Document ID: FDA-2011-N-0443-0001
Agency: fda
Document Type: Notice
Title: Scientific Evaluation of Modified Risk Tobacco Product Applications; Public Workshop
Posted Date: 2011-06-22T04:00Z

[Federal Register Volume 76, Number 120 (Wednesday, June 22, 2011)]
[Notices]
[Pages 36544-36548]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-15601]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0443]

Scientific Evaluation of Modified Risk Tobacco Product 
Applications; Public Workshop; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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    The Food and Drug Administration (FDA), Center for Tobacco Products 
is announcing a public workshop to obtain input on specific issues 
associated with the scientific evaluation of modified risk tobacco 
product (MRTP) applications. The Family Smoking Prevention and Tobacco 
Control Act (the Tobacco Control Act) establishes a requirement for 
persons to obtain an order from FDA before they can introduce or 
deliver for introduction into interstate commerce MRTPs and outlines 
the requirements that must be met before FDA will issue such an order. 
The Tobacco Control Act also directs FDA to get input from appropriate 
scientific and medical experts on the design and conduct of studies and 
surveillance required for assessment and ongoing review of MRTP 
applications. The purpose of the public workshop is to create a forum 
for appropriate scientific and medical experts and other interested 
stakeholders to provide input on these topics. FDA will take the 
information it obtains from the public workshop into account as it 
determines how best to implement the MRTPs provisions of the Tobacco 
Control Act. FDA is also opening a public docket to receive comments on 
these topics.

DATES: Dates and Times: The public workshop will be held on August 25, 
2011, from 8:30 a.m. to 5:30 p.m., and on August 26, 2011, from 8:30 
a.m. to 4 p.m. Individuals who wish to make a presentation at the 
public workshop must register by close of business on August 3, 2011. 
Submit either electronic or written comments to the docket by September 
23, 2011.
    Location: The public workshop will be held at the FDA White Oak 
Campus, 10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great 
Room (rm. 1503), Silver Spring, MD 20993-0002. Information regarding 
special accommodations due to a disability, visitor parking, and 
transportation may be accessed at: http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.

FOR FURTHER INFORMATION CONTACT: Contact Person: Anuja Patel, Office of 
Science, Center for Tobacco Products, Food and Drug Administration, 
9200 Corporate Blvd., Rockville, MD 20850, 1-877-287-1373 (choose 
option 4), FAX: 240-276-3761, e-mail: workshop.CTPOS@fda.hhs.gov.
    Registration to Attend the Workshop and Requests for Oral 
Presentation: If you wish to attend the workshop or make an oral 
presentation at the workshop, please e-mail your registration to 
workshop.CTPOS@fda.hhs.gov by close of business on August 3, 2011. 
Those without e-mail access may register by contacting Anuja Patel (see 
Contact Person). Please provide contact information for each attendee, 
including name, title, affiliation, address, e-mail address, and 
telephone number. Registration is free and will be on a first-come-
first-served basis. Early registration is recommended because seating 
is limited. FDA may limit the number of participants from each 
organization as well as the total number of participants based on space 
limitations. Registrants will receive confirmation once they have been 
accepted for the workshop. Onsite registration on the day of the 
workshop will be based on space availability. If registration reaches 
maximum capacity, FDA will post a notice closing registration for the 
workshop at http://www.fda.gov/TobaccoProducts/default.htm.
    An open comment session will be held during the public workshop on 
August 25, 2011, from 11 a.m. to 12:30 p.m., during which comments from 
the public will be accepted. If you would like to make an oral 
presentation during the open comment session, you must indicate this at 
the time of registration. FDA has included questions for comment in 
section II of this document. You should identify the question number(s) 
you will address in your presentation and the approximate time 
requested for your presentation.
    FDA will do its best to accommodate requests to speak. Individuals 
and organizations with common interests are urged to consolidate or 
coordinate their presentations and request time for a joint 
presentation. FDA will determine the amount of time allotted to each 
presenter and the approximate time that each oral presentation is 
scheduled to begin. Persons registered to make a formal presentation 
must check in at the registration table by 10 a.m. on August 25, 2011. 
In addition, we strongly encourage submitting comments to the docket 
(see Comments).
    If you need special accommodations because of a disability, please 
contact Anuja Patel (see Contact Person) at least 7 days before the 
workshop.
    Comments: Regardless of attendance at the public workshop, 
interested persons may submit comments on any questions for comment in 
section II of this document by September 23, 2011. 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. It is only necessary 
to send one set of comments. 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.

[[Page 36545]]

SUPPLEMENTARY INFORMATION:

I. Background

    On June 22, 2009, President Obama signed into law the Tobacco 
Control Act, providing FDA with the authority to regulate tobacco 
products (Pub. L. 111-31; 123 Stat. 1776). The Tobacco Control Act 
amends the Federal Food, Drug, and Cosmetic Act (the FD&C Act) by 
adding section 911 (21 U.S.C. 387k), which prohibits the introduction 
or delivery for introduction of an MRTP into interstate commerce 
without an order from FDA.
    MRTPs are tobacco products that are sold or distributed for use to 
reduce harm or the risk of tobacco-related disease associated with 
commercially marketed tobacco products. According to section 911(b)(1) 
of the FD&C Act, a tobacco product is considered to be sold or 
distributed for use to reduce harm or the risk of tobacco-related 
disease if its label, labeling, or advertising represents, either 
explicitly or implicitly, that:
     The product is less harmful or presents a lower risk of 
tobacco-related disease than one or more commercially marketed tobacco 
products; or
     The product or its smoke contains a reduced level of, 
presents a reduced exposure to, or is free of a substance.
    A tobacco product is also considered to be sold or distributed for 
use to reduce harm or the risk of tobacco-related disease if the 
product's:
     Label, labeling, or advertising uses the words ``light,'' 
``mild,'' or ``low,'' or similar descriptors; or
     Manufacturer has taken any action after June 22, 2009, 
directed to consumers through the media or otherwise (other than 
through the product's label, labeling, or advertising) that would be 
reasonably expected to result in consumers believing that the tobacco 
product or its smoke may present a reduced risk of harm, tobacco-
related disease, or exposure to a substance than one or more 
commercially marketed tobacco products.

Section 911(b)(2) of the FD&C Act

    Before an MRTP can be introduced or delivered for introduction into 
interstate commerce, an application for the product must be filed with 
FDA, and the Agency must review the application and determine whether 
it is appropriate to issue an order under section 911(g). (See section 
911(a), (d), and (g) of the FD&C Act.) Section 911(d) of the FD&C Act 
describes the required contents of an MRTP application, while section 
911(g) of the FD&C Act describes the requirements for obtaining an 
order.
    Section 911(g) of the FD&C Act sets forth two bases for obtaining 
an order from FDA for an MRTP application. Under section 911(g)(1), FDA 
shall issue an order only if FDA determines that an applicant has 
demonstrated that the product, as it is actually used by consumers, 
will:
     Significantly reduce harm and the risk of tobacco-related 
disease to individual tobacco users, and
     Benefit the health of the population as a whole, taking 
into account both users of tobacco products and persons who do not 
currently use tobacco products.
    Under section 911(g)(2), FDA may issue an order for MRTPs that may 
not satisfy the requirements under section 911(g)(1) (described 
previously) if FDA determines that an applicant has demonstrated that:
     Such an order would be appropriate to promote the public 
health;
     Any aspect of the label, labeling, and advertising for the 
product that would cause the product to be an MRTP is limited to an 
explicit or implicit representation that the tobacco product or its 
smoke does not contain or is free of a substance or contains a reduced 
level of a substance, or presents a reduced exposure to a substance in 
tobacco smoke;
     Scientific evidence is not available and, using the best 
available scientific methods, cannot be made available without 
conducting long-term epidemiological studies for an application to meet 
the standards for an order set forth in section 911(g)(1) of the FD&C 
Act; and
     The scientific evidence that is available without 
conducting long-term epidemiological studies demonstrates that a 
measurable and substantial reduction in morbidity or mortality among 
individual tobacco users is reasonably likely in subsequent studies.
    Furthermore, for FDA to issue an order under section 911(g)(2), FDA 
must find that the applicant has demonstrated that:
     The magnitude of overall reductions in exposure to the 
substance or substances that are the subject of the application is 
substantial, such substance or substances are harmful, and the product 
as actually used exposes consumers to the specified reduced level of 
the substance or substances;
     The product as actually used by consumers will not expose 
them to higher levels of other harmful substances compared to similar 
types of tobacco products then on the market unless such increases are 
minimal, and the reasonably likely overall impact of use of the product 
remains a substantial and measurable reduction in overall morbidity and 
mortality among individual tobacco users;
     Testing of actual consumer perception shows that, as the 
applicant proposes to label and market the product, consumers will not 
be misled into believing that the product is or has been demonstrated 
to be less harmful or presents or has been demonstrated to present less 
of a risk of disease than one or more other commercially marketed 
tobacco products; and
     Issuance of an order is expected to benefit the health of 
the population as a whole, taking into account both users of tobacco 
products and persons who do not currently use tobacco products.
    In making determinations regarding the benefit to the health of 
individuals and the population as a whole under section 911(g)(1) or 
(g)(2), FDA will take into account:
     The relative health risks the MRTP presents to 
individuals;
     The increased or decreased likelihood that existing 
tobacco product users who would otherwise stop using such products will 
switch to using the MRTP;
     The increased or decreased likelihood that persons who do 
not use tobacco products will start using the MRTP;
     The risks and benefits to persons from the use of the MRTP 
as compared to the use of smoking cessation drug or device products 
approved by FDA to treat nicotine dependence; and
     Comments, data, and information submitted to FDA by 
interested persons.

Section 911(g)(4) of the FD&C Act

    Each applicant receiving an order from FDA under section 911(g)(1) 
or (g)(2) will conduct postmarket surveillance and studies, either as a 
condition of receiving an order under section 911(g)(2), or as required 
by FDA for products receiving an order under section 911(g)(1). (See 
section 911(g)(2)(C)(ii) and 911(i)(1) of the FD&C Act.)
    Section 911(h) of the FD&C Act describes additional conditions for 
marketing MRTPs. For example, under section 911(h)(1) of the FD&C Act, 
the advertising and labeling of an MRTP must enable the public to 
comprehend the information concerning modified risk and understand the 
relative significance of such information in the context of total 
health and in relation to all the diseases and health-related 
conditions associated with the use of tobacco products. Under section 
911(h)(2) of the FD&C Act, FDA may require that a claim comparing an 
MRTP

[[Page 36546]]

to one or more commercially marketed tobacco products compare the MRTP 
to a commercially marketed tobacco product that is representative of 
that type of tobacco product on the market. Under that section, FDA may 
also require that the identity of the reference tobacco product and the 
percentage change and a quantitative comparison of the amount of the 
substance claimed to be reduced be stated in immediate proximity to the 
most prominent claim. Under section 911(h)(3) of the FD&C Act, FDA may 
require that an MRTP's label disclose other substances in the tobacco 
product, or substances that may be produced by the consumption of that 
tobacco product, that may affect a disease or health-related condition 
or increase the risk of other diseases or health-related conditions 
associated with the use of tobacco products. Under that section, FDA 
may also require an applicant to label the product with conditions of 
use if the conditions of use may affect the risk of the product to 
human health. Section 911(h)(4) of the FD&C Act requires than an order 
issued under section 911(g)(1) of the FD&C Act be effective for a 
specified period of time. Furthermore, under section 911(h)(5) of the 
FD&C Act, FDA may require that MRTPs that are granted an order under 
section 911(g)(1) of the FD&C Act comply with requirements relating to 
advertising and promotion of the product.
    Section 911(l) of the FD&C Act requires FDA to issue regulations or 
guidance (or any combination thereof) regarding the scientific evidence 
required for assessment and ongoing review of modified risk tobacco 
products. Among other things, the regulations or guidance must:
     To the extent that adequate scientific evidence exists, 
establish minimum standards for scientific studies needed prior to 
issuing an order under section 911(g) to show that a substantial 
reduction in morbidity or mortality among individual tobacco users 
occurs (under 911(g)(1)) or is reasonably likely (under 911(g)(2));
     Include validated biomarkers, intermediate clinical 
endpoints, and other feasible outcome measures, as appropriate;
     Establish minimum standards for postmarket studies, that 
shall include regular and long-term assessments of health outcomes and 
mortality, intermediate clinical endpoints, consumer perception of harm 
reduction, and the impact on quitting behavior and new use of tobacco 
products, as appropriate; and
     Establish minimum standards for required postmarket 
surveillance, including ongoing assessments of consumer perception.

Section 911(l) of the FD&C Act

    Section 911(l)(2) of the FD&C Act directs FDA to get input from 
appropriate scientific and medical experts on the design and conduct of 
studies and surveillance required for assessment and ongoing review of 
modified risk tobacco products.

II. Workshop Objectives and Issues for Discussion

    The purpose of this public workshop is to obtain information and 
comments from appropriate medical and scientific experts, which may 
include academia, public health groups, regulators, manufacturers of 
tobacco products, health care professionals, interested industry, and 
professional associations, and the public about the scientific issues 
associated with assessment and ongoing review of MRTPs. The input from 
the public workshop is expected to provide valuable information to 
assist the Agency in developing guidance or regulations.
    At the public workshop, FDA will provide relevant background 
information, including a brief summary of section 911 of the FD&C Act, 
as added by the Tobacco Control Act. The meeting will include 
scientific and medical expert speakers who will present on scientific 
and technical factors related to the evaluation of MRTPs. FDA 
anticipates that the key questions that will be considered at the 
public workshop are those listed in the paragraphs that follow. FDA is 
interested in receiving substantive scientific input on these questions 
at the meeting and in the docket. FDA will post the agenda and 
additional workshop background material 5 days before the workshop at: 
http://www.fda.gov/TobaccoProducts/default.htm.

A. Benefit to Individual Tobacco Users

    Modified risk tobacco products have the potential to benefit 
individual tobacco users by reducing harm and the risk of tobacco-
related disease compared to conventional tobacco products. FDA seeks 
comments and information on the following issues:
    1. What scientific evidence would inform a determination that an 
MRTP, as actually used, will significantly reduce harm and the risk of 
tobacco-related disease to users? What types (if any) of scientific 
studies other than long-term epidemiological studies could show a 
significant reduction in harm and the risk of tobacco-related disease 
to users?
    2. What scientific evidence would inform a determination that an 
MRTP, as actually used, presents a reasonable likelihood of a 
measurable and substantial reduction in tobacco-related morbidity or 
mortality among individual tobacco users?

B. Impact on the Health of the Population as a Whole

    MRTPs may offer the potential for benefitting individual tobacco 
users by reducing the risk of tobacco-related morbidity or mortality 
associated with conventional tobacco products. However, these products 
could harm the health of the population as a whole if they lead to 
continued use of tobacco products in individuals who would otherwise 
have quit, resumption of tobacco use in individuals who previously quit 
(i.e., relapse), dual use among current tobacco users, or initiation of 
tobacco use among individuals who otherwise would not have used tobacco 
products. FDA seeks comments and information on the following issues 
related to the impact of an MRTP on the health of the population as a 
whole:
    1. What scientific evidence would inform a determination of how an 
MRTP will actually be used by consumers once it is commercially 
marketed, and what are the strengths and limitations of different 
methods of studying actual consumer use?
    2. What scientific evidence, including consumer perception data, 
would inform a determination of the effect an MRTP as it is proposed to 
be labeled and marketed will have on increasing initiation of tobacco 
use among non-users, decreasing or delaying cessation due to switching 
to the MRTP among current tobacco users, encouraging use of multiple 
tobacco products instead of complete switching among current tobacco 
users, and increasing relapse among previous tobacco users who have 
quit?
    3. What scientific evidence would inform the measurement of 
potential benefits relative to potential harms to the general 
population to achieve an overall public health benefit?

C. Comparisons of MRTPs to Other Products

    In making determinations regarding the benefit to the health of 
individuals and the population as a whole under either section 
911(g)(1) or (g)(2), FDA will take into account, among other things, 
the relative health risks to individuals of the MRTP and the risks and 
benefits to users of the MRTP as compared to the use of smoking 
cessation drugs or devices approved to

[[Page 36547]]

treat nicotine dependence. (See section 911(g)(4) of the FD&C Act.) FDA 
seeks comments and information on the following issues:
    1. What comparisons should be used in scientific studies intended 
to inform a determination of the effects of an MRTP on reducing the 
risk of tobacco-related disease to individual users relative to one or 
more commercially marketed tobacco products?
    2. What comparisons should be used in scientific studies intended 
to inform a determination of the effects of an MRTP on reducing 
exposure to a harmful substance or substances?
    3. What comparisons should be used in scientific studies intended 
to inform a determination of whether an MRTP will benefit or is likely 
to benefit the health of the population as a whole?
    4. What scientific evidence would inform the evaluation of the 
risks and benefits of the use of an MRTP as compared to use of drug or 
device products approved to treat nicotine dependence?

D. Reduced Substance Exposure

    Tobacco products are considered MRTPs if their label, labeling, or 
advertising represents, either explicitly or implicitly, that the 
product or its smoke contains a reduced level of a substance or 
presents a reduced exposure to a substance, or that the product or its 
smoke does not contain or is free of a substance. (See section 
911(b)(2)(A)(i) of the FD&C Act.) For FDA to issue an order regarding 
an MRTP application under section 911(g)(2), FDA must determine that 
the applicant has demonstrated that, among other things, the magnitude 
of the overall reductions in exposure to the substance or substances 
that are the subject of the application is substantial, such substance 
or substances are harmful, and the product as actually used exposes 
consumers to the specified reduced level of the substance or 
substances. Moreover, FDA must determine that the applicant has 
demonstrated that the MRTP, as actually used by consumers, will not 
expose them to higher levels of other harmful substances compared to 
the similar types of tobacco products then on the market unless the 
increases are minimal and the reasonably likely overall impact of the 
use of the MRTP remains a substantial and measurable reduction in 
overall morbidity and mortality. FDA seeks comments and information on 
the following issues:
    1. What scientific evidence would inform a determination that an 
MRTP (or its smoke) does not contain or contains a reduced level of a 
substance?
    2. What scientific evidence would inform a determination that the 
reduction in exposure to a substance presented by an MRTP is 
substantial?
    3. What scientific evidence would inform a determination that an 
MRTP as it is actually used by consumers will expose consumers to the 
specified reduced level of a substance?
    4. What scientific evidence would inform a determination that an 
MRTP does not increase exposure to other harmful substances? If an MRTP 
does increase exposure to another harmful substance, what scientific 
evidence would inform a determination that any increase is minimal and, 
overall, there is still a likelihood of a measurable and substantial 
reduction in morbidity and mortality among individual tobacco users?

E. Consumer Perception of MRTPs

    To issue an order under section 911(g)(2), FDA must find that the 
applicant has demonstrated that testing of actual consumer perceptions 
of the tobacco product, as it is proposed to be labeled and marketed, 
shows that consumers will not be misled into believing that the product 
is or has been demonstrated to be less harmful or that it presents or 
has been demonstrated to present less risk of disease than one or more 
commercially marketed tobacco products. (See section 911(g)(2)(B)(iii) 
of the FD&C Act.) Furthermore, section 911(h)(1) requires FDA to ensure 
that any advertising or labeling concerning modified risk products 
enable the public to comprehend the information concerning modified 
risk and to understand the relative significance of such information in 
the context of total health and in relation to all of the diseases and 
health-related conditions associated with the use of tobacco products. 
(See section 911(h)(1) of the FD&C Act.) FDA seeks comments and 
information on the following issues related to consumer perception:
    1. What scientific evidence would inform a determination that 
consumers will not be misled by a representation that an MRTP or its 
smoke does not contain or contains a reduced level of a substance into 
believing that the product is or has been demonstrated to be less 
harmful, or presents, or has been demonstrated to present, less risk of 
disease than one or more other commercially marketed tobacco products?
    2. What scientific evidence would inform a determination that 
consumers will comprehend the information concerning modified risk in 
an MRTP's advertising and labeling and understand the relative 
significance of such information in the context of total health and in 
relation to all the diseases and health-related conditions associated 
with the use of tobacco products?

F. Postmarket Surveillance and Studies of Commercially Marketed MRTPs

    Each applicant receiving an order from FDA under section 911(g)(1) 
or (g)(2) will conduct postmarket surveillance and studies, either as a 
condition of receiving an order under section 911(g)(2), or as required 
for products receiving an order under section 911(g)(1). (See section 
911(g)(2)(C)(ii) and 911(i)(1) of the FD&C Act.) Such surveillance and 
studies are designed to, among other things, determine the impact of an 
FDA order on consumer perception, behavior, and health, and enable FDA 
to review the accuracy of the determinations upon which the Agency 
based its order. (See section 911(g)(2)(C)(ii) and (i)(1) of the FD&C 
Act.) FDA seeks comments and information on the following issues 
related to postmarket surveillance and studies:
    1. What types of postmarket studies could provide regular and long-
term assessments of patterns of product use (e.g., dual use, product 
switching) and the impact of the MRTP on quitting behavior, relapse, 
and initiation of tobacco use?
    2. What types of postmarket studies could provide regular and long-
term assessments of exposure levels to harmful substances?
    3. What types of postmarket studies could provide regular and long-
term assessments of applicable validated biomarkers and intermediate 
clinical endpoints?
    4. What types of postmarket studies could provide regular and long-
term assessments of health outcomes and mortality?
    5. What types of postmarket studies could provide regular and long-
term assessments of consumer perception of the MRTP and other tobacco 
products?
    6. What types of postmarket surveillance (other than postmarket 
studies) could be used to ensure appropriate collection of data 
regarding the use, consumer perception, and health risks of an MRTP?

III. Transcripts

    Please be advised that as soon as a transcript is available, it 
will be accessible at http://www.regulations.gov. It may be viewed at 
the Division of Dockets Management (see Comments). A transcript will 
also be available in either hard copy or on CD-ROM, after submission of 
a

[[Page 36548]]

Freedom of Information request. Written requests are to be sent to 
Division of Freedom of Information (HFI-35), Office of Management 
Programs, Food and Drug Administration, 5600 Fishers Lane, rm. 6-30, 
Rockville, MD 20857.

    Dated: June 17, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-15601 Filed 6-21-11; 8:45 am]
BILLING CODE 4160-01-P