[Federal Register Volume 80, Number 185 (Thursday, September 24, 2015)]
[Notices]
[Pages 57623-57627]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-24218]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-1939]


Use of Investigational Tobacco Products; Draft Guidance for 
Industry and Investigators; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry and investigators 
entitled ``Use of Investigational Tobacco Products.'' The draft 
guidance, when finalized, will describe FDA's current thinking 
regarding the definition of ``investigational tobacco product'' and 
will discuss the kind of information FDA intends to consider in making 
enforcement decisions regarding the use of investigational tobacco 
products until regulations governing the use of investigational tobacco 
products become effective or FDA provides written notice of its intent 
to change its enforcement policy.

DATES: Although you can comment on any 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draft guidance before it begins work on the final version of the 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 either electronic or written comments on the draft by 
November 23, 2015. Submit either electronic or written comments on the 
proposed collection of information by November 23, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Center for Tobacco Products, Food and Drug 
Administration, 10903 New Hampshire Ave., Silver Spring, MD 20993. 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your request or include a fax number to which the draft guidance may be 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to the draft guidance document.
    Submit electronic comments on the draft guidance, including 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 Submit written comments on the draft guidance, 
including comments on the proposed collection of information, to the 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should 
be identified with the docket number found in brackets in the heading 
of this document.

FOR FURTHER INFORMATION CONTACT: 
    With regard to the draft guidance: Laura Rich or Deirdre Jurand, 
Center for Tobacco Products, Food and Drug Administration, 10903 New 
Hampshire Ave., Silver Spring, MD 20993-0002, 1-877-287-1373, 
[email protected], [email protected], or 
[email protected].
    With regard to the proposed collection of information: FDA PRA 
Staff, Office of Operations, Food and Drug Administration, 8455 
Colesville Rd., COLE-14526, Silver Spring, MD 20993-0002, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
and investigators entitled ``Use of Investigational Tobacco Products.'' 
This draft guidance, when finalized, will describe FDA's current 
thinking regarding the definition of ``investigational tobacco 
product'' and will discuss the kind of information FDA intends to 
consider in making enforcement decisions regarding the use of 
investigational tobacco products until regulations governing the use of 
investigational tobacco products become effective or FDA provides 
written notice of its intent to change its enforcement policy. It is 
intended to provide guidance not only to persons who currently intend 
to submit study information to FDA, but to all persons who conduct 
``nonclinical laboratory studies,'' as that term is used in the draft 
guidance, and ``clinical investigations,'' as that term is used in the 
draft guidance, using investigational tobacco products.
    The draft guidance also discusses that for clinical investigations, 
a sponsor (as defined in the guidance) may submit information regarding 
a proposed use of an investigational tobacco product to FDA for review 
prior to enrolling subjects. As discussed in the guidance, FDA 
encourages this type of voluntary submission because it will allow FDA 
to work with a sponsor to help ensure that the factors FDA considers in 
making enforcement decisions are appropriately accounted for. FDA has 
created a form to assist sponsors in submitting information. While use 
of the form is voluntary, it will help ensure that complete information 
is provided for FDA's consideration and will facilitate FDA's 
processing and review. A copy of the form is attached as Appendix A to 
this guidance.
    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 amends the Federal Food, Drug, 
and Cosmetic Act (the FD&C Act) and 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.
    To introduce or deliver for introduction into interstate commerce a 
new tobacco product, there must be in effect a marketing authorization 
order issued by FDA for the tobacco product under section 
910(c)(1)(A)(i) of the FD&C Act (21 U.S.C. 387j(c)(1)(A)(i)) unless, in 
brief:
     A substantial equivalence order under section 
910(a)(2)(A)(i) of the FD&C Act is in effect for the tobacco product;
     FDA has granted a request for an exemption of the tobacco 
product from the requirement to obtain a substantial equivalence order 
and the manufacturer has made the required submission under section 
905(j)(1)(A)(ii) of the FD&C Act and waited 90 days before introducing 
its product to the market; or
     The manufacturer has submitted a substantial equivalence 
report in accordance with section 910(a)(2)(B) of the FD&C Act and 
there is no order finding that the tobacco product is not substantially 
equivalent.
    To introduce or deliver for introduction into interstate commerce a 
modified risk tobacco product, there must be in effect an order under 
section 911(g) of the FD&C Act (21 U.S.C. 387k(g)) and the applicant 
must satisfy any applicable premarket review requirements under section 
910 of the FD&C Act.
    Further, a tobacco product must conform in all respects with 
applicable tobacco product standards established under section 907 of 
the FD&C Act (21 U.S.C. 387g).
    Persons intending to file submissions with FDA to demonstrate that 
a tobacco product meets the criteria for marketing set forth in section 
910 or 911 of the FD&C Act, and other researchers seeking to study 
tobacco products, may need to conduct or sponsor studies involving 
tobacco products that do not have marketing authorization or that do 
not comply with an applicable tobacco product standard.

[[Page 57624]]

    Section 910(g) of the FD&C Act gives FDA the authority to issue 
regulations to exempt tobacco products intended for investigational use 
from the provisions of chapter IX of the FD&C Act, including premarket 
submission requirements. FDA intends to propose regulations 
establishing conditions for exempting investigational tobacco products 
from certain FD&C Act requirements. Until then, investigational tobacco 
products are not exempt from applicable FD&C Act requirements, 
including premarket submission requirements and tobacco product 
standards. This draft guidance discusses the factors FDA intends to 
consider in making enforcement decisions regarding the use of 
investigational tobacco products in both nonclinical laboratory studies 
and clinical investigations until regulations become effective or FDA 
provides written notice of its intent to change its enforcement policy.
    This draft guidance is being issued 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 ``Use of 
Investigational Tobacco Products.'' 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.

II. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (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.

Use of Investigational Tobacco Products (OMB Control Number 0910--NEW)

    FDA is announcing the availability of the draft guidance entitled 
``Use of Investigational Tobacco Products.'' This guidance, when 
finalized, will describe FDA's current thinking regarding the 
definition of ``investigational tobacco product'' and discuss the kind 
of information FDA intends to consider in making enforcement decisions 
regarding the use of investigational tobacco products until regulations 
become effective or FDA provides written notice of its intent to change 
its enforcement policy. When finalized, it is intended to provide 
guidance, not only to persons who currently intend to submit study 
information to FDA, but to all persons who conduct nonclinical 
laboratory studies and clinical investigations using investigational 
tobacco products. Such persons may include sponsors, investigators, 
sponsor-investigators, contract research organizations (CROs),\1\ and 
committees or groups formally designated to oversee research involving 
human subjects (e.g., institutional review boards (IRBs)) involved in 
investigations using investigational tobacco products.
---------------------------------------------------------------------------

    \1\ The term ``contract research organization'' (CRO) as used in 
this draft guidance means a person that assumes, as an independent 
contractor with the sponsor, one or more of the obligations of the 
sponsor (e.g., design of a protocol).
---------------------------------------------------------------------------

    We have identified the following recommendations in the draft 
guidance as collections of information.
    In the draft guidance, FDA provides examples of information that 
may help FDA to evaluate specific proposed uses of investigational 
tobacco products, and encourages persons who intend to study 
investigational tobacco products to meet with FDA to discuss certain 
topics in connection with nonclinical laboratory studies and clinical 
investigations.
    For clinical investigations, FDA encourages sponsors to submit 
information regarding a proposed use of an investigational tobacco 
product to FDA for review prior to enrolling subjects in the planned 
investigation. FDA has created a form to assist sponsors in submitting 
information. While use of this form is voluntary, its use will likely 
reduce the burden hours and will help ensure that sponsors provide 
complete information for FDA's consideration, processing, and review.
    Furthermore, to ensure that studies are conducted in a manner that 
protects human subjects, the draft guidance contains recommendations as 
to how sponsors should put procedures in place to keep FDA and the 
committee or group formally designated to oversee research involving 
human subjects informed about any changes relating to the conduct of, 
and issues that arise during, the study. In the draft guidance, FDA 
further recommends that sponsors, CROs, sponsor-investigators, and 
clinical investigators maintain documentation to permit evaluation of 
the conduct of a clinical investigation, including assessing the 
quality and integrity of the study data and protection of human 
subjects.
    In the draft guidance, FDA also recommends that sponsors consult 
with the Agency, clinical investigators, and any committee or group 
formally designated to oversee research involving human subjects when 
certain events occur during the conduct of a clinical investigation, 
including adverse experiences. In addition, FDA recommends that 
sponsors notify FDA if they choose to terminate a study (or withdraw or 
inactivate a protocol or want to withdraw all studies of a product) 
before completion and in the notification include certain information. 
Moreover, in the draft guidance, FDA recommends that under certain 
circumstances, sponsors also should inform any clinical investigators 
who participated in the discontinued investigation of the reason(s) for 
discontinuing the clinical investigation.
    FDA also makes recommendations related to nonclinical laboratory 
studies and clinical investigations of using investigational tobacco 
products conducted outside of the United States (U.S.), but intended 
for submission to FDA, and refers to section 801(e) of the FD&C Act 
with respect to exported tobacco products intended for investigational 
use. The guidance also recommends that sponsors should prepare and 
maintain certain records and reports, for studies conducted outside of 
the U.S. but intended for submission to FDA to permit FDA to evaluate 
the conduct of a clinical investigation, including assessing the 
quality and integrity of the study data and protection of human 
subjects.

[[Page 57625]]

    FDA estimates the burden of this collection of information as 
follows:

                                                       Table 1--Estimated Annual Reporting Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                            Capital and
                                           Number of      Number of     Total annual                                                       operating and
        Activity/FDA form 3934            respondents   responses per    responses        Average burden per response       Total hours     maintenance
                                                          respondent                                                                           costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Initial Submission....................              30            1             30    40.................................       1,200     ..............
Protocol Submission...................              10            1             10    20.................................         200     ..............
Protocol Amendments...................               5            1              5    0.50 (30 minutes)..................           2.5   ..............
Information Amendments................               4            1              4    15.................................          60     ..............
Administrative Amendments.............               1            1.5            1.5  0.50 (30 minutes)..................           0.75  ..............
Other Information.....................               3            1              3    0.50 (30 minutes)..................           1.5   ..............
Serious or Unexpected Adverse                        4            3             12    2..................................          24     ..............
 Experience Reports.
First year, electronic set-up safety                 4            1              4    0.33 (20 minutes)..................           1.3   ..............
 reporting portal.
First year, Electronic Gateway setup                30            1             30    42 \1\.............................       1,260             37,800
 and verification certificate (One
 time burden).
Electronic Gateway Submission                       30            1             30    3..................................          90              2,700
 (recurring).
                                       ----------------------------------------------                                     ------------------------------
    Total Reporting Burden Hours......  ..............  .............  .............  ...................................       2,840             40,500
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Respondent may already have a valid WebTrader account established for other FDA electronic submissions.

    Table 1 describes the annual reporting burden as a result of 
respondents submitting information regarding the use of investigational 
tobacco products in certain clinical investigations. FDA estimates that 
30 respondents will submit study information to FDA annually. FDA 
estimates that it will take each respondent approximately 40 hours to 
prepare the study information necessary for FDA to issue a response to 
the proposed use of an investigational tobacco product in these 
clinical investigations. FDA's estimate includes the anticipated burden 
for completing the form for the initial submission, which will include 
the initial protocol, time for intra-company edits and approvals, as 
well as the burden for assembling additional information, as described 
in the draft guidance.
    The initial submission should include an initial study protocol, 
which should in turn include certain information and call for 
recordkeeping or other steps that may involve the submission of 
information to others. In addition, sponsors may wish to provide 
protocol amendments to reflect certain changes to a protocol. FDA 
estimates that 10 respondents will submit a new protocol. The estimated 
time for submitting a new protocol is 20 hours per response. Only 4 
respondents are estimated to submit information amendments. Since this 
may take a little less than half the time of an initial submission, FDA 
estimates information amendments taking around 15 hours.
    FDA estimates that it could take respondents 30 minutes to prepare 
protocol amendments and that about 5 respondents submitting study 
information will submit protocol amendments.
    FDA estimates that respondents will infrequently need to report 
administrative amendments. The total number of respondents of this type 
of information is estimated to be 1. FDA estimates that this submission 
is estimated to take 30 minutes per respondent.
    FDA estimates that approximately 3 respondents will report other 
types of submissions. This submission is estimated to take 30 minutes 
per response.
    FDA estimates that 4 respondents will report serious or unexpected 
adverse experiences. This submission will take an average of 2 hours 
per respondent. FDA estimates that setting up an account in safety 
reporting portal for submission of serious or unexpected experiences 
will take 20 minutes per response.
    As referenced in the guidance, FDA allows for three ways of 
submission but strongly encourages the use of electronic format for 
submission. The submitter should first set up an account with WebTrader 
to go through the Electronic Submissions Gateway (ESG). FDA estimates 
from past experience with the ESG system, WebTrader, that the first 
year to set up the account and to receive the verification certificate 
takes approximately 40 hours. This burden may be minimized if the 
respondent already has an established account in WebTrader for other 
electronic submissions to FDA, but FDA is assuming that all respondents 
for these products will be setting up a WebTrader account for the first 
time in the first year. In subsequent years, the burden hours are 
estimated at 1 hour to renew the yearly required Verification 
Certification.
    FDA further estimates that the gathering, scanning, and submission 
of information and related correspondence would take approximately 2 
hours utilizing the eSubmitter system.
    Therefore, the first year will include 40 hours for the WebTrader 
system plus 2 hours for the eSubmitter submission process, resulting in 
42 hours per response for the first year. For subsequent years, it is 
estimated that only 1 hour will be necessary for the WebTrader system 
plus the 2 hours for the eSubmitter submission process, resulting in 3 
hours per response each year thereafter.
    Additionally, there are capital and operating or maintenance costs 
associated with this information collection. The costs are $30 per year 
to establish and maintain the ESG verification certificate. The total 
cost may be lower if the respondents already have a verification 
certificate for that year for other electronic submissions to FDA. 
However, for purposes of this estimate, FDA is assuming that all 
respondents for these products will be

[[Page 57626]]

incurring this cost. The total costs are estimated to be $40,500.
    The total reporting burden for this collection of information is 
estimated to be 2,840 hours. These burden estimates were computed using 
FDA staff expertise and by reviewing comments received from recent FDA 
information collections for other tobacco-related initiatives.

                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                    Average burden
   Activity records maintained       Number of      records per    Total annual         per         Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
Records by Sponsors.............              50               1              50              10             500
Records By Sponsor-Investigators              20               1              20              20             400
Records by Investigators and                  50               1              50              15             750
 CROs...........................
                                 -------------------------------------------------------------------------------
    Total Recordkeeping Burden    ..............  ..............  ..............  ..............           1,650
     Hours......................
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Table 2 describes the annual recordkeeping burden of maintaining 
records relating to the investigational use of tobacco products. FDA 
anticipates that 50 sponsors will maintain records relating to the use 
of investigational tobacco products in clinical investigations. FDA 
estimates that it will take each of them approximately 10 hours 
annually to maintain these records. FDA anticipates that there will 
generally be one investigator per investigation. FDA anticipates there 
will be a total of 120 sponsors, sponsor-investigators, investigators, 
and CROs who will maintain records relating to the use of 
investigational tobacco products in clinical investigations. FDA 
estimates that it will take each sponsor approximately 10 hours 
annually to maintain these records. FDA estimates that it will take 
each sponsor-investigator approximately 20 hours annually to maintain 
these records. FDA estimates that it will take each of these 
investigators and CROs approximately 15 hours annually to maintain 
these records. The total reporting burden for recordkeeping is 
estimated to be 1,650 hours (500 hours for sponsors + 400 hours for 
sponsor-investigators + 750 for investigators and CROs.)

                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Number of
                  Activity                       Number of      disclosures    Total annual          Average burden per disclosure          Total hours
                                                respondents   per respondent    disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
Disclosures to Investigators................              30               1              30  1.........................................              30
Disclosures to any Committee or Group.......              30               1              30  0.17 (10 minutes).........................               5
Disclosure to Study Subjects................              30               2              60  0.50 (30 minutes).........................              30
                                             ------------------------------------------------                                            ---------------
    Total...................................  ..............  ..............  ..............  ..........................................              65
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    Table 3 describes the annual third party disclosure burden.
    FDA estimates that disclosing information to investigators will 
take 1 hour per disclosure. FDA estimates that disclosing information 
to any committee or group formally designated to oversee research 
involving human subjects will average 10 minutes per disclosure.
    The guidance also references examples of disclosing information to 
study subjects such as informed consent. On average, two disclosures 
per respondent will be provided to study subjects. FDA estimates this 
will take 30 minutes per disclosure.
    The total burden for the collection of information under this draft 
guidance is estimated to be 4,455 hours.
    This draft guidance also refers to previously approved collections 
of information. The draft guidance includes a recommendation that 
persons who intend to study tobacco products meet with FDA to discuss 
research plans. Additional information about how to request meetings 
with FDA's Center for Tobacco Products can be found in FDA's guidance: 
``Meetings with Industry and Investigators on the Research and 
Development of Tobacco Products.'' The collections of information in 
the guidance referenced have been approved under OMB control number 
0910-0731. The collections of information in section 801(e) of the FD&C 
Act and 21 CFR 1.101(b) have been approved under OMB control number 
0910-0482; the collections of information for the Safety Reporting 
Portal have been approved under OMB control number 0910-0645; the 
collections of information in section 905(j) of the FD&C Act have been 
approved under OMB control number 0910-0673.

III. Request for Comments

A. General Information About Submitting Comments

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). 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.

B. Public Availability of Comments

    Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to 
the docket at http://www.regulations.gov. As a matter of Agency 
practice, FDA generally does not post comments submitted by individuals 
in their individual capacity on http://www.regulations.gov. This is

[[Page 57627]]

determined by information indicating that the submission is written by 
an individual, for example, the comment is identified with the category 
``Individual Consumer'' under the field titled ``Category (Required),'' 
on the ``Your Information'' page on www.regulations.gov. For this 
docket, however, FDA will not be following this general practice. 
Instead, FDA will post on http://www.regulations.gov comments to this 
docket that have been submitted by individuals in their individual 
capacity. If you wish to submit any information under a claim of 
confidentiality, please refer to 21 CFR 10.20.

C. Information Identifying the Person Submitting the Comment

    Please note that your name, contact information, and other 
information identifying you will be posted on http://www.regulations.gov if you include that information in the body of your 
comments. For electronic comments submitted to http://www.regulations.gov, FDA will post the body of your comment on http://www.regulations.gov along with your state/province and country (if 
provided), the name of your representative (if any), and the category 
identifying you (e.g., individual, consumer, academic, industry). For 
written submissions submitted to the Division of Dockets Management, 
FDA will post the body of your comments on http://www.regulations.gov, 
but you can put your name and/or contact information on a separate 
cover sheet and not in the body of your comments.

IV. Electronic Access

    Persons with access to the Internet may obtain an electronic 
version of this guidance document at http://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/ucm281147.htm or 
http://www.regulations.gov.

    Dated: September 16, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-24218 Filed 9-23-15; 8:45 am]
BILLING CODE 4164-01-P