[Federal Register Volume 77, Number 229 (Wednesday, November 28, 2012)]
[Proposed Rules]
[Pages 70955-70958]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-28835]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 15

[Docket No. FDA-2012-N-1148]


FDA Actions Related to Nicotine Replacement Therapies and 
Smoking-Cessation Products; Report to Congress on Innovative Products 
and Treatments for Tobacco Dependence; Public Hearing; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day 
public hearing to obtain input on certain questions related to the 
implementation of the Federal Food, Drug, and Cosmetic Act (the FD&C 
Act), as amended by the Family Smoking Prevention and Tobacco Control 
Act

[[Page 70956]]

(Tobacco Control Act). This public hearing is being held to obtain 
comments from the public on FDA consideration of applicable approval 
mechanisms and additional indications for nicotine replacement 
therapies (NRTs), and to request input on a report to Congress 
examining the regulation and development of innovative products and 
treatments for tobacco dependence.

DATES: The public hearing will be held on December 17, 2012, 8 a.m. to 
5 p.m. Individuals who wish to present at the public hearing must 
register by December 6, 2012. Section III of this document provides 
attendance and registration information. Electronic or written comments 
will be accepted after the public hearing until January 2, 2013.

ADDRESSES: The public hearing will be held at FDA's White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31, rm. 1503, Silver Spring, MD 20993. 
Individuals who wish to present at the public hearing must register by 
December 6, 2012, and provide complete contact information, including 
name, title, affiliation, address, email, and phone number (see section 
III of this document for further information).
    Submit electronic comments to http://www.regulations.gov. Submit 
written comments to the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 
20852. Identify comments with the docket number found in brackets in 
the heading of this document.
    Transcripts of the public hearing will be available for review at 
the Division of Dockets Management and on the Internet at http://www.regulations.gov approximately 30 days after the public hearing (see 
section VI of this document).
    A live Web cast of this public hearing may be seen at https://collaboration.fda.gov/Section918 on the day of the public hearing. A 
video record of the public hearing will be available at the same Web 
address for 1 year.

FOR FURTHER INFORMATION CONTACT: Ayanna Augustus, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 3219, Silver Spring, MD 20993, 301-796-
3980, FAX: 301-796-2310, email: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing a 1-day public hearing to obtain input on certain 
questions related to the implementation of section 918 of the FD&C Act 
(21 U.S.C. 387r), as amended by the Tobacco Control Act (Pub. L. 111-
31). Section 918 has two parts. Under Section 918(a), which is 
primarily focused on NRTs, the Secretary of the Department of Health 
and Human Services (the Secretary of HHS) is required to consider 
certain new approval mechanisms and additional indications for NRTs. 
Several NRTs, including nicotine-containing gums, patches, and 
lozenges, are already marketed for smoking cessation. Under section 
918(b), a broader range of products is implicated. Section 918(b) 
requires that the Secretary of HHS, after consultation with recognized 
scientific, medical, and public health experts, submit a report to 
Congress examining how best to regulate, promote, and encourage the 
development of ``innovative products and treatments (including 
nicotine-based and non-nicotine-based products and treatments)'' to 
better achieve the following three goals: (1) Total abstinence from 
tobacco use, (2) reductions in consumption of tobacco, and (3) 
reductions in the harm associated with continued tobacco use. The 
purpose of this public hearing is to create a forum for interested 
stakeholders to provide input regarding FDA's fulfillment of the 
requirements set forth in section 918, including on the following 
issues, among others: (1) The use of fast-track and accelerated 
approval authorities for smoking-cessation products, including NRTs; 
(2) the potential for extended use of NRTs (beyond currently approved 
durations of use) for the treatment of tobacco dependence; (3) the 
potential for additional indications for NRTs, including for craving 
relief or relapse prevention; and (4) how best to regulate ``innovative 
products and treatments'' targeted at tobacco users in order to achieve 
abstinence from tobacco use, reductions in consumption of tobacco, and 
reductions in the harm associated with continued tobacco use. FDA will 
consider the information it obtains from the public hearing in its 
implementation of the requirements of section 918, including in 
drafting the report to Congress required by section 918(b).

II. Purpose and Scope of the Public Hearing

    The purpose of this 21 CFR part 15 hearing is to receive 
information and comments from a broad group of stakeholders, including 
manufacturers, interested industry and professional organizations, the 
public health community, individuals affected by tobacco dependence, 
researchers, health care professionals, and the public, regarding 
implementation of section 918 of the FD&C Act. FDA is also consulting 
directly with other Federal agencies and third parties, as contemplated 
by section 918.
    FDA is particularly interested in obtaining information and public 
comment on the issues listed in sections II.A and II.B of this 
document, although comments related to any issues regarding 
implementation of section 918 are welcome.

A. Section 918(a): FDA Actions Related to NRTs and Smoking-Cessation 
Products

    Fast-Track Status for Smoking-Cessation Products, Including NRTs.
    Section 918(a)(1) of the FD&C Act provides that the Secretary of 
HHS must, ``at the request of the applicant, consider designating 
products for smoking cessation, including nicotine replacement products 
as fast track research and approval products within the meaning of 
section 506'' of the FD&C Act (21 U.S.C. 356).
    Accelerated approval and fast track designation are available under 
section 506 of the FD&C Act and FDA regulations,\1\ and these 
provisions have been used on a case-by-case basis for drug candidates 
that are intended to treat ``a serious or life-threatening condition'' 
and that have the potential to fill an unmet medical need. The Food and 
Drug Administration Safety and Innovation Act (FDASIA), which was 
enacted in July 2012, amends section 506 to define ``breakthrough 
therapy'' \2\ and provide that certain expedited review processes may 
be available to any drug candidate intended to treat a serious or life-
threatening disease or condition, whether alone or in combination with 
other drugs, provided that the drug candidate has the potential to fill 
an unmet medical need.
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    \1\ See 21 CFR part 314, subpart H, and 21 CFR part 601, subpart 
E.
    \2\ A ``breakthrough therapy'' is a drug intended, alone or in 
combination with one or more other drugs, to treat a serious or 
life-threatening disease or condition, where ``preliminary clinical 
evidence indicates that the drug may demonstrate substantial 
improvement over existing therapies on 1 or more clinically 
significant endpoints, such as substantial treatment effects 
observed early in clinical development.'' 21 U.S.C. 356(a)(1).
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    FDA seeks comment on the following issues related to section 
918(a)(1) of the FD&C Act:
    1.1. How can FDA best use its authorities under section 506 of the 
FD&C Act, as amended by FDASIA (including the designation of products 
as ``fast track products'' and as ``breakthrough therapies''), to 
facilitate expedited review and accelerated

[[Page 70957]]

approval for smoking-cessation products?
    1.2. Under what circumstances should a smoking-cessation product 
candidate be considered to fill an unmet medical need under section 
506, in light of the existing products for smoking cessation?
    1.3. What kind of preliminary clinical evidence might support the 
designation of a smoking-cessation product candidate as a 
``breakthrough therapy'' under section 506?
    Extended use of NRTs for treatment of tobacco dependence. Section 
918(a)(2) of the FD&C Act provides that the Secretary of HHS must 
``consider approving the extended use of nicotine replacement products 
(such as nicotine patches, nicotine gum, and nicotine lozenges) for the 
treatment of tobacco dependence.'' The NRTs referenced in this 
provision are currently labeled as aids to smoking cessation with a 
course of treatment generally lasting 10-12 weeks, depending on the 
product. FDA's understanding is that ``extended use'' as used in 
section 918(a)(2) refers to use beyond that period of time, for the 
treatment of tobacco dependence.
    On October 26 and 27, 2010, FDA held a public workshop entitled 
``Risks and Benefits of Long-Term Use of Nicotine Replacement Therapy 
Products.'' The questions explored in that workshop overlap with the 
issues raised in section 918(a)(2) of the FD&C Act. Although FDA does 
not seek to duplicate the discussion held at the October 2010 workshop, 
FDA is interested in receiving any new or additional information that 
might be relevant to the extended use of NRTs for tobacco dependence.
    FDA seeks comment on the following issues related to section 
918(a)(2) of the FD&C Act:
    2.1. What evidence is available to support the approval of NRTs for 
extended use to maintain abstinence in individuals who have quit?
    2.2. What evidence is available to support the approval of NRTs for 
extended use to achieve cessation (quitting)?
    2.3. With regard to both of the above indications, does the 
evidence implicate specific populations?
    Additional indications for NRTs, such as craving relief and relapse 
prevention. Section 918(a)(3) of the FD&C Act provides that the 
Secretary of HHS must ``review and consider the evidence for additional 
indications for nicotine replacement products, such as for craving 
relief or relapse prevention.'' As noted previously, the NRTs 
referenced in this provision are currently indicated as aids to smoking 
cessation. In the studies that were carried out to demonstrate 
efficacy, the endpoint was smoking cessation. These products aid 
cessation by relieving withdrawal symptoms, including cravings, that 
smokers may experience in the process of quitting. However, no 
currently approved NRT is indicated for craving relief outside of the 
context of quitting; nor is any currently approved NRT indicated for 
relapse prevention.
    FDA seeks comment on the following issues related to section 
918(a)(3) of the FD&C Act:
    3.1. If an additional indication is sought for an approved NRT in 
which craving relief itself is the endpoint of efficacy studies:
    a. How can the concept of ``craving'' be adequately characterized 
to support a potential indication for craving relief?
    b. Craving can occur in the context of acute withdrawal or long 
after a former smoker has quit (the latter may be described as 
``provoked'' or ``cue-induced'' craving). Have both types of craving 
been adequately characterized to support a potential indication for 
craving relief?
    c. Are there scientifically acceptable study designs for 
establishing efficacy for craving relief that use:
    i. Established instruments to measure patient-reported outcomes?
    ii. Analytical methods that address the degree of craving relief 
that should be considered clinically significant?
    3.2. If an additional indication is sought for an approved NRT for 
relapse prevention:
    a. How should ``relapse'' be defined and measured?
    b. How should the population of individuals at risk of relapse be 
defined?
    3.3. Are there other additional indications that might be sought 
for approved NRT products?

B. Report to Congress on How Best To Regulate Innovative Products and 
Treatments To Achieve Abstinence From Tobacco Use, Reductions in the 
Consumption of Tobacco, and Reductions in the Harm Associated With 
Continued Tobacco Use

    Section 918(b) of the FD&C Act requires that the Secretary of HHS, 
after consultation with recognized scientific, medical, and public 
health experts, submit to Congress a report that examines how best to 
regulate, promote, and encourage the development of ``innovative 
products and treatments (including nicotine-based and non-nicotine-
based products and treatments) to better achieve, in a manner that best 
protects and promotes the public health--(A) total abstinence from 
tobacco use; (B) reductions in consumption of tobacco; and (C) 
reductions in the harm associated with continued tobacco use.'' The 
report to Congress must include the recommendations of the Secretary of 
HHS on how FDA should coordinate and facilitate the exchange of 
information on these ``innovative products and treatments'' among 
relevant offices and Centers within FDA and within the National 
Institutes of Health, the Centers for Disease Control and Prevention, 
and other relevant Agencies such as the Substance Abuse and Mental 
Health Services Administration.
    One question raised by section 918(b) of the FD&C Act is how FDA 
should regulate specific ``innovative products and treatments'' that 
make claims in the three categories identified. ``Abstinence from 
tobacco use'' may be understood to include non-initiation of tobacco 
use (never starting to use) as well as cessation of tobacco use (a user 
successfully quitting). Product claims in this category might therefore 
include claims to prevent or inhibit initiation as well as claims to 
bring about cessation.
    A claim to reduce consumption of tobacco might, for example, 
suggest that the product would cause users to smoke fewer cigarettes or 
otherwise consume less tobacco. A claim to reduce the harms associated 
with continued tobacco use might, for example, suggest that the user 
could continue consuming tobacco as desired without experiencing one or 
more of the harmful effects of tobacco use.
    Section 918(b) also raises a question as to how FDA and other HHS 
Agencies can implement regulation and policy with regard to the 
``innovative products and treatments'' referenced in the statute to 
bring about the three effects identified--abstinence, reductions in 
consumption, and reductions in the harm associated with continued use--
as broader outcomes, in a manner that best protects and promotes the 
public health.
    FDA seeks comment on the following issues related to these 
provisions of section 918(b):
    4.1. What kinds of innovative products and treatments designed to 
achieve any of the above three purposes--abstinence from tobacco use, 
reduction in tobacco consumption, and reduction in the harm associated 
with continued use--might be developed to meet the criteria for 
marketing under applicable legal authorities?
    4.2. With regard to the ``abstinence'' category, what innovative 
products and treatments might be developed to better achieve either 
cessation or non-initiation? What are the established methods for 
measuring the prevention or inhibition of initiation?

[[Page 70958]]

    4.3. With regard to innovative products and treatments for 
``reduction in consumption of tobacco,''
    a. How can the reduction best be measured?
    b. If the reduction is associated with a certain goal or benefit:
    i. What evidence is available to indicate that the reduction in 
consumption will bring about that goal or achieve that benefit?
    ii. What degree and duration of reduction are necessary to achieve 
that goal or benefit?
    4.4. With regard to innovative products and treatments for 
``reduction in the harm associated with continued tobacco use'':
    a. How should the ``harm'' be identified and measured?
    b. Is there a range of harms that might be addressed, and if so, 
which are the most important to address?
    4.5. With regard to innovative products and treatments making 
claims in any of the three categories identified in section 918(b), 
what barriers exist to development and marketing approval?
    4.6 In regulating the innovative products and treatments referenced 
in section 918(b), how can FDA and other HHS Agencies act to ensure 
that the three effects mentioned in section 918(b)--total abstinence 
from tobacco use, reductions in consumption of tobacco, and reductions 
in the harm associated with continued tobacco use--are achieved as 
broader outcomes, in a manner that best protects and promotes the 
public health?
    4.7. How can these broader outcomes be taken into account in FDA's 
premarket evaluation of new product candidates?

III. Attendance and Registration

    The FDA Conference Center at the White Oak location is a Federal 
facility with security procedures and limited seating. Attendance is 
free and will be on a first-come, first-served basis. Individuals who 
wish to present at the public hearing must register by December 6, 
2012, and provide complete contact information, including name, title, 
affiliation, address, email, and phone number. Those without email 
access may register by contacting Ayanna Augustus (see FOR FURTHER 
INFORMATION CONTACT). FDA has included questions for comment in section 
II of this document. You should identify the number of each question 
you wish to address in your presentation, so that FDA can consider that 
in organizing the presentations. Individuals and organizations with 
common interests should consolidate or coordinate their presentations 
and request time for a joint presentation. FDA will do its best to 
accommodate requests to speak and will determine the amount of time 
allotted for each oral presentation, and the approximate time that each 
oral presentation is scheduled to begin. FDA will notify registered 
presenters of their scheduled times, and make available an agenda at 
http://www.fda.gov/Drugs/NewsEvents/ucm324938.htm approximately 1 week 
prior to the public hearing. Once FDA notifies registered presenters of 
their scheduled times, presenters should submit to FDA an electronic 
copy of their presentation to [email protected] by 
December 10, 2012.
    If you need special accommodations because of a disability, please 
contact Ayanna Augustus (see FOR FURTHER INFORMATION CONTACT) at least 
7 days before the meeting.
    A live Web cast of this public hearing may be seen at https://collaboration.fda.gov/Section918 on the day of the public hearing. A 
video record of the public hearing will be available at the same Web 
address for 1 year.

IV. 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 part 15 (21 CFR part 15). The 
hearing will be conducted by a presiding officer, who will be 
accompanied by senior management and technical experts from various 
offices within FDA.
    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 may 
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 (part 10 (21 CFR part 10, subpart C)). Under Sec.  10.205, 
representatives of the electronic 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 section VI of this document). To the extent that the 
conditions for the hearing, as described in this document, conflict 
with any provisions set out in part 15, this document acts as a waiver 
of those provisions as specified in Sec.  15.30(h).

V. Request for Comments

    Regardless of attendance at the public hearing, interested persons 
may submit either electronic or written comments to the Division of 
Dockets Management (see ADDRESSES). It is no longer necessary to send 
two copies of mailed comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday.

VI. Transcripts

    Transcripts of the public hearing will be available for review at 
the Division of Dockets Management (see ADDRESSES) and on the Internet 
at http://www.regulations.gov approximately 30 days after the public 
hearing. A transcript will also be made available in either hard copy 
or on CD-ROM, upon submission of a Freedom of Information request. 
Written requests should be sent to the Division of Freedom of 
Information (ELEM-1029), Food and Drug Administration, 12420 Parklawn 
Dr., Element Bldg., Rockville, MD 20857.

    Dated: November 21, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-28835 Filed 11-27-12; 8:45 am]
BILLING CODE 4160-01-P