[Federal Register Volume 82, Number 229 (Thursday, November 30, 2017)]
[Proposed Rules]
[Pages 56759-56763]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-25671]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 15

[Docket No. FDA-2017-N-6529]


The Food and Drug Administration's Approach To Evaluating 
Nicotine Replacement Therapies; Public Hearing; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notification of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
announcing a public hearing on FDA's approach to evaluating the safety 
and efficacy of nicotine replacement therapy (NRT) products, including 
how they should be used and labeled.

DATES: The public hearing will be held on Friday, January 26, 2018, 
from 9 a.m. to 5 p.m. The public hearing may be extended or may end 
early depending on the level of public participation. Persons seeking 
to attend or to present at the public hearing must register by Tuesday, 
January 2, 2018. Section II provides attendance and registration 
information. Electronic or written comments will be accepted after the 
public hearing until Thursday, February 15, 2018.

ADDRESSES: The public hearing will be held at the FDA White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room A, 
Silver Spring, MD 20993-0002. Entrance for public hearing participants 
(non-FDA employees) is through Building 1 where routine security check 
procedures will be performed. For parking and security information, 
please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows. Please note that late, untimely 
filed comments will not be considered. Electronic comments must be 
submitted on or before February 15, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of February 15, 2018. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are postmarked or the delivery 
service acceptance receipt is on or before that date.
    You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2017-N-6529 for ``FDA's Approach to Evaluating Nicotine Replacement 
Therapies''; Public Hearing; Request for Comments. Received comments 
will be placed in the docket and, except for those submitted as 
``Confidential Submissions,'' publicly viewable at https://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

[[Page 56760]]

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 https://www.regulations.gov. Submit both copies to the Dockets 
Management Staff. If you do not wish your name and contact information 
to be 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: https://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the received electronic and written/paper comments, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Allison Hoffman, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 1, Rm. 1314, Silver 
Spring, MD 20993, 301-796-9203, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    A majority (roughly 70%) of adult smokers in the United States 
report that they want to quit, and nearly half of them make a quit 
attempt each year. Many of those quit attempts involve the use of NRT 
products, which are designed to help people quit smoking by supplying 
controlled amounts of nicotine to ease their withdrawal symptoms. FDA 
has approved two types of prescription \1\ NRT products--a nicotine 
nasal spray and nicotine inhaler--and three types of over-the-counter 
(OTC) NRT products--a nicotine gum, transdermal nicotine patch, and 
nicotine lozenge (see Appendix A). Most of these products have been 
approved for over 20 years.\2\ The use of approved prescription and OTC 
NRT products is generally considered to double the likelihood of a 
successful quit attempt, although there is variation in efficacy among 
the types of products.
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    \1\ Non-nicotine prescription medications are also available to 
aid in smoking cessation, but are beyond the scope of this document.
    \2\ Only the lozenge formulation has been approved for less than 
20 years; it was approved in 2002.
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    Although the formulations and routes of administration of currently 
approved NRT products have remained relatively unchanged for decades, 
there have been developments in research regarding NRT products and 
corresponding changes in the regulatory landscape. For example, in 
2013, FDA recommended changing the statements on concomitant use and 
duration of use in the labeling for OTC NRT products because evidence 
gathered since 1984--the year the first NRT product was approved--
suggested that the statements were no longer necessary to ensure the 
safe use of OTC NRT products for smoking cessation.\3\ Specifically, 
the Agency recommended that the statement in the labeling for OTC NRT 
products warning consumers that they should not use an NRT product if 
they are still smoking, or using any other product that contains 
nicotine--including another NRT--be removed. FDA also recommended that 
the directions in the labeling for OTC NRT products be modified to 
remove the statement advising consumers to stop using the product at 
the end of the labeled duration of use. Instead of this statement, FDA 
recommended that consumers be advised to talk to their health care 
provider if they feel the need to use the product for longer than the 
labeled duration of use to keep from smoking. To facilitate these 
labeling changes, FDA invited the submission of supplemental new drug 
applications (labeling supplements).
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    \3\ See the Federal Register, available at https://www.federalregister.gov/documents/2013/04/02/2013-07528/modifications-to-labeling-of-nicotine-replacement-therapy-products-for-over-the-counter-human-use. Recommendations also included other 
language revisions that were not related to dosing or duration.
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    On July 28, 2017, the FDA announced a new comprehensive plan that 
places nicotine, and the issue of addiction, at the center of the 
Agency's tobacco regulation efforts. This plan will serve as a multi-
year roadmap to better protect children and significantly reduce 
tobacco-related disease and death in the United States. One of the 
first actions of this comprehensive approach will be an advanced notice 
of proposed rulemaking (ANPRM) to seek input on the potential impacts 
of reducing nicotine levels in cigarettes to minimally or non-addictive 
levels. A key piece of the FDA's comprehensive plan is a recognition 
that nicotine--while highly addictive--is delivered through products 
that represent a continuum of risk and is most harmful when delivered 
through combustible tobacco products. Accordingly, the Agency is 
committed to increasing access to and use of nicotine replacement 
therapy, which could help more smokers quit. Therefore, the Agency is 
seeking public input on its approach to evaluating the safety and 
efficacy of NRT products.
    As a part of its mission to protect and promote public health, FDA 
is responsible for ensuring that approved drugs, including NRT 
products, are safe and effective.\4\ For FDA to approve a new drug, it 
must find that the applicant has submitted ``substantial evidence'' of 
effectiveness based on adequate and well-controlled studies \5\ and 
that the drug is safe for use under the conditions set forth in the 
labeling.\6\ Generally, the safety of a product is assessed by 
determining whether its benefits outweigh its risks. The benefit-risk 
assessment takes into account the extensive evidence of safety and 
effectiveness submitted by a sponsor in a marketing application as well 
as many other factors.\7\
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    \4\ Section 1003(b) of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act), 21 U.S.C. 393(b).
    \5\ Section 505(d) of the FD&C Act; 21 U.S.C. 355(d).
    \6\ 21 U.S.C. 355(d). FDA also noted in the preamble to the 
final rule on new drug approvals (NDA final rule) that the new drug 
approval process and the supplemental application requirements ``are 
intended to ensure that the drug is safe, that its benefits outweigh 
its risks, and that it is effective.'' See 50 FR 7452, 7469 
(February. 22, 1985).
    \7\ See FDA's Structured Approach to Benefit-Risk Assessment in 
Drug Regulatory Decision-Making, Draft PDUFA V Implementation Plan--
February 2013, Fiscal Years 2013-2017, available at https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM329758.pdf.
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II. Purpose and Scope of the Public Hearing

    To enable a thorough assessment of its approach for evaluating the 
safety and efficacy NRT products and how they should be used and 
labeled, FDA is holding a public hearing to receive information and 
comments from a broad group of stakeholders, including the public 
health community, researchers, health care professionals, 
manufacturers, interested industry and professional organizations, and 
the public, on the appropriate study designs and methods for evaluating 
the safety and efficacy of OTC NRT drug products. FDA is also seeking 
input on the warnings and directions sections of the Drug Facts 
labeling (among other

[[Page 56761]]

aspects) for approved OTC NRT products, specifically regarding the 
possible impact of current warnings on likelihood of use. The Agency 
has determined that a public hearing is the most appropriate way to 
ensure public engagement on these important public health issues. FDA 
believes it is critical to obtain input across the research and medical 
fields, the tobacco and pharmaceutical industries, and among public 
health stakeholders regarding how evolving science could influence 
FDA's approach to evaluating the safety and effectiveness of NRT 
products.

Questions for Commenters To Address

    Although FDA welcomes all feedback on any public health, 
scientific, regulatory or legal considerations relating to NRT products 
and their use in tobacco use cessation, we encourage commenters to 
consider the following questions as they prepare their comments or 
statements. Responses to questions should include supporting scientific 
justification.
    1. Might there be ways to improve upon the currently available 
delivery systems to yield new OTC NRT products that might be more 
effective? If so, what evidence would be needed to support such 
changes, and how should they be evaluated?
    2. Are there additional indications or regimens for OTC NRT 
products that could be explored? Concepts to consider could include 
relapse prevention, craving reduction, maintenance, reduce to quit, use 
of short- and long-acting products in combination, or cessation of non-
cigarette tobacco products. What evidence would be needed to support 
each indication or regimen?
    3. What data would be required to demonstrate health benefits of 
reduction in consumption of combustible tobacco products?
    4. Are there OTC NRT products that could be studied for use in 
combination that might result in reduced tobacco-related health 
impacts? What evidence would be needed to support the safety and 
efficacy of these products when used in combination?
    5. Is there other information that could be added to labeling for 
currently approved or new dosage forms of OTC NRT products that would 
maximize their ability to be used to support smoking cessation? Please 
consider the various sections of the Drug Facts labeling, including the 
Uses, Warnings, and Directions sections.
    6. Generally, the labeling of OTC NRT products contains a dosing 
schedule based on duration of use, and FDA has recommended the labeling 
on OTC NRT products be modified to include the following: ``If you feel 
you need to use [the NRT product] for a longer period to keep from 
smoking, talk to your health care provider.'' What is the impact of 
longer term NRT treatment? What is the impact on likelihood of 
cessation or relapse prevention? What data would support an affirmative 
recommendation to use approved OTC NRT products for durations that 
exceed those currently included in the Drug Facts labeling of approved 
OTC NRT products, or would support a chronic or maintenance drug 
treatment indication for such products?
    Registration and Requests for Oral Presentations: The FDA 
Conference Center at the White Oak location is a Federal facility with 
security procedures and limited seating. Attendance will be free and on 
a first-come, first-served basis. If you wish to attend (either in 
person or by webcast (see Streaming Webcast of the Public Hearing)) 
and/or present at the hearing, please register for the hearing and/or 
make a request for oral presentations or comments by email to 
[email protected] by Tuesday, January 2, 2018. The email should 
contain complete contact information for each attendee (i.e., name, 
title, affiliation, address, email address, and telephone number). For 
those wishing to present at the hearing, the email should also include 
a presentation title. Those without email access can register by 
contacting Allison Hoffman at 301-796-9203 by Tuesday, January 2, 2018 
(see FOR FURTHER INFORMATION CONTACT).
    FDA will try to accommodate all persons who wish to make a 
presentation. Individuals wishing to present should identify the number 
of the specific question, or questions, they wish to address. This will 
help FDA organize the presentations. Individuals and organizations with 
common interests should consolidate or coordinate their presentations 
and request time for a joint presentation. FDA will notify registered 
presenters of their scheduled presentation times. The time allotted for 
each presentation will depend on the number of individuals who wish to 
speak. Presenters are encouraged to submit an electronic copy of their 
presentation to [email protected] on or before Friday, January 
19, 2018. Persons registered to make an oral presentation are 
encouraged to arrive at the hearing room early and check in at the 
onsite registration table to confirm their designated presentation 
time. An agenda for the hearing and any other background materials will 
be made available 5 days before the hearing at https://www.fda.gov/NewsEvents/MeetingsConferencesWorkshops/ucm580561.htm.
    If you need special accommodations because of a disability, please 
contact [email protected] (see FOR FURTHER INFORMATION CONTACT) 
no later than Tuesday, January 2, 2018, at 12 noon Eastern Time.
    Streaming Webcast of the Public Hearing: For those unable to attend 
in person, FDA will provide a live webcast of the hearing. To join the 
hearing via the webcast, please go to https://collaboration.fda.gov/part15nicotine.
    Transcripts: Please be advised that as soon as a transcript is 
available, it will be accessible at https://www.regulations.gov. It may 
be viewed at the Dockets Management Staff (see ADDRESSES).

III. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs is announcing that the public 
hearing will be held in accordance with 21 CFR part 15. The hearing 
will be conducted by a presiding officer, who will be accompanied by 
FDA senior management from the Office of the Commissioner, the Center 
for Drug Evaluation and Research, and the Center for Tobacco Products. 
Under Sec.  15.30(f), the hearing is informal and the rules of evidence 
do not apply. No participant may interrupt the presentation of another 
participant. Only the presiding officer and panel members can pose 
questions; they can question any person during or at the conclusion of 
each presentation. Public hearings under part 15 are subject to FDA's 
policy and procedures for electronic media coverage of FDA's public 
administrative proceedings (21 CFR part 10, subpart C). Under Sec.  
10.205, representatives of the media may be permitted, subject to 
certain limitations, to videotape, film, or otherwise record FDA's 
public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in Sec.  
15.30(b) (see Transcripts). To the extent that the conditions for the 
hearing, as described in this notice, conflict with any provisions set 
out in part 15, this notice acts as a waiver of those provisions as 
specified in Sec.  15.30(h).

IV. References

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

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Register, but Web sites are subject to change over time.

1. Babb S, Malarcher A, Schauer G, Asman K, and Jamal A. 2017. 
Quitting Smoking Among Adults--United States, 2000-2015. Morbidity 
and Mortality Weekly Report 65:1457-1464.
2. Etter J-F and Stapleton JA. 2006. Nicotine Replacement Therapy 
for Long-Term Smoking Cessation: A Meta-Analysis. Tobacco Control 
15:280-285.
3. Silagy C, Mant D, Fowler G, and Lodge M. 1994. Meta-Analysis on 
Efficacy of Nicotine Replacement Therapies in Smoking Cessation. 
Lancet 343:139-142.

Appendix A: Summary of FDA-Approved Active New Drug Applications (NDAs) 
of Nicotine Replacement Therapies (September 18, 2017)

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                                       OTC or Rx (date approved;                                                              Labeled treatment duration
    Product name (NDA #; holder)           date Rx[rarr]OTC)              Route (doses)                  Indication                  and schedule
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Nicorette gum (nicotine polacrilex)   Approved as prescription on  Oral (2, 4 mg gum).........  Reduces withdrawal           12 weeks:
 (NDA 018612 for 2 mg, NDA 020066      1/13/84 for 2 mg; 6/8/92                                  symptoms, including          Wk 1-6: 1 per 1-2
 for 4 mg; GSK).                       for 4 mg; Rx[rarr]OTC for                                 nicotine craving,            hr.
                                       both on 2/9/16.                                           associated with quitting     Wk 7-9: 1 per 2-4
                                                                                                 smoking (under Directions:   hr.
                                                                                                 If you are under 18 years    Wk 10-12: 1 per 4-
                                                                                                 of age ask a doctor before   8 hr.
                                                                                                 use).                       If smoke 1st cigarette
                                                                                                                              within 30 min of waking
                                                                                                                              up, use 4 mg; if more than
                                                                                                                              30 min, use 2 mg.
NicoDerm CQ (nicotine) (NDA 020165;   Approved as prescription on  Patch (7, 14, 21 mg).......  Same use as above..........  10 weeks and 8 weeks:
 GSK, Sanofi Aventis).                 11/7/91; Rx[rarr]OTC on 8/                                                            If >10 cigarettes/day:
                                       2/96.                                                                                  Wk 1-6: one 21 mg/
                                                                                                                              day.
                                                                                                                              Wk 7-8: one 14 mg/
                                                                                                                              day.
                                                                                                                              Wk 9-10: one 7 mg/
                                                                                                                              day.
                                                                                                                             If <=10 cigarettes/day:
                                                                                                                              Wk 1-6: one 14 mg/
                                                                                                                              day.
                                                                                                                              Wk 7-8: one 7 mg/
                                                                                                                              day.
Habitrol (nicotine) (NDA 020076;      Approved as prescription on  Patch (7, 14, 21 mg).......  Same use as above..........  8 weeks:
 Ciba-Geigy, Novartis, Dr. Reddy's).   11/27/91; Rx[rarr]OTC on                                                              If >10 cigarettes/day:
                                       11/12/99.                                                                              Wk 1-4: one 21 mg/
                                                                                                                              day.
                                                                                                                              Wk 5-6: one 14 mg/
                                                                                                                              day.
                                                                                                                              Wk 7-8: one 7 mg/
                                                                                                                              day.
                                                                                                                             If <=10 cigarettes/day:
                                                                                                                              Wk 1-6: one 14 mg/
                                                                                                                              day.
                                                                                                                              Wk 7-8: one 7 mg/
                                                                                                                              day.
Nicotrol NS (nicotine) (NDA 020385;   Prescription (3/22/96; N/A)  Nasal spray................   Indicated as an     The label does not specify
 Pfizer).                                                                                        aid to smoking cessation     the recommended duration
                                                                                                 for the relief of nicotine   of treatment, but notes
                                                                                                 withdrawal symptoms.         the following in the
                                                                                                 Should be used as    Indications and Usage
                                                                                                 a part of a comprehensive    section:
                                                                                                 behavioral smoking          The safety and efficacy of
                                                                                                 cessation program.           the continued use of
                                                                                                                              Nicotrol NS for periods
                                                                                                                              longer than 6 months have
                                                                                                                              not been adequately
                                                                                                                              studied and such use is
                                                                                                                              not recommended.
Nicotrol Inhaler (nicotine) (NDA      Prescription (5/2/97; N/A).  Inhalant...................   Indicated as an     The recommended duration of
 020714; Pharmacia and Upjohn).                                                                  aid to smoking cessation     treatment is 3 months,
                                                                                                 for the relief of nicotine   after which patients may
                                                                                                 withdrawal symptoms.         be weaned from the inhaler
                                                                                                 Recommended for      by gradual reduction of
                                                                                                 use as part of a             the daily dose over the
                                                                                                 comprehensive behavioral     following 6 to 12 weeks.
                                                                                                 smoking cessation program.  The safety and efficacy of
                                                                                                                              the continued use of
                                                                                                                              Nicotrol Inhaler for
                                                                                                                              periods longer than 6
                                                                                                                              months have not been
                                                                                                                              studied and such use is
                                                                                                                              not recommended.

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Commit lozenge (nicotine polacrilex)  OTC (10/3/02; N/A).........  Oral (2, 4 mg).............  Reduces withdrawal           12 weeks:
 (NDA 021330; GSK).                                                                              symptoms, including          Wk 1-6: 1 per 1-2
                                                                                                 nicotine craving,            hr.
                                                                                                 associated with quitting     Wk 7-9: 1 per 2-4
                                                                                                 smoking (under Directions:   hr.
                                                                                                 If you are under 18 years    Wk 10-12: 1 per 4-
                                                                                                 of age ask a doctor before   8 hr.
                                                                                                 use).                       If smoke 1st cigarette
                                                                                                                              within 30 min of waking
                                                                                                                              up, use 4 mg; if more than
                                                                                                                              30 min, use 2 mg.
Nicorette mini lozenge (nicotine      OTC (5/18/09; N/A).........  Oral (2, 4 mg).............  Same use as above..........  12 weeks; same schedule as
 polacrilex) (NDA 022366; GSK).                                                                                               Commit lozenge.
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    Dated: November 22, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-25671 Filed 11-29-17; 8:45 am]
 BILLING CODE 4164-01-P


