Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information Regarding Dosage Forms, 35669-35672 [2011-14768]
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Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 / Proposed Rules
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 352
[Docket No. FDA–1978–N–0018; formerly
Docket No. 1978N–0038]
RIN 0910–ZA40
Sunscreen Drug Products for Over-theCounter Human Use; Request for Data
and Information Regarding Dosage
Forms
AGENCY:
Food and Drug Administration,
HHS.
Advance notice of proposed
rulemaking; request for data and
information.
ACTION:
We (Food and Drug
Administration or FDA) are asking
sunscreen manufacturers and other
interested parties to submit data on
over-the-counter (OTC) sunscreen drug
products marketed without approved
applications that are formulated in
certain dosage forms. These data are
necessary to address questions about
these dosage forms. For spray dosage
forms, we are requesting data to resolve
specific questions about both
effectiveness and safety. We are also
inviting comment on possible labeling
and testing requirements for spray
dosage forms. This information will be
used in establishing monograph
conditions, including dosage forms, for
sunscreens that are generally recognized
as safe and effective (GRASE) and not
misbranded.
SUMMARY:
Submit data and information
either electronically or in writing by
September 15, 2011.
ADDRESSES: You may submit comments,
identified by docket number FDA–
1978–N–0018 (formerly Docket No.
1978N–0038) and/or RIN number 0910–
ZA40, by any of the following methods:
DATES:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting comments.
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Written Submissions
Submit written submissions in the
following ways:
• Fax: 301–827–6870.
• Mail/Hand delivery/Courier (for
paper, disk, or CD–ROM submissions):
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
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Instructions: All submissions received
must include the agency name and
docket number FDA–1978–N–0018 and
RIN 0910–ZA40 for this rulemaking. All
comments received may be posted
without change to https://
www.regulations.gov, including any
personal information provided if not
marked as confidential.
Docket: For access to the docket to
read background documents or
comments received, go to https://
www.regulations.gov, insert the docket
numbers, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Division of Dockets
Management, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Reynold Tan, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Mail Stop
5411, Silver Spring, MD 20993, 301–
796–2090.
SUPPLEMENTARY INFORMATION:
I. Purpose of This Document
FDA is requesting additional data
necessary to establish monograph
conditions for sunscreens, including
specification of certain dosage forms. In
this document, we discuss those dosage
forms that we consider currently to be
part of the OTC Drug Review, and thus
eligible for potential inclusion in a
sunscreen monograph, and those dosage
forms that we do not consider eligible.
For the dosage forms that are eligible,
we seek to ensure that the record is
complete, so as to support a future
monograph identifying conditions,
including dosage forms and appropriate
testing and labeling, for sunscreens to be
GRASE and not misbranded. Finally, as
explained below, sunscreens in certain
dosage forms such as wipes, towelettes,
powders, body washes, and shampoos
are not currently considered eligible for
inclusion in the sunscreen monograph,
and even if their eligibility were
established, they lack a sufficient record
to support inclusion in the sunscreen
monograph.
Although spray dosage forms are
among those dosage forms we consider
potentially eligible for inclusion in the
final sunscreen monograph, they
currently lack a record comparable to
other dosage forms that could be
included in the sunscreen monograph.
Considering the greatly increasing
number of sunscreen products
formulated as sprays, it is critical that
the safety and effectiveness of this
dosage form be adequately supported.
From their existing marketing of spray
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35669
sunscreens, manufacturers may have the
necessary data, but to date these data
have not been submitted to FDA. To
further encourage submission of data
and allow us to move to a proposed rule
as quickly as possible, we have
developed possible labeling and testing
specific to sprays, for which we solicit
comment.
Although at this time we expect to
receive the necessary data, if we do not
obtain sufficient data to support
monograph conditions for sunscreen
products formulated in certain dosage
forms, these products may not be
included in the future OTC sunscreen
monograph. Any sunscreen product not
included in a future final monograph
could obtain approval to market by
submitting new drug applications
(NDAs) under section 505 of the Federal
Food, Drug, and Cosmetic Act (FD&C
Act). These products might in the future
be able to submit NDA deviations in
accordance with 21 CFR 330.11,
limiting the scope of review necessary
to obtain approval. It should be noted
that, where a final monograph exists,
the content of an NDA that deviates
only in limited respects from the
monograph may omit all information
except that pertinent to the deviation.
II. Enforcement Policy
In the absence of an effective final
monograph for OTC sunscreen products,
questions may arise regarding FDA’s
enforcement policy for OTC sunscreen
products in various dosage forms that
are marketed without approved
applications. For clarification, we are
issuing a draft guidance document that
explains the Agency’s intended
enforcement policy on the various
dosage forms for OTC sunscreen
products that are marketed during the
absence of an effective sunscreen final
monograph. This draft guidance
document is being published elsewhere
in this issue of the Federal Register. We
are also publishing elsewhere in this
issue of the Federal Register a final rule
for OTC sunscreen products containing
certain ingredients and marketed
without approved applications that
specifies labeling and testing
requirements, without regard to dosage
form.
III. Dosage Forms Currently Eligible for
Inclusion in a Sunscreen Monograph
We have not explicitly stated in
previous rulemakings which dosage
forms of OTC sunscreen drug products
we would consider to be GRASE and
not misbranded. However, in 21 CFR
352.52(d), we identified several dosage
forms, including sprays, for the
purposes of labeling: ‘‘(e.g., cream, gel,
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lotion, oil, spray, etc.).’’ In 21 CFR
352.72(e), we further identified oils,
lotions, creams, gels, butters, and pastes
and ointments for the purposes of
testing. We also identified sticks in the
August 25,1978, advanced notice of
proposed rulemaking (ANPR) (43 FR
38206 at 38207, 38223, 38224, 38229,
and 38239) as lip protectants, which are
allowed to contain sunscreen active
ingredients and are formulated as sticks
(existing 21 CFR 352.60).
For a drug product to be eligible for
review, the drug product must either be
a product that can be substantiated to
have been marketed OTC before the
OTC Drug Review began in 1972, or it
must be determined to be eligible
through submission of a time and extent
application (21 CFR 330.14). With
respect to OTC sunscreen drug
products, the following dosage forms are
eligible for review and potential
inclusion in the monograph:
• Oils
• Lotions
• Creams
• Gels
• Butters
• Pastes
• Ointments
• Sticks
• Sprays
On the existing record, we anticipate
that all of these listed dosage forms,
except sprays, would be included in the
future OTC sunscreen monograph as
GRASE and not misbranded under the
labeling and testing established in new
21 CFR 201.327. However, the record
does not yet contain comparable safety
and effectiveness data and information
for spray dosage forms.
Although we have information about
how sunscreens in eligible dosage forms
other than sprays are applied, including
data on the amounts of oils, creams, and
lotions consumers typically apply (Refs.
1 and 2), spray dosage forms are
sufficiently different from other eligible
dosage forms identified during the
course of development of the sunscreen
monograph that the data and
information for these dosage forms are
not directly applicable. The nature of
other eligible dosage forms identified
during the course of development of the
sunscreen monograph (oils, creams,
lotions, gels, butters, pastes, ointments,
sticks) requires that consumers dispense
the product into their hand or directly
onto their skin and rub these products
into the skin to some extent, with most
of the amount dispensed applied.
Sprays, however, in particular
aerosolized sprays, are dispensed in a
more diffuse manner even when applied
directly to the body. Due to the different
modes of dispensing and application
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between sprays and the other dosage
forms, we do not know if consumers
obtain the same protection with sprays
as these other dosage forms. With
sprays, we also do not know how much
of the typical dispensed amount is
effectively transferred to the skin.
Adequate, uniform coverage of sprays
may also be difficult to assess, because
some sprays are applied in a thin, clear
layer which is more difficult to visualize
than other dosage forms. Some spray
products are similarly meant to be
rubbed into the skin, but we do not
know if consumers typically rub these
spray products into the skin. Thus,
upon review of the record, we have
determined that additional data or
information (as outlined below) are
necessary, and must be sufficient to
support appropriate monograph
conditions (e.g., testing and labeling
specific to sprays) to be included in the
future final monograph. Thus, we are
soliciting data to address the following
questions to build a record comparable
to other dosage forms such as lotions:
• What amounts of sunscreen spray
do consumers typically dispense and
what amounts are effectively transferred
to the skin?)
• How uniform is the sunscreen
application across the sun-exposed area
of skin?
• How frequently do consumers
reapply the product?
• If a product is labeled with a
direction to rub it into the skin, do
consumers typically follow this
direction?
• How does rubbing the product into
the skin change the effectiveness?
• How do the protection levels (SPF
values) when typical amounts are
applied compare with those under
laboratory conditions?
• Should the SPF and broad spectrum
tests be modified to address sprays? If
so, how?
In addition to answering these
questions for spray dosage forms, it
would be useful if studies also directly
compared spray dosage forms to the
other eligible dosage forms previously
identified during the course of
development of the sunscreen
monograph. We are interested in
whether use of sunscreen sprays differs
enough from use of other eligible
sunscreen dosage forms that the SPF
values on sunscreen sprays are not
comparable to those on other
sunscreens. We are also interested in
whether use differs among sunscreen
spray products. Some sunscreen sprays
are dispensed by pumps rather than as
aerosolized sprays. Other sprays may
turn into a foam upon contact with the
skin. We would be interested in data
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and information that helps us assess
how our concerns about sunscreen
sprays in general apply to different
types of sunscreen sprays. (See section
V. ‘‘Submission of Data and
Information’’ for information on
submitting these data.)
As we have done previously for other
spray OTC products, we are also
requesting data to understand the
possibility and consequences of
unintentional inhalation of spray
sunscreens, an issue not presented by
the other eligible dosage forms because
they are applied directly to the skin:
• What are the risks associated with
inhalation of sunscreen active
ingredients and propellants?
• What are typical particle size
distributions for sunscreen spray
products?
• Are animal toxicity studies
necessary for determining the potential
for toxicity resulting from inhalation?
• Is the labeling discussed in this
document adequate to prevent
unintentional inhalation? If not, please
provide alternative labeling.
In responding to the first question,
(What are the risks associated with
inhalation of sunscreen active
ingredients and propellants?), we
request submission of any reports of
adverse events associated with
unintentional inhalations of currently
marketed sunscreen spray products.
To encourage submission and in
anticipation of receiving this necessary
data/information, we have used the
available data and information on
sprays to develop possible labeling and
testing for comment. To address the
possibility that inhalation of aerosolized
particulates could cause adverse health
effects, we are considering proposing a
warning for sunscreen spray products
that reads:
• ‘‘When using this product keep
away from face to avoid breathing it.’’
We are also considering specific
directions for sunscreen spray products
that read:
• ‘‘hold container 4 to 6 inches from
the skin to apply’’
• ‘‘do not spray directly into face.
Spray on hands then apply to face.’’
• ‘‘do not apply in windy conditions’’
• ‘‘use in a well-ventilated area’’
Sunscreen spray products would be
required to be labeled with these
warnings and directions in addition to
the other warnings and directions
required for all sunscreen products.
We are also considering a proposal to
modify a directions statement to ensure
that sunscreen products in spray dosage
forms are applied comparably to
sunscreen products in other dosage
forms. The sun protection factor (SPF)
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and broad spectrum test procedures in
the 2011 final rule (published elsewhere
in this issue of the Federal Register)
require that test products be applied in
an amount of 2 milligrams per square
centimeter (mg/cm2) and 0.75 mg/cm2,
respectively, and then spread evenly by
hand (21 CFR 201.327(i)(4)(iii) and
(j)(2)). Comparable product application
during testing, as required by these
standard testing conditions, is necessary
to ensure consistent and comparable test
values between sunscreen products.
However, valid comparison of SPF test
values and broad spectrum test results
between products further requires
comparable product application during
actual use. Therefore, we are
considering proposing directions for the
application of sprays to more closely
follow the way they are applied in SPF
and broad spectrum testing. The
modified directions statement would
read:
• ‘‘spray [select one of the following:
‘liberally’ or ‘generously’] and spread
evenly by hand 15 minutes before sun
exposure.’’
We invite comment on all of the
labeling statements we are considering.
If there are other labeling statements
that should be considered, in order for
us to propose them for inclusion in a
final monograph, we will need adequate
data supporting the alternative labeling,
just as we are requesting data to support
the labeling we have already developed
for consideration. In developing any
alternative labeling for consideration,
we advise submitters that the directions
for application should reflect how the
SPF and broad spectrum test procedures
are performed.
We are considering adding the
following sentence to the SPF and broad
spectrum test procedures (21 CFR
201.327(i) and (j), respectively) to
require the following regarding
application of test material: ‘‘For spray
formulations, dispense the product into
a weighing vessel and then apply the
appropriate weight of liquid.’’ This
revision is based upon the one public
test modification for a sunscreen spray
product that we are aware of (Ref. 3).
However, the information regarding the
test method did not contain validation
of the test as it relates to sprays. To
support proposing this modification as
a monograph condition, we need data to
validate the modified test method; we
also remain open to any other testing
alternative that is supported by
sufficient data to demonstrate that it
would be an appropriate monograph
condition for sprays. To support a
testing alternative, data would need to
show that testing a spray product
according to the alternative test
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produces SPF and broad spectrum test
results that can be validly compared to
SPF and broad spectrum test results for
other dosage forms. We solicit comment
on whether this test modification would
be appropriate for all spray dosage
forms and whether modifications are
needed to address differences in
dispensing and application between
spray dosage forms. For example, some
current spray labels direct the user to
spray directly onto skin and some also
direct the user to rub in. As noted, we
are soliciting comment on directions
calling for spray products to be spread
by hand, as is done under the current
test method. If spray manufacturers
instead seek labeling indicating that
spray application is alone sufficient
(e.g., ‘‘no-rub’’ labeling), we seek
validated testing to support this
labeling. We invite manufacturers to
discuss possible methods and
validations with us.
The foregoing discussion concentrates
on specific dosage forms that we have
concluded are eligible for potential
inclusion in the sunscreen monograph.
Although we particularly solicit specific
data regarding sprays, we welcome the
submission of any additional
information relevant to the safety and
effectiveness of other eligible dosage
forms. We also invite submitters to
identify any additional dosage forms
that may be eligible for inclusion in the
OTC monograph based on marketing
prior to the outset of the OTC drug
review in 1972, and to provide
information to support their eligibility.
If eligible, any additional dosage forms
will also require a sufficient record to
support finding them to be generally
recognized as safe and effective if they
are to be proposed for inclusion in the
OTC sunscreen monograph. See 21 CFR
330.10 for information regarding the
types of information to be submitted to
support eligibility and inclusion in an
OTC drug monograph.
IV. Dosage Forms Not Eligible for
Inclusion in a Sunscreen Monograph
In response to the August 27, 2007,
proposed rule for OTC sunscreen
products (72 FR 49070), several
submissions recommended that we
include the following dosage forms in
the final sunscreen monograph (Ref. 4):
• Wipes
• Towelettes
• Powders
• Body washes
• Shampoos
We currently do not consider these
dosage forms eligible for review under
the OTC monograph process. We were
unable to identify any sunscreen
products in wipe, towelette, powder,
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body wash, or shampoo dosage forms
that were marketed OTC before the OTC
Drug Review began. To determine
eligibility for the OTC Drug Review, we
must have actual product labeling or a
facsimile of labeling that documents the
conditions of marketing of the product
prior to May 1972 (21 CFR 330.10(a)(2)).
Conditions include active ingredient,
dosage form, dosage strength, route of
administration, and specific OTC use of
the product (21 CFR 330.14(a)). These
are the same criteria used to establish
that OTC drugs initially marketed in the
United States after the OTC Drug
Review began or without U.S. marketing
experience meet the ‘‘material extent’’
or ‘‘material time’’ provisions of the
FD&C Act’s ‘‘new drug’’ definition (21
U.S.C. part 201, section 201(p)(2)) and
are eligible for the OTC Drug Review (21
CFR 330.14(c)(3)). We also have not
received any time and extent
applications for OTC sunscreen
products formulated as wipes,
towelettes, powders, body washes or
shampoos. Therefore, sunscreens
formulated as wipes, towelettes,
powders, body washes, or shampoos are
not currently eligible for review under
the OTC sunscreen monograph. If their
eligibility is to be established, the
required information must be submitted
in the form of a time and extent
application (21 CFR 330.14).
Determination of eligibility would not
itself be sufficient for inclusion in the
OTC sunscreen monograph. As
discussed in 21 CFR 330.14(e), we
would publish a notice of eligibility if
the dosage form was found eligible and
then we would request data to
demonstrate the safety and effectiveness
of the dosage form for its intended OTC
use (21 CFR 330.14(f)).
V. Submission of Data and Information
Interested persons may submit data
and information as described under the
ADDRESSES heading at the beginning of
this document. Submit a single copy of
electronic submissions or two paper
copies of any mailed submissions,
except that individuals may submit one
paper copy. Submissions are to be
identified with the docket number
found in brackets in the heading of this
document. Received submissions may
be viewed electronically at https://
www.regulations.gov or by visiting the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
VI. References
The following references are on
display in the Division of Dockets
Management (see ADDRESSES), under
docket number FDA–1978–N–0018
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(formerly Docket No. 1978N–0038)
unless otherwise noted, and may be
seen by interested persons between
9 a.m. and 4 p.m., Monday through
Friday.
1. Neale et al., Archives of
Dermatology, 138:1319–25, 2002.
2. Autier et al., British Journal of
Dermatology, 144:288–91, 2001.
3. Docket No. FDA–1978–N–0018
(formerly Docket No. 1978N–0038):
C712, Schering Plough.
4. Docket No. FDA–1978–N–0018
(formerly Docket No. 1978N–0038): FDA
List of Docket Submissions Regarding
Dosage Forms Issues: C683, C712, C716,
EC2720.
This ANPR is issued under 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 and under the
authority of the Commissioner of Food
and Drugs.
Dated: June 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 201
[Docket No. FDA–1978–N–0018; formerly
Docket No. 1978N–0038]
RIN 0910–AF43
Revised Effectiveness Determination;
Sunscreen Drug Products for Over-theCounter Human Use
Food and Drug Administration,
HHS.
ACTION:
Proposed rule.
The Food and Drug
Administration (FDA) is proposing to
limit the maximum labeled SPF value
for over-the-counter (OTC) sunscreen
drug products to ‘‘50+.’’ We are issuing
this proposed rule after reviewing data
and information we received on the
safety and effectiveness of OTC
sunscreen drug products after
publication of our 2007 proposed rule.
The record does not currently contain
sufficient data to indicate that there is
additional clinical benefit above SPF 50.
This proposal is part of FDA’s ongoing
review of these products to ensure their
safety and effectiveness.
DATES: Submit either electronic or
written comments on the proposed rule
by September 15, 2011. Submit
comments on information collection
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B. Discussion of Maximum SPF Values in
Previous Sunscreen Rulemakings
C. Validity of Testing Sunscreen Products
With SPF Values Higher Than 50
D. Insufficient Evidence of Additional
Benefit at SPF Values Higher Than 50
E. Data Necessary To Demonstrate
Additional Benefit
F. Alternatives for Addressing Maximum
SPF Value
III. Analysis of Impacts
A. Background
B. Cost to Relabel SPF 50+ Products
C. Small Business Analysis
IV. Paperwork Reduction Act of 1995
V. Environmental Impact
VI. Federalism
VII. Proposed Effective Date
VIII. References
Electronic Submissions
Table of Contents
A. Summary of Proposal
This document proposes to specify
one of the conditions under which OTC
sunscreen products are considered to be
generally recognized as safe and
effective (GRASE) and not misbranded.
We are proposing a maximum labeled
sun protection factor (SPF) value of
‘‘50+’’ for all monograph sunscreen
products. In a final monograph issued in
1999, and stayed prior to becoming
effective, we determined that the
maximum SPF permitted under the
monograph should be ‘‘30+’’ (64 FR
27666 at 27674 through 27675, May 21,
1999). In a 2007 proposed rule, we
proposed to amend the sunscreen
monograph in part 352 to permit
products marketed under the
monograph to be labeled with SPF
values up to ‘‘50+,’’ and we expressed
particular concern that sunscreen
products with SPF test values above 50
could not be tested with acceptable
accuracy and reproducibility (72 FR
49070 at 49085 through 49087, August
27, 2007) (the 2007 proposed rule).
Although submissions in response to
the 2007 proposed rule demonstrated
the accuracy and reproducibility of such
tests at values as high as SPF 80, we are
again proposing a maximum labeled
SPF value of ‘‘50+’’ for sunscreen
products marketed without approved
applications, because the record
continues to lack data demonstrating
that sunscreen products with SPF
values above 50 provide additional
clinical benefit compared to SPF 50
products. In this document, we are
inviting the submission of data
demonstrating additional clinical
benefit provided by sunscreen products
with SPF values greater than 50.
I. Overview of This Document
A. Summary of Proposal
B. Enforcement Policy
II. Maximum Labeled SPF
A. Summary of Public Submissions
B. Enforcement Policy
Elsewhere in this issue of the Federal
Register, we are issuing a final
regulation establishing effectiveness
Submit electronic comments in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting comments.
Written Submissions
[FR Doc. 2011–14768 Filed 6–14–11; 8:45 am]
AGENCY:
issues under the Paperwork Reduction
Act of 1995 (the PRA) by July 18, 2011,
(see the ‘‘Paperwork Reduction Act of
1995’’ section of this document). See
section VII of this document for the
proposed effective date of a final rule
based on this proposal.
ADDRESSES: You may submit comments,
identified by Docket No. FDA–1978–N–
0018 and RIN number 0910–AF43, by
any of the following methods, except
that comments on information
collection issues under the PRA must be
submitted to the Office of Regulatory
Affairs, Office of Management and
Budget (OMB) (see the ‘‘Paperwork
Reduction Act of 1995’’ section of this
document).
Submit written submissions in the
following ways:
• Fax: 301–827–6870.
• Mail/Hand delivery/Courier (for
paper, disk, or CD–ROM submissions):
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville,
MD 20852.
Instructions: All submissions received
must include the Agency name, Docket
No. FDA–1978–N–0018, and RIN 0910–
AF43 for this rulemaking. All comments
received may be posted without change
to https://www.regulations.gov, including
any personal information provided.
Docket: For access to the docket to
read background documents or
comments received, go to https://
www.regulations.gov, insert the docket
numbers, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Division of Dockets
Management, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT:
Reynold Tan, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, rm. 5411,
Silver Spring, MD 20993–0002, 301–
796–2090.
SUPPLEMENTARY INFORMATION:
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I. Overview of This Document
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]]>Agencies
[Federal Register Volume 76, Number 117 (Friday, June 17, 2011)]
[Proposed Rules]
[Pages 35669-35672]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-14768]
Federal Register / Vol. 76, No. 117 / Friday, June 17, 2011 /
Proposed Rules
[[Page 35669]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 352
[Docket No. FDA-1978-N-0018; formerly Docket No. 1978N-0038]
RIN 0910-ZA40
Sunscreen Drug Products for Over-the-Counter Human Use; Request
for Data and Information Regarding Dosage Forms
AGENCY: Food and Drug Administration, HHS.
ACTION: Advance notice of proposed rulemaking; request for data and
information.
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SUMMARY: We (Food and Drug Administration or FDA) are asking sunscreen
manufacturers and other interested parties to submit data on over-the-
counter (OTC) sunscreen drug products marketed without approved
applications that are formulated in certain dosage forms. These data
are necessary to address questions about these dosage forms. For spray
dosage forms, we are requesting data to resolve specific questions
about both effectiveness and safety. We are also inviting comment on
possible labeling and testing requirements for spray dosage forms. This
information will be used in establishing monograph conditions,
including dosage forms, for sunscreens that are generally recognized as
safe and effective (GRASE) and not misbranded.
DATES: Submit data and information either electronically or in writing
by September 15, 2011.
ADDRESSES: You may submit comments, identified by docket number FDA-
1978-N-0018 (formerly Docket No. 1978N-0038) and/or RIN number 0910-
ZA40, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Fax: 301-827-6870.
Mail/Hand delivery/Courier (for paper, disk, or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the agency name
and docket number FDA-1978-N-0018 and RIN 0910-ZA40 for this
rulemaking. All comments received may be posted without change to
https://www.regulations.gov, including any personal information provided
if not marked as confidential.
Docket: For access to the docket to read background documents or
comments received, go to https://www.regulations.gov, insert the docket
numbers, found in brackets in the heading of this document, into the
``Search'' box and follow the prompts and/or go to the Division of
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Reynold Tan, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Mail Stop 5411, Silver Spring, MD 20993, 301-
796-2090.
SUPPLEMENTARY INFORMATION:
I. Purpose of This Document
FDA is requesting additional data necessary to establish monograph
conditions for sunscreens, including specification of certain dosage
forms. In this document, we discuss those dosage forms that we consider
currently to be part of the OTC Drug Review, and thus eligible for
potential inclusion in a sunscreen monograph, and those dosage forms
that we do not consider eligible. For the dosage forms that are
eligible, we seek to ensure that the record is complete, so as to
support a future monograph identifying conditions, including dosage
forms and appropriate testing and labeling, for sunscreens to be GRASE
and not misbranded. Finally, as explained below, sunscreens in certain
dosage forms such as wipes, towelettes, powders, body washes, and
shampoos are not currently considered eligible for inclusion in the
sunscreen monograph, and even if their eligibility were established,
they lack a sufficient record to support inclusion in the sunscreen
monograph.
Although spray dosage forms are among those dosage forms we
consider potentially eligible for inclusion in the final sunscreen
monograph, they currently lack a record comparable to other dosage
forms that could be included in the sunscreen monograph. Considering
the greatly increasing number of sunscreen products formulated as
sprays, it is critical that the safety and effectiveness of this dosage
form be adequately supported. From their existing marketing of spray
sunscreens, manufacturers may have the necessary data, but to date
these data have not been submitted to FDA. To further encourage
submission of data and allow us to move to a proposed rule as quickly
as possible, we have developed possible labeling and testing specific
to sprays, for which we solicit comment.
Although at this time we expect to receive the necessary data, if
we do not obtain sufficient data to support monograph conditions for
sunscreen products formulated in certain dosage forms, these products
may not be included in the future OTC sunscreen monograph. Any
sunscreen product not included in a future final monograph could obtain
approval to market by submitting new drug applications (NDAs) under
section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act).
These products might in the future be able to submit NDA deviations in
accordance with 21 CFR 330.11, limiting the scope of review necessary
to obtain approval. It should be noted that, where a final monograph
exists, the content of an NDA that deviates only in limited respects
from the monograph may omit all information except that pertinent to
the deviation.
II. Enforcement Policy
In the absence of an effective final monograph for OTC sunscreen
products, questions may arise regarding FDA's enforcement policy for
OTC sunscreen products in various dosage forms that are marketed
without approved applications. For clarification, we are issuing a
draft guidance document that explains the Agency's intended enforcement
policy on the various dosage forms for OTC sunscreen products that are
marketed during the absence of an effective sunscreen final monograph.
This draft guidance document is being published elsewhere in this issue
of the Federal Register. We are also publishing elsewhere in this issue
of the Federal Register a final rule for OTC sunscreen products
containing certain ingredients and marketed without approved
applications that specifies labeling and testing requirements, without
regard to dosage form.
III. Dosage Forms Currently Eligible for Inclusion in a Sunscreen
Monograph
We have not explicitly stated in previous rulemakings which dosage
forms of OTC sunscreen drug products we would consider to be GRASE and
not misbranded. However, in 21 CFR 352.52(d), we identified several
dosage forms, including sprays, for the purposes of labeling: ``(e.g.,
cream, gel,
[[Page 35670]]
lotion, oil, spray, etc.).'' In 21 CFR 352.72(e), we further identified
oils, lotions, creams, gels, butters, and pastes and ointments for the
purposes of testing. We also identified sticks in the August 25,1978,
advanced notice of proposed rulemaking (ANPR) (43 FR 38206 at 38207,
38223, 38224, 38229, and 38239) as lip protectants, which are allowed
to contain sunscreen active ingredients and are formulated as sticks
(existing 21 CFR 352.60).
For a drug product to be eligible for review, the drug product must
either be a product that can be substantiated to have been marketed OTC
before the OTC Drug Review began in 1972, or it must be determined to
be eligible through submission of a time and extent application (21 CFR
330.14). With respect to OTC sunscreen drug products, the following
dosage forms are eligible for review and potential inclusion in the
monograph:
Oils
Lotions
Creams
Gels
Butters
Pastes
Ointments
Sticks
Sprays
On the existing record, we anticipate that all of these listed
dosage forms, except sprays, would be included in the future OTC
sunscreen monograph as GRASE and not misbranded under the labeling and
testing established in new 21 CFR 201.327. However, the record does not
yet contain comparable safety and effectiveness data and information
for spray dosage forms.
Although we have information about how sunscreens in eligible
dosage forms other than sprays are applied, including data on the
amounts of oils, creams, and lotions consumers typically apply (Refs. 1
and 2), spray dosage forms are sufficiently different from other
eligible dosage forms identified during the course of development of
the sunscreen monograph that the data and information for these dosage
forms are not directly applicable. The nature of other eligible dosage
forms identified during the course of development of the sunscreen
monograph (oils, creams, lotions, gels, butters, pastes, ointments,
sticks) requires that consumers dispense the product into their hand or
directly onto their skin and rub these products into the skin to some
extent, with most of the amount dispensed applied. Sprays, however, in
particular aerosolized sprays, are dispensed in a more diffuse manner
even when applied directly to the body. Due to the different modes of
dispensing and application between sprays and the other dosage forms,
we do not know if consumers obtain the same protection with sprays as
these other dosage forms. With sprays, we also do not know how much of
the typical dispensed amount is effectively transferred to the skin.
Adequate, uniform coverage of sprays may also be difficult to assess,
because some sprays are applied in a thin, clear layer which is more
difficult to visualize than other dosage forms. Some spray products are
similarly meant to be rubbed into the skin, but we do not know if
consumers typically rub these spray products into the skin. Thus, upon
review of the record, we have determined that additional data or
information (as outlined below) are necessary, and must be sufficient
to support appropriate monograph conditions (e.g., testing and labeling
specific to sprays) to be included in the future final monograph. Thus,
we are soliciting data to address the following questions to build a
record comparable to other dosage forms such as lotions:
What amounts of sunscreen spray do consumers typically
dispense and what amounts are effectively transferred to the skin?)
How uniform is the sunscreen application across the sun-
exposed area of skin?
How frequently do consumers reapply the product?
If a product is labeled with a direction to rub it into
the skin, do consumers typically follow this direction?
How does rubbing the product into the skin change the
effectiveness?
How do the protection levels (SPF values) when typical
amounts are applied compare with those under laboratory conditions?
Should the SPF and broad spectrum tests be modified to
address sprays? If so, how?
In addition to answering these questions for spray dosage forms, it
would be useful if studies also directly compared spray dosage forms to
the other eligible dosage forms previously identified during the course
of development of the sunscreen monograph. We are interested in whether
use of sunscreen sprays differs enough from use of other eligible
sunscreen dosage forms that the SPF values on sunscreen sprays are not
comparable to those on other sunscreens. We are also interested in
whether use differs among sunscreen spray products. Some sunscreen
sprays are dispensed by pumps rather than as aerosolized sprays. Other
sprays may turn into a foam upon contact with the skin. We would be
interested in data and information that helps us assess how our
concerns about sunscreen sprays in general apply to different types of
sunscreen sprays. (See section V. ``Submission of Data and
Information'' for information on submitting these data.)
As we have done previously for other spray OTC products, we are
also requesting data to understand the possibility and consequences of
unintentional inhalation of spray sunscreens, an issue not presented by
the other eligible dosage forms because they are applied directly to
the skin:
What are the risks associated with inhalation of sunscreen
active ingredients and propellants?
What are typical particle size distributions for sunscreen
spray products?
Are animal toxicity studies necessary for determining the
potential for toxicity resulting from inhalation?
Is the labeling discussed in this document adequate to
prevent unintentional inhalation? If not, please provide alternative
labeling.
In responding to the first question, (What are the risks associated
with inhalation of sunscreen active ingredients and propellants?), we
request submission of any reports of adverse events associated with
unintentional inhalations of currently marketed sunscreen spray
products.
To encourage submission and in anticipation of receiving this
necessary data/information, we have used the available data and
information on sprays to develop possible labeling and testing for
comment. To address the possibility that inhalation of aerosolized
particulates could cause adverse health effects, we are considering
proposing a warning for sunscreen spray products that reads:
``When using this product keep away from face to avoid
breathing it.''
We are also considering specific directions for sunscreen spray
products that read:
``hold container 4 to 6 inches from the skin to apply''
``do not spray directly into face. Spray on hands then
apply to face.''
``do not apply in windy conditions''
``use in a well-ventilated area''
Sunscreen spray products would be required to be labeled with these
warnings and directions in addition to the other warnings and
directions required for all sunscreen products.
We are also considering a proposal to modify a directions statement
to ensure that sunscreen products in spray dosage forms are applied
comparably to sunscreen products in other dosage forms. The sun
protection factor (SPF)
[[Page 35671]]
and broad spectrum test procedures in the 2011 final rule (published
elsewhere in this issue of the Federal Register) require that test
products be applied in an amount of 2 milligrams per square centimeter
(mg/cm\2\) and 0.75 mg/cm\2\, respectively, and then spread evenly by
hand (21 CFR 201.327(i)(4)(iii) and (j)(2)). Comparable product
application during testing, as required by these standard testing
conditions, is necessary to ensure consistent and comparable test
values between sunscreen products. However, valid comparison of SPF
test values and broad spectrum test results between products further
requires comparable product application during actual use. Therefore,
we are considering proposing directions for the application of sprays
to more closely follow the way they are applied in SPF and broad
spectrum testing. The modified directions statement would read:
``spray [select one of the following: `liberally' or
`generously'] and spread evenly by hand 15 minutes before sun
exposure.''
We invite comment on all of the labeling statements we are
considering. If there are other labeling statements that should be
considered, in order for us to propose them for inclusion in a final
monograph, we will need adequate data supporting the alternative
labeling, just as we are requesting data to support the labeling we
have already developed for consideration. In developing any alternative
labeling for consideration, we advise submitters that the directions
for application should reflect how the SPF and broad spectrum test
procedures are performed.
We are considering adding the following sentence to the SPF and
broad spectrum test procedures (21 CFR 201.327(i) and (j),
respectively) to require the following regarding application of test
material: ``For spray formulations, dispense the product into a
weighing vessel and then apply the appropriate weight of liquid.'' This
revision is based upon the one public test modification for a sunscreen
spray product that we are aware of (Ref. 3). However, the information
regarding the test method did not contain validation of the test as it
relates to sprays. To support proposing this modification as a
monograph condition, we need data to validate the modified test method;
we also remain open to any other testing alternative that is supported
by sufficient data to demonstrate that it would be an appropriate
monograph condition for sprays. To support a testing alternative, data
would need to show that testing a spray product according to the
alternative test produces SPF and broad spectrum test results that can
be validly compared to SPF and broad spectrum test results for other
dosage forms. We solicit comment on whether this test modification
would be appropriate for all spray dosage forms and whether
modifications are needed to address differences in dispensing and
application between spray dosage forms. For example, some current spray
labels direct the user to spray directly onto skin and some also direct
the user to rub in. As noted, we are soliciting comment on directions
calling for spray products to be spread by hand, as is done under the
current test method. If spray manufacturers instead seek labeling
indicating that spray application is alone sufficient (e.g., ``no-rub''
labeling), we seek validated testing to support this labeling. We
invite manufacturers to discuss possible methods and validations with
us.
The foregoing discussion concentrates on specific dosage forms that
we have concluded are eligible for potential inclusion in the sunscreen
monograph. Although we particularly solicit specific data regarding
sprays, we welcome the submission of any additional information
relevant to the safety and effectiveness of other eligible dosage
forms. We also invite submitters to identify any additional dosage
forms that may be eligible for inclusion in the OTC monograph based on
marketing prior to the outset of the OTC drug review in 1972, and to
provide information to support their eligibility. If eligible, any
additional dosage forms will also require a sufficient record to
support finding them to be generally recognized as safe and effective
if they are to be proposed for inclusion in the OTC sunscreen
monograph. See 21 CFR 330.10 for information regarding the types of
information to be submitted to support eligibility and inclusion in an
OTC drug monograph.
IV. Dosage Forms Not Eligible for Inclusion in a Sunscreen Monograph
In response to the August 27, 2007, proposed rule for OTC sunscreen
products (72 FR 49070), several submissions recommended that we include
the following dosage forms in the final sunscreen monograph (Ref. 4):
Wipes
Towelettes
Powders
Body washes
Shampoos
We currently do not consider these dosage forms eligible for review
under the OTC monograph process. We were unable to identify any
sunscreen products in wipe, towelette, powder, body wash, or shampoo
dosage forms that were marketed OTC before the OTC Drug Review began.
To determine eligibility for the OTC Drug Review, we must have actual
product labeling or a facsimile of labeling that documents the
conditions of marketing of the product prior to May 1972 (21 CFR
330.10(a)(2)). Conditions include active ingredient, dosage form,
dosage strength, route of administration, and specific OTC use of the
product (21 CFR 330.14(a)). These are the same criteria used to
establish that OTC drugs initially marketed in the United States after
the OTC Drug Review began or without U.S. marketing experience meet the
``material extent'' or ``material time'' provisions of the FD&C Act's
``new drug'' definition (21 U.S.C. part 201, section 201(p)(2)) and are
eligible for the OTC Drug Review (21 CFR 330.14(c)(3)). We also have
not received any time and extent applications for OTC sunscreen
products formulated as wipes, towelettes, powders, body washes or
shampoos. Therefore, sunscreens formulated as wipes, towelettes,
powders, body washes, or shampoos are not currently eligible for review
under the OTC sunscreen monograph. If their eligibility is to be
established, the required information must be submitted in the form of
a time and extent application (21 CFR 330.14). Determination of
eligibility would not itself be sufficient for inclusion in the OTC
sunscreen monograph. As discussed in 21 CFR 330.14(e), we would publish
a notice of eligibility if the dosage form was found eligible and then
we would request data to demonstrate the safety and effectiveness of
the dosage form for its intended OTC use (21 CFR 330.14(f)).
V. Submission of Data and Information
Interested persons may submit data and information as described
under the ADDRESSES heading at the beginning of this document. Submit a
single copy of electronic submissions or two paper copies of any mailed
submissions, except that individuals may submit one paper copy.
Submissions are to be identified with the docket number found in
brackets in the heading of this document. Received submissions may be
viewed electronically at https://www.regulations.gov or by visiting the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
VI. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES), under docket number FDA-1978-N-0018
[[Page 35672]]
(formerly Docket No. 1978N-0038) unless otherwise noted, and may be
seen by interested persons between 9 a.m. and 4 p.m., Monday through
Friday.
1. Neale et al., Archives of Dermatology, 138:1319-25, 2002.
2. Autier et al., British Journal of Dermatology, 144:288-91, 2001.
3. Docket No. FDA-1978-N-0018 (formerly Docket No. 1978N-0038):
C712, Schering Plough.
4. Docket No. FDA-1978-N-0018 (formerly Docket No. 1978N-0038): FDA
List of Docket Submissions Regarding Dosage Forms Issues: C683, C712,
C716, EC2720.
This ANPR is issued under 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 and under the authority of the Commissioner of Food and Drugs.
Dated: June 9, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-14768 Filed 6-14-11; 8:45 am]
BILLING CODE 4160-01-P
