 
if there is any change in the lamp bulb or the optical filtering 
components (i.e., filters, mirrors, lenses, collimating devices, or 
focusing devices). Daily solar simulator radiation intensity should be 
monitored with a broadband radiometer with a response weighted to match 
the erythema action spectrum in ISO 17166 CIE S 007/E entitled 
``Erythemal reference action spectrum and standard erythema dose,'' 
which is incorporated by reference in paragraph (i)(1)(ii)(C) of this 
section. If a lamp must be replaced due to failure or aging during a 
phototest, broadband device readings consistent with those obtained for 
the original calibrated lamp will suffice until measurements can be 
performed with the spectroradiometer at the earliest possible 
opportunity.
    (2) SPF standard. (i) Preparation. The SPF standard should be a 
formulation containing 7-percent padimate O and 3-percent oxybenzone.

          Composition of the Padimate O/oxybenzone SPF Standard
------------------------------------------------------------------------
                                                              Percent by
                        Ingredients                             weight
------------------------------------------------------------------------
Part A:
  Lanolin..................................................         4.50
  Cocoa butter.............................................         2.00
  Glyceryl monostearate....................................         3.00
  Stearic acid.............................................         2.00
  Padimate O...............................................         7.00
  Oxybenzone...............................................         3.00
Part B:
  Purified water USP.......................................        71.60
  Sorbitol solution........................................         5.00
  Triethanolamine, 99 percent..............................         1.00
  Methylparaben............................................         0.30
  Propylparaben............................................         0.10
Part C:
  Benzyl alcohol...........................................         0.50
Part D:
  Purified water USP.......................................       QS \1\
------------------------------------------------------------------------
\1\ Quantity sufficient to make 100 grams.

    Step 1. Add the ingredients of Part A into a suitable stainless 
steel kettle equipped with a propeller agitator. Mix at 77 to 82 [deg]C 
until uniform.
    Step 2. Add the water of Part B into a suitable stainless steel 
kettle equipped with a propeller agitator and begin mixing at 77 to 82 
[deg]C. Add the remaining ingredients of Part B and mix until uniform.
    Step 3. Add the batch of Step 1 to the batch of Step 2 and mix at 
77 to 82 [deg]C until smooth and uniform. Slowly cool the batch to 49 
to 54 [deg]C.
    Step 4. Add the benzyl alcohol of Part C to the batch of Step 3 at 
49 to 54 [deg]C. Mix until uniform. Continue to cool batch to 35 to 41 
[deg]C.
    Step 5. Add sufficient water of Part D to the batch of Step 4 at 35 
to 41 [deg]C to obtain 100 grams of SPF standard. Mix until uniform. 
Cool batch to 27 to 32 [deg]C.
    (ii) HPLC assay. Use the following high performance liquid 
chromatography (HPLC) procedure to verify the concentrations of 
padimate O and oxybenzone in the SPF standard:
    (A) Instrumentation. (1) Equilibrate a suitable liquid 
chromatograph to the following or equivalent conditions:

------------------------------------------------------------------------
 
------------------------------------------------------------------------
(i) Column................................  C-18, 250 millimeters (mm)
                                             length, 4.6 mm inner
                                             diameter (5 microns)
(ii) Mobile Phase.........................  85:15:0.5 methanol: water:
                                             acetic acid
(iii) Flow Rate...........................  1.5 milliliters (mL) per
                                             minute
(iv) Temperature..........................  Ambient
(v) Detector..............................  UV spectrophotometer at 308
                                             nanometers
(vi) Attenuation..........................  As needed
------------------------------------------------------------------------

    (2) Use HPLC grade reagents for mobile phase.
    (B) Preparation of the HPLC reference standard. (1) Weigh 0.50 gram 
(g) of oxybenzone USP reference standard into a 250-mL volumetric 
flask. Dissolve and dilute to volume with isopropanol. Mix well.
    (2) Weigh 0.50 g of padimate O USP reference standard into a 250-mL 
volumetric flask. Dissolve and dilute to volume with isopropanol. Mix 
well.
    (3) Pipet 3.0 mL of the oxybenzone solution and 7.0 mL of the 
padimate O solution into a 100-mL volumetric flask. Dilute to volume 
with isopropanol and mix well.
    (C) HPLC system suitability. (1) Make three replicate 10-microliter 
injections of the HPLC reference standard (described in paragraph 
(i)(2)(ii)(B) of this section). The relative standard deviation in peak 
areas should not be more than 2.0 percent for either oxybenzone or 
padimate O.
    (2) Calculate the resolution (R) between the oxybenzone and 
padimate O peaks from one chromatogram as follows:
[GRAPHIC] [TIFF OMITTED] TR17JN11.003


Where to = retention time for oxybenzone
tp = retention time for padimate O
Wo = oxybenzone peak width at baseline
Wp = padimate O peak width at baseline


If the resolution (R) is less than 3.0, adjust the mobile phase or 
replace the column.
    (D) SPF standard assay.
    (1) The SPF standard is diluted to the same concentration as the 
HPLC reference standard according to the following steps:
    (i) Step 1. Weigh 1.0 g of the SPF standard (described in paragraph 
(i)(2)(i) of this section) into a 50-mL volumetric flask.
    (ii) Step 2. Add approximately 30 mL of isopropanol and heat with 
swirling until contents are evenly dispersed.
    (iii) Step 3. Cool to room temperature (15 to 30 [deg]C) and dilute 
to volume with isopropanol. Mix well.
    (iv) Step 4. Pipet 5.0 mL of the preparation into a 50-mL 
volumetric flask and dilute to volume with isopropanol. Mix well.
    (2)(i) Inject 10-microliter of diluted SPF standard from paragraph 
(i)(2)(D)(1) of this section and calculate the amount of oxybenzone and 
padimate O as follows:

[[Page 35663]]

[GRAPHIC] [TIFF OMITTED] TR17JN11.004

    (ii) The percent of oxybenzone and padimate O in the SPF standard 
should be between 95 and 105.
    (3) Test subjects. (i) Number of subjects. A test panel should 
include enough subjects to produce a minimum of 10 valid test results. 
A maximum of three subjects may be rejected from this panel based on 
paragraph (i)(5)(v)) of this section.
    (ii) Medical history. (A) Obtain a medical history from each 
subject with emphasis on the effects of sunlight on the subject's skin. 
Determine that each subject is in good general health with skin type I, 
II, or III as follows:
    (1) Always burns easily; never tans (sensitive).
    (2) Always burns easily; tans minimally (sensitive).
    (3) Burns moderately; tans gradually (light brown) (normal).
    (4) Burns minimally; always tans well (moderate brown) (normal).
    (5) Rarely burns; tans profusely (dark brown) (insensitive).
    (6) Never burns; deeply pigmented (insensitive).
    (B) Skin type is based on first 30 to 45 minutes of sun exposure 
after a winter season of no sun exposure. Determine that each subject 
is not taking topical or systemic medication that is known to alter 
responses to UV radiation. Determine that each subject has no history 
of sensitivities to topical products and/or abnormal responses to 
sunlight, such as a phototoxic or photoallergic response.
    (iii) Physical examination. Conduct a physical examination to 
determine the presence of sunburn, suntan, scars, active dermal 
lesions, and uneven skin tones on the areas of the back to be tested. A 
suitable source of low power UVA, such as a Woods lamp, is helpful in 
this process. If any of these conditions are present, the subject is 
not qualified to participate in the study. The presence of nevi, 
blemishes, or moles will be acceptable if, in the physician's judgment, 
they will neither compromise the study nor jeopardize a subject's 
safety. Subjects with dysplastic nevi should not be enrolled. Excess 
hair on the back is acceptable if the hair is clipped. Shaving is 
unacceptable because it may remove a significant portion of the stratum 
corneum and temporarily alter the skin's response to UV radiation.
    (iv) Informed consent. Obtain legally effective written informed 
consent from all test subjects.
    (4) Sunscreen application. (i) Test site. Test sites are locations 
on each subject's back, between the beltline and the shoulder blades 
(scapulae) and lateral to the midline, where skin responses to UV 
radiation are determined. Responses on unprotected skin (no test 
material applied) and protected skin (sunscreen test product(s) or SPF 
standard applied) are determined at separate unprotected and protected 
test sites, respectively. Test sites should be randomly located in a 
blinded manner. Each test site should be a minimum of 30 square 
centimeters and outlined with indelible ink.
    (ii) Test subsite. Test subsites are the locations to which UV 
radiation is administered within a test site. At least five test 
subsites should receive UV doses within each test site. Test subsites 
should be at least 0.5 square centimeters (cm\2\) in area and should be 
separated from each other by at least 0.8 cm. Each test subsite should 
be outlined with indelible ink.
    (iii) Applying test materials. Apply the sunscreen test product and 
the SPF standard at 2 milligrams per square centimeter (mg/cm\2\) to 
their respective test sites. Use a finger cot compatible with the 
sunscreen to spread the product as evenly as possible.
    (iv) Waiting period. Wait at least 15 minutes after applying a 
sunscreen product before exposing the test sites to UV radiation as 
described in paragraph (i)(5)) of this section. For water resistant 
sunscreen products, proceed with the water resistance testing procedure 
described in paragraph (i)(7) of this section after waiting at least 15 
minutes.
    (5) UV exposure. (i) Definition of minimal erythema dose (MED). The 
minimal erythema dose (MED) is the smallest UV dose that produces 
perceptible redness of the skin (erythema) with clearly defined borders 
at 16 to 24 hours after UV exposure. The MED for unprotected skin 
(MEDu) is determined on a test site that does not have 
sunscreen applied. The MED for protected skin (MEDp) is 
determined on a test site that has sunscreen applied. An 
MEDp is determined for the SPF standard (ssMEDp). 
An MEDp is determined for the sunscreen test product 
(tpMEDp).
    (ii) UV exposure for initial MEDu. For each test 
subject, administer a series of UV radiation doses expressed as J/m\2\-
eff (as determined according to paragraph (a)(2) of this section) to 
the test subsites within an unprotected test site using an accurately 
calibrated solar simulator. Select doses that are a geometric series 
represented by 1.25\n\ (i.e., each dose is 25 percent greater than the 
previous dose).
    (iii) UV exposure for final MEDu, ssMEDp, and 
tpMEDp. For each subject, determine the final 
MEDu, ssMEDp, and tpMEDp by 
administering a series of five UV doses to the appropriate test sites. 
The middle dose (X) in each of these dose series (i.e., the third dose) 
should equal the initial MEDu times the expected SPF. Note 
that the expected SPF equals 1 and 16.3 for the final MEDu 
and ssMEDp, respectively. The remaining UV doses in the 
series depend upon the expected SPF value of the sunscreen test 
product(s).
    For products with an expected SPF less than 8, administer UV doses 
that increase by 25 percent with each successive dose (i.e., 0.64X, 
0.80X, 1.00X, 1.25X, and 1.56X). For products with an expected SPF from 
8 to 15, administer UV doses that increase by 20 percent with each 
successive dose (i.e., 0.69X, 0.83X, 1.00X, 1.20X, and 1.44X). For 
products with an expected SPF higher than 15, administer UV doses that 
increase by 15 percent with each successive dose (i.e., 0.76X, 0.87X, 
1.00X, 1.15X, and 1.32X).
    (iv) Evaluation of test subsites. In order that the person who 
evaluates the test subsites is not biased, he/she should not be the 
same person who applied the sunscreen drug product to the test site or 
administered the UV doses. After UV doses are administered, all 
immediate responses should be recorded. These may include an immediate 
darkening or tanning, typically grayish or purplish in color, which 
fades in 30 to 60 minutes; an immediate reddening at the subsite, due 
to heating of the skin, which fades rapidly; and an immediate 
generalized heat response, spreading beyond the subsite, which fades in 
30 to 60

[[Page 35664]]

minutes. After the immediate responses are noted, each subject should 
shield the exposed area from further UV radiation until the MED is 
determined. Determine the MED 16 to 24 hours after UV exposure. Because 
erythema is evaluated 16 to 24 hours after UV exposure, the final 
MEDu, ssMEDp, and tpMEDp are typically 
determined the day following determination of the initial 
MEDu. Evaluate the erythema responses of each test subsite 
using either tungsten or warm white fluorescent lighting that provides 
at least 450 lux of illumination at the test site. For the evaluation, 
the test subject should be in the same position as when the test site 
was irradiated.
    (v) Invalid test data. Reject test data for a test subject if 
erythema is not present on either the unprotected or protected test 
sites; or erythema is present at all subsites; or the responses are 
inconsistent with the series of UV doses administered; or the subject 
was noncompliant (e.g., the subject withdraws from the test due to 
illness or work conflicts or does not shield the exposed testing sites 
from further UV radiation until the MED is determined).
    (6) Determination of SPF. (i) Calculate an SPF value for each test 
subject (SPFi) as follows:
[GRAPHIC] [TIFF OMITTED] TR17JN11.005

    (ii) Calculate the mean
    [GRAPHIC] [TIFF OMITTED] TR17JN11.009
    

and the standard deviation (s) from the SPFi values. 
Calculate the standard error (SE), which equals s/[radic]n (where n 
equals the number of subjects who provided valid test results). Obtain 
the t value from Student's t distribution table corresponding to the 
upper 5-percent point with n--1 degrees of freedom. Determine the 
labeled SPF value, which equals the largest whole number less than
[GRAPHIC] [TIFF OMITTED] TR17JN11.012


 In order for the SPF determination of a test product to be considered 
valid, the SPF value of the SPF standard should fall within the 
standard deviation range of the expected SPF (i.e., 16.3  
3.43).
    (7) Determination of water resistance. The following procedure 
should be performed in an indoor fresh water pool, whirlpool, and/or 
hot tub maintained at 23 to 32 [deg]C. Fresh water is clean drinking 
water that meets the standards in 40 CFR part 141. The pool and air 
temperature and the relative humidity should be recorded.
    (i) Water resistance (40 minutes). The labeled SPF should be 
determined after 40 minutes of water immersion using the following 
procedure:
    (A) Step 1: Apply the sunscreen as described in paragraph (d) of 
this section.
    (B) Step 2: Perform moderate activity in water for 20 minutes.
    (C) Step 3: Rest out of water for 15 minutes. Do not towel test 
site(s).
    (D) Step 4: Perform moderate activity in water for 20 minutes.
    (E) Step 5: Allow test sites to dry completely without toweling.
    (F) Step 6: Apply the SPF standard as described in paragraph (d) of 
this section.
    Step 1. Expose test sites to UV doses as described in paragraph (e) 
of this section.
    (ii) Water resistance (80 minutes). The labeled SPF should be 
determined after 80 minutes of water immersion using the following 
procedure:
    (A) Step 1: Apply the sunscreen as described in paragraph (d) of 
this section.
    (B) Step 2: Perform moderate activity in water for 20 minutes.
    (C) Step 3: Rest out of water for 15 minutes. Do not towel test 
site(s).
    (D) Step 4: Perform moderate activity in water for 20 minutes.
    (E) Step 5: Rest out of water for 15 minutes. Do not towel test 
site(s).
    (F) Step 6: Perform moderate activity in water for 20 minutes.
    (G) Step 7: Rest out of water for 15 minutes. Do not towel test 
site(s).
    (H) Step 8: Perform moderate activity in water for 20 minutes.
    (I) Step 9: Allow test sites to dry completely without toweling.
    (J) Step 10: Apply the SPF standard as described in paragraph (d) 
of this section.
    (K) Step 11: Expose test sites to UV doses as described in 
paragraph (e) of this section.
    (j) Broad spectrum test procedure. (1) UV Spectrometry. (i) Plate. 
Use optical-grade polymethylmethacrylate (PMMA) plates suitable for UV 
transmittance measurements. The plate should be roughened on one side 
to a three dimensional surface topography measure (Sa) between 2 and 7 
micrometers and must have a rectangular application area of at least 16 
square centimeters (with no side shorter than 4 cm).
    (ii) Sample holder. The sample holder should hold the PMMA plate in 
a horizontal position to avoid flowing of the sunscreen drug product 
from one edge of the PMMA plate to the other. It should be mounted as 
close as possible to the input optics of the spectrometer to maximize 
capture of forward scattered radiation. The sample holder should be a 
thin, flat plate with a suitable aperture through which UV radiation 
can pass. The PMMA plate should be placed on the upper surface of the 
sample holder with the roughened side facing up.
    (iii) Light source. The light source should produce a continuous 
spectral distribution of UV radiation from 290 to 400 nanometers.
    (iv) Input optics. Unless the spectrometer is equipped with an 
integrating sphere, an ultraviolet radiation diffuser should be placed 
between the sample and the input optics of the spectrometer. The 
diffuser will be constructed from any UV radiation transparent material 
(e.g., Teflon[reg] or quartz). The diffuser ensures that the radiation 
received by the spectrometer is not collimated. The spectrometer input 
slits should be set to provide a bandwidth that is less than or equal 
to 1 nanometer.
    (v) Dynamic range of the spectrometer. The dynamic range of the 
spectrometer should be sufficient to measure transmittance accurately 
through a highly absorbing sunscreen product at all terrestrial solar 
UV wavelengths (290 to 400 nm).
    (2) Sunscreen product application to PMMA plate. The accuracy of 
the test depends upon the application of a precisely controlled amount 
of sunscreen product with a uniform distribution over the PMMA plate. 
The product is applied at 0.75 mg per square centimeter to the 
roughened side of the PMMA plate. The sunscreen product should be 
applied in a series of small dots over the entire PMMA plate and then 
spread evenly using a gloved finger. Spreading should be done with a 
very light spreading action for approximately 30 seconds followed by 
spreading with greater pressure for approximately 30 seconds. The plate 
should then be allowed to equilibrate for 15 minutes in the dark before 
the pre-irradiation described in paragraph (c) of this section.
    (3) Sunscreen product pre-irradiation. To account for lack of 
photostability, apply the sunscreen product to the PMMA plate as 
described in paragraph (b) of this section and then irradiate with a 
solar simulator described in section 352.70(b) of this chapter. The 
irradiation dose should be 4 MEDs which is equivalent to an erythemal 
effective dose of 800 J/m\2\ (i.e., 800 J/m\2\-eff).
    (4) Calculation of mean transmittance values. After pre-irradiation 
described in paragraph (c) of this section, mean transmittance values 
should be

[[Page 35665]]

determined for each wavelength [lambda] over the full UV spectrum (290 
to 400 nanometers). The transmittance values should be measured at 1 
nanometer intervals. Measurements of spectral irradiance transmitted 
for each wavelength [lambda] through control PMMA plates coated with 15 
microliters of glycerin (no sunscreen product) should be obtained from 
at least 5 different locations on the PMMA plate [C1([lambda]), 
C2([lambda]), C3([lambda]), C4([lambda]), and C5([lambda])]. In 
addition, a minimum of 5 measurements of spectral irradiance 
transmitted for each wavelength [lambda] through the PMMA plate covered 
with the sunscreen product will be similarly obtained after pre-
irradiation of the sunscreen product [P1([lambda]), P2([lambda]), 
P3([lambda]), P4([lambda]), and P5([lambda])]. The mean transmittance 
for each wavelength,
[GRAPHIC] [TIFF OMITTED] TR17JN11.010


is the ratio of the mean of the C([lambda]) values to the mean of the 
P([lambda]) values, as follows:
[GRAPHIC] [TIFF OMITTED] TR17JN11.006


Where n >= 5

    (5) Calculation of mean absorbance values. (i) Mean transmittance 
values,
[GRAPHIC] [TIFF OMITTED] TR17JN11.010


are converted into mean absorbance values,
[GRAPHIC] [TIFF OMITTED] TR17JN11.011


at each wavelength by taking the negative logarithm of the mean 
transmittance value as follows:
[GRAPHIC] [TIFF OMITTED] TR17JN11.008

    (ii) The calculation yields 111 monochromatic absorbance values in 
1 nanometer increments from 290 to 400 nanometers.
    (6) Number of plates. For each sunscreen product, mean absorbance 
values should be determined from at least three individual PMMA plates. 
Because paragraph (d) of this section requires at least 5 measurements 
per plate, there should be a total of at least 15 measurements.
    (7) Calculation of the critical wavelength. The critical wavelength 
is identified as the wavelength at which the integral of the spectral 
absorbance curve reaches 90 percent of the integral over the UV 
spectrum from 290 to 400 nm. The following equation defines the 
critical wavelength:
[GRAPHIC] [TIFF OMITTED] TR17JN11.007


Where [lambda]c = critical wavelength
A([lambda]) = mean absorbance at each wavelength
d[lambda] = wavelength interval between measurements


A mean critical wavelength of 370 nm or greater is classified as broad 
spectrum protection.

PART 310--NEW DRUGS

0
4. 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.


0
5. Section 310.545 is amended by revising paragraphs (a)(29) and 
(d)(31) and by adding new paragraph (d)(40) 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.
    (i) Ingredients.

Diethanolamine methoxycinnamate
Digalloyl trioleate
Ethyl 4-[bis(hydroxypropyl)] aminobenzoate
Glyceryl aminobenzoate
Lawsone with dihydroxyacetone
Red petrolatum

    (ii) Any ingredients labeled with any of the following or similar 
claims. Instant protection or protection immediately upon application.
    Claims for ``all-day'' protection or extended wear claims citing a 
specific number of hours of protection that is inconsistent with the 
directions for application in 21 CFR 201.327.
* * * * *
    (d) * * *
    (31) December 31, 2002, for products subject to paragraph 
(a)(29)(i) of this section.
* * * * *
    (40) June 18, 2012, for products subject to paragraph (a)(29)(ii) 
of this section. June 17, 2013, for products with annual sales less 
than $25,000.

    Dated: June 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-14766 Filed 6-14-11; 8:45 am]
BILLING CODE 4160-01-P