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

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

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

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

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

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

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

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

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:

    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

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

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

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

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

(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

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

    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

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