Document ID: FDA-1978-N-0018-0697
Agency: fda
Document Type: Proposed Rule
Title: Sunscreen Drug Products for Over-the-Counter Human Use; Request for Data and Information Regarding Dosage Forms
Posted Date: 2011-06-17T04:00Z

[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: http://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 
http://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 http://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 http://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