[Federal Register Volume 77, Number 64 (Tuesday, April 3, 2012)]
[Notices]
[Pages 20026-20030]
From the Federal Register Online via the Government Publishing 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Draft Guidance for Industry: Modified Risk Tobacco Product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availability of a draft guidance for industry entitled ``Modified Risk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 The draft guidance provides information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 The draft
guidance describes the information that the FD&C Act requires you to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 The draft guidance also permits the filing of a single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Agency considers your comment on this draft guidance before it begins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comments on the draft guidance by June 4, 2012.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ADDRESSES: Submit written requests for single copies of the draft
guidance document entitled ``Modified Risk Tobacco Product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your request or include a fax number to which the draft guidance may be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to the draft guidance document.
Submit electronic comments on the draft guidance, including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,
[email protected] or [email protected].
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, [email protected].
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))
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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]
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