
[Federal Register Volume 77, Number 64 (Tuesday, April 3, 2012)]
[Notices]
[Pages 20026-20030]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-7908]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-D-0071]


Draft Guidance for Industry: Modified Risk Tobacco Product 
Applications; Availability; Agency Information Collection Activities; 
Proposed Collection; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Modified Risk 
Tobacco Product Applications.'' The draft guidance provides information 
about submitting applications for modified risk tobacco products under 
the Federal Food, Drug, and Cosmetic Act (the FD&C Act). The draft 
guidance describes the information that the FD&C Act requires you to 
submit in your modified risk tobacco product application and the 
scientific evidence FDA recommends you submit to support your 
application. The draft guidance also permits the filing of a single 
application for any modified risk tobacco product that is also a new 
tobacco product under the FD&C Act.

DATES: Although you can submit written or electronic comments on this 
guidance at any time (see 21 CFR 10.115(g)(5)), to ensure that the 
Agency considers your comment on this draft guidance before it begins 
work on the final version of the guidance, submit electronic or written 
comments on the draft guidance by June 4, 2012. Submit electronic or 
written comments on the proposed collection of information by June 4, 
2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance document entitled ``Modified Risk Tobacco Product 
Applications'' to the Center for Tobacco Products, Food and Drug 
Administration, 9200 Corporate Blvd., Rockville, MD 20850-3229. Send 
one self-addressed adhesive label to assist that office in processing 
your request or include a fax number to which the draft guidance may be 
sent. See the SUPPLEMENTARY INFORMATION section for electronic access 
to the draft guidance document.
    Submit electronic comments on the draft guidance, including 
comments on the proposed collection of information, 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.

FOR FURTHER INFORMATION CONTACT:  With regard to the draft guidance: 
Gail Schmerfeld or Kristin Davis, Center for Tobacco Products, 9200 
Corporate Blvd., Rockville, MD 20850-3229, 1-877-287-1373, 
gail.schmerfeld@fda.hhs.gov or kristin.davis@fda.hhs.gov.
    With regard to the proposed collection of information: Daniel 
Gittleson, Office of Information Management, Food and Drug 
Administration, 1350 Piccard Dr., P150-400B, Rockville, MD 20850, 301-
796-5156, Daniel.Gittleson@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    On June 22, 2009, the President signed the Family Smoking 
Prevention and Tobacco Control Act (Pub. L. 111-31) (Tobacco Control 
Act) into law. The Tobacco Control Act grants FDA authority to regulate 
the manufacture, marketing, and distribution of tobacco products to 
protect public health generally and to reduce tobacco use by minors. 
Congress found that it is essential that, prior to marketing tobacco 
products for use to reduce harm or the risk of tobacco-related disease 
or to reduce exposure to harmful substances associated with tobacco 
products, manufacturers be required to ``demonstrate that such products 
* * * meet a series of rigorous criteria, and will benefit the health 
of the population as a whole'' (section 2(36) of the Tobacco Control 
Act). Thus, section 101 of the Tobacco Control Act added section 911 
(21 U.S.C. 387k) to the FD&C Act to prohibit the introduction or 
delivery for introduction into interstate commerce of any modified risk 
tobacco product unless an order

[[Page 20027]]

issued by FDA pursuant to section 911(g) of the FD&C Act is effective 
with respect to such product. A modified risk tobacco product is any 
tobacco product that is sold or distributed for use to reduce harm or 
the risk of tobacco-related disease associated with commercially 
marketed tobacco products (section 911(b)(1) of the FD&C Act).
    Section 911(l)(1) of the FD&C Act directs FDA to issue regulations 
or guidance (or any combination thereof) on the scientific evidence 
required for assessment and ongoing review of modified risk tobacco 
products. FDA is issuing this draft guidance in compliance with section 
911(l)(1). When finalized, the draft guidance will provide industry 
with information on who submits modified risk tobacco product 
applications (MRTPAs), when to submit a MRTPA, what information section 
911 of the FD&C Act requires applicants to submit in a MRTPA, what 
scientific evidence FDA recommends applicants include in a MRTPA, what 
information should be collected through postmarket surveillance and 
studies, how to organize and submit the MRTPA, and FDA's timeframe for 
review of a MRTPA. It will also provide for the filing of a single 
application for any modified risk tobacco product that is also a new 
tobacco product.
    Section 911(l)(2) of the FD&C Act directs FDA to consult with the 
Institute of Medicine (IOM), and get the input of other appropriate 
scientific and medical experts, on the design and conduct of studies 
required for the assessment and ongoing review of modified risk tobacco 
products. FDA gave IOM its charge on February 2, 2011. IOM published 
its report on December 14, 2011. The report is available through http://www.iom.edu/Reports/2011/Scientific-Standards-for-Studies-on-Modified-Risk-Tobacco-Products.aspx and will be placed in the docket for this 
draft guidance. In order to get input from other experts, FDA held a 
public workshop on August 25 and 26, 2011, and established a docket, 
FDA-2011-N-0443, to receive public comments. FDA intends to consider 
the IOM report and comments submitted to the public workshop docket in 
preparing the final guidance.

II. Significance of Guidance

    FDA is issuing this draft guidance document consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The draft guidance, 
when finalized, will represent the Agency's current thinking on 
``Modified Risk Tobacco Product Applications.'' It does not create or 
confer any rights for or on any person and does not operate to bind FDA 
or the public. An alternative approach may be used if such approach 
satisfies the requirements of the applicable statute and regulations.

III. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 
3501-3520), Federal Agencies must obtain approval from the Office of 
Management and Budget (OMB) for each collection of information they 
conduct or sponsor. ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal Agencies to provide a 
60-day notice in the Federal Register concerning each proposed 
collection of information before submitting the collection to OMB for 
approval. To comply with this requirement, FDA is publishing notice of 
the proposed collection of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

Draft Guidance for Industry: Modified Risk Tobacco Product Applications 
(OMB Control Number 0910-NEW)

    This draft guidance describes the information that the FD&C Act 
requires you to submit in your MRTPA as well as FDA's recommendations 
regarding the scientific evidence that should be contained in a MRTPA 
for FDA to make an assessment and conduct an ongoing review of modified 
risk tobacco products. The draft guidance also permits the filing of a 
single application for any modified risk tobacco product that is also a 
new tobacco product under section 910 of the FD&C Act. The draft 
guidance document discusses, among other things: Who submits MRTPAs, 
when to submit a MRTPA, what information section 911 of the FD&C Act 
requires applicants to submit in a MRTPA, what scientific evidence FDA 
recommends applicants include in a MRTPA, what information should be 
collected through postmarket surveillance and studies, and how to 
organize and submit a MRTPA. The purpose of the proposed information 
collection is to allow FDA to collect statutorily mandated information 
regarding modified risk tobacco products and other information that 
will facilitate FDA's effective and efficient review of MRTPAs.
    Modified risk tobacco products 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 (section 
911(b)(1) of the FD&C Act). No person may introduce or deliver for 
introduction into interstate commerce any modified risk tobacco product 
unless an order issued pursuant to section 911(g) of the FD&C Act is 
effective with respect to that product (section 911(a) of the FD&C 
Act).
    Under section 911(d) of the FD&C Act, a MRTPA must contain:
     A description of the proposed product and any proposed 
advertising and labeling;
     The conditions for using the product;
     The formulation of the product;
     Sample product labels and labeling;
     All documents (including underlying scientific 
information) relating to research findings conducted, supported, or 
possessed by the tobacco product manufacturer relating to the effect of 
the product on tobacco-related diseases and health-related conditions, 
including information both favorable and unfavorable to the ability of 
the product to reduce risk or exposure and relating to human health;
     Data and information on how consumers actually use the 
tobacco product; and
     Such other information as the Secretary may require.
    Further, FDA's regulation implementing the National Environmental 
Policy Act of 1969 requires that ``[a]ll applications or petitions 
requesting agency action require the submission of an [environmental 
assessment] or a claim of categorical exclusion'' (21 CFR 25.15(a)).
    Section 911(g) of the FD&C Act describes the demonstrations 
applicants must make to obtain an order from FDA. Sections 911(g)(1) 
and (2) of the FD&C Act set forth two bases for FDA to issue an order.

[[Page 20028]]

    A ``risk modification order'' is an order permitting the 
introduction or delivery for introduction into interstate commerce of a 
tobacco product that FDA has found meets the criteria for an order 
under section 911(g)(1) of the FD&C Act. In order for FDA to issue a 
risk modification order under section 911(g)(1) of the FD&C Act, the 
applicant must demonstrate that the proposed modified risk tobacco 
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.
    An ``exposure modification order'' is an order permitting the 
introduction or delivery for introduction into interstate commerce of a 
tobacco product that reduces or eliminates exposure to a substance and 
for which the available scientific evidence suggests that a measurable 
and substantial reduction in morbidity and mortality is likely to be 
demonstrated in future studies. In order for FDA to issue an exposure 
modification order, the applicant must satisfy all of the criteria for 
issuance of an order under section 911(g)(2) of the FD&C Act.
    FDA may issue an exposure modification order under section 
911(g)(2) of the FD&C Act (the ``special rule'') if it determines that 
the 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 a modified risk tobacco 
product 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 obtaining an order under section 911(g)(1); 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 
(section 911(g)(2)(A) of the FD&C Act).
    Furthermore, for FDA to issue an exposure modification order, FDA 
must find that the applicant has demonstrated that:
     The magnitude of overall reductions in exposure to the 
substance or substances, which 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 the 
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 the exposure modification 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 (section 911(g)(2)(B) of the FD&C Act).
    In evaluating the benefit to health of individuals and of the 
population as a whole under sections 911(g)(1) and (g)(2) of the FD&C 
Act, FDA must take into account:
     The relative health risks the modified risk tobacco 
product 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 modified risk tobacco product;
     The increased or decreased likelihood that persons who do 
not use tobacco products will start using the modified risk tobacco 
product;
     The risks and benefits to persons from the use of the 
modified risk tobacco product 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).
    Furthermore, FDA must ensure that the advertising and labeling of 
the MRTP 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 tobacco-related diseases and health conditions (section 911(h)(1) 
of the FD&C Act).
    FDA intends to determine whether it will issue an order under 
section 911(g) within 360 days after the receipt of a complete 
application and will issue such an order only if the application 
satisfies all the applicable requirements in section 911.
    A risk modification order issued under section 911(g)(1) will be 
effective for the period of time specified in the order issued by FDA 
(section 911(h)(4) of the FD&C Act). An applicant to whom a risk 
modification order is issued under section 911(g)(1) must conduct 
postmarket surveillance and studies (section 911(i)(1) of the FD&C 
Act).
    An exposure modification order issued under section 911(g)(2) will 
be effective for a term of not more than 5 years. FDA may renew an 
exposure modification order if the applicant files a new application, 
and FDA finds that the requirements for such order under section 
911(g)(2) continue to be satisfied (section 911(g)(2)(C)(i) of the FD&C 
Act). Further, an exposure modification order will be conditioned on 
the applicant's agreement to conduct postmarket surveillance and 
studies and to submit the results of such surveillance and studies to 
FDA annually (section 911(g)(2)(C)(ii) and (iii) of the FD&C Act).
    The postmarket surveillance and studies that all applicants who 
receive orders are required to conduct are intended to determine the 
effect of issuance of an order on consumer perception, behavior, and 
health, and enable FDA to review the accuracy of the determinations 
upon which an order was based (section 911(g)(2)(C)(ii) and (i)(1) of 
the FD&C Act). An applicant who receives a risk modification order must 
also conduct postmarket surveillance and studies that provide 
information FDA determines is otherwise necessary regarding the use or 
health risks involving the tobacco product (section 911(i)(1) of the 
FD&C Act).
    If the proposed modified risk tobacco product is a new tobacco 
product within the meaning of section 910(a)(1), the new tobacco 
product must satisfy any applicable premarket review requirements under 
section 910 of the FD&C Act, in addition to any requirements under 
section 911 of the

[[Page 20029]]

FD&C Act. A new tobacco product must be found to be substantially 
equivalent, exempt from the requirement to obtain a substantial 
equivalence determination, or have a marketing authorization order 
under section 910(c)(1)(A)(i). The collections of information relating 
to premarket review described in the ``Guidance for Industry: Section 
905(j) Reports: Demonstrating Substantial Evidence for Tobacco 
Products'' (OMB control number 0910-0673), 21 CFR part 1107 
(Establishment Registration, Product Listing, and Substantial 
Equivalence Reports) (OMB control number 0910-0684), and ``Draft 
Guidance for Industry: Applications for Premarket Review of New Tobacco 
Products'' (OMB control number 0910-NEW) have been previously approved, 
or are pending approval, by OMB. An applicant may file the appropriate 
report or application to satisfy any applicable premarket review 
requirements and a separate application under section 911. In the 
alternative, the applicant may file a single application. The single 
application must include the information required for the applicable 
premarket review (i.e., substantial equivalence report, request of 
exemption from substantial equivalence requirements, or the information 
required for premarket review under section 910(b) of the FD&C Act), as 
well as the information required to support issuance of an order under 
section 911(g) of the FD&C Act. To the extent data or information 
contained in the premarket review portion of the application is also 
relevant to or required for the modified risk determination, the 
applicant may cross-reference that data or information rather than 
duplicate it in the modified risk portion of the application.
    Description of respondents: The respondents to this collection of 
information are applicants who are responsible for creating and 
submitting modified risk tobacco product applications and who wish to 
obtain an FDA order to allow them to market their product. While it is 
expected that many of the respondents will be manufacturers, 
respondents could include importers, distributors, and retailers of 
tobacco products.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                                                      Average
      Information collected          Number of       Number of     Total annual     burden per     Total annual
          (section(s))              respondents    responses per     responses     response  (in       hours
                                                    respondent                        hours)
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MRTPA (911(d) of FD&C Act)......               3               1               3          45,200         135,600
Environmental analysis (21 CFR                 3               1               3              10              30
 25.15).........................
Request for a meeting prior to                 8               1               8               8              64
 submitting a MRTPA.............
Submission of postmarket                       3               1               3              30              90
 surveillance and study
 protocols (911(g)(2)(C)(ii) and
 911(i)(2)).....................
Conduct of postmarket                          5               1               5          40,200         201,000
 surveillance and studies
 (911(g)(2)(C)(ii) and
 911(i)(1)).....................
Annual submission of results of                5               1               5             140             700
 postmarket surveillance and
 studies (911(g)(2)(C)(iii) and
 911(i)(1)).....................
Requests for renewal                           1               1               1             140             140
 (911(g)(2)(C)(i) and 911(h)(4))
                                 -------------------------------------------------------------------------------
    Total Reporting Burden Hours  ..............  ..............  ..............  ..............         337,624
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

    Table 1 describes the annual reporting burden as a result of 
submitting a MRTPA. FDA estimates that it will receive 3 MRTPAs 
annually and that it will take the applicant 200 hours to collect the 
information necessary to submit a MRTPA under section 911 of the FD&C 
Act. FDA estimates it will take the applicant an additional 45,000 
hours to conduct studies needed to support its MRTPA. FDA is also 
including an estimation of the burden associated with preparing 
environmental analyses. FDA estimates that it will take an additional 
10 hours to prepare any environmental analyses. FDA encourages persons 
considering developing a MRTPA to meet with CTP to discuss MRTPA 
submission and investigational requirements. FDA anticipates that eight 
persons considering developing MRTPAs may request meetings with FDA. 
FDA estimates it will take 8 hours to prepare a meeting request, 
including background information.
    Section 911 of the FD&C Act requires applicants to whom FDA issues 
orders to conduct postmarket surveillance and studies and submit 
relevant information to FDA on an annual basis. Applicants must submit 
and receive FDA approval of surveillance protocols. FDA estimates that 
it will take 30 hours to collect and submit the protocol information to 
FDA. FDA estimates it will take the applicant an additional 40,200 
hours to conduct the postmarket surveillance and studies. FDA estimates 
5 applicants will submit results of postmarket surveillance and studies 
annually and it will take 140 hours to prepare each submission.
    Because orders issued under section 911(g) are valid for only a set 
number of years, FDA expects applicants will submit requests for 
renewal. Because the dates on which orders are issued and the length of 
the period for which the order is valid will vary, FDA expects one 
request for renewal annually. FDA estimates that it will take 140 hours 
to prepare the request for renewal.
    The total number of hours for this collection of information is 
estimated to be 337,624 ((3 x (45,200 + 10)) + (8 x 8) + (3 x 30) + (5 
x 40,200) + (5 x 140) + (1 x 140)). These burden estimates were 
computed using FDA staff expertise and by reviewing comments received 
from recent FDA information collections for other tobacco-related 
initiatives.

IV. Request for Comments

    FDA requests comments from interested parties on any of the topics 
addressed in the draft guidance. In addition, as stated in the ``I. 
Background'' section, FDA intends to consider the IOM report in 
preparing the final guidance. Therefore, FDA requests comments from 
interested parties on the IOM report, which was issued on December 14, 
2011. FDA specifically requests comments on:
     IOM's Recommendation 2: ``The FDA should establish 
guidance that conveys an expected sequencing of studies, such that 
preclinical work is

[[Page 20030]]

completed and submitted to the FDA before clinical (human subjects) 
work commences, and [FDA should establish] that there is a reasonable 
expectation based on preclinical work that a reduction or lack of harm 
will be seen in humans.'' Should FDA address expected sequencing of 
studies in its guidance? If the Agency should, what guidance should the 
Agency provide?; and
     IOM's Recommendation 10: ``MRTP sponsors should consider 
use of independent third parties to undertake one or more key 
functions, including the design and conduct of research, the oversight 
of specific studies, and the distribution of sponsor funds for 
research. Such independent third parties should be approved by the FDA 
in advance of the research.'' Should FDA recommend such an approach in 
its guidance? If the Agency should, what guidance should the Agency 
provide?
    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of 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.

V. Electronic Access

    Persons with access to the Internet may obtain an electronic 
version of the draft guidance document at http://www.regulations.gov 
and http://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/default.htm.

    Dated: March 28, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-7908 Filed 3-30-12; 11:15 am]
BILLING CODE 4160-01-P


