[Federal Register Volume 88, Number 83 (Monday, May 1, 2023)]
[Notices]
[Pages 26559-26561]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-09170]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-0297]


Smoking Cessation and Related Indications: Developing Nicotine 
Replacement Therapy Drug Products; Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a final guidance for industry entitled ``Smoking 
Cessation and Related Indications: Developing Nicotine Replacement 
Therapy Drug Products; Guidance for Industry.'' The document provides 
guidance to assist sponsors in the clinical development of nicotine 
replacement therapy (NRT) drug products, including but not limited to 
those intended for smoking cessation and related chronic indications. 
This guidance finalizes the draft guidance of the same title issued on 
February 22, 2019.

DATES: The announcement of the guidance is published in the Federal 
Register on May 1, 2023.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time 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-2019-D-0297 for ``Smoking Cessation and Related Indications: 
Developing Nicotine Replacement Therapy Drug Products.'' 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 Dockets Management Staff between 9

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a.m. and 4 p.m., Monday through Friday, 240-402-7500.
     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 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.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, 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, 240-402-7500.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Heather Dorsey, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Silver Spring, MD 20903-0002, 240-429-4192, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Smoking Cessation and Related Indications: Developing 
Nicotine Replacement Therapy Drug Products.'' This guidance reflects 
the FDA's current thinking regarding overall development programs to 
support the approval of NRT drug products for smoking cessation and 
related chronic indications. There are several FDA-approved 
prescription and nonprescription NRT drug products for cessation of 
smoking cigarettes, but the Agency encourages the development of 
additional NRT drug products, which could help more smokers quit.
    The guidance focuses on drug development and trial design issues 
that are specific to the study of NRT drug products. NRT drug products 
are typically studied and labeled for use as adjuncts to behavioral 
self-help materials and to date have involved single treatment regimens 
that begin on the patient's quit day (first day without a cigarette). 
Alternate treatment regimens (e.g., pretreatment before quit day, 
quitting by gradual reduction (reduce to quit), using multiple NRT drug 
products together) are discussed in the guidance.
    As outlined in the guidance, NRT drug products can be developed for 
smoking cessation and/or reduction in risk of relapse. NRT drug 
products that first have demonstrated efficacy for at least one of 
these indications can also include additional information in labeling 
by demonstrating efficacy in certain secondary endpoints. Sponsors can 
evaluate reduction in the urge to smoke or relief of cue-induced 
craving in former smokers as secondary endpoints. Additionally, 
sponsors that can demonstrate, via a secondary endpoint, that the drug 
product provides relief of withdrawal symptoms in smokers who are not 
trying to quit smoking may be able to include labeling instructions to 
address situations when such individuals are required to abstain and 
therefore experience withdrawal symptoms (e.g., while traveling on an 
airplane).
    FDA is aware of the serious risks associated with smoking and is 
committed to facilitating the development of therapies to support 
smoking cessation efforts. Both the regulatory pathway for an NRT drug 
product and the amount of nonclinical or clinical data needed to 
support approval will depend on the characteristics of the proposed NRT 
drug product relative to an approved NRT drug product. This guidance 
outlines general considerations for NRT drug development and trial 
design, and FDA encourages sponsors to contact FDA for feedback on 
their proposed development plans. Sponsors developing nonprescription 
drug product should bear in mind that it is often not possible to 
answer all regulatory questions in a single trial, and additional 
sequential steps may be needed.
    This guidance finalizes the draft guidance entitled ``Smoking 
Cessation and Related Indications: Developing Nicotine Replacement 
Therapy Drug Products'' issued on February 22, 2019 (84 FR 5693). FDA 
considered comments received on the draft guidance as the guidance was 
finalized. Changes from the draft to the final guidance include 
clarification that the document does not address the development of NRT 
to aid in the cessation of non-combustible tobacco products (e.g., e-
cigarettes); information regarding the pathway described in section 
505(b)(2) (21 U.S.C. 355(b)(2)) of the Federal Food, Drug, and Cosmetic 
Act and reliance on published literature; and clarification regarding 
mode of administration and route of administration. In addition, 
editorial changes were made to improve clarity. This guidance is being 
issued consistent with FDA's good guidance practices regulation (21 CFR 
10.115). The guidance represents the current thinking of FDA on 
``Smoking Cessation and Related Indications: Developing Nicotine 
Replacement Therapy Drug Products.'' It does not establish any rights 
for any person and is not binding on FDA or the public. You can use an 
alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.

II. Paperwork Reduction Act of 1995

    While this guidance contains no collection of information, it does 
refer to previously approved FDA collections of information. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information in 21 CFR part 312 pertaining to the submissions of 
investigational new drug applications, including clinical trial design 
and study protocols, have been approved under OMB control number 0910-
0014. The

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collections of information in 21 CFR part 314 regarding the submission 
of new drug applications including formal meetings with sponsors and 
applicants for Prescription Drug User Fee Act products, abbreviated new 
drug applications and supplemental applications have been approved 
under OMB control number 0910-0001. The collections of information in 
21 CFR part 601 pertaining to the submission of biologics license 
applications have been approved under OMB control number 0910-0338. The 
collections of information relating to expedited program for serious 
conditions for drug and biological product development programs have 
been approved under OMB control number 0910-0765. The collections of 
information pertaining to the submission of special protocol 
assessments have been approved under OMB control number 0910-0470. The 
collections of information in 21 CFR 201.56 and 201.57 for the 
submission of certain prescription drug product labeling have been 
approved under OMB control number 0910-0572. The collections of 
information in 21 CFR parts 50 and 56 (Protection of Human Subjects: 
Informed Consent; Institutional Review Boards) have been approved under 
OMB control number 0910-0130. The collections of information pertaining 
to good clinical practice have been approved under OMB control number 
0910-0843. The collections of information pertaining to adverse events 
reporting have been approved under OMB control number 0910-0291.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: April 26, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-09170 Filed 4-28-23; 8:45 am]
BILLING CODE 4164-01-P


