Document ID: FDA-2016-N-0543-0001
Agency: fda
Document Type: Proposed Rule
Title: Food and Drug Administration Review and Action on Over-the-Counter Time and Extent Applications
Posted Date: 2016-04-04T04:00Z

[Federal Register Volume 81, Number 64 (Monday, April 4, 2016)]
[Proposed Rules]
[Pages 19069-19086]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-07612]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 330

[Docket No. FDA-2016-N-0543]
RIN 0910-AH30

Food and Drug Administration Review and Action on Over-the-
Counter Time and Extent Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is proposing 
to amend its nonprescription (over-the-counter or OTC) drug 
regulations. The proposed rule, if finalized as proposed, would 
supplement the time and extent application (TEA) process for OTC drugs 
by establishing timelines and performance metrics for FDA's review of 
non-sunscreen TEAs, as required by the Sunscreen Innovation Act (SIA). 
We are also proposing other changes to make the TEA process more 
efficient.

DATES: Submit either electronic or written comments on the proposed 
rule by June 3, 2016. Submit comments on information collection issues 
under the Paperwork Reduction Act of 1995 by June 3, 2016, (see the 
``Paperwork Reduction Act of 1995'' section of this document).

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2016-N-0543 for ``Food and Drug Administration Review and Action on 
Over-the-Counter Time and Extent Applications.'' Received comments will 
be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be

[[Page 19070]]

made publicly available, you can provide this information on the cover 
sheet and not in the body of your comments and you must identify this 
information as ``confidential.'' Any information marked as 
``confidential'' will not be disclosed except in accordance with 21 CFR 
10.20 and other applicable disclosure law. For more information about 
FDA's posting of comments to public dockets, see 80 FR 56469, September 
18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, 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.
    Submit comments on information collection issues to the Office of 
Management and Budget in the following ways:
     Fax to the Office of Information and Regulatory Affairs, 
OMB, Attn: FDA Desk Officer, FAX: 202-395-7285, or email to 
oira_submission@omb.eop.gov. All comments should be identified with the 
title, Food and Drug Administration Review and Action on 
Over[hyphen]the[hyphen]Counter Time and Extent Applications.

FOR FURTHER INFORMATION CONTACT: With regard to the proposed rule: 
Kristin Hardin, Center for Drug Evaluation and Research (CDER), Food 
and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD 
20993, 240-402-4246, Kristen.Hardin@fda.hhs.gov.
    With regard to the information collection: Ila Mizrachi, Office of 
Operations, Food and Drug Administration, 8455 Colesville Rd., Rm. 
14526, Silver Spring, MD 20993-0002, PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Executive Summary
    A. Purpose and Scope of the Proposed Rule
    B. Summary of the Major Provisions of the Proposed Rule
    C. Legal Authority
    D. Costs and Benefits
II. Table of Abbreviations and Acronyms Commonly Used in This 
Document
III. Background
    A. FDA Regulation of Over-The-Counter (OTC) Drugs
    B. The Sunscreen Innovation Act (SIA)
IV. Legal Authority
V. Description of the Proposed Rule
    A. Timelines for FDA Review and Action on Time and Extent 
Applications and Safety and Effectiveness Data Submissions (Proposed 
New Sec.  330.15)
    B. Amendments to Sec.  330.14 ``Additional criteria and 
procedures for classifying OTC drugs as generally recognized as safe 
and effective and not misbranded''
VI. Proposed Effective Date
VII. Economic Analysis of Impacts
    A. Introduction
    B. Summary
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. References

I. Executive Summary

A. Purpose and Scope of the Proposed Rule

    This proposed rule is intended to implement part of the Sunscreen 
Innovation Act (SIA) (21 U.S.C. Ch. 9 sub. 5 part I, enacted November 
26, 2014). Among other provisions, the SIA amended the Federal Food, 
Drug, and Cosmetic Act (FD&C Act) by adding section 586F to the FD&C 
Act. Section 586F(b) directs FDA to issue regulations establishing 
timelines and related performance metrics for the review of certain 
submissions under FDA's regulation governing TEAs, which is codified at 
21 CFR 330.14. The TEA regulation sets forth criteria and procedures by 
which OTC drugs initially marketed in the United States after the OTC 
Drug Review began in 1972 and OTC drugs without any U.S. marketing 
experience can be considered in the OTC drug monograph system. If a 
drug meets each of the conditions contained in any applicable OTC drug 
monograph, and other applicable regulations, it is considered generally 
recognized as safe and effective (GRASE) and not misbranded, and is not 
required by FDA to be approved in a new drug application (NDA) under 
section 505 of the FD&C Act. Drugs determined to be not GRASE (or non-
monograph) must be approved under section 505 of the FD&C Act before 
being marketed in the United States (see section II.A. for more detail 
on the OTC Drug Review and the TEA process).
    Section 586F(b) of the FD&C Act specifically requires FDA to issue 
regulations providing for the timely and efficient review of 
submissions under the TEA regulation, including establishing (1) 
reasonable timelines for reviewing and acting on such submissions for 
non-sunscreen OTC active ingredients and other conditions (non-
sunscreen TEA conditions) and (2) measurable metrics for tracking the 
extent to which such timelines are met.
    FDA is also proposing to amend the TEA regulation to make the TEA 
process more efficient and predictable for both product sponsors and 
FDA by adding filing determination requirements and criteria and by 
addressing the withdrawal of consideration of TEA and safety and 
effectiveness data submissions.
    The timelines and metrics in this proposed rule would apply to non-
sunscreen TEA conditions (see section V.A for more detail). FDA is 
addressing timelines for review of sunscreen active ingredients and 
other related topics regarding sunscreens separately, under other 
provisions of the SIA (see section II.B for more detail).

B. Summary of the Major Provisions of the Proposed Rule

    The proposed rule implements the SIA requirements for non-sunscreen 
TEAs by adding proposed new Sec.  330.15 to FDA's OTC drug monograph 
regulations (21 CFR part 330). The proposed new section has two major 
provisions regarding actions to be taken by FDA, consistent with 
requirements in the SIA. In particular, proposed Sec.  330.15(c) 
establishes timelines for FDA to review and take action on non-
sunscreen TEA conditions, and proposed Sec.  330.15(b) describes 
measurable metrics that FDA will use for tracking the extent to which 
the timelines set forth in the regulations are met. Proposed Sec.  
330.15(a) generally limits the applicability of these timelines to non-
sunscreen TEAs submitted after the enactment of the SIA, with one 
exception.
    We are proposing to amend Sec.  330.14 to:
     Add provisions concerning filing determinations regarding 
safety and effectiveness data submissions for eligible TEA conditions 
(i.e., determinations as to whether such submissions are sufficiently 
complete to permit a substantive review by FDA) (Sec.  330.14(j)),
     add provisions regarding the withdrawal of consideration 
of TEAs and safety and effectiveness data submissions (Sec.  
330.14(k)),
     add certain definitions (Sec.  330.14(a)), and
     make minor conforming and clarifying changes.

C. Legal Authority

    This rule is proposed under FDA's authority to regulate OTC drug 
products under the FD&C Act (see sections 201, 501, 502, 503, 505, 510, 
586F, and 701(a) of the FD&C Act (21 U.S.C. 321, 351, 352, 353, 355, 
360, 360fff-6, and 371(a))). As stated in the Federal Register of 
January 22, 2002 (67 FR 3069), in which the final rule establishing the 
TEA process was published, submission of an NDA has

[[Page 19071]]

been required before marketing a new drug since passage of the FD&C Act 
in 1938 (21 U.S.C. 355). To market a new drug, it must first be 
approved under section 505 of the FD&C Act. Section 701(a) of the FD&C 
Act authorizes FDA to issue regulations for the efficient enforcement 
of the FD&C Act. FDA's regulations in 21 CFR part 330 describe the 
conditions for a drug to be considered GRASE and not misbranded. If a 
drug meets each of the conditions contained in part 330, as well as 
each of the conditions contained in any applicable OTC drug monograph, 
and other applicable regulations, it is considered GRASE and not 
misbranded, and is not required by FDA to obtain approval under section 
505 of the FD&C Act.
    In addition, section 586F of the FD&C Act requires FDA to issue 
regulations providing for the timely and efficient review of certain 
submissions under the TEA regulation at 21 CFR 330.14. Section 586F of 
the FD&C Act specifically requires these regulations to include 
timelines and metrics associated with the review of those submissions 
under the TEA regulation. Proposed Sec.  330.15 would add timeline and 
metrics provisions that are intended to implement section 586F of the 
FD&C Act.

D. Costs and Benefits

    We expect that the proposed rule would make the TEA process more 
efficient and predictable, and improve communication between FDA and 
sponsors. Sponsors may benefit from knowing if additional data is 
needed and what optimal steps to take to receive a GRASE determination, 
and we would be able to bring resolution to TEA conditions. However, we 
do not know the monetary value of added predictability to sponsors.
    We expect the rule would create a minimal burden on sponsors, 
primarily when they send a letter to request a meeting with us. Thus, 
we anticipate no increase in annual recurring costs for either small or 
large sponsors. We expect the six current sponsors of non-sunscreen 
TEAs covering conditions that have been found eligible to be considered 
for inclusion in the OTC drug monograph system would incur one-time 
costs to read and understand the proposed rule. We also estimate 
sponsors will submit two additional TEAs annually, and each of these 
sponsors would also spend time reading and understanding the proposed 
rule. The present value of the total costs over 10 years ranges from 
about $17,000 to $35,000 with a 7 percent discount rate and from about 
$19,000 to $38,000 with a 3 percent discount rate. With a discount rate 
of 7 percent and 3 percent, we estimate that on average affected 
sponsors would incur less than $150 of annualized costs per year.

II. Table of Abbreviations and Acronyms Commonly Used in This Document

ANDA Abbreviated New Drug Application
FDA Food and Drug Administration
FD&C Act Federal Food, Drug, and Cosmetic Act
GRASE Generally Recognized as Safe and Effective
HHS U.S. Department of Health and Human Services
NDA New Drug Application
NOE Notice of Eligibility
NPRM Notice of Proposed Rulemaking
OMB Office of Management and Budget
OTC Over-the-Counter
PRA Paperwork Reduction Act
SIA Sunscreen Innovation Act of 2014
TEA Time and Extent Application

III. Background

A. FDA Regulation of Over-the-Counter (OTC) Drugs

    The OTC drug monograph system was established to evaluate the 
safety and effectiveness of all OTC drug products marketed in the 
United States before May 11, 1972, that were not covered by new drug 
applications (NDAs) and all OTC drug products covered by ``safety'' 
NDAs that were marketed in the United States before enactment of the 
1962 drug amendments to the FD&C Act. In 1972, FDA began its OTC Drug 
Review to evaluate OTC drugs by categories or classes (e.g., 
sunscreens, antacids), rather than on a product-by-product basis, and 
to develop ``conditions'' under which classes of OTC drugs are GRASE 
and not misbranded.
    FDA publishes these conditions in the Federal Register in the form 
of OTC drug monographs, which consist primarily of active ingredients, 
labeling, and other general requirements. Final monographs for OTC 
drugs that are GRASE and not misbranded are codified in 21 CFR part 
330. Manufacturers of drugs that meet each of the conditions contained 
in part 330, including each of the conditions contained in any 
applicable OTC drug monograph, and other applicable regulations, need 
not seek FDA clearance before marketing.
    Initially, OTC drug conditions not marketed in the U.S. prior to 
the inception of the OTC Drug Review were not eligible for review under 
the OTC drug monograph process. The TEA process, established by 
regulations finalized in 2002 (21 CFR 330.14), expanded the scope of 
the OTC Drug Review. A ``condition,'' for purposes of the TEA 
regulation, is an active ingredient or botanical drug substance (or a 
combination of active ingredients or botanical drug substances), dosage 
form, dosage strength, or route of administration marketed for a 
specific OTC use. The TEA process provides a potential pathway for OTC 
conditions, including newer active ingredients that previously had no 
U.S. marketing history or that were marketed in the United States after 
the OTC Drug Review began, to be marketed under an OTC drug monograph.
    Active ingredients and other conditions that satisfy the TEA 
eligibility requirements are subject to the same safety, effectiveness, 
and labeling standards that apply to other conditions under the OTC 
monograph process (see 21 CFR 330.14(g)). The TEA regulation requires 
multi-step, notice-and-comment rulemaking procedures before an active 
ingredient or other condition is added to an OTC drug monograph.
    The TEA process begins with the submission of a TEA containing data 
documenting the OTC marketing history of the active ingredient, 
combination of active ingredients, or other condition(s) (e.g., a new 
dosage strength for an active ingredient already included in an OTC 
drug monograph). FDA reviews the application and determines whether the 
sponsor's marketing data establish that the condition or conditions 
have been marketed to a material extent and for a material time, as set 
forth in the TEA regulation's eligibility requirements. If the 
condition is not found eligible, FDA will send a letter to the sponsor 
explaining why the condition was not found acceptable. If the marketing 
data satisfy the TEA regulation's eligibility criteria, FDA publishes a 
notice of eligibility (NOE) in the Federal Register announcing that the 
active ingredient or other condition is being considered for inclusion 
in an OTC drug monograph and calling for submissions of safety and 
efficacy data for the proposed OTC use.
    We note that although a TEA is the application regarding the time 
and extent of marketing, which leads to an eligibility determination 
(resulting in publication of an NOE or a letter of ineligibility), 
references to TEAs or applications under section 330.14 (including in 
the SIA) sometimes encompass FDA's review of the condition's 
eligibility and the GRASE determination for the condition. Thus, these 
references may be used to mean the TEA itself, the safety and

[[Page 19072]]

effectiveness data submission, FDA's GRASE determination, associated 
order or rulemaking actions, or all of these. In this proposed rule and 
preamble, the terms ``TEA'' and ``safety and effectiveness data 
submission'' are used, where appropriate, to describe the two distinct 
submissions under the TEA regulation. However, the term ``TEA process'' 
may be used when referring to one or more actions under the TEA 
regulation.
    If, after FDA reviews the safety and effectiveness data, the Agency 
initially determines that the active ingredient or other condition is 
GRASE, it will publish a proposed rule to include the condition in an 
appropriate OTC drug monograph.
    If the condition is initially determined not to be GRASE, FDA will 
inform the sponsor and other interested parties that submitted data of 
its decision by letter, and will include the letter in the relevant 
public docket (Sec.  330.14(g)(4)). The Agency will also publish a 
notice of proposed rulemaking to include the condition in Sec.  
310.502. The sponsor and other interested parties will have an 
opportunity to submit comments and new data on FDA's initial 
determination and proposed rule (Sec.  330.14(g)(5)). After evaluation 
of any additional data submitted, FDA will either issue a final rule or 
a new proposed rule, if necessary, in the Federal Register.

B. The Sunscreen Innovation Act (SIA)

    In November 2014, Congress passed the SIA to supplement the TEA 
process with regard to both sunscreen and non-sunscreen OTC drug 
products. Proposed Sec.  330.15 addresses section 586F of the FD&C Act, 
which was added by the SIA and only applies to TEAs for drugs other 
than nonprescription sunscreen active ingredients or combinations of 
nonprescription sunscreen active ingredients (see sections 586 and 586F 
of the FD&C Act, as amended by the SIA). For FDA review of non-
sunscreen TEA conditions, section 586F includes two main requirements, 
one regarding timelines for review of eligible TEA conditions pending 
before the date of enactment of the SIA, and the other regarding 
timelines and performance metrics for the TEA process going forward.
    The first general requirement (see FD&C Act section 586F(a)) is 
that FDA provide the option of selecting one of four frameworks for 
review to each non-sunscreen TEA sponsor who (1) had submitted a TEA 
for a condition that had been deemed eligible to be considered for 
inclusion in the OTC monograph system before the date of enactment of 
the SIA, and (2) requested the framework option within 180 days after 
enactment. FDA was required to provide the framework options to 
requesting sponsors by no later than one year after enactment of the 
SIA (by November 26, 2015). Before the date of SIA enactment, there 
were six non-sunscreen TEAs for conditions that had been found eligible 
to be considered for inclusion in the OTC drug monograph system: (1) 
Piroctone olamine (for dandruff control) (69 FR 7652, 2/18/04; Docket 
2004N-0050 (FDA-2004-N-0037)); (2) triclosan (for oral healthcare) (69 
FR 40640, 7/6/04; Docket 1981N-0033P (FDA-1981-N-0015)); (3) triclosan 
(for acne treatment) (70 FR 72447, 12/5/05; Docket 2005N-0445 (FDA-
2005-N-0454)); (4) climbazole (for dandruff control) (70 FR 72448, 12/
5/05; Docket 2005N-0444 (FDA-2005-N-0021)); (5) sodium picosulfate (for 
laxative use) (71 FR 35917, 6/22/06; Docket 2006O-0232 (FDA-2006-O-
0057)); and (6) sodium shale oil sulfonate (for dandruff control) (74 
FR 15741, 4/7/09; Docket FDA-2009-N-0146).
    The sponsors of three of those TEAs requested that FDA provide a 
review framework by the deadline established in section 586F(a) of the 
FD&C Act. The three TEAs are for: (1) Piroctone olamine (for dandruff 
control) (69 FR 7652, 2/18/04; Docket 2004N-0050 (FDA-2004-N-0037)); 
(2) sodium picosulfate (for laxative use) (71 FR 35917, 6/22/06; Docket 
2006O-0232 (FDA-2006-O-0057)); and (3) sodium shale oil sulfonate (for 
dandruff control) (74 FR 15741, 4/7/09; Docket FDA-2009-N-0146). FDA 
provided the review framework options to the requesting sponsors on 
November 24, 2015. With regard to the three sponsors who did not 
request or elect a framework in accordance with section 586F(a) of the 
FD&C Act, the eligible conditions addressed by their TEAs will be 
reviewed under the timelines set forth in proposed Sec.  330.15 (if 
finalized as proposed).
    The second general requirement (see FD&C Act section 586F(b)) is 
that FDA issue a regulation that includes (1) timelines for review of 
non-sunscreen TEA conditions and (2) measurable metrics for tracking 
the extent to which the timelines are met. This proposed rule includes 
both timelines and metrics, as required by the SIA.
    FDA has determined that with regard to non-sunscreen TEAs, the best 
way to both address the statutory requirements of the SIA and to make 
certain FDA-initiated modifications to the TEA process set forth in 
Sec.  330.14 is to (1) establish a new section (proposed Sec.  330.15) 
that is specific to non-sunscreen TEA conditions, and (2) amend Sec.  
330.14 with regard to process improvements for TEAs for all OTC drugs 
(such as providing format and content criteria for a filing 
determination and addressing withdrawal of consideration).
    In addition to developing new Sec.  330.15, which implements SIA 
requirements with regard to the TEA process for non-sunscreens, FDA 
proposes to make certain changes to the process set forth in Sec.  
330.14 that we believe will make the TEA process more clear and 
efficient for both sponsors and FDA. These proposed changes to Sec.  
330.14 are discussed in more detail in this document, but notably 
include provisions that address filing determination requirements with 
regard to safety and effectiveness data submissions (to allow FDA to 
determine, and sponsors to know, early on whether a submission is 
sufficiently complete to permit a substantive review) and provisions 
regarding withdrawal of consideration of a TEA or safety and 
effectiveness data submission.

IV. Legal Authority

    This rule is being proposed under FDA's authority to regulate OTC 
drug products under the FD&C Act (see sections 201, 501, 502, 503, 505, 
586F, and 701(a) of the FD&C Act (21 U.S.C. 321, 351, 352, 353, 355, 
360fff-6, and 371(a))). As stated in the Federal Register of January 
22, 2002 (67 FR 3069), in which the final rule establishing the TEA 
process was published, submission of an NDA has been required before 
marketing a new drug since passage of the FD&C Act in 1938 (21 U.S.C. 
355). To market a new drug, it must first be approved under section 505 
of the FD&C Act. Section 701(a) of the FD&C Act authorizes FDA to issue 
regulations for the efficient enforcement of the FD&C Act. FDA's 
regulations in 21 CFR part 330 describe the conditions for a drug to be 
considered GRASE and not misbranded. If a drug meets each of the 
conditions contained in part 330, as well as each of the conditions 
contained in any applicable OTC drug monograph, and other applicable 
regulations, it is considered GRASE and not misbranded, and is not 
required by FDA to obtain approval under section 505 of the FD&C Act.
    In addition, section 586F of the FD&C Act requires FDA to issue 
regulations providing for the timely and efficient review of certain 
submissions under the TEA regulation at 21 CFR 330.14. Section 586F of 
the FD&C Act specifically requires these regulations to

[[Page 19073]]

include timelines and metrics associated with the review of certain 
submissions under the TEA regulation. Proposed Sec.  330.15 would add 
timeline and metrics provisions that are intended to implement section 
586F of the FD&C Act.

V. Description of the Proposed Rule

    In this rule, we are proposing to establish new Sec.  330.15 and to 
amend current Sec.  330.14. In particular, we are proposing to: (1) 
Establish timelines and metrics for review of non-sunscreen TEA 
conditions, (2) add provisions concerning filing determination 
requirements with regard to the content and format of safety and 
effectiveness data submissions under Sec.  330.14(f), (3) address 
withdrawal of consideration of TEAs and safety and effectiveness data 
submissions, (4v) add related definitions, and (5) make clarifying and 
conforming changes to the TEA regulation. These proposed changes are 
discussed in detail in this section.

A. Timelines for FDA Review and Action on Time and Extent Applications 
and Safety and Effectiveness Data Submissions (Proposed Sec.  330.15)

    The SIA mandates that FDA issue regulations to establish timelines 
and metrics regarding the review of non-sunscreen TEA conditions, and 
provides that the proposed timelines may vary based on the content, 
complexity, and format of the submission, and that they must (1) 
reflect FDA's public health priorities, including the potential public 
health benefits posed by the inclusion of additional drugs in the OTC 
drug monograph system, (2) take into consideration the availability of 
FDA resources for carrying out such priorities and the relevant review 
processes and procedures, and (3) be reasonable, taking into account 
the required consideration of priorities and resources (FD&C Act 
section 586F(b)(2)). Proposed Sec.  330.15 is intended to implement 
these requirements.
1. Applicability (See Proposed Sec.  330.15(a))
    As a general matter, the timeline provisions in proposed Sec.  
330.15 apply to FDA and are triggered by specific actions by sponsors, 
such as submission of a TEA or submission of a safety and effectiveness 
data submission (as defined in proposed Sec.  330.14(a)) and, in some 
cases, FDA (e.g., the date of filing). The metrics provisions also 
apply to FDA.
    Proposed Sec.  330.15(a) describes which TEA conditions are subject 
to the timelines for FDA review and action in this section and which 
are not. We invite comment on the proposed applicability of this 
section. In particular, FDA is proposing that the review of an active 
ingredient or other condition in a TEA submitted under Sec.  330.14 for 
consideration in the OTC drug monograph system would be subject to the 
proposed timelines, with two exceptions.
    First, in Sec.  330.15(a)(1), FDA proposes that Sec.  330.15 does 
not apply to a sunscreen active ingredient or a combination of 
sunscreen active ingredients or other conditions for such ingredients. 
Section 586F(b) of the FD&C Act directs the Agency to issue regulations 
establishing timelines for drugs other than nonprescription sunscreen 
active ingredients or combinations of nonprescription sunscreen active 
ingredients. The SIA recognizes that active ingredients can only be 
GRASE under specified conditions. For example, section 586A of the FD&C 
Act, which was added by the SIA to provide an alternative route for 
inclusion in the sunscreen monograph, states that a person may submit a 
request to FDA for a determination of whether a nonprescription 
sunscreen active ingredient or combination of ingredients, for use 
under specified conditions, to be prescribed, recommended, or suggested 
in the labeling thereof (including dosage form, dosage strength, and 
route of administration) is GRASE. Because the TEA regulation addresses 
active ingredients and other conditions, including dosage forms, and an 
active ingredient can only be GRASE under specified conditions, we 
understand the reference to TEAs for drugs other than sunscreen active 
ingredients in section 586F(b) of the FD&C Act to be distinguishing 
sunscreen active ingredients and related conditions from non-sunscreen 
active ingredients and related conditions. Furthermore, ``pending 
requests'' for sunscreen active ingredients under the SIA are subject 
to the provisions of section 586C(b) of the FD&C Act, as amended by the 
SIA (21 U.S.C. 360fff-3(b)), which include timeframes for FDA review 
and action. Therefore, under proposed Sec.  330.15(a), Sec.  330.15 
would not apply to sunscreen active ingredients and related conditions.
    Second, in Sec.  330.15(a)(2), FDA proposes that Sec.  330.15 
generally does not apply to non-sunscreen active ingredients or other 
conditions submitted in TEAs under Sec.  330.14 on or before the date 
of enactment of the SIA. Section 586F(b)(1) of the FD&C Act directs the 
Agency to issue regulations establishing timelines for the review of 
TEA conditions submitted after the date of enactment of the SIA. 
However, as provided in the SIA, any non-sunscreen TEA conditions 
determined to be eligible to be considered for inclusion in the OTC 
drug monograph system before the date of enactment of the SIA, for 
which the sponsor did not request a framework for review under section 
586F(a)(1), will also be reviewed under the timelines set forth in 
Sec.  330.15(c) of this proposed rule (see FD&C Act section 
586F(a)(1)(C)) (if finalized as proposed). Accordingly, the scope of 
the exclusion in proposed Sec.  330.15(a)(2) references section 
586F(a)(1)(C) of the FD&C Act to account for such TEA conditions.
    For sponsors of TEAs covering conditions that had been found 
eligible to be considered for inclusion in the OTC drug monograph 
system before the date of enactment of the SIA who elected to choose a 
framework for review, FDA was required to provide four optional 
frameworks that set forth timelines for FDA review (FD&C Act section 
586F(a)((2)). The frameworks included timelines for review if the 
sponsors choose an order process with or without a filing 
determination, or a rulemaking process with or without a filing 
determination. A notification of optional frameworks was provided to 
each requesting sponsor on November 24, 2015. Before the date of 
enactment of the SIA, there were six non-sunscreen TEA conditions that 
were found by FDA to be eligible to be considered for inclusion in the 
OTC drug monograph system (listed in section II.B). Of these, three 
sponsors elected a framework for review, and three did not (listed in 
section II.B).
2. Timelines for FDA Review and Action (Proposed New Sec.  330.15(c)).
    As discussed in the introduction to section V.A, section 586F(b) of 
the FD&C Act, as amended by the SIA, directs FDA to establish timelines 
for the review of certain TEA conditions. As also discussed in section 
V.A.1, in addition to applying to new non-sunscreen TEAs, these 
timelines would apply to certain non-sunscreen TEA conditions that were 
found to be eligible before November 26, 2014. Section 586F(b) of the 
FD&C Act also requires timelines for internal procedures related to the 
review of safety and effectiveness data submissions.
    FDA is proposing to establish the timelines described in this 
section of the document for FDA review and action, as described in 
proposed new Sec.  330.15(c).
    Note that terms for certain actions that begin review timelines for 
FDA are defined in proposed amendments to

[[Page 19074]]

Sec.  330.14 (e.g., ``date of filing''). In addition to clarifying that 
its definitions apply to proposed Sec.  330.15, proposed Sec.  
330.14(a) would clarify the applicability of the definitions in section 
201 of the FD&C Act by expressly stating that any relevant definitions 
in that section, such as the definition of ``person'' at section 
201(e), would apply to Sec. Sec.  330.14 and 330.15.
a. Proposed Timelines
    The proposed timelines are:
     FDA will issue a notice of eligibility or post to the 
docket a letter of ineligibility, in accordance with Sec.  330.14(d) 
and (e), within 180 days of submission of a TEA under Sec.  330.14(c).
     FDA will issue a filing determination in accordance with 
Sec.  330.14(j) within 90 days of receipt by FDA of a safety and 
effectiveness data submission from the sponsor under Sec.  330.14(f). 
Under proposed Sec.  330.14(a)(5), a safety and effectiveness data 
submission is defined as a data package submitted by a sponsor that 
includes safety and effectiveness data and information under Sec.  
330.14(f) and that is represented by the sponsor as being a complete 
submission. Therefore, FDA will not start the 90-day filing 
determination period until the sponsor has confirmed that it considers 
the submission to contain all data and information required under Sec.  
330.14(f) by providing a statement that the submission is a complete 
safety and effectiveness data submission. If the sponsor submitted such 
a safety and effectiveness data submission at the same time as the 
sponsor submitted the TEA, and the condition addressed in the TEA is 
deemed eligible for consideration, FDA will issue a filing 
determination within 90 days after issuing the notice of eligibility.
     If the active ingredient or other condition is initially 
determined not to be GRASE, FDA will inform the sponsor and other 
interested parties who have submitted data of its determination by 
feedback letter in accordance with Sec.  330.14(g)(4), within 730 days 
(generally 24 months) from the date of filing. FDA is considering 
whether to add a codified provision to address sponsor requests for 
additional time in response to a feedback letter and how that would 
affect the timeline for review. We welcome comments on this issue.
     FDA will issue a notice of proposed rulemaking within 
1,095 days (generally 36 months) from the date of filing to either:
    [cir] Include the active ingredient or other condition in an 
appropriate OTC monograph(s), either by amending an existing 
monograph(s) or establishing a new monograph(s), if necessary; or
    [cir] Include the active ingredient or other condition in Sec.  
310.502 (which would require the sponsor to seek approval under section 
505 of the FD&C Act before marketing).
     FDA will issue a final rule within 912 days (generally 30 
months) of the closing of the docket of the proposed rulemaking under 
Sec.  330.15(c)(4). If the docket is reopened, the final rule will be 
issued within 912 days of the closing of the re-opened docket.
    For non-sunscreen TEA conditions that were found to be eligible 
before enactment of the SIA and that would be subject to the timelines 
in proposed Sec.  330.15, FDA intends to treat the date of publication 
of the final rule for Sec.  330.15 to be the date of filing for 
purposes of Sec. Sec.  330.14 and 330.15. Therefore, upon the 
publication of the final rule, the timelines in proposed Sec.  
330.15(c)(3), if applicable, and Sec.  330.15(c)(4) would begin for 
these eligible TEA conditions.
b. Development of Timelines
    As required by the SIA (section 586F(b)(2) of the FD&C Act), FDA 
considered specific factors in developing the timelines in proposed new 
Sec.  330.15(c). In particular, the SIA provides that the timelines for 
the review of non-sunscreen TEA conditions may vary based on the 
content, complexity, and format of the submission, and shall (1) 
reflect FDA public health priorities (including potential public health 
benefits of including additional drugs in the OTC drug monograph 
system), (2) take into consideration the resources available for 
carrying out such public health priorities and the relevant review 
processes and procedures, and (3) be reasonable, taking into account 
the required consideration of priorities and resources just described 
(section 586F(b)(2)(A) and (B) of the FD&C Act).
    FDA is allowed (for the ``may'' factors) or required (for the 
``shall'' factors) to take these factors into account in the timelines 
for review of non-sunscreen TEAs and related submissions. These SIA 
provisions recognized factors that could possibly affect how long it 
may take FDA to complete review of a particular TEA and related 
submissions. The timelines proposed in Sec.  330.15 factored in the 
considerations that are required under the SIA; they reflect the 
projected time necessary for FDA to complete its review of marketing, 
filing, and scientific data and other information, as well as to make 
tentative and final determinations about the adequacy of the 
submissions to ultimately support a finding that the active ingredient 
or other condition is or is not GRASE and not misbranded for 
nonprescription use, based on the Agency's public health priorities and 
the resources available to carry them out. The timelines also include 
the projected time necessary to draft and finalize the letters or rules 
(proposed and final), and when applicable, prepare the document for 
publication in the Federal Register. In addition, the timelines take 
into account other activities that may occur during the review, such as 
convening an advisory committee meeting, meeting with sponsors, or 
both. FDA believes that the proposed timelines are reasonable, taking 
into consideration FDA's priorities and resources. More detail on how 
FDA took these factors into account is provided in this section.
i. FDA Public Health Priorities
    Under section 586F(b)(2)(B)(i) of the FD&C Act, the timelines must 
reflect FDA's public health priorities, including the potential public 
health benefits posed by the inclusion of additional drugs in the OTC 
drug monograph system. FDA has a very broad mandate and multiple public 
health priorities, with limited resources to address these priorities.
    FDA's Center for Drug Evaluation and Research (CDER) is responsible 
for regulating the safety and efficacy of both prescription and 
nonprescription human drugs. Like FDA as a whole, CDER must continually 
balance multiple important public health priorities, of which the OTC 
Drug Review is one. CDER does, and will continue to, consider the OTC 
Drug Review among its priorities as it endeavors to appropriately 
allocate staff and resources within the context of all CDER 
responsibilities.
    Examples of how FDA public health priorities may affect the time 
required for the review of non-sunscreen TEA conditions under the 
proposed timelines include situations such as a public health emergency 
or competing high priority work that requires diversion of the staff 
assigned to a TEA or safety and effectiveness data submission.
ii. Resources Available for Carrying Out Such Priorities
    Under section 586F(b)(2)(B)(ii), the timelines must take into 
consideration Agency resources available for carrying out its public 
health priorities and the processes and procedures related to the 
review of TEA conditions. Examples of resource constraints that may 
affect the time required for review include, but are

[[Page 19075]]

not limited to: multiple TEAs arriving at or near the same time; 
general expected staff and budget constraints; unexpected staff and 
budget constraints; personnel turnover and lag times in hiring new 
staff; etc. For example, FDA has only a certain number of trained staff 
available to assign to TEA review work, and these staff generally have 
other assigned work in addition to TEA reviews.
iii. Reasonableness, Taking Into Consideration Agency Priorities and 
Resources
    In developing the timelines set forth in proposed new Sec.  
330.15(c), FDA has attempted to set reasonable timelines that will be 
achievable in most circumstances, given our experience to date with 
TEAs and related safety and effectiveness data submissions. While FDA 
expects that the filing determination requirements we propose adding to 
Sec.  330.14(j) will help to avoid major content and format 
deficiencies in incoming safety and effectiveness data submissions, 
there is likely still to be some variation in the formatting of 
incoming TEAs and safety and effectiveness data submissions, and a 
related variation in the ease and efficiency of review.
    In determining reasonable timelines, FDA also considered the 
potential effect on stakeholders, including TEA sponsors and the 
public. In addition to considering the benefits that the proposed 
timelines and related metrics would provide to sponsors (e.g., more 
transparency regarding the TEA review process, increased predictability 
regarding how long each major process step is expected to take, and 
metrics on how long each step actually takes), FDA also considered 
other potential impacts of the proposed timelines on sponsors, 
including concerns regarding the time required to complete the review 
and rulemaking process. For each step in the TEA process, FDA attempted 
to determine a timeline that is achievable, consistent with timelines 
for similar FDA activities in other contexts to the extent possible 
(e.g., NDA process timelines, general rulemaking experience), 
consistent with the Agency's priorities and resources, and that 
reasonably takes into consideration the interests of the public (in 
safe and effective OTC drug products) and sponsors (in a timely and 
efficient review process). For some steps, this resulted in FDA setting 
a shorter timeline than it had previously estimated for the step. For 
example, the proposed timeline for the eligibility determination step 
(proposed new Sec.  330.15(c)(1)) is 180 days from receipt of a TEA, 
which is roughly half the time estimated by FDA for this step in a 2011 
guidance to industry (Ref. 1).
Eligibility Determination
    With respect to the eligibility determination (Sec.  330.15(c)(1)), 
FDA is proposing to review and issue a notice of eligibility or post to 
the docket a letter of ineligibility within 180 days of receipt of a 
TEA, which FDA considers to be a reasonable timeline, taking into 
consideration Agency priorities and resources. As stated previously, in 
a 2011 final guidance to industry, FDA previously estimated a 1-year 
timeframe for taking this action (Ref. 1).
Filing Determination
    FDA is proposing to issue a filing determination within 90 days of 
submission by the sponsor of a safety and effectiveness data 
submission, which is defined in proposed Sec.  330.14(a), in part, as a 
submission that the sponsor has confirmed it considers to be complete 
(i.e., contains all data and information required under Sec.  
330.14(f)). While this timeline is 30 days longer than the filing 
provisions in 21 CFR 314.101 for NDAs and ANDAs, we anticipate that the 
filing review of a safety and effectiveness data submission for a 
nonprescription active ingredient or other condition may require more 
time than an NDA or ANDA review because the submission may consist of 
data and information from a wider variety of sources, with possibly a 
greater reliance on certain sources (e.g., published literature).
Rulemaking and Feedback Letter
    Notice and comment rulemaking is generally a lengthy and multistep 
process (Ref. 2). The timelines in this proposed rule are consistent 
with the length of time typically required for other rulemaking, and 
reflect the amount of time FDA anticipates will be required for the 
reviews of safety and effectiveness data submissions and related 
rulemaking.
    Major steps for FDA rulemaking generally include determination that 
a rule is needed and what the rule should say; drafting, reviewing, and 
finalizing the proposed rule; publishing the proposed rule; a public 
comment period and review of the comments; revising the proposed rule 
as appropriate; reviewing the draft final rule and finalizing it, and 
publishing the final rule in the Federal Register.
    As noted previously, rulemaking is often a lengthy process, and the 
OTC Drug Review process (of which the TEA process is a part) offers 
additional rulemaking challenges, such as were discussed in a public 
meeting on OTC process reform held by FDA in 2014 (``Over-The-Counter 
Drug Monograph System--Past, Present and Future; Public Hearing,'' 79 
FR 10168, February 24, 2014; Docket No. FDA-2014-N-0202). Additional 
information, such as the hearing transcript, is available at http://www.fda.gov/Drugs/NewsEvents/ucm380446.htm. For TEA active ingredients 
and other conditions, the timelines for rulemaking involve conducting 
the scientific review, making a GRASE determination, and drafting and 
finalizing the rule for publication in the Federal Register. FDA 
estimates that initial scientific review of a complete safety and 
effectiveness data submission, including for new molecular entities 
that have never been marketed in the United States, will take 
approximately 730 days (generally 24 months). In addition to conducting 
this comprehensive review, the timeline may also include other 
activities, such as convening an advisory committee (or, under rare 
circumstances, an advisory review panel under Sec.  330.10) and meeting 
with sponsors.
    If the active ingredient or other condition is initially determined 
not to be GRASE for OTC use in the United States, FDA will also issue a 
feedback letter within this 730-day (generally 24-month) timeline. The 
feedback letter may identify the specific gaps in the data or 
information necessary to make a GRASE determination, and it provides 
the sponsor with time before the NPRM is published that could be used 
to begin collecting the data or information required for potential 
inclusion in a monograph. We note that a feedback letter reflects the 
Agency's initial determination. If FDA does not issue a feedback 
letter, it does not guarantee that we will ultimately determine that an 
ingredient is GRASE and not misbranded.
    FDA proposes to issue an NPRM within 1,095 days (generally 36 
months) from the date of filing (as defined in proposed Sec.  
330.15(a)(6)). For an active ingredient or other condition that is 
initially determined to be GRASE, FDA would issue a proposed rule to 
include the condition in the appropriate OTC monograph. For an active 
ingredient or other condition that is initially determined not to be 
GRASE, FDA would issue a proposed rule to include the condition in 21 
CFR 310.502 (the regulation listing drugs that have been accorded new 
drug status through rulemaking and must be approved under section 505 
of the FD&C Act before marketing). In general, FDA intends to close the 
public comment period for the proposed rule at 90 days,

[[Page 19076]]

unless a request to defer further rulemaking to allow the submission of 
new safety or effectiveness data to the record is granted.
    FDA is proposing to issue a final rule within 912 days (generally 
30 months) of the closing of the comment period for the proposed rule. 
During this 912-day time period, FDA will review and consider any new 
data, information, and public comments submitted to the docket and 
draft and publish a final regulation.
    Timelines for FDA review and action for sunscreen active 
ingredients under sections 586B and 586C of the FD&C Act, as amended by 
the SIA, are generally shorter than those in this proposed rule. The 
most notable differences are the timelines for proposed and final GRASE 
determinations which, under the SIA requirements for sunscreen active 
ingredients, are made through an order process rather than a rulemaking 
process. The order process eliminates some of the requirements of 
rulemaking that are time-consuming and resource intensive.
    A 2009 Government Accountability Office (GAO) report (Ref. 3) 
examined, among other things, how long agencies, including FDA, take to 
issue rules. For the 16 case studies, the report found significant 
variation in time to complete rulemaking, with an average of about four 
years and a range of one to nearly 14 years. Factors that influenced 
the time needed to issue a rule included the complexity of the issues, 
Agency priorities, and the amount of internal and external review 
required (Ref. 3 at p. 19).
    In summary, based on the type of data typically submitted in a TEA, 
along with the potential variability in the content and formatting of 
that submission, and because of the complex scientific review required 
to determine if an active ingredient or other condition is GRASE for 
OTC use, the possible use of an advisory committee, and the 
requirements for the rulemaking process itself, FDA considers the 
timelines put forth in this proposed rule to be reasonable, taking into 
consideration Agency priorities and resources. As described in further 
detail in the paragraphs that follow, if a TEA and the related safety 
and effectiveness data submission are straightforward, well-organized, 
and complete, FDA may be able to take action within shorter timeframes 
than proposed in this rule.
    As stated previously, under section 586F(b)(2)(A) of the FD&C Act, 
the timelines established in the regulations required under that 
section could vary based on the content, complexity, and format of the 
submission. FDA considered a number of timeline options. Ultimately, 
FDA determined that instead of setting multiple proposed timelines for 
submissions of varying content, complexity, and format, it would be 
more efficient and sensible to set one general timeline for the review 
of non-sunscreen TEA conditions that accommodates anticipated variation 
among submissions. There is likely to be some variation in how quickly 
each submission is reviewed, because each will present a unique set of 
data and each review will occur in the context of multiple ongoing FDA 
activities and priorities. This may result in a review step taking less 
time than proposed in Sec.  330.15(c) (for example, if a submission is 
well-organized, complete when submitted, and straightforward). In 
unusual circumstances, a review or rulemaking step may require a longer 
time than proposed in Sec.  330.15(c) (e.g., an unusually high volume 
of TEAs submitted, an especially complex new ingredient or other 
condition, or a public health emergency that diverts Agency resources). 
However, FDA would endeavor to meet the proposed timelines in Sec.  
330.15(c) for all submissions, and any missed timelines would be 
reflected in the metrics set forth in proposed Sec.  330.15(b). In 
summary, the provisions in Sec.  330.15(c) provide sponsors and the 
public with consistent timeframes for expected Agency action. In the 
paragraphs that follow, we discuss some practical examples of how 
certain factors might be expected to impact FDA review of a non-
sunscreen TEA condition:
[cir] Content
    The quantity and quality of submitted data can generally impact 
FDA's review. If a TEA or safety and effectiveness data submission 
includes all the information that is required and all information that 
the sponsor wishes to have considered in the initial submission to FDA, 
it is likely possible to complete review of the TEA or safety and 
effectiveness data submission more quickly than if it has poor quality 
data, if FDA finds that clarification or additional data is needed, or 
if the sponsor submits additional spontaneous data supplements during 
the substantive review.
[cir] Complexity
    Complexity, including, among other things, the nature of the active 
ingredient or other condition that is the subject of the TEA and the 
status of the monograph for the therapeutic category (i.e., final, 
tentative, or new) may also impact FDA's review. For example, review of 
a TEA and safety and effectiveness data submission for an active 
ingredient that has not previously been evaluated under the monograph 
for any use would likely be more complex than for an ingredient that is 
the subject of a GRASE determination in another monograph category. In 
addition, a review that involves a new technology would be more complex 
than one that does not.
    The OTC monograph status for the therapeutic category (final, 
tentative, or new) and the U.S. Pharmacopeia (USP) monograph status 
(whether establishment of a USP monograph is required or not) may each 
affect the time required for review and rulemaking, in that addition of 
an active ingredient or other condition to a final OTC monograph once 
the GRASE determination is made would generally be faster than working 
with a tentative or new OTC monograph. Also, because a USP monograph 
for the ingredient is required before FDA can issue a final rule adding 
an active ingredient to an OTC monograph (Sec.  330.14(i)), the USP 
monograph status may lengthen the review and rulemaking time.
    Finally, if FDA determines that an advisory committee or an 
advisory review panel is appropriate (e.g., for a particularly complex 
new issue), that process could increase the time required to complete 
the review, particularly if the committee's recommendations raised 
additional issues to review.
[cir] Format
    The format including, among other things, whether a TEA or safety 
and effectiveness data submission is well-organized or poorly-
organized, whether some or all of the information is submitted in 
electronic format, etc., could also impact FDA's review. We note that 
FDA recently issued draft guidance for industry regarding the format 
and content of data submissions for nonprescription sunscreen active 
ingredients (Ref. 4). A well-formatted TEA can generally be reviewed 
more quickly and efficiently than a poorly-organized TEA. In addition, 
review could take longer (or result in a refusal to file) if a safety 
and effectiveness data submission is disorganized with a structure that 
does not facilitate review for completeness, if there are electronic 
submissions that cannot be opened or that cannot be readily navigated 
(e.g., hyperlinks do not operate), or if there are data tabulations or 
graphic displays that are not interpretable, inadequately labeled, or 
do not indicate data sources. These issues may arise, in particular, 
with regard to safety and effectiveness

[[Page 19077]]

data submissions that are filed over protest.
3. Metrics (Proposed New Sec.  330.15(b))
    Section 586F(b) of the FD&C Act requires FDA to establish 
measurable metrics for tracking the extent to which the timelines set 
forth in the regulations are met (see proposed timelines under Sec.  
330.15(c)). FDA is proposing to maintain a publicly available posting 
of metrics for the review of TEAs and safety and effectiveness data 
submissions submitted under Sec.  330.14 that are subject to the 
timelines under proposed Sec.  330.15(a), and update the posting 
annually. The posting will contain the metrics listed in this section, 
as proposed in Sec.  330.15(b), for submissions received during the 
previous calendar year.
     Number and percent of eligibility notices or ineligibility 
letters issued within 180 days of submission of a TEA (i.e., for new 
TEAs submitted during the year, the number and percentage for which FDA 
issued either an eligibility notice or an ineligibility letter within 
180 days).
     Number and percent of filing determinations issued within 
90 days of submission of a safety and effectiveness data submission 
(i.e., for safety and effectiveness data submissions received during 
the year, the number and percentage for which FDA issued a filing 
determination within 90 days).
     If applicable, number and percent of feedback letters 
issued within 730 days (generally 24 months) from the date of filing 
(i.e., the number of feedback letters issued during the year, if any, 
and the number and percent of these that were issued within 730 days 
from the date of filing the safety and effectiveness data submission).
     Number and percent of notices for proposed rulemaking 
issued within 1,095 days (generally 36 months) from the date of filing 
(i.e., the number of notices of proposed rulemaking issued during the 
year, if any, and the number and percent of these that were issued 
within 1,095 days from the date of filing).
     Number and percent of final rules issued within 912 days 
(generally 30 months) of closing of the docket of the proposed 
rulemaking (i.e., the number of final rules issued during the year, if 
any, and the number and percent of these that were issued within 912 
days of the closing of the docket of the proposed rulemaking). We note 
that if the docket is reopened, the 912 days will be measured from the 
date the reopened docket is closed.
     Total number of TEAs submitted under Sec.  330.14; FDA may 
also post a total number of TEAs that have been submitted in all 
previous years.
    For purposes of the metrics, a lack of FDA action in response to a 
triggering event in the previous calendar year will not be factored in 
unless the response was due in the previous calendar year. In other 
words, if a sponsor submits a TEA in October of the previous calendar 
year, and FDA has not yet issued a notice of eligibility or letter of 
ineligibility because 180 days has not elapsed by the end of the 
calendar year, under the proposed metrics, FDA would not consider the 
lack of response as missing the timeline. Whether FDA met the timeline 
or not would be reflected in the next year's metrics.
    FDA intends to track these metrics and post them publically on the 
FDA Internet site. The Agency routinely uses its Internet site to post 
information and track progress and performance metrics on various 
initiatives (Ref. 5).
    The Agency anticipates that the proposed metrics web posting will 
improve transparency by providing sponsors and the public with 
information that will enable them to quickly ascertain the number of 
TEAs that have been submitted to FDA, and the Agency's performance in 
meeting the proposed timelines. Over time, these measurements may also 
assist the Agency with resource planning and utilization.

B. Amendments to Sec.  330.14 ``Additional Criteria and Procedures for 
Classifying OTC Drugs as Generally Recognized as Safe and Effective and 
Not Misbranded''

    FDA is proposing to revise Sec.  330.14 to add new definitions and 
requirements. The new proposed definitions are primarily meant to 
clarify the beginning or ending of the timelines for FDA review and 
action as proposed in new Sec.  330.15. The new proposed requirements 
include filing determination provisions under proposed new Sec.  
330.14(j) and ``withdrawal of consideration'' provisions under proposed 
new Sec.  330.14(k), which are intended to make the TEA process more 
efficient for both sponsors and FDA.
1. Definitions (Proposed Revised Sec.  330.14(a))
    FDA is proposing new definitions that, in general, are intended to 
clarify the beginning or ending of the timelines for FDA review and 
action as proposed in Sec.  330.15. FDA is adding these definitions to 
Sec.  330.14 instead of proposed new Sec.  330.15 because Sec.  330.14 
describes the TEA process to which these definitions apply. The 
definitions for ``condition'' and ``botanical drug substance,'' 
proposed under Sec.  330.14(a)(1) and (2) respectfully, are unchanged 
from the current definitions under Sec.  330.14(a). FDA is proposing to 
add the following new definitions of terms that apply to Sec.  330.14.
     FDA is proposing that the term ``sponsor'' mean the person 
(as defined in section 201(e) of the FD&C Act) that submitted a TEA 
under Sec.  330.14(c). Because the TEA process involves a public 
rulemaking process, comments from other interested parties, such as 
additional safety and effectiveness data, may be submitted to the 
docket for a TEA condition. FDA is proposing this definition to make 
clear that the sponsor is the person that submitted the TEA and related 
safety and effectiveness data submission, and will be the recipient of 
certain letters communicating FDA decisions. Because this is a public 
process, such letters will also be posted publicly to the relevant 
docket.
     FDA is proposing that the term ``time and extent 
application (TEA)'' mean a submission by a sponsor under Sec.  
330.14(c), which will be evaluated by the Agency to determine 
eligibility of a condition for consideration in the OTC drug monograph 
system. FDA is proposing this definition to make clear the difference 
between a submission to FDA for the purposes of establishing that the 
condition has been marketed for a material time and to a material 
extent versus a submission to FDA for the purposes of establishing that 
the condition is GRASE.
     FDA is proposing that the phrase ``safety and 
effectiveness data submission'' mean a data package submitted by a 
sponsor that includes safety and effectiveness data and information 
under Sec.  330.14(f) and that is represented by the sponsor as being a 
complete submission. FDA is proposing this definition to differentiate 
this type of submission from the TEA. It also clarifies that FDA will 
not begin its filing determination under Sec.  330.14(j) unless the 
sponsor first asserts that the submission is complete.
     FDA is proposing that the phrase ``date of filing'' mean 
the date of the notice from FDA informing the sponsor that FDA has made 
a threshold determination that the safety and effectiveness data 
submission is sufficiently complete to permit a substantive review. For 
submissions filed over protest in accordance with Sec.  330.14(j)(3), 
the date of filing is the date of the notice from FDA informing the 
sponsor that FDA has filed the submission over protest. This date will 
be no later than 30 days after the sponsor's request that FDA file the 
submission over protest. FDA is

[[Page 19078]]

proposing this definition to make clear the start of the timeframe for 
FDA review and action under Sec.  330.15(c)(3) and (4).
     FDA is proposing that the term ``feedback letter'' mean a 
letter issued by the Agency in accordance with Sec.  330.14(g)(4) that 
informs the sponsor and other interested parties who have submitted 
data under paragraph (f) of this section that a condition is initially 
determined not to be GRASE. FDA is proposing this definition to clarify 
the FDA action under Sec.  330.14(g)(4) and the timeframe for such 
action under Sec.  330.15(c)(3).
2. Filing Determination (Proposed New Sec.  330.14(j))
    FDA is proposing new requirements that specify certain filing 
determination requirements that are intended, in part, to help improve 
the content and format of a safety and effectiveness data submission. 
FDA is also proposing timelines related to these proposed new 
requirements. For example, submission criteria include factors such as 
whether the submission includes all required information, whether the 
submission is organized and formatted in a manner that allows FDA to 
readily determine if it is sufficiently complete to permit a 
substantive review, and whether the submission includes all required 
certifications.
    The proposed new section also sets forth processes that apply 
whether the submission is accepted for filing, refused, or filed over 
protest. If the submission is filed, the date of filing, as defined in 
proposed Sec.  330.14(a), represents the start of FDA's initial review 
for a GRASE determination, and triggers the start of timelines under 
proposed Sec. Sec.  330.15(c)(3) and (4).
    FDA believes that these proposed requirements would benefit both 
TEA sponsors and FDA, as well as potentially benefitting other 
interested parties. In FDA's experience, TEA-related submissions vary 
widely in their content and format and are sometimes difficult or 
extremely time-consuming and resource-intensive to review as submitted 
(e.g., missing data; copies of articles in foreign languages without an 
accompanying translation; hyperlinks that do not work; data submitted 
piecemeal; data not organized in any discernable manner, such as a 
submission with no listing of contents, page numbers, data categories, 
etc.). The proposed new requirements would provide more clarity and 
certainty to sponsors as to the content and format of a safety and 
effectiveness data submission and would provide for FDA to let sponsors 
know early on in the process if there is missing material or a 
problematic format that could delay review. For FDA, the proposed new 
requirements would be expected to result in more complete and clear 
data submissions from sponsors, to allow FDA to more easily and quickly 
determine whether the submission is sufficiently complete to permit FDA 
to go forward with a substantive review, and to ensure that once FDA 
begins its substantive review, the data and other information necessary 
for a complete review are available. If the submission is not 
sufficiently complete to allow substantive review, the new requirements 
would provide a clear pathway to communicate this issue to sponsors via 
a filing determination, and to communicate what additional information 
or format changes are required. Because safety and effectiveness data 
submissions are posted to the public docket, once filed, a more 
complete submission may also benefit other interested parties. Among 
other things, it may be easier for non-sponsor interested parties to 
determine whether there is information not otherwise reflected in the 
docket that they would like to submit for FDA to consider in the GRASE 
determination.
    We note that while the SIA did not require FDA to issue a 
regulation regarding filing determination criteria for safety and 
effectiveness data submissions under Sec.  330.14, it did require FDA 
to issue draft and final guidance on the format and content of 
information submitted by a sponsor in support of a ``request'' under 
section 586A of the FD&C Act and a ``pending request,'' which are 
related to sunscreens (see FD&C Act section 586D(a)(1)(A) and (B)). A 
notice of availability of the draft guidance on this topic was 
published in the Federal Register on November 23, 2015 (Ref. 4). When 
final, this guidance will provide the Agency's current thinking about 
the criteria for the content and format of the safety and effectiveness 
data submitted by the sponsor of a TEA for a nonprescription sunscreen 
active ingredient or related condition. As noted in the draft guidance, 
when finalized, parts of the general advice in that guidance about the 
content and format of sunscreen safety and effectiveness data 
submissions may also be useful to persons preparing submissions for 
non-sunscreen TEA conditions.
    As stated earlier in this section, proposed Sec.  330.14(j) sets 
forth criteria FDA would use in making a filing determination for a 
safety and effectiveness data submission, as well as timing and 
processes related to the determination. In particular, in Sec.  
330.14(j)(1), FDA proposes that after FDA receives a safety and 
effectiveness data submission, the Agency will determine whether the 
submission may be filed. The determination would be whether or not to 
accept the submission for filing, after an initial review of the 
submission regarding whether the submission contains the data and 
information required under Sec.  330.14(f) in an acceptable format, and 
satisfies the other filing criteria under Sec.  330.14(j)(4). The 
filing of a submission under proposed Sec.  330.14(j)(2) would mean 
that FDA has made a threshold determination that the submission is 
sufficiently complete to permit a substantive review.
    In Sec.  330.14(j)(2), FDA proposes that the date of filing will 
begin the FDA timelines described in Sec.  330.15(c)(3) and (4).
    In Sec.  330.14(j)(3), FDA proposes to describe the process for 
cases in which FDA refuses to file the safety and effectiveness data 
submission. If this happens, the Agency would notify the sponsor in 
writing and state the reason for the refusal under proposed Sec.  
330.14(j)(4). Proposed Sec.  330.14(j)(3) provides the sponsor 30 days 
in which to request an informal conference with the Agency about 
whether the Agency should file the submission and sets forth the 
procedures if the sponsor wishes to file the submission over protest 
following the informal conference. Proposed Sec.  330.14(j)(3) further 
provides that FDA will convene the informal conference within 30 days 
of the request from the sponsor. It also provides that if, within 120 
days after the informal conference, the sponsor requests that FDA file 
the submission (with or without correcting the deficiencies), the 
Agency will file the safety and effectiveness data submission over 
protest under Sec.  330.14(j)(2), notify the sponsor in writing, and 
review it as filed. The sponsor need not resubmit a copy of a safety 
and effectiveness data submission that is filed over protest.
    In proposed Sec.  330.14(j)(4), FDA describes the conditions under 
which FDA may refuse to file a safety and effectiveness data 
submission. These include a submission that:
    [cir] Is incomplete because it does not contain information 
required under Sec.  330.14(f) (if such information is not provided 
because it is not relevant, the submission must clearly identify and 
explain the omission);
    [cir] Is not organized or formatted in a manner to enable the 
Agency to readily determine if it is sufficiently complete to permit a 
substantive review;

[[Page 19079]]

    [cir] Does not contain a signed statement that the submission 
represents a complete safety and effectiveness data submission and that 
the submission includes all the safety and effectiveness data and 
information available to the sponsor at the time of the submission, 
whether positive or negative;
    [cir] Does not contain an analysis and summary of the data and 
other supporting information, organized by clinical or nonclinical 
area;
    [cir] Does not contain a supporting document summarizing the 
strategy used for literature searches, including search terms, sources, 
dates accessed and years reviewed;
    [cir] Does not contain a reference list and copy of supporting 
information; or
    [cir] Includes data or information relevant to the GRASE 
determination that is marked as confidential without a statement that 
the information may be released to the public (if the relevant data was 
produced and marked confidential by a third party, the sponsor would 
need to 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).
    In addition, the following four filing determination factors relate 
to requirements under other sections of the regulations. FDA may refuse 
to file a safety and effectiveness data submission if the submission:
    [cir] Does not contain either a complete environmental assessment 
or information supporting a categorical exclusion under part 25 (see 21 
CFR part 25, ``Environmental impact considerations'');
    [cir] Does not contain a statement for each nonclinical laboratory 
study that it was conducted in compliance with part 58 requirements 
(see 21 CFR part 58, ``Good laboratory practice for nonclinical 
laboratory studies'') (or a statement of reasons for the 
noncompliance);
    [cir] Does not contain a statement for each clinical investigation 
involving human subjects that it was conducted in compliance with part 
56 institutional review board regulations (see 21 CFR part 56, 
``Institutional Review Boards'') or was not subject to those 
regulations, and that it was conducted in compliance with part 50 
informed consent regulations (see 21 CFR part 50, ``Protection of human 
subjects''); or
    [cir] Does not include required part 54 financial certification and 
disclosure statements (see 21 CFR part 54, ``Financial disclosure by 
clinical investigators'').
3. Withdrawal of Consideration of a TEA or Safety and Effectiveness 
Data Submission (Proposed New Sec.  330.14(k))
    The Agency is also proposing to add withdrawal provisions to new 
Sec.  330.14(k). These proposed provisions acknowledge that a sponsor 
may request withdrawal of consideration of a TEA or safety and 
effectiveness data submission. In addition, inaction by a sponsor in 
certain circumstances may be deemed by FDA as a request for withdrawal 
of consideration (e.g., prolonged failure of a sponsor to submit any 
safety and effectiveness data after receipt of an NOE, failure of a 
sponsor to respond to FDA communications). These proposed requirements 
are expected to help provide clarity on the status of TEAs and safety 
and effectiveness data submissions, and the effect of a withdrawal of 
consideration on the docket. They would also permit FDA to suspend work 
on those TEAs or safety and effectiveness data submissions that are no 
longer being pursued by the sponsor and for which FDA does not believe 
that the GRASE determination should go forward.
    The Agency believes that the proposed provisions on withdrawal of 
consideration would allow the Agency to better allocate resources for 
the review of TEA conditions than the current process. Based on past 
experience with the OTC monograph process, FDA has found that following 
an Agency action, a sponsor may not respond to a request for data from 
FDA. For example, the Agency issued an NOE and request for safety and 
effectiveness data in 2005 for a TEA active ingredient (70 FR 72447, 
December 5, 2005) and to date, FDA has not received data or a response 
from the sponsor. Without an established deadline for submitting data 
or otherwise responding to an Agency request, a sponsor may never 
submit the requested data and a TEA condition may remain unresolved. To 
better utilize FDA resources as well as to address the withdrawal of 
consideration of a TEA or a safety and effectiveness data submission, 
the Agency is proposing to amend Sec.  330.14 to add paragraph (k) to 
address such withdrawal of consideration.
    In Sec.  330.14(k)(1), we propose that FDA may withdraw 
consideration of a TEA or safety and effectiveness data submission if: 
(1) The sponsor requests that its submission be withdrawn from 
consideration, or (2) FDA deems the submission to be withdrawn from 
consideration due to the sponsor's failure to act on the submission or 
failure to respond to communications from FDA. For purposes of this 
provision, withdrawal of consideration of a TEA would include the 
withdrawal of consideration of a TEA condition that had been found to 
be eligible, but for which a safety and effectiveness data submission 
is not received by the Agency. If a sponsor requests withdrawal of 
consideration for its TEA or safety and effectiveness data submission, 
FDA generally intends to stop its review. However, we note that while 
FDA may withdraw consideration of a TEA or safety and effectiveness 
determination, we may determine not to do so in some cases. For 
example, if FDA has already issued a proposed rule that tentatively 
determines that the active ingredient or other condition is GRASE for 
OTC use, or is not GRASE for OTC use, FDA may continue to rely on the 
information submitted to the docket and proceed to issue a final rule.
    In Sec.  330.14(k)(2), we propose that FDA will notify the sponsor 
of a submission that FDA intends to deem withdrawn under paragraph 
(k)(1)(ii), and that the sponsor will then have 30 days from the date 
of the notice to request that FDA not withdraw consideration of the TEA 
or safety and effectiveness data submission and request additional time 
needed to submit relevant data and information. For example, a sponsor 
may request that FDA not withdraw consideration of a safety and 
effectiveness data submission to allow the submission of new safety or 
effectiveness data to the record if the sponsor needs additional time 
to conduct a study and submit the data. If, within 30 days of FDA's 
notice, the sponsor requests that FDA not withdraw consideration under 
proposed Sec.  330.14(k)(1)(ii), we will continue to consider the 
submission. If we continue to consider the submission, that does not 
preclude the possibility of withdrawing consideration under Sec.  
330.14(k)(1) at a later time. FDA recommends that sponsors keep FDA 
apprised of the anticipated timing for submission of requested data to 
facilitate the review process and better utilize FDA resources.
    In Sec.  330.14(k)(3), FDA proposes to clarify that if 
consideration of a TEA or safety and effectiveness data submission is 
withdrawn, information that has been posted to the public docket for 
the TEA at the time of the withdrawal (such as an NOE or a safety and 
effectiveness data submission that has been accepted for filing and 
posted to the docket) will remain on the public docket. The TEA process 
is primarily a public process and withdrawal of consideration of a TEA 
or safety and effectiveness data submission will not cause previously 
public information to be removed from

[[Page 19080]]

the docket. We also note that the original sponsor or other interested 
parties may wish to pursue review of the active ingredient or other 
condition at some point in the future. In that case, a new safety and 
effectiveness data submission may be submitted for the same active 
ingredient or other condition after consideration of the original 
submission has been withdrawn. If the Agency has already issued an NOE 
that determined that the active ingredient or other condition is 
eligible for review under the TEA process, another interested party may 
submit safety and effectiveness data for the eligible condition for the 
Agency's review.
    In Sec.  330.14(k)(4), FDA proposes that if a TEA or safety and 
effectiveness data submission being reviewed in accordance with Sec.  
330.15 is withdrawn, the timelines under Sec.  330.15(c) and the 
metrics under Sec.  330.15(b) no longer apply.
4. Minor Changes to Sec.  330.14 for Clarity and Consistency
    FDA is proposing to reorganize paragraph (a) of Sec.  330.14 to 
create an introductory paragraph that includes the current text under 
Sec.  330.14(a), except for the definitions of ``condition'' and 
``botanical drug substance,'' which would be moved to the proposed 
definitions section in Sec.  330.14(a). FDA is proposing to eliminate 
the paragraph heading ``introduction,'' and in its place, propose the 
paragraph heading ``definitions'' and a statement that the definitions 
that follow apply to this section and Sec.  330.15. Under this new 
heading, FDA is proposing to include the definitions and current text 
for the terms ``condition'' and ``botanical drug substance.'' FDA is 
also proposing to add to the end of the introductory paragraph of Sec.  
330.14 a sentence stating that Sec.  330.15 sets forth timelines for 
FDA review and action.
    FDA is proposing several minor amendments to Sec.  330.14(f) for 
clarity and for consistency with the OTC monograph regulations under 
Sec.  330.10.
     FDA is proposing to revise paragraph (f) to use 
terminology consistent with the new definition in Sec.  330.14(a)(5) 
for ``safety and effectiveness data submission'' when referring to the 
data package submitted by the sponsor.
     FDA is proposing to revise the first sentence and add the 
second sentence to differentiate between, in the NOE, requesting the 
safety and effectiveness data submission from the sponsor, and 
requesting data and views from other interested parties.
     FDA is proposing to add a sentence that references the new 
filing determination requirements at proposed new Sec.  330.14(j) and 
makes clear that the safety and effectiveness data submission must be 
sufficiently complete to be filed by the Agency under proposed 
paragraph (j)(2).
     FDA is proposing to add a sentence that references the 
requirements for compliance with good laboratory practices, 
institutional review board, informed consent, and financial 
certification or disclosure statement requirements, under Sec.  
330.10(c), (e), and (f), and makes clear that those requirements also 
apply to the safety and effectiveness data and information submitted 
under this paragraph. This proposed sentence does not impose new 
requirements. The sentence was added for clarity and consistency with 
Sec.  330.10.
    FDA is proposing to add the word ``feedback'' prior to the word 
``letter'' in the first sentence of Sec.  330.14(g)(4) to use 
terminology consistent with the proposed new definition for ``feedback 
letter'' in Sec.  330.14(a)(7).

VI. Proposed Effective Date

    The SIA directs the Agency to issue a final rule regarding the 
timelines and metrics described in section 586F(b) of the FD&C Act 
within 27 months after the enactment of the SIA (by February 26, 2017). 
The SIA also requires that the final rule be published not less than 30 
calendar days before the effective date of the regulation. 
Consequently, the final rule implementing the timeline and metrics 
provisions of section 586F(b) will become effective 30 calendar days 
after the date of the final rule's publication in the Federal Register.
    Beginning on that date, the timelines and metrics set forth in the 
regulation will apply to the review of TEAs and safety and 
effectiveness data submissions to which that regulation is applicable, 
and any amended provisions of Sec.  330.14 will apply to the TEA 
process under that regulation.

VII. Economic Analysis of Impacts

A. Introduction

    We have examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct us to assess all costs 
and benefits of available regulatory alternatives and, when regulation 
is necessary, to select regulatory approaches that maximize net 
benefits (including potential economic, environmental, public health 
and safety, and other advantages; distributive impacts; and equity). We 
have developed a comprehensive Economic Analysis of Impacts that 
assesses the impacts of the proposed rule. We believe that this 
proposed rule is not a significant regulatory action as defined by 
Executive Order 12866.
    The Regulatory Flexibility Act requires us to analyze regulatory 
options that would minimize any significant impact of a rule on small 
entities. Because this proposed rule does not impose significant new 
economic burdens on any entity, we propose to certify that the proposed 
rule will not have a significant economic impact on a substantial 
number of small entities.
    The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires 
us to prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $144 million, using the most current (2014) Implicit 
Price Deflator for the Gross Domestic Product. This proposed rule would 
not result in an expenditure in any year that meets or exceeds this 
amount.
    In table 1, we provide the Regulatory Information Service Center/
Office of Information and Regulatory Affairs Consolidated Information 
System accounting information.

[[Page 19081]]

                                                  Table 1--Economic Data: Costs and Benefits Statement
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                        Units year      Discount rate    Period covered
           Category            Primary estimate    Low estimate      High estimate        dollars            (%)             (yrs.)           Notes
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits:
    Annualized...............  ................  ................  ................  ................  7..............  ...............  ...............
    Monetized................  ................  ................  ................  ................  3..............  ...............  ...............
    $millions/year...........  ................  ................  ................  ................  ...............  ...............  ...............
    Annualized...............  ................  ................  ................  ................  7..............  ...............  ...............
    Quantified...............  ................  ................  ................  ................  3..............  ...............  ...............
                              --------------------------------------------------------------------------------------------------------------------------
    Qualitative..............  The proposed rule would improve the TEA review process by establishing timelines and clarifying requirements and increase
                                                                           the predictability of the process.
                              --------------------------------------------------------------------------------------------------------------------------
Costs:
    Annualized...............  $0.00...........  $0.00...........  $0.00...........  2015............  7..............  10.............  ...............
    Monetized................  0.00............  0.00............  0.00............  2015............  3..............  10.............  ...............
    $millions/year...........  ................  ................  ................  ................  ...............  ...............  ...............
    Annualized...............  ................  ................  ................  ................  7..............  ...............  ...............
    Quantified...............  ................  ................  ................  ................  3..............  ...............  ...............
    Qualitative..............  ................  ................  ................  ................  ...............  ...............  ...............
    Transfers................  ................  ................  ................  ................  ...............  ...............  ...............
    Federal..................  ................  ................  ................  ................  7..............  ...............  ...............
    Annualized Monetized.....  ................  ................  ................  ................  3..............  ...............  ...............
    $millions/year...........  ................  ................  ................  ................  ...............  ...............  ...............
    From/To..................  From:...........  ................  ................  To:.............  ...............  ...............  ...............
    Other....................  ................  ................  ................  ................  7..............  ...............  ...............
    Annualized Monetized.....  ................  ................  ................  ................  3..............  ...............  ...............
    $millions/year...........  ................  ................  ................  ................  ...............  ...............  ...............
    From/To..................  From:...........  ................  ................  To:.............  ...............  ...............  ...............
    Effects..................  ................  ................  ................  ................  ...............  ...............  ...............
--------------------------------------------------------------------------------------------------------------------------------------------------------
State, Local, and/or Tribal Government: No effects
Small Business: No effects
Wages: No effect
Growth: No effect
--------------------------------------------------------------------------------------------------------------------------------------------------------

B. Summary

1. Baseline Conditions
    We regulate nonprescription drug products under two primary 
pathways: (1) The new drug application (NDA) process, described in 21 
CFR part 314; or (2) the nonprescription (over-the-counter or OTC) drug 
monograph process, described in part 330. There are important 
differences between these two pathways. Under the NDA process, the 
sponsor of an application must submit to us nonclinical and clinical 
data that supports the safety and effectiveness of its drug product, 
and we must review and approve the application before the sponsor can 
market such product. By contrast, OTC drug monographs are regulations 
describing conditions (Sec.  330.14 defines condition as an active 
ingredient or botanical drug substance (or combination of both), dosage 
form, dosage strength, or route of administration marketed for a 
particular specific OTC use) that certain OTC drugs (such as antacids) 
must meet to be considered as GRASE and not misbranded. In contrast 
with the application pathway, once a sponsor submits safety and 
effectiveness data to amend a monograph (which is posted to a public 
docket), the data are public. Drug products that comply with an 
applicable OTC drug monograph and other applicable regulations may be 
marketed without an NDA.
    Initially, active ingredients and other conditions that were not 
marketed in the United States before the inception of the OTC Drug 
Review in 1972 were not eligible for review under the OTC drug 
monograph process. However, the TEA process, established by regulations 
finalized in 2002 (21 CFR 330.14), expanded the scope of this OTC drug 
review. The TEA process offers a pathway for OTC conditions to be 
marketed under an OTC drug monograph. OTC conditions can include newer 
active ingredients that previously had no U.S. marketing history, or 
that were marketed in the United States after the OTC drug review 
began. Active ingredients and other conditions that satisfy the TEA 
eligibility requirements are subject to the same safety, effectiveness, 
and labeling standards that apply to other conditions under the OTC 
monograph process.
    The TEA process requires multi-step, notice-and-comment rulemaking 
procedures before a new active ingredient or other condition is added 
to an OTC drug monograph. After determining that an active ingredient 
or other condition is eligible for consideration under the OTC 
monograph process, we issue a notice in the Federal Register announcing 
the TEA determination and requesting safety and effectiveness data for 
the proposed OTC use. Next, after reviewing data submitted to the 
docket, we issue a proposed rule to either include the condition in the 
appropriate OTC drug monograph or, if the condition is initially 
determined not to be GRASE for OTC use, include it in Sec.  310.502, 
which would require the sponsor to seek approval under the NDA pathway 
to market the condition. The proposed rule allows for public comments 
and for sponsors and other interested parties to submit additional data 
for safety and effectiveness. If a monograph is amended, by publishing 
a final rule, an OTC condition that complies with the OTC monograph and 
the general requirements for OTC drugs may be marketed in the United 
States without an NDA (examples of other general requirements include 
requirements to comply with Current Good Manufacturing Practice, to 
register and

[[Page 19082]]

list products, to use drug facts labeling, etc.).
    Although our multi-step TEA process allows sponsors to learn about 
the progress of our review of an application (for example when an NOE 
is issued, and if a feedback letter is issued), there are no 
established timelines to review applications or for sponsors to submit 
data. The lack of timelines can create unpredictability for interested 
parties because they may lack key information. For example, they may 
not know: (1) Whether the safety and effectiveness data submitted is 
sufficient or in the right format for us to conduct a substantive 
review; (2) when they need to submit new information; or (3) when to 
expect our determinations regarding eligibility or other feedback. The 
unpredictability in the process could result in sponsors not performing 
a required action within reasonable time for our review, performing 
unnecessary actions (examples of unnecessary actions may include 
collecting unnecessary or inadequate data, performing tests or studies 
that do not contribute to data needed by us to make a GRASE 
determination), or creating unnecessary effort for us and for them. For 
example, if a TEA remains inactive for a significant amount of time, 
scientific knowledge may evolve thus creating the need to amend the 
original TEA. Without specific timelines sponsors may not know whether 
their initial data submission was insufficient to review, was 
sufficient but is under review, or whether we require additional 
information. In addition, without specific timelines, we don't know if 
sponsors intend to submit additional data or whether they do not intend 
to pursue their application any further.
2. Purpose of This Proposed Rule
    This proposed rule complies with certain mandates of the Sunscreen 
Innovation Act (Pub. L. 113-195), enacted in November 2014. In 
particular, the proposed rule would establish timelines and metrics for 
review of TEAs for non-sunscreen OTC drug products. Specific timelines 
applicable to non-sunscreen TEA conditions would be added in a new 
section to Title 21 of the CFR, Sec.  330.15. The first proposed 
timeline is to issue a Notice of Eligibility or a post a letter of 
ineligibility to the TEA docket within 180 days of submission of a TEA. 
The second proposed timeline is to issue a filing determination within 
90 days of receipt of a complete safety and effectiveness data 
submission from the sponsor once such sponsor has confirmed that it 
considers the submission to be complete. If we initially determine the 
active ingredient or other condition not to be GRASE, we will inform 
sponsors and interested parties within 730 days from the date of filing 
as defined in proposed Sec.  330.14(a). The next proposed timeline is 
to issue a notice of proposed rulemaking (NPRM) within 1,095 days from 
the date of filing. Lastly, we propose to issue a final rule within 912 
days of the closing of the docket of the proposed rulemaking.
    The proposed rule would also amend the existing Sec.  330.14 by: 
(1) Setting forth clear filing determination requirements with regard 
to the content and format of safety and effectiveness data submissions 
for TEAs, and by (2) addressing withdrawal of consideration of a TEA or 
safety and effectiveness data submission. These amendments would apply 
to all TEAs, and their goal is to provide early notification to 
sponsors whether their applications meet the filing requirements and to 
provide more clarity regarding withdrawal of a TEA-related submissions. 
The proposed amendments are intended to provide us with feedback from 
sponsors whether they intend to actively pursue their applications, and 
specify that we may withdraw consideration of a TEA or safety and 
effectiveness data submission in certain circumstances (such as at a 
sponsor's request or after prolonged inaction and lack of response to 
FDA communications). Finally, the proposed rule would also add 
definitions and make clarifying changes to the TEA regulation in Sec.  
330.14.
    The proposed clarifications and establishment of timelines for the 
TEA process seek to dissipate uncertainties that may be preventing 
interested parties from submitting all the necessary data for us to 
grant final GRASE determination to existing TEA conditions that have 
been found to be eligible to be considered for inclusion in the OTC 
drug monograph system. Since the TEA review process became effective in 
2002 (67 FR 3060 at 3074, January 23, 2002), we have received six TEAs 
for non-sunscreen active ingredients, including applications for 
dandruff, laxative, anti-gingivitis, and anti-acne products. However, 
we have not yet issued a proposed rule regarding whether any of these 
ingredients are GRASE under specified conditions of use. In fact, as of 
December 2015, the sponsor of one of these TEAs has not yet submitted 
safety and effectiveness data for our review.
3. Benefits
    We lack data to quantify the potential benefits of the proposed 
rule. With the proposed rule, we expect the proposed timelines and data 
submission clarifications would make the TEA process, including 
establishing a new OTC drug monograph, more efficient and predictable, 
and improve communication between us and sponsors. Sponsors may benefit 
from knowing if additional data is needed and what optimal steps to 
take to receive a GRASE determination, and we would be able to bring 
resolution to TEA conditions. However, we do not know the monetary 
value of added predictability to sponsors. Also, because we have not 
yet issued tentative GRASE determinations for any of the non-sunscreen 
TEA conditions under review, as of December 2015, and because we do not 
know the increase in the probability of granting tentative GRASE 
determinations resulting from the proposed rule, we request comment on 
the potential benefits of the proposed rule.
4. Costs
    This proposed rule supplements the TEA process. We expect the rule 
would create a minimal burden on sponsors from the possible cost 
associated with sending a meeting request letter to us in the event 
that we refuse to file a safety and effectiveness data submission and 
the sponsor would like to meet with us to discuss the decision, or the 
possible cost of calling or writing FDA to request that we not withdraw 
consideration of a submission in the event that we deem a submission 
withdrawn under proposed 330.14(k)(ii). Therefore, we anticipate no 
increase in annual recurring costs for either small or large sponsors.
    We expect the six current sponsors would spend time reading and 
understanding the proposed rule, and this would take from about 6.5 
hours to 13 hours. With an hourly wage rate of $133 including 100 
percent overhead, each sponsor would incur one-time costs ranging from 
about $865 to $1,730. We also estimate that we would receive two 
additional TEAs annually, and thus during a 10-year horizon we estimate 
potentially twenty additional applicants would spend the time to read 
and understand the proposed rule. The present value of the total costs 
over 10 years ranges from about $17,000 to $35,000 with a 7 percent 
discount rate and from about $19,000 to $38,000 with a 3 percent 
discount rate. With a discount rate of 7 percent and 3 percent, we 
estimate that on average sponsors would incur less than $150 of 
annualized costs per year.

[[Page 19083]]

5. Impact on Small Entities
    The Regulatory Flexibility Act requires a Regulatory Flexibility 
Analysis (RFA) unless the Agency can certify that the proposed rule 
would have no significant impact on a substantial number of small 
entities. The proposed rule would affect few entities. Moreover, we 
estimate one-time costs under $2,000 per entity, costs well below 0.01 
percent of annual revenues for the smallest entities, and we propose to 
certify that the rule would not have a significant economic impact on a 
substantial number of small entities.
    We invite comments on this analysis.

VIII. Analysis of Environmental Impact

    We have determined under 21 CFR 25.31(a) that this action is of a 
type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

IX. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by OMB under the Paperwork Reduction Act of 1995 
(44 U.S.C. 3501-3520). The title, description, and respondent 
description of the information collection are given under this section 
with an estimate of the annual reporting burden. Included in the 
estimate is the time for reviewing instructions, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing the collection of information.
    We invite comments on these topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: Food and Drug Administration Review and Action on Over-the-
Counter Time and Extent Applications
    Description: The proposed rule would amend FDA's TEA regulations to 
establish timelines and performance metrics for FDA's review of non-
sunscreen TEAs and safety and effectiveness data submissions, as 
required by the SIA. FDA also proposes other changes to make the TEA 
process more efficient.
    FDA has OMB approval (Control Number 0910-0688) for the information 
collection in 21 CFR 330.14, which specifies additional criteria and 
procedures by which OTC drugs that were initially marketed in the 
United States after the OTC Drug Review began and OTC drugs without any 
U.S. marketing experience may become eligible for consideration in the 
OTC drug monograph system.
    The proposed rule would amend the TEA regulations in Sec.  330.14 
to make the process more efficient and to make conforming and 
clarifying changes. Proposed Sec.  330.14(j) would clarify the 
requirements on content and format criteria for a safety and 
effectiveness data submission, and would provide procedures for FDA's 
review of the submissions and determination of whether a submission is 
sufficiently complete to permit a substantive review. Proposed Sec.  
330.14(j)(3) would describe the process for cases in which FDA refuses 
to file the safety and effectiveness data submission. Under proposed 
Sec.  330.14(j)(3), if FDA refuses to file the submission, the Agency 
will notify the sponsor in writing, state the reason(s) for the 
refusal, and provide the sponsor with 30 days in which to submit a 
written request for an informal conference with the Agency about 
whether the Agency should file the submission. A sponsor's submission 
of a written request for an informal conference is not already approved 
under OMB Control Number 0910-0688. We estimate that approximately one 
sponsor (``number of respondents'' in table 2, row 1) will annually 
submit to FDA approximately one request for an informal conference 
(``total annual responses'' in table 2, row 1), and that preparing and 
submitting each request will take approximately one hour for each 
sponsor (``average burden per response'' in table 2, row 1).
    Under proposed Sec.  330.14(j)(4)(iii), the safety and 
effectiveness data submission must contain a signed statement that the 
submission represents a complete safety and effectiveness data 
submission and that the submission includes all the safety and 
effectiveness data and information available to the sponsor at the time 
of the submission, whether positive or negative. A sponsor's signed 
statement is not already approved under OMB Control Number 0910-0688. 
We estimate that approximately two sponsors (``number of respondents'' 
in table 2, row 2) will annually submit to FDA approximately two signed 
statements as described previously (``total annual responses'' in table 
2, row 2), and that preparing and submitting each signed statement will 
take approximately one hour for each sponsor (``average burden per 
response'' in table 2, row 2).
    Under proposed Sec.  330.14(k)(1), FDA, in response to a written 
request from a sponsor, may withdraw consideration of a TEA submitted 
under Sec.  330.14(c) or a safety and effectiveness data submission 
submitted under Sec.  330.14(f). A sponsor's request that FDA withdraw 
consideration of a TEA or safety and effectiveness data submission is 
not already approved under OMB Control Number 0910-0688. We estimate 
that approximately one sponsor (``number of respondents'' in table 2, 
row 3) will annually submit to FDA approximately one request (``total 
annual responses'' in table 2, row 3), and that preparing and 
submitting each request will take approximately one hour for each 
sponsor (``average burden per response'' in table 2, row 3).
    Under proposed Sec.  330.14(k)(2), a sponsor may request that FDA 
not withdraw consideration of a TEA or safety and effectiveness data 
submission. A sponsor's request for FDA to not deem its submission 
withdrawn from consideration is not already approved under OMB Control 
Number 0910-0688. We estimate that approximately one sponsor (``number 
of respondents'' in table 2, row 4) will annually submit to FDA 
approximately one request (``total annual responses'' in table 2, row 
4), and that preparing and submitting each request will take 
approximately two hours for each sponsor (``average burden per 
response'' in table 2, row 4).

[[Page 19084]]

    FDA estimates the burden of this information collection as follows:

                                 Table 2--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
         21 CFR Section              Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
330.14(j)(3)--Sponsor request                  1               1               1               1               1
 for informal conference on
 FDA's refusal to file..........
330.14(j)(4)(iii)--Sponsor's                   2               1               2               1               2
 signed statement that the
 submission is complete.........
330.14(k)(1)--Sponsor request                  1               1               1               1               1
 for FDA to withdraw
 consideration of a TEA or
 safety and effectiveness data
 submission.....................
330.14(k)(2)--Sponsor request                  1               1               1               2               2
 for FDA to not deem its
 submission withdrawn from
 consideration..................
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    In compliance with the PRA (44 U.S.C. 3507(d)), we have submitted 
the information collection requirements of this proposed rule to OMB 
for review. Interested persons are requested to send comments on this 
information collection to the Office of Information and Regulatory 
Affairs, OMB (see ADDRESSES).

X. Federalism

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

XI. References

    The following references are on display in the Division of Dockets 
Management (see ADDRESSES) and are available for viewing by interested 
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also 
available electronically at http://www.regulations.gov. FDA has 
verified the Web site addresses, as of the date this document publishes 
in the Federal Register, but Web sites are subject to change over time.

    1. FDA, Guidance for Industry, ``Time and Extent Applications 
for Nonprescription Drug Products,'' September 2011, available at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078902.pdf.
    2. Office of the Federal Register, ``A Guide to the Rulemaking 
Process,'' 2011, available at https://www.federalregister.gov/uploads/2011/01/the_rulemaking_process.pdf.
    3. GAO, ``Federal Rulemaking, Improvements Needed to Monitoring 
and Evaluation of Rules Development as Well as to the Transparency 
of OMB Regulatory Reviews,'' April 2009 (GAO-09-205), available at 
http://www.gao.gov/assets/290/288538.pdf.
    4. FDA, Draft Guidance for Industry, ``Nonprescription Sunscreen 
Drug Products: Content and Format of Data Submissions To Support a 
GRASE Determination Under the Sunscreen Innovation Act,'' November 
2015, available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM473772.pdf.
    5. Examples of FDA internet pages that include progress reports 
or other metrics include: FDA's FDA-TRACK Web page, http://www.fda.gov/AboutFDA/Transparency/track/ucm195010.htm; FDA's 
``Sunscreen Innovation Act (SIA)'' Web page, http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ucm434782.htm, and 
FDA's ``Rulemaking History for OTC Time and Extent Applications'' 
Web page, http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm072455.htm.

List of Subjects in 21 CFR Part 330

    Over-the-counter drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, we propose 
that 21 CFR part 330 be amended as follows:

PART 330--OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY 
RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED

0
1. The authority citation for part 330 is revised to read as follows:

    Authority:  21 U.S.C. 321, 351, 352, 353, 355, 360, 360fff-6, 
371.

0
2. Section 330.14 is amended as follows:
0
a. Redesignate paragraph (a) as introductory text, revise the newly 
redesignated introductory text, and add new paragraph (a);
0
b. Revise paragraphs (f) introductory text and (g)(4);
0
c. Add paragraphs (j) and (k).
    The revisions and additions read as follows:

Sec.  330.14  Additional criteria and procedures for classifying OTC 
drugs as generally recognized as safe and effective and not misbranded.

    This section sets forth additional criteria and procedures by which 
over-the-counter (OTC) drugs initially marketed in the United States 
after the OTC drug review began in 1972 and OTC drugs without any U.S. 
marketing experience can be considered in the OTC drug monograph 
system. This section also addresses conditions regulated as a cosmetic 
or dietary supplement in a foreign country that would be regulated as 
OTC drugs in the United States. Section 330.15 sets forth timelines for 
FDA review and action.
    (a) Definitions. The definitions and interpretations contained in 
section 201 of the Federal Food, Drug, and Cosmetic Act and the 
following definitions of terms apply to this section and to Sec.  
330.15.
    (1) Condition means an active ingredient or botanical drug 
substance (or a combination of active ingredients

[[Page 19085]]

or botanical drug substances), dosage form, dosage strength, or route 
of administration, marketed for a specific OTC use, except as excluded 
in paragraph (b)(2) of this section.
    (2) Botanical drug substance means a drug substance derived from 
one or more plants, algae, or macroscopic fungi, but does not include a 
highly purified or chemically modified substance derived from such a 
source.
    (3) Sponsor means the person that submitted a time and extent 
application (TEA) under paragraph (c) of this section.
    (4) Time and extent application (TEA) means a submission by a 
sponsor under paragraph (c) of this section, which will be evaluated by 
the agency to determine eligibility of a condition for consideration in 
the OTC drug monograph system.
    (5) Safety and effectiveness data submission means a data package 
submitted by a sponsor that includes safety and effectiveness data and 
information under paragraph (f) of this section and that is represented 
by the sponsor as being a complete submission.
    (6) Date of filing means the date of the notice from FDA informing 
the sponsor that FDA has made a threshold determination that the safety 
and effectiveness data submission is sufficiently complete to permit a 
substantive review; or, if the submission is filed over protest in 
accordance with paragraph (j)(3) of this section, the date of filing is 
the date of the notice from FDA informing the sponsor that FDA has 
filed the submission over protest (this date will be no later than 30 
days after the sponsor's request that FDA file the submission over 
protest).
    (7) Feedback letter means a letter issued by the agency in 
accordance with paragraph (g)(4) of this section that informs the 
sponsor and other interested parties who have submitted data under 
paragraph (f) of this section that a condition is initially determined 
not to be generally recognized as safe and effective (GRASE).
* * * * *
    (f) Safety and effectiveness data submission. The notice of 
eligibility shall request that the sponsor submit a safety and 
effectiveness data submission that includes published and unpublished 
data to demonstrate the safety and effectiveness of the condition for 
its intended OTC use(s). The notice of eligibility will also request 
data and views from other interested parties. These data shall be 
submitted to a docket established in the Division of Dockets Management 
and shall be publicly available for viewing at that office, except data 
deemed confidential under 18 U.S.C. 1905, 5 U.S.C. 552(b), or 21 U.S.C. 
331(j). Data considered confidential under these provisions must be 
clearly identified. Any proposed compendial standards for the condition 
shall not be considered confidential. The safety and effectiveness data 
submission must be sufficiently complete to be filed by the agency 
under paragraph (j)(2) of this section. Safety and effectiveness data 
and other information submitted under this paragraph are subject to the 
requirements in Sec.  330.10(c), (e), and (f). The safety and 
effectiveness data submission must include the following:
* * * * *
    (g) * * *
    (4) If the condition is initially determined not to be GRASE for 
OTC use in the United States, the agency will inform the sponsor and 
other interested parties who have submitted data of its determination 
by feedback letter, a copy of which will be placed on public display in 
the docket established in the Division of Dockets Management. The 
agency will publish a notice of proposed rulemaking to include the 
condition in Sec.  310.502 of this chapter.
* * * * *
    (j) Filing determination. (1) After FDA receives a safety and 
effectiveness data submission, the agency will determine whether the 
submission may be filed. The filing of a submission means that FDA has 
made a threshold determination that the submission is sufficiently 
complete to permit a substantive review.
    (2) If FDA finds that none of the reasons in paragraph (j)(4) of 
this section for refusing to file the safety and effectiveness data 
submission apply, the agency will file the submission and notify the 
sponsor in writing. The date of filing begins the FDA timelines 
described in Sec.  330.15(c)(3) and (4).
    (3) If FDA refuses to file the safety and effectiveness data 
submission, the agency will notify the sponsor in writing and state the 
reason(s) under paragraph (j)(4) of this section for the refusal. The 
sponsor may request in writing, within 30 days of the date of the 
agency's notification, an informal conference with the agency about 
whether the agency should file the submission, and FDA will convene the 
meeting within 30 days of the request. If, within 120 days after the 
informal conference, the sponsor requests that FDA file the submission 
(with or without correcting the deficiencies), the agency will file the 
safety and effectiveness data submission over protest under paragraph 
(j)(2) of this section, notify the sponsor in writing, and review it as 
filed. The sponsor need not resubmit a copy of a safety and 
effectiveness data submission that is filed over protest.
    (4) FDA may refuse to file a safety and effectiveness data 
submission if any of the following applies:
    (i) The submission is incomplete because it does not contain 
information required under paragraph (f) of this section. If the 
submission does not contain required information because such 
information or data are not relevant to the condition, the submission 
must clearly identify and provide an explanation for the omission.
    (ii) The submission is not organized or formatted in a manner to 
enable the agency to readily determine if it is sufficiently complete 
to permit a substantive review.
    (iii) The submission does not contain a signed statement that the 
submission represents a complete safety and effectiveness data 
submission and that the submission includes all the safety and 
effectiveness data and information available to the sponsor at the time 
of the submission, whether positive or negative.
    (iv) The submission does not contain an analysis and summary of the 
data and other supporting information, organized by clinical or 
nonclinical area, such as clinical efficacy data, clinical safety data, 
clinical pharmacology, adverse event reports, animal toxicology, 
chemistry data, and compendial status.
    (v) The submission does not contain a supporting document 
summarizing the strategy used for literature searches, including search 
terms, sources, dates accessed and years reviewed.
    (vi) The submission does not contain a reference list of supporting 
information, such as published literature, unpublished information, 
abstracts and case reports, and a copy of the supporting information.
    (vii) The submission includes data or information relevant for 
making a GRASE determination marked as confidential without a statement 
that the information may be released to the public.
    (viii) The submission does not contain a complete environmental 
assessment under Sec.  25.40 of this chapter or fails to provide 
sufficient information to establish that the requested action is 
subject to categorical exclusion under Sec.  25.30 or Sec.  25.31 of 
this chapter.
    (ix) The submission does not contain a statement for each 
nonclinical laboratory study that it was conducted in compliance with 
the requirements set forth in part 58 of this chapter, or, if it

[[Page 19086]]

was not conducted in compliance with part 58 of this chapter, a brief 
statement of the reason for the noncompliance.
    (x) The submission does not contain a statement for each clinical 
investigation involving human subjects that it was conducted in 
compliance with the institutional review board regulations in part 56 
of this chapter, or was not subject to those regulations, and that it 
was conducted in compliance with the informed consent regulations in 
part 50 of this chapter.
    (xi) The submission does not include financial certification or 
disclosure statements, or both, as required by part 54 of this chapter, 
accompanying any clinical data submitted.
    (k) Withdrawal of consideration. (1) FDA may withdraw consideration 
of a TEA submission or a safety and effectiveness data submission if:
    (i) The sponsor requests that its submission be withdrawn from 
consideration, or
    (ii) FDA deems the submission to be withdrawn from consideration 
due to the sponsor's failure to act on the submission or failure to 
respond to communications from FDA.
    (2) Before FDA deems a submission withdrawn under paragraph 
(k)(1)(ii) of this section, FDA will notify the sponsor of the 
submission. If, within 30 days from the date of the notice from FDA, 
the sponsor requests that FDA not withdraw consideration of the 
submission, FDA will not deem the submission to be withdrawn.
    (3) If FDA withdraws consideration of a submission under paragraph 
(k)(1) of this section, FDA will post a notice of withdrawal to the 
docket. Information that has been posted to the public docket for the 
TEA at the time of the withdrawal (such as a notice of eligibility or a 
safety and effectiveness data submission that has been accepted for 
filing and posted to the docket) will remain on the public docket.
    (4) If FDA withdraws consideration of a submission under paragraph 
(k)(1) of this section, the timelines under Sec.  330.15(c) will no 
longer apply as of the date of withdrawal, and the submission will not 
be included in the metrics under Sec.  330.15(b).
0
3. Add Sec.  330.15 to subpart B to read as follows:

Sec.  330.15  Timelines for FDA review and action on time and extent 
applications and safety and effectiveness data submissions.

    (a) Applicability. This section applies to the review of a 
condition in a time and extent application (TEA) submitted under Sec.  
330.14 for consideration in the over-the-counter (OTC) drug monograph 
system. This section does not apply to:
    (1) A sunscreen active ingredient or combination of sunscreen 
active ingredients, and other conditions for such ingredients, or
    (2) A non-sunscreen active ingredient or combination of non-
sunscreen active ingredients and other conditions for such ingredients 
submitted in a TEA under Sec.  330.14 prior to November 27, 2014, 
subject to section 586F(a)(1)(C) of the Federal Food, Drug, and 
Cosmetic Act.
    (b) Metrics. FDA will maintain and update annually, a publicly 
available posting of metrics for the review of TEAs and safety and 
effectiveness data submissions that are subject to the timelines in 
this section. The posting will contain the following information for 
tracking the extent to which the timelines set forth in paragraph (c) 
of this section were met during the previous calendar year.
    (1) Number and percent of eligibility notices or ineligibility 
letters issued within 180 days of submission of a TEA;
    (2) Number and percent of filing determinations issued within 90 
days of submission of a safety and effectiveness data submission;
    (3) If applicable, number and percent of feedback letters issued 
within 730 days from the date of filing;
    (4) Number and percent of notices for proposed rulemaking issued 
within 1,095 days from the date of filing;
    (5) Number and percent of final rules issued within 912 days of 
closing of the docket of the proposed rulemaking; and
    (6) Total number of TEAs submitted under Sec.  330.14.
    (c) Timelines for FDA review and action. FDA will review and take 
an action within the following timelines:
    (1) Within 180 days of submission of a TEA under Sec.  330.14(c), 
FDA will issue a notice of eligibility or post to the docket a letter 
of ineligibility, in accordance with Sec.  330.14(d) and (e).
    (2) Within 90 days of submission by the sponsor of a safety and 
effectiveness data submission, FDA will issue a filing determination in 
accordance with Sec.  330.14(j). The date of filing begins the FDA 
timelines in paragraphs (c)(3) and (4) of this section.
    (3) Within 730 days from the date of filing, if the condition is 
initially determined not to be GRASE for OTC use in the United States, 
FDA will inform the sponsor and other interested parties who have 
submitted data of its determination by feedback letter in accordance 
with Sec.  330.14(g)(4).
    (4) Within 1,095 days from the date of filing of a safety and 
effectiveness data submission, FDA will issue a notice of proposed 
rulemaking to either:
    (i) Include the condition in an appropriate OTC monograph(s), 
either by amending an existing monograph(s) or establishing a new 
monograph(s), if necessary; or
    (ii) Include the condition in Sec.  310.502 of this chapter.
    (5) Within 912 days of the closing of the docket of the proposed 
rulemaking under paragraph (c)(4) of this section, FDA will issue a 
final rule.

    Dated: March 29, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-07612 Filed 4-1-16; 8:45 am]
 BILLING CODE 4164-01-P