Nonprescription Sunscreen Drug Products – Format and Content of Data Submissions

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Nonprescription Sunscreen Drug
Products 	 	Format and Content of
Data Submissions
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
November 2016
OTC

Nonprescription Sunscreen Drug
Products 	 	Format and Content of
Data Submissions
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4 th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
November 2016
OTC

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	INTRODUCTION............................................................................................................. 1
II. 	BACKGROUND ............................................................................................................... 3
A. 	Regulation of Sunscreen Products ................................................................................... 3
B. 	FDA’S Filing Determinations and Refusal to File a Request........................................ 4
C. 	Scope of This Guidance .................................................................................................... 5
D. 	Related Guidance .............................................................................................................. 6
III. 	CHARACTERISTICS OF A COMPLETE GRASE DATA SUBMISSION .............. 6
A. 	General Recommendations .............................................................................................. 6
B. 	Recommended Organization and Contents .................................................................... 8
C. 	Characteristics of an Incomplete Request and GRASE Data Submission That Could
Cause FDA to Refuse to File the Request ..................................................................... 11
D. 	How and Where to Submit GRASE Data Submissions ............................................... 12

Contains Nonbinding Recommendations
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Nonprescription Sunscreen Drug Products 
Format and Content of Data Submissions
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA office responsible for this guidance listed on the title
page.
I. 	INTRODUCTION
This guidance addresses the current thinking of the Food and Drug Administration (FDA or
Agency) on the format and content of information provided to support a request submitted under
section 586A (586A request) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 360fff-1), as amended by the Sunscreen Innovation Act (SIA) (21 U.S.C. Ch. 9 Sub. 5
Part I, enacted November 26, 2014), or in support of a pending request, as defined under section
586(6) of the FD&C Act (21 U.S.C. 360fff(6)).2 The requests addressed in this guidance seek a
determination from FDA of whether an over-the-counter (OTC or nonprescription) sunscreen
active ingredient,3 or a combination of nonprescription sunscreen active ingredients, is generally
recognized as safe and effective (GRASE) for use under specified conditions and should be
included in the OTC sunscreen drug monograph.4 The GRASE determination is primarily based
on FDA’s review of safety and effectiveness data and other information submitted by the
request’s sponsor (GRASE data submission) but also on information and comments submitted to
1 This guidance has been prepared by the Division of Nonprescription Drug Products and the Office of Regulatory
Policy in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration.
2 The SIA defines a pending request to mean a request for a nonprescription sunscreen active ingredient to be
included in the over-the-counter monograph that was originally submitted as a Time and Extent Application under
21 CFR 330.14 and that was determined to be eligible for review and for which safety and effectiveness data were
submitted prior to the enactment of the SIA (section 586(6) of the FD&C Act).
3 As defined in the SIA, sunscreen means a drug containing one or more sunscreen active ingredients (section 586(9)
of the FD&C Act), and the term sunscreen active ingredient means an active ingredient that is intended for
application to the skin of humans for purposes of absorbing, reflecting, or scattering ultraviolet radiation (section
586(10) of the FD&C Act).
4 See section 586(4) of the FD&C Act (21 U.S.C. 360fff-1) (definition of “GRASE determination”). Under the
SIA, FDA must also make an initial determination of whether a nonprescription sunscreen ingredient or combination
of sunscreen ingredients that is the subject of a 586A request has been marketed for a material time and to a material
extent and thus whether that ingredient or combination of sunscreen ingredients is eligible for review under the SIA
(section 586B(a) of the FD&C Act (21 U.S.C. 360fff-2(a))).

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the public docket by other interested parties.5 Before that review may begin, however, FDA
must review the GRASE data submission for completeness and determine whether to file or
refuse to file it for substantive review (filing determination). If the submission is not sufficiently
complete to enable us to conduct a substantive GRASE review, including being formatted in a
manner that will enable us to evaluate its completeness, we will refuse to file the submission.6
We are issuing this guidance as directed by the SIA, which calls for FDA to publish a draft and
final guidance on the format and content of information submitted by a sponsor in support of a
586A request or a pending request. The recommendations in this guidance will help sponsors
prepare GRASE data submissions for 586A requests that are sufficiently complete to be filed for
substantive review,7 as well as help guide FDA’s filing determinations. Only data submissions
provided by a sponsor are subject to a filing determination as described in this guidance, and we
anticipate that information provided by other interested parties will supplement the sponsor’s
data submission rather than duplicate the full extent of a complete data submission as described
in this guidance. However, we encourage other interested parties to follow the recommendations
in this guidance to the extent that they are applicable to a given submission. We anticipate that
the advice in this guidance will also be useful to persons who are preparing safety and
effectiveness data submissions for review by FDA in other regulatory proceedings whose
purpose is to determine whether particular nonprescription drug active ingredients or other OTC
conditions are GRASE and therefore may be included in an applicable OTC monograph (such as
in a future non-sunscreen Time and Extent Application (TEA) or in response to a request for
additional data in an ongoing SIA proceeding).
Section II of this guidance provides background information on the sunscreen OTC monograph
process and the new procedures governing GRASE determinations under the SIA (the SIA
process). Section II also summarizes the filing determination process for GRASE data
submissions and describes what sponsors can do if FDA refuses to file a GRASE data
submission. Section III describes FDA’s current thinking on the recommended format and
content of a GRASE data submission that will be considered complete and therefore fileable for
substantive review.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
5 Section 586B(b)(1) of the FD&C Act. An SIA sponsor is a person who has submitted a 586A request, a pending
request, or any other application subject to the SIA (section 586(8) of the FD&C Act).
6 Section 586B(b)(2) of the FD&C Act.
7 The recommendations in this guidance are primarily pertinent to future 586A requests because initial GRASE data
submissions for all pending requests were received before the SIA was enacted and did not require filing
determinations when submitted. However, any pending request is now subject to proposed sunscreen orders that
identify additional safety and effectiveness data needed to support a final GRASE determination. We recommend
that any future data submissions regarding the eight pending requests follow the format and content
recommendations outlined in this guidance to the extent practicable.

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II. 	BACKGROUND
A. 	Regulation of Sunscreen Products8
All sunscreens are regulated as drugs in the United States under one of two processes:
• 	The new drug approval process described in part 314 (21 CFR part 314)
• 	The OTC drug monograph process (also known as the OTC Drug Review) described in
part 330 (21 CFR part 330), as supplemented by the SIA
Products regulated under the new drug approval process may not be marketed without FDA’s
prior review and approval of either a new drug application (NDA) or abbreviated new drug
application (ANDA) for each product. Products marketed under the OTC drug monograph
process are not individually reviewed and approved prior to marketing. Instead, the OTC drug
monograph process categorizes drugs by therapeutic categories, such as sunscreens. For each
category, the monograph establishes conditions under which any drug that satisfies those
conditions and FDA’s general regulations for OTC drugs is considered to be GRASE and not
misbranded when used under the conditions prescribed, recommended, or suggested in labeling.9
Initially, active ingredients that were not used in sunscreens in the United States prior to the
inception of the OTC Drug Review were not eligible for the OTC Drug Review. FDA
considered a drug that was ineligible for inclusion in the OTC monograph system to be subject to
the new drug approval process.
In 2002, before the SIA was enacted, FDA published the TEA regulation in § 330.14(c). This
TEA regulation established a process through which any person could request that an active
ingredient or other OTC drug condition, including one not previously marketed in the United
States before the inception of the OTC Drug Review, be added to an existing OTC drug
monograph.
Now, for OTC sunscreens, the SIA process supplements the TEA regulation. The SIA amended
the FD&C Act in part by providing new procedures for establishing that nonprescription
sunscreen active ingredients or combinations of nonprescription sunscreen active ingredients are
GRASE and not misbranded when used under the conditions specified in a final sunscreen
order.10 Active ingredients that are determined to be GRASE in a final sunscreen order may be
8 We have previously published Federal Register notices about rulemaking actions for OTC sunscreen monograph
products and about actions taken under the SIA. Information about these rulemaking actions can be found on our
Status of OTC Rulemakings Web site
(http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-
CounterOTCDrugs/StatusofOTCRulemakings/default.htm) and on our Sunscreens Web site
(http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-
CounterMedicines/ucm239463.htm).
9 Part 330.
10 Section 586C of the FD&C Act (21 U.S.C. 360fff-3).

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used in U.S.-marketed sunscreens without first obtaining an approved NDA or ANDA. Because
the monograph and SIA processes are public, anyone, not just the sponsor who originated the
request, may submit data during public comment periods.
As with the TEA process, the SIA process calls for an initial eligibility determination,11 followed
by submissions of safety and effectiveness data, and a GRASE determination phase. However,
the SIA process also requires FDA to make a filing determination as described in this guidance,
and to make proposed and final GRASE determinations in the form of administrative orders
rather than the rulemaking required by the TEA regulation. The SIA process also establishes
strict timelines for the necessary administrative actions.
B. 	FDA’s Filing Determinations and Refusal to File a Request
The SIA requires FDA to conduct an initial filing review to determine whether a sponsor’s
submission of safety and effectiveness data and other relevant information to support a 586A
request for a sunscreen active ingredient is sufficiently complete to enable us to conduct a
substantive GRASE review (including being organized so that we can determine its
completeness).12 The initial filing review will help conserve FDA resources and streamline the
GRASE review for nonprescription sunscreen active ingredients by making the start of the
GRASE review contingent on a determination that the submission is sufficiently complete to
support a GRASE substantive review. As a result, it is the date of filing by FDA, and not the
date when the submission was submitted to or received by FDA, that triggers FDA’s statutory
time frame for completing the GRASE determination and issuing a proposed sunscreen order
(which in turn triggers various other action dates under the SIA).13
No later than 60 days after receiving a sponsor’s GRASE data submission, FDA must take one of
the following two sets of actions:
• 	If FDA determines that the submission is sufficiently complete, FDA will file the
sponsor’s 586A request, notify the sponsor in writing that the request has been filed, and
make the notification publicly available.14
• 	If FDA determines that the submission is not sufficiently complete, FDA will refuse to
file the sponsor’s 586A request and GRASE data submission, notify the sponsor in
writing of the determination to refuse to file the request, and make the notification
11 Section 586B(a) of the FD&C Act.
12 We note that section 586F(a)(1)(B) of the FD&C Act (21 U.S.C. 360fff-6) provides the possibility that sponsors
of non-sunscreen TEAs submitted prior to enactment of the SIA may choose a review framework that would
incorporate “an initial filing review under the processes and procedures described in section 586B(b).” FDA expects
to conduct initial filing reviews for such applications in the same manner as 586A requests for sunscreen active
ingredients.
13 Section 586C(a)(1) of the FD&C Act.
14 Section 586B(b)(2)(A) of the FD&C Act.

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publicly available. The notification will explain the reasons for the refusal, including
why the GRASE submission was not sufficiently complete.15
If FDA refuses to file the sponsor’s request, the sponsor may, within 30 days of receipt of the
notification, request in writing a meeting with FDA to discuss the refusal to file.16 The sponsor
may also submit additional data or other information to FDA. If the sponsor requests a meeting,
FDA will convene that meeting within 30 days of the meeting request.17 Following such a
meeting, FDA may file the 586A request within 60 days after the meeting date, the sponsor may
submit additional data or other information, or the sponsor may, within 120 days after the
meeting, direct FDA to file the request over protest with or without amendments to correct any
deficiencies in the request.18 If the sponsor submits additional data or other information (before,
after, or in the absence of a meeting), FDA must reconsider its initial refusal to file, along with
this additional information, and make a new filing determination within 60 days of the data
submission.19 If, after a meeting, the sponsor elects to have FDA file the request, FDA will file
the request over protest within 30 days of the sponsor’s election, notify the sponsor in writing
that the request has been filed, and make such notification public.20
C. 	Scope of This Guidance
This guidance describes our current thinking on the format and content of a complete and
fileable request under the SIA. The recommendations in this guidance will provide advice to
sponsors on how to prepare a successful GRASE submission, as well as guide FDA’s filing
determinations.
As noted in section II.B above, the “refusal to file” provision in the SIA applies only to GRASE
data submissions made by sponsors to support 586A requests.21 However, we anticipate that the
advice in this guidance will also be useful to persons who are preparing safety and effectiveness
data submissions for review by FDA in other regulatory proceedings whose purpose is to
determine whether particular nonprescription drug active ingredients or other OTC conditions
are GRASE and therefore may be included in an applicable OTC monograph (such as a future
non-sunscreen TEA request or a request for additional data in an ongoing monograph or SIA
proceeding).
15 Section 586B(b)(2)(B) of the FD&C Act.
16 Section 586B(b)(3) of the FD&C Act.
17 Section 586B(b)(3)(B) of the FD&C Act.
18 Section 586B(b)(3).
19 Section 586B(b)(3)(C) of the FD&C Act.
20 Section 586B(b)(3)(B)(ii)((III) of the FD&C Act.
21 As previously noted, non-sponsors also may submit partial or supplemental information and views to the
applicable public docket (such as scientific articles, professional opinions, or statements from public advocacy
groups). Although such submissions are not subject to filing review, we recommend that interested parties consult
the recommendations in this draft guidance to the extent that they are applicable to a given submission.

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This guidance does not detail the specific clinical and nonclinical studies and other data that
should be submitted to support a GRASE determination for a nonprescription sunscreen active
ingredient. Instead, this guidance broadly identifies the key structural elements, topics to be
addressed, and recommended organization of a complete and fileable request, including a
GRASE data submission. For the Agency’s current thinking on the specific scientific testing and
data recommended to support GRASE determinations for sunscreen active ingredients, see the
FDA guidance for industry Nonprescription Sunscreen Products--Safety and Effectiveness Data
(Safety and Effectiveness Data Guidance).22 Sponsors are encouraged to read that guidance
document and meet with FDA before preparing and submitting a GRASE data submission.
D. 	Related Guidance
In addition to this guidance, the SIA directs FDA to issue draft and final guidance documents on
three other topics.23 These topics include:
• 	The data required to meet the safety and effectiveness standard for determining whether a
nonprescription sunscreen active ingredient is GRASE and not misbranded (Safety and
Effectiveness Data Guidance)
• 	The process for withdrawing a 586A request or a pending request
• 	The process by which FDA will carry out section 586C(c) of the FD&C Act (21 U.S.C.
360fff-3), as amended by the SIA, including the process for requesting an advisory
committee meeting, the circumstances that limit the number and frequency of advisory
committee meetings that FDA is required to convene, and the number of requests to be
considered per advisory committee meeting
FDA has issued guidances on these three topics. As they become available, guidances are posted
on the FDA Drugs guidance Web page at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
III. 	CHARACTERISTICS OF A COMPLETE GRASE DATA SUBMISSION
A. 	General Recommendations
FDA will refuse to file 586A requests for which the data and other information submitted are not
sufficiently complete. GRASE data submissions that are materially incomplete or inadequately
formatted do not permit FDA to conduct a substantive review. A complete submission by the
sponsor should generally have the following characteristics:
22 We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA
Drugs guidance Web page at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
23 Section 586D(a)(1)(A) & (B) of the FD&C Act (21 U.S.C. 360fff-4(a)(1)(A) & (B)).

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1. 	A separate submission should be provided for each active ingredient that is the subject of
a 586A request.
2. 	All data and information relevant to the requested GRASE determination should be
provided in a single submission. A complete GRASE submission should include all of
the data on which the sponsor intends to rely.24
3. 	If the sponsor wants FDA to consider data or information previously provided to FDA
(such as data submitted to an NDA or ANDA, to the OTC sunscreen monograph
proceeding, to another SIA docket, or in a citizen petition), the submission should
identify the prior submission, submission date, and docket number (if applicable) and
provide a complete copy of the previously submitted information.
4. 	If the submission refers to a literature search or searches, the submission should identify
the databases included in each search, the date of the search, and the search terms used.
The submission should include complete copies of scientific articles or other published
materials that the sponsor wishes FDA to consider as part of its review. Each literature
search should be placed (by subject) in the appropriate section of the submission, as
described in section III.B of this guidance. Copies of scientific articles and other
published materials should also be placed in the relevant sections by subject.
5. 	For electronic submissions, all items in reference lists and all in-text references citing
scientific articles or other published materials should include a hyperlink to a full copy of
the referenced article or other published material. If the submission is not electronic,
each item in the reference list and all in-text references should provide specific location
data for the full copy of the referenced material.
6. 	The submission should be in the English language. If any portion of a submission is in a
foreign language, the sponsor should provide a complete and accurate English translation.
7. 	The SIA requires that any information included in a GRASE data submission that the
sponsor considers to be confidential must be identified by the sponsor at the time of the
submission.25 However, the sponsor might consider not including in the submission any
information that is clearly not relevant to the determination to be made, such as personal
privacy information (e.g., the names of lower-level employees).
24 The recommendations in this guidance are primarily directed to sponsors who are preparing a complete safety and
effectiveness data submission. After such a submission has been made, sponsors should limit any further
(supplemental) submissions to important, newly acquired data (such as safety data or results of newly completed or
newly published studies). A supplemental submission should both identify the original submission and the original
submission date and include a label identifying the submission as a supplement.
Depending on the volume and complexity of a supplemental submission and when it is submitted, it may be difficult
or impossible for FDA to conduct a thorough scientific review within the stringent timelines prescribed by the SIA.
Nonetheless, FDA encourages the submission of important new adverse safety information at any time during the
review process.
25 Section 586B(b)(4) of the FD&C Act.

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8. 	Safety and effectiveness data that are not available to the public cannot be relied on to
support a conclusion that an active ingredient is generally recognized as safe and
effective. Accordingly, sponsors should not submit, and FDA generally does not
intend to rely on, any evidence of safety and effectiveness that bears a confidential
mark unless the sponsor includes a statement that the information may be released to the
public. Similarly, if the submission includes data or information marked as confidential
by a third party (such as by a contract research organization or consultant), the sponsor
should either include a statement that the sponsor is authorized to make the information
publicly available or include an authorization from the third party permitting the
information to be publicly disclosed. If a data submission includes studies or other
information that were previously submitted to an NDA or ANDA submission without
marking them as confidential, FDA intends to presume that the sponsor intends to make
such data publicly available.
To enable a timely filing review, Module 126 should include, under the heading
“Confidential Information,” a statement that all information considered by the sponsor to
be confidential has been identified in the data submission, with a description of the
method used to designate the information as confidential. All pages should be numbered.
9. 	FDA encourages electronic submissions.
B. 	Recommended Organization and Contents
FDA recommends that the GRASE data submission be organized using the general structure and
table of contents (TOC) described in the Common Technical Document (CTD) in effect at the
time of the submission.27 The CTD is an internationally harmonized set of specifications for
preparing applications relating to new drugs that is maintained by the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and has been
recommended by FDA in multiple guidance documents. This organized approach will
streamline FDA’s GRASE review because the CTD format is familiar to and routinely used by
FDA’s subject matter reviewers, and this approach is sufficiently flexible to accommodate a
variety of types and sources of information.
A submission using the electronic CTD (eCTD) TOC should be organized into the following five
modules:
1. 	Administrative Information
2. 	Summaries
3. 	Relevant Quality Information
4. 	Nonclinical Study Data
26 For more information on Module 1, see section III.B.
27 Current International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
guidances and FDA guidances use the term eCTD (or electronic CTD) rather than CTD to reflect the transition to
mandatory electronic submissions for regulatory submissions other than the GRASE data submissions addressed in
this guidance.

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5. 	Clinical Study Data
The TOC in a GRASE data submission should be detailed, including both major section
headings and subheadings. However, it is neither necessary nor recommended that GRASE
data submissions meet the full technical specifications of an eCTD or include all of the
information identified in the CTD TOC headings. Because the eCTD TOC is designed to
accommodate multiple types of regulatory applications, it contains many headings and
subheadings that are not pertinent to the safety and effectiveness of sunscreen active ingredients.
Only pertinent information identified in the CTD should be included in a GRASE data
submission. However, we recommend that your TOC include all of the major headings from the
CTD TOC (using the appropriate heading numbers) and indicate, when appropriate, that no
information is being submitted for a given heading.
Whether the submission is electronic or paper, it should include navigation aids. If the
submission is electronic, the TOC should include hyperlinks to each section. An electronic
document that references another document in the submission should contain hyperlinks to the
cross-referenced document or relevant part of the document. If a submission is not electronic,
the submission should also be organized using the eCTD TOC. For paper submissions, cross-
references to other documents should either point to a unique page number (or numbers) or
clearly direct the reviewer to the cross-referenced document.
A complete GRASE data submission based on the eCTD TOC should generally have the
following characteristics:
M ODULE 1: ADMINISTRATIVE INFORMATION
• 	Should include any administrative and labeling information
• 	Should include statements about confidential information recommended in item 7 of
section III.A
• 	Should include a cover letter that identifies the type of submission, the sponsor, the
full contact information of the sponsor, the submission date, the active ingredient that
is the subject of the submission, and the applicable docket number
• 	Should include any financial disclosure information, if applicable
M ODULE 2: S UMMARIES
• 	Overall Summary: Should include a concise narrative summary of (1) the evidence
supporting a conclusion that the active ingredient is GRASE for the intended
nonprescription use and (2) the data that are not supportive of a determination that the
active ingredient is GRASE. The summary should clearly identify and address each
of the major topics addressed in the submission.

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Should also include a summary table listing all studies included in the submission
with their corresponding titles (as they appear in the study reports), study numbers,
and location in the submission (with hyperlinks to each study if the submission is
submitted electronically). There should be one clearly identified study number for
each study submitted.
• 	Overall Quality Summary: Should include a summary of all chemistry and
manufacturing data included in the submission.
• 	Nonclinical Summary: Should include a narrative summary of all nonclinical data
included in the submission. This summary should address data that are both
supportive and non-supportive of a determination that the ingredient is GRASE.
• 	Clinical Summary: Should include a narrative summary of all clinical data included
in the submission. This summary should address data that are both supportive and
non-supportive of a determination that the active ingredient is GRASE.
M ODULE 3: QUALITY DATA
• 	Compendial Status: Should include the compendial status of the active ingredient(s),
including the current status of the United States Pharmacopeia (USP) National
Formulary (NF) monograph.
• 	Chemical and/or Manufacturing Characteristics: Should include any known chemical
and/or manufacturing characteristics of the active ingredient that may be relevant to
FDA’s GRASE evaluation. Such characteristics should include both known
interactions with other sunscreen active ingredients or commonly used sunscreen
vehicle components and information on particle size for micronized or nanoscale
active ingredients. Sponsors should also include any aspects of formulation needed to
ensure stability or any other characteristics needed to establish conditions under
which the active ingredient is GRASE for use in sunscreens.
M ODULE 4: NONCLINICAL S TUDY R EPORTS
This module should include data and reports from the nonclinical studies discussed in the
Safety and Effectiveness Data Guidance (for example, dermal and systemic carcinogenicity
studies, developmental and reproductive toxicity studies, and animal toxicokinetic studies),
as well as data and reports from any other types of nonclinical information (e.g., literature
searches, scientific articles, or other published materials). Full copies of all published
materials should be provided. The specific ingredient and formulation(s) used in each study
should be described in detail.
Each individual study report in the submission should include its own TOC and summary.
Complete data sets (not selected or summary data) should be included in the submission. We
expect that data from studies provided only in summary form will generally not be
considered sufficient evidence that an active ingredient is GRASE.

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M ODULE 5: C LINICAL S TUDY R EPORTS
Module 5 should include separate comprehensive integrated summaries of effectiveness and
clinical safety. The summary of effectiveness should include the active ingredient’s
mechanism of action and the specific doses, concentrations, and formulations proposed for
use. The summary of clinical safety should include exposure data, and, if available, address
safety in specific populations, such as in children, the elderly, and pregnant or lactating
women. The summary of clinical safety should also address specific safety issues expected
with either the ingredient or its application. For sunscreens, examples of such safety issues
could include dermal safety, hypersensitivity, accidental ocular exposure, or inhalational
safety. All available effectiveness and safety data, including both supportive data and any
data demonstrating potential safety signals, should be submitted.
This module should also include full reports of (1) all clinical effectiveness and safety studies
and other clinical data and (2) all clinical pharmacology and human toxicokinetic data. In
addition to actual study reports, all other types of clinical data (e.g., from literature searches,
scientific articles, or other published materials) should be included in this module. Full copies of
all published materials should be provided. Each study report should contain a description of the
specific ingredient and formulation(s) used. For literature reports, this information may be
included in the relevant summary document.
Human studies that should be included in Module 5 are discussed in the Safety and Effectiveness
Data Guidance. These human studies include sun protection factor studies and other
effectiveness studies (such as in vitro broad spectrum studies, if performed), human irritation and
sensitization studies, human photosafety studies, human absorption studies, and human maximal
usage trials.
Module 5 should also include reports of in vitro testing performed by the sponsor in connection
with human maximal usage trials to support final formulation safety testing if the active
ingredient is determined to be GRASE, as discussed in the Safety and Effectiveness Data
Guidance.
Each individual study report in the submission should include its own TOC and summary.
Complete data sets (not selected or summary data) should be included in the submission.
Generally, we intend not to consider study data provided only in summary form to be sufficient
evidence that an active ingredient is GRASE.
Further, postmarketing safety data as discussed in the Safety and Effectiveness Data Guidance
should be included in Module 5. For adverse event reports, there should be a TOC with a
separate link to each adverse event report. The section on adverse event reports should be
organized according to the “System Organ Class” categories in the Medical Dictionary for
Regulatory Activities MedDRA.28
28 For more information on these categories, see the MedDRA Web site at www.MedDRA.org.

Contains Nonbinding Recommendations
12
C. 	Characteristics of an Incomplete Request and GRASE Data Submission That
Could Cause FDA to Refuse to File the Request
Some examples of incomplete information or an inadequate organization of GRASE data that
may render the GRASE data submission insufficiently complete29 for review are listed below.30
These characteristics could cause FDA to refuse to file a GRASE data submission.
1. 	The submission is unreasonably disorganizedthat is, its structure does not permit ready
review for completeness because the submission, for example, lacks a recommended
TOC that itemizes the submission’s elements and data.
2. 	Electronic submissions cannot be opened or readily navigated (e.g., hyperlinks do not
operate).
3. 	Data tabulations or graphic displays are not interpretable, are inadequately labeled, or do
not indicate data sources.
4. 	Summaries or TOCs do not indicate or link to the location of specific discussions,
studies, or other information referenced elsewhere in the submission.
5. 	The submission is materially incomplete on its face (e.g., it does not include sufficient
information for FDA to make a GRASE determination because it fails to include some or
all of the information identified in Section III.B of this guidance, unless the sponsor
explains the reasons why the missing information is not included and why the active
ingredient or other condition should be found to be GRASE in its absence).
6. 	All or essential portions of the submission are marked as confidential.
D. 	How and Where to Submit GRASE Data Submissions
GRASE data submissions can be sent (1) in hard copy to the Division of Dockets Management
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852
or (2) electronically to http://www.regulations.gov using the previously established docket
number. In addition, a copy of the cover letter should be sent to the Division of Nonprescription
Drug Products, Food and Drug Administration, Bldg. 22, Mail Stop 5411, 10903 New
Hampshire Ave., Silver Spring, MD 20993.
29 See section 586B(b)(2) of the FD&C Act.
30 Please note that this list is not exhaustive.