manufacturers are already included among the respondents counted for
that collection, and that many of those manufacturers who have spray
dosage products may already be conducting flammability and drying time
testing (e.g., many are including flammability statements and
information about drying time in current product labeling), the
proposed inclusion of these requirements in the sunscreen regulations
is new. The proposed rule specifies the particle size, flammability,
and drying time limitations that would be required for sunscreens in
spray dosage forms to be GRASE under the monograph. The proposed rule
also specifies that compliance with these limitations must be verified
through batch and lot testing. While this greater specificity as to
required testing might have a marginal effect on the burden associated
with recordkeeping for manufacturing facilities that are not already
conducting such testing, FDA believes that the total change would be
minimal in light of the total recordkeeping burden under parts 210 and
211, which is estimated across thousands of manufacturers of a wide
variety of drugs. We request comment on these assumptions. If FDA
determines that the assumptions are incorrect, then, concurrent with
publication of the final rule, FDA plans to amend its approved
information collection 0910-0139, if necessary, to adjust the
respective burden estimate(s) to account for any change. We request
comment on the accuracy of our assumptions and the resulting burden
estimate.

B. Regulatory Status of Testing Entities

    Proposed Sec.  201.327(k) clarifies the regulatory status of final
formulation testing, including that final formulation testing conducted
pursuant to Sec.  201.327 constitutes ``manufacture'' of a drug. As
such, this testing must be conducted in an establishment registered in
accordance with part 207 and section 510 of the FD&C Act, and entities
conducting final formulation testing required by this section must
comply with CGMP and associated recordkeeping requirements, including
those set forth in Sec.  201.327(l) and in parts 210 and 211. As this
provision is intended only to clarify an existing requirement, it does
not create a new information collection.
    Entities covered by this provision are already included in the
burden estimates for the information collections associated with
registration and listing requirements. Recordkeeping obligations
related to registration and listing under part 207 and section 510 of
the FD&C Act are part of FDA's approved information collection for part
207 (OMB control number 0910-0829). CGMP recordkeeping obligations are
part of FDA's approved information collection for part 211 (OMB control
number 0910-0139).

C. Generating and Maintaining Records of SPF and Broad Spectrum Testing

    FDA is proposing specific recordkeeping requirements for SPF and
broad spectrum testing to enable FDA to better monitor responsible
persons' compliance with the requirements of Sec.  201.327.
Recordkeeping is essential for FDA to evaluate whether required testing
of final formulations is being conducted properly (both as to human
subject protection and as to study design) and to enable the Agency to
investigate postmarketing product failures or adverse events.
Appropriate recordkeeping also enables FDA to conduct better and more
efficient inspections of entities conducting final formulation testing.
The proposed recordkeeping requirements are in alignment with the
records required for other types of manufacturing under CGMPs as set
forth in parts 210 and 211.
    Failure to maintain adequate records of testing equipment, methods,
and observations can raise broad questions

about the reliability of final formulation testing. In FDA's
experience, there has been a lack of uniformity in testing entities'
approaches to recordkeeping for final formulation testing, raising
concerns about the Agency's ability to assess the reliability of the
results of final formulation testing. The proposed regulation would
address these concerns, clarify FDA's expectations, and align the
regulation with current best practices.
    a. Potential transfer of obligations. Proposed Sec.  201.327(a)(1)
permits a responsible person (defined in Sec.  201.327(a)) to transfer
some or all of its obligations to another entity (a ``transferee''),
except for obligations with respect to recordkeeping under Sec.
201.327(l). We note that this could create some situations in which
both the responsible person and the transferee would be required to
comply with applicable recordkeeping requirements. The proposed
provision would also require a written record of the transfer of
obligations to be maintained by both parties to the transfer.
    Regarding the record of an obligation transfer, FDA believes that
it is usual and customary business practice for a written record of a
transfer of obligations to be maintained by both parties to the
transfer. FDA does not believe this requirement would incur any
additional recordkeeping burden and believes it would meet the
exception at 5 CFR 1320.3(b)(2). Regarding the potential for some
recordkeeping obligations to fall on both responsible persons and
transferees, although proposed Sec.  201.327(a)(1) does not itself
impose a specific requirement to generate records, it does create the
potential for some recordkeeping obligations to fall on both
responsible persons and transferees. In particular, if a responsible
person has delegated all other responsibilities under Sec.  201.327(i)
and (j), they would nonetheless need to maintain a copy of the records
of final formulation testing required by Sec.  201.327(l)(2) and (3).
We have included the burden associated with keeping this copy in our
assumption that there are 782 respondents for recordkeeping obligations
as described below (20 entities that conduct testing, 10 of whom are
also responsible persons, plus 762 responsible persons that delegate
their responsibility for conducting testing (e.g., to one of the 10
independent testing entities that are not themselves responsible
persons)). We invite comment on whether our estimates properly reflect
the recordkeeping obligations.
    b. Maintenance records and related burden. Proposed Sec.
201.327(l)(1) addresses maintenance records. The proposed rule
clarifies that, as manufacturing, final formulation testing must comply
with CGMPs, and, accordingly, records documenting proper maintenance of
equipment used in final formulation testing must be generated and
maintained by testing entities, consistent with existing obligations in
part 211.
    Regarding proposed Sec.  201.327(l)(1), the existing maintenance
record obligations are part of FDA's approved information collection
for part 211 (OMB control number 0910-0139), and FDA believes that most
of the respondents for this collection of information (the
approximately 20 entities we believe are conducting final formulation
testing) are already included among the recordkeepers counted for that
collection. The proposed rule provides greater specificity regarding
what information should be included in maintenance records maintained
by facilities conducting final formulation testing. While this greater
specificity might have a marginal effect on the burden associated with
recordkeeping for these facilities, and the number of respondents for
this requirement may need to be increased by 10 (to reflect contract
testing entities that may not be currently registered as
manufacturers), FDA believes that the total change would be minimal in
light of the total recordkeeping burden under parts 210 and 211, which
is estimated across thousands of manufacturers of a wide variety of
drugs. We request comment on these assumptions. If FDA determines that
the assumptions are incorrect, then, concurrent with publication of the
final rule, FDA plans to amend its approved information collection
under OMB control number 0910-0139 as necessary to adjust the
respective burden estimate(s) in order to account for any change.
    c. SPF testing records and related burden. Proposed Sec.
201.327(l)(2) addresses SPF testing records and requires that
respondents keep records related to the identification of the entity
conducting the testing, the formulation being tested, equipment used,
investigators, SPF standards, specific subject and test result data,
and records demonstrating compliance with Sec.  201.327(i)(1) governing
the establishment of adequate clinical testing procedures and
conditions. This is important because failure of testing entities to
keep adequate records to support final formulation testing may leave
FDA unable to verify the reliability of the results of SPF testing.
Because one testing entity may conduct final formulation testing on
behalf of multiple responsible persons, an error at one testing entity
may affect data across multiple clinical SPF testing studies for
multiple different final formulations that are ultimately sold under
different labels.
    In particular, proposed Sec.  201.327(l)(2) requires that, in
addition to any records required to be kept pursuant to parts 210 and
211, records of SPF testing must include: (1) Identification of the
testing entity; (2) the product identifier and expected SPF; (3)
characterization of the SPF standard sunscreen required by proposed
Sec.  201.327(i)(3) (lot number, manufacturing date, and results of
high performance liquid chromatography (HPLC) SPF standard assay); (4)
documentation linking any blinded samples with the product lot number
and formulation tested; (5) specific testing records for each human
subject (identification of the UV source used for testing and various
specific test results and the individual(s) who determined the values);
(6) the mean and standard deviation from SPFi values, standard error
and determined SPF value derived as set forth in proposed Sec.
201.327(i)(7); (7) records for water resistance testing of pool
temperature, air temperature, and relative humidity as required by
proposed Sec.  201.327(i)(8); and (8) records demonstrating compliance
with proposed Sec.  201.327(i)(1) requirements for adequate clinical
testing procedures and conditions (e.g., individual case histories and
documentation of IRB review).
    Table 10, row 2 provides FDA's estimate that approximately 20
respondents will need to generate SPF testing records in accordance
with proposed Sec.  201.327(l)(2) for existing products that will be
reformulated. FDA estimates 85.5 records per recordkeeper for a total
of 1,710 records. This is a one-time burden. FDA estimates a burden of
24 hours per recordkeeping. We estimate the total burden of this
recordkeeping to be 41,040 hours.
    Table 10, row 3 provides FDA's estimate that up to 20 respondents
will need to generate SPF testing records in accordance with proposed
Sec.  201.327(l)(2) for new formulations. FDA estimates 48.75 records
per recordkeeper for a total of 975 records. FDA estimates a burden of
24 hours per recordkeeping. We estimate the total burden of this
recordkeeping to be 23,400.
    Table 10, row 4 provides FDA's estimate that up to 782 respondents
will need to keep SPF testing records in accordance with proposed Sec.
201.327(l)(2) for existing products that will be reformulated. This is
a one-time

burden. FDA estimates 2.1867 records per recordkeeper for a total of
1,710 records. FDA estimates a burden of 0.33 hours per recordkeeping.
We estimate the total burden of this recordkeeping to be 564.3 hours.
    Table 10, row 5 provides FDA's estimate that up to 782 respondents
will need to keep SPF testing records in accordance with proposed Sec.
201.327(l)(2) for new formulations. FDA estimates 1.2468 records per
recordkeeper for a total of 975 records. FDA estimates a burden of 0.33
hours per recordkeeping. We estimate the total burden of this
recordkeeping to be 321.75 hours.
    With regard to the testing-related estimates, we note that the
requirements for obtaining certain medical history information from
test subjects are not considered collections of information because
information collected from subjects of clinical testing does not
constitute information under 5 CFR 1320.3(h)(5), and that the
referenced informed consent and IRB requirements under parts 50 and 56
are covered by existing approvals, as previously discussed.
    d. Broad spectrum testing records and related burden. Proposed
Sec.  201.327(l)(3) addresses broad spectrum testing records. The
proposed rule requires records related to the identification of the
entity conducting the testing, the formulation being tested, equipment
used, investigators, UV standards, sunscreen application, and specific
test result data. This is important because failure of testing entities
to keep adequate records to support broad spectrum testing may leave
FDA unable to verify the reliability of testing results. Failure at one
testing entity may affect data across multiple broad spectrum testing
studies for multiple different final formulations that are ultimately
sold under different labels.
    In particular, proposed Sec.  201.327(l)(3) requires that records
of broad spectrum testing must include: (1) Identification of the
testing entity; (2) records of sample information (product identifier
and expected SPF, master key for blinded samples, sample number and
identifier code, polymethylmethacrylate (PMMA) plate surface topography
measurement, and sample holder orientation); (3) identification of each
UV source used for sunscreen product pre-irradiation; (4) records of
sunscreen product application (sample weights, equipment
identification); (5) measurements required by proposed Sec.
201.327(j)(4) to (6)); (6) records of critical wavelength and UVA1/UV
ratio values; (7) for each sample: The identity of the individual(s)
conducting specific testing steps; and (8) test dates for the broad
spectrum test conducted pursuant to Sec.  201.327(j), and sample report
forms and supporting data.
    Table 10, row 6 provides FDA's estimate that approximately 20
respondents will need to generate broad spectrum testing records in
accordance with proposed Sec.  201.327(l)(3) for existing products. As
with records of SPF testing, this number of respondents reflects FDA's
assumption that most responsible persons will delegate responsibility
for conducting testing under Sec.  201.327(j) to the approximately 20
testing entities. FDA estimates 203.9 records per recordkeeper for a
total of 4,078 records. This is a one-time burden. FDA estimates a
burden of 1.5 hours per recordkeeping. We estimate the total burden of
this recordkeeping to be 6,117 hours.
    Table 10, row 7 provides FDA's estimate that up to 20 respondents
will need to generate broad spectrum testing records in accordance with
proposed Sec.  201.327(l)(3) for new formulations. FDA estimates 48.75
records per recordkeeper for a total of 975 records. FDA estimates a
burden of 1.5 hours per recordkeeping. We estimate the total burden of
this recordkeeping to be 1,462.5 hours.
    Table 10, row 8 provides FDA's estimate that up to 782 respondents
will need to keep broad spectrum testing records in accordance with
proposed Sec.  201.327(l)(3) for existing products. This is a one-time
burden. FDA estimates 5.215 records per recordkeeper for a total of
4,078 records. FDA estimates a burden of 0.17 hours per recordkeeping.
We estimate the total burden of this recordkeeping to be 693.3 hours.
    Table 10, row 9 provides FDA's estimate that up to 782 respondents
will need to keep broad spectrum testing records in accordance with
proposed Sec.  201.327(l)(3) for new formulations. FDA estimates 1.2468
records per recordkeeper for a total of 975 records. FDA estimates a
burden of 0.17 hours per recordkeeping. We estimate the total burden of
this recordkeeping to be 165.75 hours.
    The recordkeeping burden is estimated as described in the tables at
the end of the PRA discussion.
    With the exceptions noted above, we conclude that the other
provisions of this rule are not subject to OMB review under the PRA.
    The proposed changes to part 310 do not include any collections of
information subject to the PRA.
    The remaining sections of part 347 do not include any collections
of information not already addressed in this analysis.
    Section 201.327 and the remaining sections of part 352 either do
not contain an information collection subject to PRA, or contain
specific labeling information, including directions and warnings, which
are a ``public disclosure of information originally supplied by the
Federal Government to the recipient for the purpose of disclosure to
the public'' (5 CFR 1320.3(c)(2)) and, therefore, are not collections
of information.
    FDA estimates the burden of this information collection as follows:

                                                     Table 9--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
         Activity and 21 CFR section              Number of     responses per   Total annual          Average burden per response           Total hours
                                                 respondents     respondent       responses
--------------------------------------------------------------------------------------------------------------------------------------------------------
Inform FDA and investigators of significant                20              40             800  0.5 (30 minutes).........................             400
 new adverse effects or risks (Sec.
 201.327(i)(1)(i)) and new safety and other
 observations (Sec.   201.327(i)(1)(v)).
Investigators provide safety reports in                    20            24.4             488  0.5 (30 minutes).........................             244
 accordance with Sec.   201.327(i)(1)(vii)(A).
Investigators provide a final report in                    20           48.75             975  3........................................           2,925
 accordance with Sec.   201.327(i)(1)(vii)(B)
 (one time per study).
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................           3,569
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

                                                   Table 10--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
         Activity and 21 CFR section              Number of      records per    Total annual        Average burden per recordkeeping        Total hours
                                                recordkeepers   recordkeeper       records
--------------------------------------------------------------------------------------------------------------------------------------------------------
Obtain and keep a signed investigator                      20               2              40  0.6 (36 minutes).........................              24
 statement and CV in accordance with Sec.
 201.327(i)(1)(i) and (iv)(B).
Generate SPF testing records for existing                  20            85.5           1,710  24.......................................          41,040
 products (Sec.   201.327(l)(2)) (one-time).
Generate SPF testing records for new                       20           48.75             975  24.......................................          23,400
 formulations (Sec.   201.327(l)(2)).
Keep SPF testing records for existing                     782          2.1867           1,710  0.33 (20 minutes)........................           564.3
 products (Sec.   201.327(l)(2)) (one-time).
Keep SPF testing records for new formulations             782          1.2468             975  0.33.....................................          321.75
 (Sec.   201.327(l)(2)).                                                                       (20 minutes).............................
Generate Broad Spectrum testing records for                20           203.9           4,078  1.5......................................           6,117
 existing products (Sec.   201.327(l)(3)).
Generate Broad Spectrum testing records for                20           48.75             975  1.5......................................         1,462.5
 new formulations (Sec.   201.327(l)(3).
Keep Broad Spectrum testing records for                   782           5.215           4,078  0.17 (10 minutes)........................           693.3
 existing products (Sec.   201.327(l)(3)).
Keep Broad Spectrum testing records for new               782          1.2468             975  0.17 (10 minutes)........................          165.75
 formulations (Sec.   201.327(l)(3)).
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................       773,788.6
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating or maintenance costs associated with this collection of information.

                                              Table 11--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
         Activity and 21 CFR section              Number of      disclosures    Total annual         Average burden per disclosure          Total hours
                                                 respondents   per respondent    disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
Create PDP labeling in accordance with                    772          5.2824           4,078  0.5 (30 minutes).........................           2,039
 statement of identity and SPF value
 requirements (Sec.   201.327(b)(1), (b)(2)
 and (h)(1)) for currently marketed sunscreen
 formulations (one-time burden).
Create PDP labeling in accordance with                    772           1.943           1,500  0.5 (30 minutes).........................             750
 statement of identity and SPF value
 requirements (Sec.   201.327(b)(1), (b)(2),
 and (h)(1)) for new formulations.
Conduct SPF testing in accordance with Sec.                20             111           2,220  24.......................................          53,280
 201.327(i) to determine SPF value for
 currently marketed sunscreen formulations
 (if not already done) (one-time burden).
Conduct SPF testing in accordance with Sec.                20           48.75             975  24.......................................          23,400
 201.327(i) to determine SPF value for new
 sunscreen formulations.
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................          79,469
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating or maintenance costs associated with this collection of information.

    In compliance with the PRA (44 U.S.C. 3407(d)), the Agency has
submitted the information collection provisions of this proposed rule
to OMB for review. These requirements will not be effective until FDA
obtains OMB approval. FDA will publish a notice concerning OMB approval
of these requirements in the Federal Register.

XVI. Federalism

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. Section 4(a) of the
Executive order requires Agencies to ``construe . . . a Federal statute
to preempt State law only where the statute contains an express
preemption provision or there is some other clear evidence that the
Congress intended preemption of State law, or where the exercise of
State authority conflicts with the exercise of Federal authority under
the Federal statute.'' The sole statutory provision giving preemptive
effect to this proposed rule is section 751 of the FD&C Act (21 U.S.C.
379r). We have complied with all of the applicable requirements under
the Executive order and have determined that the preemptive effect of
this proposed rule, if finalized, would be consistent with Executive
Order 13132. Through publication of this proposed rule, we are
providing notice and an opportunity for State and local officials to
comment on this rulemaking.

XVII. Consultation and Coordination With Indian Tribal Governments

    We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, on the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal

Government and Indian Tribes. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.

XVIII. References

    The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register, but websites
are subject to change over time.

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2. Matlack, S., ``From Tanning Accessory to Health Necessity:
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List of Subjects

21 CFR Part 201

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

21 CFR Part 310

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

21 CFR Part 347

    Labeling, Over-the-counter drugs.

21 CFR Part 352

    Labeling, Over-the-counter drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, we propose
that 21 CFR parts 201, 310, 347, and 352 be amended as follows:

PART 201--LABELING

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

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

0
2. Revise Sec.  201.327 to read as follows:

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

    The following provisions apply to an over-the-counter (OTC)
sunscreen drug product that is intended for application to the skin of
humans for purposes of absorbing, reflecting, or scattering radiation
in the ultraviolet (UV) range at wavelengths from 290 to 400 nanometers
(nm), and that contains one or more of the following as an active
ingredient: Avobenzone, cinoxate, dioxybenzone, ensulizole, homosalate,
meradimate, octinoxate, octisalate, octocrylene, oxybenzone, padimate
O, sulisobenzone, titanium dioxide, or zinc oxide, alone or in
combination. The provisions do not apply to OTC sunscreen drug products
marketed under approved new drug applications or abbreviated new drug
applications. The failure of a product covered by this section to
comply with any provision of this section, including the labeling of
such a product with any effectiveness claim based on testing that fails
to comply with any provision of this section, renders that product
misbranded under section 502 of the Federal Food, Drug, and Cosmetic
Act.
    (a) General obligations of responsible persons. As used in this
section, a ``responsible person'' is the manufacturer, packer, or
distributor whose name appears on the labeling of a product covered by
this section. A responsible person must assure that final formulation
testing conducted on its product(s) pursuant to paragraphs (i) and (j)
of this section complies with all applicable provisions of this
section.
    (1) Transfer of obligations. (i) A responsible person may transfer
responsibility for any or all of its obligations set forth in this
section to another entity (e.g., a contract research organization and/
or testing laboratory), except as set forth in paragraph (l)
(recordkeeping) of this section. Any such transfer must be described in
writing. If not all obligations are transferred, the writing is
required to describe each of the obligations being assumed by the
transferee. If all obligations are transferred, a general statement
that all obligations have been transferred is acceptable. Any
obligation not covered by the written description will be deemed not to
have been transferred. A written record of the transfer of obligations
must be maintained by both parties to the transfer for the time period
set forth in paragraph (l) of this section.
    (ii) An entity that assumes any obligation(s) of a responsible
person must comply with the provisions of this section applicable to
the assumed obligation and will be subject to the same regulatory
action as a responsible person for failure to comply with any
obligation assumed under this section. Thus, all references to
``responsible person'' in this section apply to another entity (e.g., a
contract research organization or testing laboratory) to the extent
that it assumes one or more obligations of a responsible person.
    (2) Personnel. A responsible person must select only investigators
and other personnel qualified by appropriate training and/or experience
to conduct final formulation testing pursuant to this section.
Personnel engaged in testing under this section must have the
education, training, and experience, or any combination thereof, to
enable that person to adequately perform their assigned functions.
    (b) Principal display panel. The following labeling must be
prominently placed on the principal display panel:
    (1) Statement of identity--(i) Placement. The principal display
panel of an over-the-counter sunscreen drug product bears a statement
of identity as one of its principal features. Except as set forth in
paragraph (h) of this section, the statement of identity consists of
the name of each sunscreen active ingredient in the product as
identified in this section, listed in alphabetical order and followed
by ``Sunscreen'' and ``[Dosage form]'' (e.g., ``Lotion'' ``Spray'').
    (ii) Prominence. The statement of identity must appear on the
principal display panel in boldface type at least one-quarter as large
as the size of the most prominent printed matter on the principal
display panel, in lines generally parallel to the base on which the
package rests as it is designed to be displayed and in direct
conjunction with the most prominent display of the proprietary name or
designation. The entire text of the statement of identity must appear
in the same font style, size, and color with the same background color,
and as continuous text with no intervening text or graphic, other than
additional text provided in accordance with paragraph (h) of this
section.
    (2) Effectiveness claim. For purposes of this section, the term
``determined SPF value'' refers to the SPF value that equals the
largest whole number less than SPF-(t*SE), determined for a sunscreen
product in accordance with paragraph (i) of this section.
    (i) SPF Broad Spectrum Statement. For a product that has been shown
to pass the broad spectrum test in paragraph (j) of this section, the
labeling states ``Broad Spectrum SPF [insert the labeled SPF value
associated with the range into which the determined SPF value falls, as
set forth in the following table.]''

           Table 1 to Paragraph (b)(2)(i)--SPF Labeling Ranges
------------------------------------------------------------------------
      Range of determined SPF values        Associated labeled SPF value
------------------------------------------------------------------------
60-80.....................................  60+.
50-59.....................................  50.
40-49.....................................  40.
30-39.....................................  30.
25-29.....................................  25.
20-24.....................................  20.
15-19.....................................  15.
2-14......................................  Determined SPF Value.
------------------------------------------------------------------------

    (ii) SPF Statement. For a product that has not been shown to pass
the broad spectrum test in paragraph (j) of this section, the labeling
states ``SPF [insert labeled SPF value associated with the range into
which the determined SPF value falls, as set forth in the table in
paragraph (b)(2)(i) of this section]''.
    (iii) For a product with a determined SPF value of at least 2 but
less than 15. The SPF statement is immediately followed by an asterisk
(``*''), and the associated statement ``*See Skin Cancer/Skin Aging
Alert'' appears in the bottom 30 percent of the principal display
panel.
    (iv) Prominence of required statements. The SPF Broad Spectrum
statement, SPF statement, and ``*See Skin Cancer/Skin Aging Alert''
statement, as applicable, must appear in boldface type at least one-
quarter as large as the most prominent printed matter on the principal
display panel and in lines generally parallel to the base on which the
package rests as it is designed to be displayed. The entire text of the
Broad Spectrum SPF or SPF statement, as applicable, must appear in the
same font style, size, and color with the same background color and
must appear as continuous text with no intervening text or graphic. The
entire text of the ``See Skin Cancer/Skin Aging Alert'' statement, as
applicable, must appear in the same font style, size, and color with
the same background color and must appear as continuous text with no
intervening text or graphic.
    (3) Water resistance statements--(i) For products that provide 40
minutes of water resistance according to the test in paragraph
(i)(8)(i) of this section. The

labeling states ``Water Resistant (40 minutes).''
    (ii) For products that provide 80 minutes of water resistance
according to the test in paragraph (i)(8)(ii) of this section. The
labeling states ``Water Resistant (80 minutes).''
    (iii) Prominence of water resistance statement. For all products
bearing a water resistance statement, the statement must appear in
boldface type at least one-quarter as large as the most prominent
printed matter on the principal display panel and in lines generally
parallel to the base on which the package rests as it is designed to be
displayed. The entire text of the water resistance statement must
appear in the same font style, size, and color with the same background
color, and as continuous text with no intervening text or graphic.
    (c) Indications. The labeling of the product states, under the
heading ``Uses,'' the phrases listed in this paragraph, as appropriate.
Other truthful and nonmisleading statements, describing only the uses
that have been established and listed in this paragraph, may also be
used, as provided in Sec.  330.1(c)(2) of this chapter, subject to the
provisions of section 502 of the Federal Food, Drug, and Cosmetic Act
relating to misbranding and the prohibition in section 301(d) of the
Federal Food, Drug, and Cosmetic Act against the introduction or
delivery for introduction into interstate commerce of unapproved new
drugs in violation of section 505(a) of the Federal Food, Drug, and
Cosmetic Act.
    (1) For all sunscreen products, the following indication statement
must be included under the heading ``Uses'': ``[bullet] helps prevent
sunburn''. See Sec.  201.66(b)(4) for definition of bullet.
    (2) For sunscreen products that have been shown to pass the broad
spectrum test in paragraph (j) of this section and have a determined
SPF value of 15 or higher, the labeling may include the following
statement in addition to the indication in paragraph (c)(1) of this
section: ``[bullet] if used as directed with other sun protection
measures (see Directions [in bold italic font]), decreases the risk of
skin cancer and early skin aging caused by the sun''.
    (3) Any labeling or promotional materials that suggest or imply
that the use, alone, of any sunscreen reduces the risk of or prevents
skin cancer or early skin aging will cause the product to be misbranded
under section 502 of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 352).
    (d) Warnings. The labeling of the product contains the following
warnings under the heading ``Warnings''.
    (1) For all sunscreen products. (i) The labeling states ``Do not
use [bullet] on damaged or broken skin.''
    (ii) The labeling states ``When using this product [bullet] keep
out of eyes. Rinse with water to remove.''
    (iii) The labeling states ``Stop use and ask a doctor if [bullet]
rash occurs.''
    (2) For sunscreen products that are broad spectrum with determined
SPF values of at least 2 but less than 15 according to the SPF test in
paragraph (i) of this section or that have not been shown to pass the
broad spectrum test in paragraph (j) of this section. The first
statement under the heading ``Warnings'' states ``Skin Cancer/Skin
Aging Alert [in bold font]: Spending time in the sun increases your
risk of skin cancer and early skin aging. This product has been shown
only to help prevent sunburn, not [in bold font] skin cancer or early
skin aging.''
    (3) For products in a spray dosage form that meet the definition of
either the term ``flammable'' or the term ``combustible'' as defined in
Sec.  352.3(g) or (h) of this chapter, as applicable, when tested in
accordance with 16 CFR 1500.43a--(i) Labeling statement. The labeling
states [bullet] ``Flammable'' or ``Combustible'' (as applicable)
followed by a colon and the statement ``Keep away from fire or flame.''
    (ii) For products that have a drying time of less than 5 minutes.
The labeling states [bullet] ``Wait 5 minutes after application before
approaching a source of heat or flame, or before smoking.''
    (iii) For products that have a drying time of at least 5 minutes
but less than 10 minutes. The labeling states [bullet] ``Wait 10
minutes after application before approaching a source of heat or flame,
or before smoking.''
    (e) Directions. The labeling of the product contains the following
statements, as appropriate, under the heading ``Directions.'' More
detailed directions applicable to a particular product formulation may
also be included.
    (1) For all sunscreen products. (i) As an option, the labeling may
state ``For sunscreen use:''.
    (ii) The labeling states ``[bullet] apply [select one of the
following: `liberally' or `generously'] [and, as an option: `and
evenly'] 15 minutes before sun exposure''.
    (iii) As an option, the labeling may state ``[bullet] apply to all
skin exposed to the sun''.
    (iv) The labeling states ``[bullet] children under 6 months of age:
Ask a doctor''.
    (2) For sunscreen products that have been shown to pass the broad
spectrum test in paragraph (j) of this section and have a determined
SPF value of 15 or higher. The labeling states ``[bullet] Sun
Protection Measures. [in bold font] Spending time in the sun increases
your risk of skin cancer and early skin aging. To decrease this risk,
regularly use a sunscreen with a Broad Spectrum SPF value of 15 or
higher and other sun protection measures including: [bullet] limit time
in the sun, especially from 10 a.m.-2 p.m. [bullet] wear long-sleeved
shirts, pants, hats, and sunglasses''.
    (3) For products that satisfy the water resistance test in
paragraph (i)(8) of this section. The labeling states ``[bullet]
reapply: [bullet] after [select one of the following determined by
water resistance test: `40 minutes of' or `80 minutes of'] swimming or
sweating [bullet] immediately after towel drying [bullet] at least
every 2 hours''.
    (4) For products that do not satisfy the water resistance test in
paragraph (i)(8) of this section. The labeling states ``[bullet]
reapply at least every 2 hours [bullet] use a water resistant sunscreen
if swimming or sweating''.
    (5) For sunscreen products in a spray dosage form. The labeling
states ``[bullet] Hold container 4 to 6 inches from the skin to apply.
[bullet] Do not spray directly into face. Spray on hands then apply to
face. [bullet] Do not apply in windy conditions. [bullet] Use in a
well-ventilated area and avoid inhalation''.
    (f) Other information. The labeling of the product contains the
following statement under the heading ``Other information:'' ``[bullet]
protect the product in this container from excessive heat and direct
sun''.
    (g) False or misleading claims. There are claims that would be
false and/or misleading on sunscreen products. These claims include but
are not limited to the following: ``Sunblock,'' ``sweatproof,'' and
``waterproof.'' These or similar claims will cause the product to be
misbranded under section 502 of the Federal Food, Drug, and Cosmetic
Act.
    (h) Labeling of products containing a combination of sunscreen and
skin protectant active ingredients. Statements of identity,
indications, warnings, and directions for use, respectively, applicable
to each ingredient in the product may be combined to eliminate
duplicative words or phrases so that the resulting information is clear
and understandable. Labeling provisions in Sec.  347.50(e) of this
chapter do not apply to these products.
    (1) Statement of identity. The statement of identity of a sunscreen
product that also contains one or more skin protectant active
ingredients, identified in Sec. Sec.  347.10(a), (d), (e), (g), h),

(i), (k), (l), (m), and (r) of this chapter, consists of the names of
all sunscreen and skin protectant active ingredients in alphabetical
order followed by ``Sunscreen/Skin Protectant'' and ``[Dosage form].''
The statement of identity must be prominently placed on the principal
display panel and presented in accordance with paragraph (b)(1)(ii) of
this section.
    (2) Indications. The labeling of the product states, under the
heading ``Uses,'' any or all of the applicable indication(s) included
in Sec.  347.50(b) of this chapter or in paragraph (c) of this section.
Other truthful and nonmisleading statements, describing only the
indications for use that have been established in Sec.  347.50(b) of
this chapter or listed in paragraph (c) of this section, may also be
used, as provided by Sec.  330.1(c)(2) of this chapter, subject to the
provisions of section 502 of the Federal Food, Drug, and Cosmetic Act
relating to misbranding and the prohibition in section 301(d) of the
Federal Food, Drug, and Cosmetic Act against the introduction or
delivery for introduction into interstate commerce of unapproved new
drugs in violation of section 505(a) of the Federal Food, Drug, and
Cosmetic Act.
    (3) Warnings. The labeling of the product states, under the heading
``Warnings,'' the applicable warnings for sunscreens in paragraph (d)
of this section and for skin protectants in Sec.  347.50(c) of this
chapter.
    (4) Directions. The labeling of the product states, under the
heading ``Directions,'' any or all of the applicable directions for
sunscreens, as set forth in paragraph (e) of this section, and for skin
protectants, as set forth in Sec. Sec.  347.50(d) and 347.60(d) of this
chapter, unless otherwise stated in this paragraph. When the time
intervals or age limitations for administration of the individual
ingredients differ, the directions for the product may not contain any
dosage that exceeds those established for any individual ingredient in
the applicable OTC drug monograph(s), and may not provide for use by
any age group lower than the highest minimum age limit established for
any individual ingredient. When the directions for administration of
the sunscreen and skin protectant differ in any other way, the
directions for sunscreens in paragraph (e) of this section should be
used.
    (i) Sun Protection Factor (SPF) testing--(1) Adequate clinical
testing procedures and conditions--(i) General obligations of
responsible persons for testing under this paragraph. Responsible
persons must provide investigators and other personnel engaged in SPF
testing with the information they need to conduct an investigation
properly; must obtain a signed investigator statement from each
investigator; must ensure proper monitoring of the investigation(s);
must ensure that the investigation(s) is conducted in accordance with
written general investigational plan(s) and protocol(s); must ensure
compliance with paragraphs (i)(1)(ii) and (iii) of this section; and
must ensure that FDA and all participating investigators are promptly
informed of significant new adverse effects or risks with respect to
the drug.
    (ii) Informed consent. Effective informed consent, as defined in
part 50 of this chapter, must be obtained from all human subjects
before initiating clinical final formulation testing under this
paragraph (i).
    (iii) Institutional review board (IRB) approval. Clinical testing
under this paragraph (i), must be reviewed and approved by an IRB
meeting the requirements of FDA's regulations in part 56 of this
chapter.
    (iv) Control of personnel--(A) General obligations. A responsible
person is responsible for ensuring that investigators and other
personnel conducting any testing under this paragraph (i), conduct all
investigations in accordance with the signed investigator statement,
the investigational plan, and applicable regulations. Responsible
persons must ensure the implementation of adequate safeguards to
protect the rights, safety, and welfare of subjects under he
investigator's care. The responsible person must also ensure that
investigators or other study personnel will promptly report to the IRB
all changes in the clinical final formulation testing and all
unanticipated problems involving risk to human subjects or others, and
that investigators or other personnel will not make any changes in the
clinical final formulation testing without IRB approval, except where
necessary to eliminate apparent immediate hazards to human subjects.
    (B) Obtaining information from the investigator. Before permitting
an investigator to begin participating in clinical final formulation
testing under this paragraph (i), the responsible person must obtain
the following:
    (1) Investigator statement. A signed investigator statement
containing the name and address of the investigator and a commitment by
the investigator that he or she--
    (i) Will conduct the testing in accordance with the relevant,
current protocol(s) and will only make changes in a protocol after
notifying the responsible person and the IRB, except when necessary to
protect the safety, the rights, or welfare of subjects;
    (ii) Will comply with all requirements regarding the obligations of
clinical investigators and all other pertinent requirements in this
subpart;
    (iii) Will personally conduct or supervise the described
investigation(s);
    (iv) Will inform any potential subjects that the drugs are being
used for investigational purposes and will comply with the requirements
relating to obtaining informed consent (part 50 of this chapter) and
institutional review board review and approval (part 56 of this
chapter);
    (v) Will report to the responsible person adverse experiences that
occur during the investigation(s);
    (vi) Will ensure that all personnel assisting in the conduct of the
testing are informed about their obligations in meeting the above
commitments.
    (2) Curriculum vitae. A curriculum vitae or other statement of
qualifications of the investigator showing the education, training, and
experience that qualifies the investigator to conduct the final
formulation testing pursuant to this paragraph (i).
    (v) Informing investigators. The responsible person must, as the
overall investigation proceeds, keep each participating investigator
informed of new observations discovered by or reported to the
responsible person on the drug, particularly with respect to adverse
effects and safe use.
    (vi) Review of ongoing investigations. (A) The responsible person
must monitor the progress of all clinical testing being conducted on
its final formulation pursuant to this paragraph (i).
    (B) A responsible person who discovers noncompliance by an
investigator or other personnel with the signed agreement, the general
investigational plan, or the requirements of this paragraph (i) or
other applicable regulations (e.g., parts 50 and 56 of this chapter)
must promptly either secure compliance or end the investigator's or
other personnel's participation in testing conducted under this
paragraph (i).
    (C) The responsible person must review and evaluate the evidence
relating to the safety and effectiveness of the final formulation as it
is obtained from the investigator.
    (vii) Investigator reports--(A) Safety reports. An investigator
must immediately report to the responsible person any serious adverse
event, whether or not considered related to the final formulation,
including those listed in the protocol, and must include an

assessment of whether there is a reasonable possibility that the final
formulation being tested caused the adverse event. The investigator
must record nonserious adverse events and report them to the
responsible person according to the timetable specified in the
protocol.
    (B) Final report. An investigator must provide the responsible
person with an adequate report shortly after completion of each
investigation conducted by that investigator for the responsible person
under this paragraph (i).
    (2) UV source (solar simulator)--(i) Emission spectrum. Filter a
single port or multiport solar simulator so that it provides a
continuous emission spectrum from 290 to 400 nanometers (nm) with a
limit of 1,500 watts per square meter (W/m\2\) on total irradiance for
all wavelengths between 250 and 1,400 nm.
    (A) The solar simulator must have the following percentage of
erythema-effective radiation in each specified range of wavelengths:

  Table 2 to Paragraph (i)(2)(i)(A)--Solar Simulator Emission Spectrum
------------------------------------------------------------------------
                                                             Percent
                 Wavelength range (nm)                      erythemal
                                                         contribution 1
------------------------------------------------------------------------
<290..................................................              <0.1
290-300...............................................           1.0-8.0
290-310...............................................         49.0-65.0
290-320...............................................         85.0-90.0
290-330...............................................         91.5-95.5
290-340...............................................         94.0-97.0
290-400...............................................        99.9-100.0
------------------------------------------------------------------------
1 Calculation of erythema action spectrum described in paragraph
  (i)(2)(ii) of this section.

    (B) In addition, UVA II (320-340 nm) irradiance must equal or
exceed 20 percent of the total UV (290-400 nm) irradiance. UVA I (340-
400 nm) irradiance must equal or exceed 60 percent of the total UV
irradiance.
    (ii) Erythema action spectrum. (A) Calculate the erythema action
spectrum weighting factor (Vi) at each wavelength [lgr]:

(1) Vi ([lgr]) = 1.0 (250 <[lgr] <=298 nm)
(2) Vi ([lgr]) = 10\0.094\ * (\298\ - [lgr]) (298 <[lgr]
<=328 nm)
(3) Vi ([lgr]) = 10\0.015\ * (\140\ - [lgr]) (328 <[lgr]
<=400 nm)

    (B) Calculate the erythema-effective UV dose (E) delivered by a
solar simulator as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.003

Where

Vi([lgr]) = erythema action spectrum weighting factor at
each wavelength [lgr]
I([lgr]) = irradiance (Watts per square meter) at each wavelength
[lgr]
t = exposure time (seconds)
Erythema-effective dose (E) is expressed as effective Joules per
square meter (J/m\2\-eff).

    (C) The solar simulator radiation intensity must be determined
using a handheld radiometer with a response weighted to match the
spectrum in ISO 17166 CIE S 007/E entitled ``Erythemal reference action
spectrum and standard erythema dose,'' dated 1999 (First edition, 1999-
12-15; corrected and reprinted 2000-11-15), which is incorporated by
reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may
obtain a copy from the ISO Copyright Office, Case Postale 56, CH-1211,
Geneva 20, Switzerland, telephone +41-22-749-01-11 or fax +41-22-74-09-
47. https://www.iso.org. You may inspect a copy at the Center for Drug
Evaluation and Research, 10903 New Hampshire Ave., Bldg. 22, Silver
Spring, MD 20993, call<PHONE_NUMBER>, or at the National Archives and
Records Administration (NARA). For information on the availability of
this material at NARA, call<PHONE_NUMBER>, or go to: https://www.archives.gov/federal-register/cfr/ibr-locations.html. The solar
simulator output should be measured before and after each phototest or,
at a minimum, at the beginning and end of each test day. This
radiometer should be calibrated using side-by-side comparison with the
spectroradiometer (using the weighting factors determined according to
paragraph (i)(2)(ii)(A) of this section) at the time of the annual
spectroradiometric measurement of the solar simulator as described in
paragraph (i)(2)(iv) of this section.
    (iii) Operation. A solar simulator must have no significant time-
related fluctuations (within 20 percent) in radiation emissions after
an appropriate warm-up time and demonstrate good beam uniformity
(within 20 percent) in the exposure plane. The delivered dose to the UV
exposure site must be within 10 percent of the expected dose.
    (iv) Periodic measurement. To ensure that the solar simulator
delivers the appropriate spectrum of UV radiation, the emission
spectrum of the solar simulator must be measured at least annually with
an appropriate and accurately calibrated spectroradiometer system
(results should be traceable to the National Institute for Standards
and Technology). In addition, the solar simulator must be recalibrated
if there is any change in the lamp bulb or the optical filtering
components (i.e., filters, mirrors, lenses, collimating devices, or
focusing devices). Daily solar simulator radiation intensity should be
monitored with a broadband radiometer with a response weighted to match
the erythema action spectrum in ISO 17166 CIE S 007/E entitled
``Erythemal reference action spectrum and standard erythema dose,''
which is incorporated by reference in paragraph (i)(2)(ii)(C) of this
section. If a lamp must be replaced due to failure or aging during a
phototest, broadband device readings consistent with those obtained for
the original calibrated lamp will suffice until measurements can be
performed with the spectroradiometer at the earliest possible
opportunity.
    (3) SPF standard--(i) Preparation. The SPF standard must be a
formulation containing 7-percent padimate O and 3-percent oxybenzone.

Table 3 to Paragraph (i)(3)(i)--Composition of the Padimate O/Oxybenzone
                              SPF Standard
------------------------------------------------------------------------
                                                            Percent by
                       Ingredients                            weight
------------------------------------------------------------------------
Part A:
    Lanolin.............................................            4.50
    Cocoa butter........................................            2.00
    Glyceryl monostearate...............................            3.00
    Stearic acid........................................            2.00
    Padimate O..........................................            7.00
    Oxybenzone..........................................            3.00
Part B:
    Purified water USP..................................           71.60
    Sorbitol solution...................................            5.00
    Triethanolamine, 99 percent.........................            1.00
    Methylparaben.......................................            0.30
    Propylparaben.......................................            0.10
Part C:
    Benzyl alcohol......................................            0.50
Part D:
    Purified water USP..................................            QS 1
------------------------------------------------------------------------
\1\ Quantity sufficient to make 100 grams.

    (A) Step 1. Add the ingredients of Part A into a suitable stainless
steel kettle equipped with a propeller agitator. Mix at 77 to 82 [deg]C
until uniform.
    (B) Step 2. Add the water of Part B into a suitable stainless steel
kettle equipped with a propeller agitator and begin mixing at 77 to 82
[deg]C. Add the remaining ingredients of Part B and mix until uniform.
    (C) Step 3. Add the batch of Step 1 to the batch of Step 2 and mix
at 77 to 82 [deg]C until smooth and uniform. Slowly cool the batch to
49 to 54 [deg]C.
    (D) Step 4. Add the benzyl alcohol of Part C to the batch of Step 3
at 49 to 54 [deg]C. Mix until uniform. Continue to cool batch to 35 to
41 [deg]C.
    (E) Step 5. Add sufficient water of Part D to the batch of Step 4
at 35 to 41 [deg]C to obtain 100 grams of SPF standard. Mix until
uniform. Cool batch to 27 to 32 [deg]C.

    (ii) HPLC assay. Use the following high performance liquid
chromatography (HPLC) procedure to verify the concentrations of
padimate O and oxybenzone in the SPF standard:
    (A) Instrumentation--(1) Equilibrate a suitable liquid
chromatograph to the following or equivalent conditions:

----------------------------------------------------------------------------------------------------------------

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

    (2) Use HPLC grade reagents for mobile phase.
    (B) Preparation of the HPLC reference standard. (1) Weigh 0.5 gram
(g) of oxybenzone USP reference standard into a 250-mL volumetric
flask. Dissolve and dilute to volume with isopropanol. Mix well.
    (2) Weigh 0.5 g of padimate O USP reference standard into a 250-mL
volumetric flask. Dissolve and dilute to volume with isopropanol. Mix
well.
    (3) Pipet 3 mL of the oxybenzone solution and 7 mL of the padimate
O solution into a 100-mL volumetric flask. Dilute to volume with
isopropanol and mix well.
    (C) HPLC system suitability. (1) Make three replicate 10-microliter
injections of the HPLC reference standard (described in paragraph
(i)(3)(ii)(B) of this section). The relative standard deviation in peak
areas should not be more than 2 percent for either oxybenzone or
padimate O.
    (2) Calculate the resolution (R) between the oxybenzone and
padimate O peaks from one chromatogram as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.004

Where

to = retention time for oxybenzone
tp = retention time for padimate O
Wo = oxybenzone peak width at baseline
Wp = padimate O peak width at baseline
If the resolution (R) is less than 3, adjust the mobile phase or
replace the column.

    (D) SPF standard assay. (1) The SPF standard is diluted to the same
concentration as the HPLC reference standard according to the following
steps:
    (i) Step 1. Weigh 1 g of the SPF standard (described in paragraph
(i)(3)(i) of this section) into a 50-mL volumetric flask.
    (ii) Step 2. Add approximately 30 mL of isopropanol and heat with
swirling until contents are evenly dispersed.
    (iii) Step 3. Cool to room temperature (15 to 30 [deg]C) and dilute
to volume with isopropanol. Mix well.
    (iv) Step 4. Pipet 5.0 mL of the preparation into a 50-mL
volumetric flask and dilute to volume with isopropanol. Mix well.
    (2)(i) Inject 10-microliter of diluted SPF standard from paragraph
(i)(3)(ii)(D)(1) of this section and calculate the amount of oxybenzone
and padimate O as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.005

    (ii) The percent of oxybenzone and padimate O in the SPF standard
must be between 95 and 105.
    (4) Test subjects--(i) Number of subjects. A test panel should
include enough subjects to produce a minimum of 10 valid test results.
A maximum of three subjects may be rejected from this panel based on
paragraph (i)(6)(v) of this section.
    (ii) Medical history. (A) Obtain a medical history from each
subject with emphasis on the effects of sunlight on the subject's skin.
Determine that each subject is in good general health with skin type I,
II, or III as follows:
    (1) Always burns easily; never tans (sensitive).
    (2) Always burns easily; tans minimally (sensitive).
    (3) Burns moderately; tans gradually (light brown) (normal).
    (4) Burns minimally; always tans well (moderate brown) (normal).
    (5) Rarely burns; tans profusely (dark brown) (insensitive).
    (6) Never burns; deeply pigmented (insensitive).
    (B) Skin type is based on first 30 to 45 minutes of sun exposure
after a winter season of no sun exposure. Determine that each subject
is not taking topical or systemic medication that is known to alter
responses to UV radiation. Determine that each subject has no history
of sensitivities to topical products and/or abnormal responses to
sunlight, such as a phototoxic or photoallergic response.
    (iii) Physical examination. Conduct a physical examination to
determine the presence of sunburn, suntan, scars, active dermal
lesions, and uneven skin tones on the areas of the back to be tested.
Adequate time must have passed following any previous UV exposure
(e.g., participation in a prior SPF clinical study, tanning, etc.) so
that the test subject has no preexisting skin pigmentation at the time
of enrollment. A suitable source of low power UVA, such as a Woods
lamp, is helpful in this process. If any of these conditions are
present, the subject is not qualified to participate in the study. The
presence of nevi, blemishes, or moles will be acceptable if, in the
physician's judgment, they will neither compromise the study nor
jeopardize a subject's safety. Subjects with dysplastic nevi should not
be enrolled. Excess hair on the back is acceptable if the hair is
clipped. Shaving is unacceptable because it may remove a significant
portion of the stratum corneum and temporarily alter the skin's
response to UV radiation.
    (iv) Informed consent. Obtain legally effective written informed
consent from all test subjects as required by paragraph (i)(1)(ii) of
this section.

    (5) Sunscreen application--(i) Test site. Test sites are locations
on each subject's back, between the beltline and the shoulder blades
(scapulae) and lateral to the midline, where skin responses to UV
radiation are determined. Responses on unprotected skin (no test
material applied) and protected skin (sunscreen test product(s) or SPF
standard applied) are determined at separate unprotected and protected
test sites, respectively. Test sites should be randomly located in a
blinded manner. Each test site should be a minimum of 30 square
centimeters and outlined with indelible ink.
    (ii) Test subsite. Test subsites are the locations to which UV
radiation is administered within a test site. Administer UV doses to at
least five test subsites within each test site. Test subsites must be
at least 0.5 square centimeters (cm\2\) in area and must be separated
from each other by at least 0.8 cm. Each test subsite must be outlined
with indelible ink.
    (iii) Applying test materials. Apply the sunscreen test product and
the SPF standard at 2 milligrams per square centimeter (mg/cm\2\) to
their respective test sites. Use a finger cot compatible with the
sunscreen to spread the product as evenly as possible.
    (iv) Waiting period. Wait at least 15 minutes after applying a
sunscreen product before exposing the test sites to UV radiation as
described in paragraph (i)(6) of this section. For water resistant
sunscreen products, proceed with the water resistance testing procedure
described in paragraph (i)(8) of this section after waiting at least 15
minutes.
    (6) UV exposure and erythema reading--(i) Definition of minimal
erythema dose (MED). The minimal erythema dose (MED) is the smallest UV
dose (quantity of erythema-effective energy expressed as Joules per
square meter) that produces perceptible redness of the skin (erythema)
with clearly defined borders at 16 to 24 hours after UV exposure. The
MED for unprotected skin (MEDu) is determined on a test site
that does not have sunscreen applied. The MED for protected skin
(MEDp) is determined on a test site that has sunscreen
applied. An MEDp is determined for the SPF standard
(ssMEDp). An MEDp is determined for the sunscreen
test product (tpMEDp).
    (ii) UV exposure for initial MEDu. For each test
subject, no more than 1 day before testing a product, determine the
initial MEDu by administering a series of UV radiation doses
expressed as J/m\2\-eff (as determined according to paragraph
(i)(2)(ii)(B) of this section) to the test subsites within an
unprotected test site using an accurately calibrated solar simulator.
Select doses that are a geometric series represented by 1.25\n\ (i.e.,
each dose is 25 percent greater than the previous dose).
    (iii) UV exposure for final MEDu,
ssMEDp, and tpMEDp. For
each subject, determine the final MEDu,
ssMEDp, and tpMEDp by
administering a series of five UV doses to the appropriate test sites.
The middle dose (X) in each of these dose series (i.e., the third dose)
should equal the initial MEDu times the expected SPF. Note
that the expected SPF equals 1 and 16.3 for the final MEDu
and ssMEDp, respectively. The remaining UV doses in the
series depend upon the expected SPF value of the sunscreen test
product(s). For products with an expected SPF less than 8, administer
UV doses that increase by 25 percent with each successive dose (i.e.,
0.64X, 0.80X, 1.00X, 1.25X, and 1.56X). For products with an expected
SPF from 8 to 15, administer UV doses that increase by 20 percent with
each successive dose (i.e., 0.69X, 0.83X, 1.00X, 1.20X, and 1.44X). For
products with an expected SPF higher than 15, administer UV doses that
increase by 15 percent with each successive dose (i.e., 0.76X, 0.87X,
1.00X, 1.15X, and 1.32X).
    (iv) Evaluation of test subsites. In order that the study personnel
who evaluates the test subsites is not biased, he/she should not be the
same study personnel who applied the sunscreen product to the test site
or administered the UV doses. After UV doses are administered, record
all immediate responses. These may include an immediate darkening or
tanning, typically grayish or purplish in color, which fades in 30 to
60 minutes; an immediate reddening at the subsite, due to heating of
the skin, which fades rapidly; and an immediate generalized heat
response, spreading beyond the subsite, which fades in 30 to 60
minutes. After the immediate responses are noted, each subject should
shield the exposed area from further UV radiation until the MED is
determined. Determine the final MEDu,
ssMEDp, and tpMEDp 16 to 24
hours after UV exposure. Evaluate the erythema responses of each test
subsite using either tungsten or warm white fluorescent lighting that
provides at least 450 lux of illumination at the test site. For the
evaluation, the test subject should be in the same position as when the
test site was irradiated.
    (v) Invalid test data. Reject test data for a test subject if
erythema is not present on either the unprotected or protected test
sites; or erythema is present at all subsites; or the responses are
inconsistent with the series of UV doses administered; or the subject
was noncompliant (e.g., the subject withdraws from the test due to
illness or work conflicts or does not shield the exposed testing sites
from further UV radiation until the MED is determined).
    (7) Determination of SPF. (i) Calculate an SPF value for each test
subject (SPFi) as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.006

    (ii) Calculate the mean
    [GRAPHIC] [TIFF OMITTED] TP26FE19.007

and the standard deviation(s) from the SPFi values.
Calculate the standard error (SE), which equals s/[radic]n (where n
equals the number of subjects who provided valid test results). Obtain
the t value from Student's t distribution table corresponding to the
upper 5-percent point with n - 1 degrees of freedom. Determine the SPF
value that is equal to the largest whole number less than
[GRAPHIC] [TIFF OMITTED] TP26FE19.008

In order for the SPF determination of a test product to be considered
valid, the SPF value of the SPF standard must fall within the standard
deviation range of the expected SPF (i.e., 16.3  3.43).
    (8) Determination of water resistance. To support labeling claims
of water resistance in accordance with paragraph (b) of this section,
the following procedure must be performed in an indoor fresh water
pool, whirlpool, and/or hot tub maintained at 23 to 32 [deg]C. Fresh
water is clean drinking water that meets the standards in 40 CFR part
141. The pool and air temperature and the relative humidity must be
recorded.
    (i) Water resistance (40 minutes). Determine the SPF value after 40
minutes of water immersion using the following procedure:
    (A) Step 1: Apply the sunscreen test product as described in
paragraph (i)(5) of this section.
    (B) Step 2: Perform moderate activity in water for 20 minutes.
    (C) Step 3: Rest out of water for 15 minutes. Do not towel test
site(s).
    (D) Step 4: Perform moderate activity in water for 20 minutes.
    (E) Step 5: Allow test sites to dry completely without toweling.
    (F) Step 6: Apply the SPF standard as described in paragraph (i)(5)
of this section.
    (G) Step 7: Expose test sites to UV doses as described in paragraph
(i)(6) of this section.
    (ii) Water resistance (80 minutes). Determine the SPF value after
80 minutes of water immersion using the following procedure:

    (A) Step 1: Apply the sunscreen test product as described in
paragraph (i)(5) of this section.
    (B) Step 2: Perform moderate activity in water for 20 minutes.
    (C) Step 3: Rest out of water for 15 minutes. Do not towel test
site(s).
    (D) Step 4: Perform moderate activity in water for 20 minutes.
    (E) Step 5: Rest out of water for 15 minutes. Do not towel test
site(s).
    (F) Step 6: Perform moderate activity in water for 20 minutes.
    (G) Step 7: Rest out of water for 15 minutes. Do not towel test
site(s).
    (H) Step 8: Perform moderate activity in water for 20 minutes.
    (I) Step 9: Allow test sites to dry completely without toweling.
    (J) Step 10: Apply the SPF standard as described in paragraph
(i)(5) of this section.
    (K) Step 11: Expose test sites to UV doses as described in
paragraph (i)(6) of this section.
    (j) Broad spectrum testing--(1) UV Spectrometry--(i) Plate. Use
optical-grade polymethylmethacrylate (PMMA) plates suitable for UV
transmittance measurements. The plate should be roughened on one side
to a three-dimensional surface topography measure (Sa) between 2 and 7
micrometers and must have a rectangular application area of at least 16
square centimeters (with no side shorter than 4 cm).
    (ii) Sample holder. The sample holder should hold the PMMA plate in
a horizontal position to avoid flowing of the sunscreen product from
one edge of the PMMA plate to the other. Mount the PMMA plate as close
as possible to the input optics of the spectrometer to maximize capture
of forward scattered radiation. The sample holder should be a thin,
flat plate with a suitable aperture through which UV radiation can
pass. Place the PMMA plate on the upper surface of the sample holder
with the roughened side facing up.
    (iii) Light source. The light source must produce a continuous
spectral distribution of UV radiation from 290 to 400 nanometers.
    (iv) Input optics. Unless the spectrometer is equipped with an
integrating sphere, an ultraviolet radiation diffuser should be placed
between the sample and the input optics of the spectrometer. The
diffuser will be constructed from any UV radiation transparent material
(e.g., Teflon or quartz). The diffuser ensures that the radiation
received by the spectrometer is not collimated. Set the spectrometer
input slits to provide a bandwidth that is less than or equal to 5
nanometers.
    (v) Dynamic range of the spectrometer. The dynamic range of the
spectrometer should be sufficient to measure transmittance accurately
through a highly absorbing sunscreen product at all terrestrial solar
UV wavelengths (290 to 400 nm).
    (2) Sunscreen product application to PMMA plate. The accuracy of
the test depends upon the application of a precisely controlled amount
of sunscreen product with a uniform distribution over the PMMA plate.
The product is applied at 0.75 mg per square centimeter to the
roughened side of the PMMA plate. The sunscreen product should be
applied in a series of small amounts over the entire PMMA plate and
then spread evenly using a gloved finger. Spreading should be done with
a very light spreading action for approximately 30 seconds followed by
spreading with greater pressure for approximately 30 seconds. The plate
should then be allowed to equilibrate for 15 minutes in the dark before
the pre-irradiation described in paragraph (j)(3) of this section.
    (3) Sunscreen product pre-irradiation. To account for lack of
photostability, irradiate the PMMA plate with a solar simulator
described paragraph (i)(2) of this section. The irradiation dose must
be 4 MEDs which is equivalent to an erythemal effective dose of 800 J/
m\2\ (i.e., 800 J/m\2\-eff).
    (4) Calculation of mean transmittance values. (i) After pre-
irradiation, determine the mean transmittance values for each
wavelength [lambda] over the full UV spectrum (290 to 400 nanometers).
Measure the transmittance values at 1 nanometer intervals. Measurements
of spectral irradiance transmitted for each wavelength [lambda] through
control PMMA plates coated with 15 microliters of glycerin (no
sunscreen product) must be obtained from at least five different
locations on the PMMA plate [C1([lambda]), C2([lambda]), C3([lambda]),
C4([lambda]), and C5([lambda])]. In addition, a minimum of five
measurements of spectral irradiance transmitted for each wavelength
[lambda] through the PMMA plate covered with the sunscreen product will
be similarly obtained after pre-irradiation of the sunscreen product
[P1([lambda]), P2([lambda]), P3([lambda]), P4([lambda]), and
P5([lambda])].
    (ii) The mean transmittance for each wavelength is the ratio of the
mean of the C([lambda]) values to the mean of the P([lambda]) values,
as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.009

Where

n >=5

    (5) Calculation of mean absorbance values. (i) Mean transmittance
values,
[GRAPHIC] [TIFF OMITTED] TP26FE19.010

are converted into mean absorbance values,
[GRAPHIC] [TIFF OMITTED] TP26FE19.011

at each wavelength by taking the negative logarithm of the mean
transmittance value as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.012

    (ii) The calculation yields 111 monochromatic absorbance values in
1 nanometer increments from 290 to 400 nanometers.
    (6) Number of plates. For each sunscreen product, determine mean
absorbance values from at least three individual PMMA plates. Because
paragraph (j)(4) of this section requires at least 5 measurements per
plate, there must be a total of at least 15 measurements.
    (7) Calculation of the critical wavelength. The critical wavelength
is identified as the wavelength at which the integral of the spectral
absorbance curve reaches 90 percent of the integral over the UV
spectrum from 290 to 400 nm. The following equation defines the
critical wavelength:
[GRAPHIC] [TIFF OMITTED] TP26FE19.013

Where

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

    (8) Calculation of the UVA I/UV ratio. The ratio of UVA I/UV is
calculated as the area (per unit wavelength) under the UVA I portions
of a plot of wavelength versus A([lambda]), divided by the area (per
unit wavelength) under the total curve, as follows:
[GRAPHIC] [TIFF OMITTED] TP26FE19.014

Where

A([lambda]) = effective absorbance given as -log T([lambda])mean
absorbance at each wavelength,
d([lambda]) = wavelength interval between measurements
B([lambda]) = any biological action spectrum factor
Because no appropriate biological action spectrum for UVA radiation
damage has been universally accepted, no action spectrum is
specified. The value of B([lambda]) is, therefore, equal to 1.0 for
all wavelengths.

    (9) Determination of broad spectrum protection. A product that has
both a mean critical wavelength of 370 nm or

greater, calculated in accordance with paragraph (j)(7) of this
section, and a mean UVA I/UV ratio of 0.70 or greater, calculated in
accordance with paragraph (j)(8) of this section, is determined to pass
the broad spectrum test.
    (k) Regulatory status of final formulation testing and related
requirements. Final formulation testing required under this section is
considered a part of the manufacture of a sunscreen product. Therefore,
final formulation testing required under this section must be performed
in an establishment registered in accordance with part 207 of this
chapter and section 510 of the Federal Food, Drug, and Cosmetic Act.
Entities conducting final formulation testing required by this section
must also comply with current good manufacturing practices (CGMPs) and
associated recordkeeping requirements including those set forth in
paragraph (l) of this section and in parts 210 and 211 of this chapter.
Failure to comply with CGMPs or recordkeeping requirements will mean
that any product labeled in reliance on that testing will be
adulterated.
    (l) Recordkeeping. Records required to be kept under this section
must be maintained for at least 1 year after the expiration date of all
products labeled in reliance on that testing or, in the case of certain
OTC drug products lacking expiration dating because they meet the
criteria for exemption under Sec.  211.137 of this chapter, 3 years
after distribution of the last lot of drug product bearing labeling
that relies on the testing. Recordkeeping requirements under this
section may not be transferred. Maintenance records required to be kept
under (l)(1) must be kept by the testing entity. Records of final
formulation testing as described in paragraphs (l)(2) and (3) of this
section must be kept by the responsible person and any entity that is
performing final formulation testing required by this section on behalf
of a responsible person pursuant to a transfer of obligations.
    (1) Maintenance records. Entities performing final formulation
testing are expected to maintain equipment in accordance with paragraph
(k) of this section and, as applicable, parts 210 and 211 of this