[Federal Register Volume 84, Number 35 (Thursday, February 21, 2019)]
[Notices]
[Pages 5448-5453]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-02971]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Use of Investigational Tobacco Products; Revised Draft Guidance 
for Industry and Investigators; Availability; Agency Information 
Collection Activities; Proposed Collection; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a revised draft guidance for industry and investigators 
entitled ``Use of Investigational Tobacco Products.'' The revised draft 
guidance replaces the draft guidance of the same title announced in the 
Federal Register of September 24, 2015 (September 2015 draft guidance). 
The revised draft guidance, when finalized, will describe FDA's current 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DATES: Submit either electronic or written comments on the draft 
guidance by April 22, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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 
proposed collection of information by April 22, 2019.

ADDRESSES: You may submit comments on any guidance at any time as 
follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2014-D-1939 for ``Use of Investigational Tobacco Products; Revised 
Draft Guidance for Industry and Investigators; Availability; Agency 
Information Collection Activities; Proposed Collection; Comment 
Request.'' Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at https://www.regulations.gov or at the Dockets Management Staff 
between 9 a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    Submit written requests for single copies of this draft guidance to 
the Center for Tobacco Products, Food and Drug Administration, Document 
Control Center, Bldg. 71, Rm. G335, 10903 New Hampshire Ave., Silver 
Spring, MD 20993-0002. 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 information on electronic access to the draft guidance.

FOR FURTHER INFORMATION CONTACT: 
    With regard to the draft guidance: Laura Rich or Samantha 
LohCollado,

[[Page 5449]]

Center for Tobacco Products, Food and Drug Administration, Document 
Control Center, Bldg. 71, Rm. G335, 10903 New Hampshire Ave., Silver 
Spring, MD 20993-0002, 1-877-287-1373, email: [email protected].
    With regard to the proposed collection of information: Amber 
Sanford, Office of Operations, Food and Drug Administration, Three 
White Flint North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 
20852, 301-796-8867, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a revised draft guidance for 
industry entitled ``Use of Investigational Tobacco Products.'' This 
revised draft guidance replaces the September 2015 draft guidance and, 
when final, 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 
are issued and become effective or FDA provides written notice of its 
intent to change its enforcement policy. It is intended to provide 
guidance to persons who currently intend to submit study information on 
tobacco products to FDA as well as to persons who conduct 
investigations using investigational tobacco products.
    The Family Smoking Prevention and Tobacco Control Act (Pub. L. 111-
31) (Tobacco Control Act), enacted on June 22, 2009, amended the 
Federal Food, Drug, and Cosmetic Act (the FD&C Act) and provided FDA 
with the authority to regulate the manufacture, marketing, and 
distribution of tobacco products to protect the 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:
     The manufacturer has submitted a substantial equivalence 
report for the tobacco product under section 905(j) of the FD&C Act (21 
U.S.C. 387e(j)) and obtained from FDA a substantial equivalence order 
under section 910(a)(2)(A)(i) of the FD&C Act;
     The manufacturer has submitted, under 21 CFR 1107.1, a 
request for an exemption for the tobacco product from the requirement 
to obtain a substantial equivalence order, FDA has granted the 
exemption request, 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.
    Furthermore, 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). Any tobacco product, including a tobacco 
product intended for investigational use, is deemed adulterated if it 
is subject to a tobacco product standard established under section 907 
of the FD&C Act and does not in all respects conform with such 
standard.
    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.
    FDA recognizes that researchers may seek to study tobacco products 
that do not have marketing authorization or that do not comply with an 
applicable tobacco product standard. Until regulations governing the 
use of investigational tobacco products are issued and finalized, FDA 
intends to evaluate specific uses of investigational tobacco products 
according to potential human subject protection concerns or other 
impacts on public health. This revised draft guidance discusses the 
factors FDA intends to consider in making enforcement decisions 
regarding the use of investigational tobacco products.
    FDA issued the September 2015 draft guidance in the Federal 
Register of September 24, 2015 (80 FR 57623). Interested parties were 
given an opportunity to submit comments by November 23, 2015. FDA 
received numerous comments on the September 2015 draft guidance. Based 
on careful review of these comments, FDA is issuing this revised draft 
guidance to clarify the Agency's thinking.

II. Significance of Draft Guidance

    FDA is issuing this revised draft guidance consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The revised draft 
guidance replaces the September 2015 draft guidance. The draft 
guidance, when finalized, will represent the current thinking of FDA 
regarding the definition of ``investigational tobacco product'' and 
discuss the factors FDA intends to consider in making enforcement 
decisions regarding the use of investigational tobacco products until 
regulations are issued or FDA provides written notice of its intent to 
change its enforcement policy. It does not establish any rights for any 
person and is not binding on FDA or the public. You can use an 
alternative approach if it satisfies the requirements of the applicable 
statutes and regulations. This draft guidance is not subject to 
Executive Order 12866.

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)

[[Page 5450]]

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: Use of Investigational Tobacco Products

OMB Control Number 0910-NEW

    FDA is announcing the availability of the revised draft guidance 
entitled ``Use of Investigational Tobacco Products.'' This revised 
draft guidance supersedes the September 2015 draft guidance and, when 
final, 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 are issued 
and become effective or FDA provides written notice of its intent to 
change its enforcement policy. The revised draft guidance is intended 
to provide guidance to persons who currently intend to submit study 
information on tobacco products to FDA and to persons who conduct 
investigations using investigational tobacco products. Such persons may 
include sponsors, investigators, sponsor-investigators, and contract 
research organizations (CROs). This revised draft guidance is also 
intended to provide recommendations to committees or groups formally 
designated to oversee human subject research (e.g., institutional 
review boards) involving investigational tobacco products.
    FDA recognizes that researchers may seek to study tobacco products 
that do not have marketing authorization or that do not comply with an 
applicable tobacco product standard. Until regulations governing the 
use of investigational tobacco products are issued and finalized, as 
discussed in the guidance, FDA intends to evaluate specific uses of 
investigational tobacco products according to potential human subject 
protection concerns or other impacts on public health.
    FDA has identified the following recommendations in the revised 
draft guidance as collections of information.
    In the revised 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 investigations. FDA does not recommend that 
investigators engaging in nonclinical laboratory investigations 
correspond with FDA about use of investigational tobacco products in 
nonclinical studies in all situations. However, sponsors of nonclinical 
studies may elect to meet with FDA early in the development process to 
discuss what, if any, animal testing is appropriate and the suitability 
and acceptability of non-animal tests for a particular tobacco product.
    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 entitled ``Proposed Use of an 
Investigational Tobacco Product'' to assist sponsors in submitting 
information. Although 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. The amount of information the revised draft guidance recommends 
that a sponsor submit depends on the scope of the investigation. For 
example, the revised draft guidance encourages persons conducting 
studies with investigational tobacco products that involve minor 
modifications to legally marketed products to meet with FDA before 
making a submission. This is because in such cases, it may be 
appropriate to submit less information. Although the submission of 
information is voluntary, FDA encourages it, so that sponsors can 
ensure their investigations account for the factors FDA considers in 
making enforcement decisions.
    Regardless of whether a sponsor intends to consult with FDA in 
conducting research with an investigational tobacco product, the 
revised draft guidance contains recommendations for information to 
include within the study protocol. This information may be considered 
should FDA assess the enforcement priority of a particular 
investigation.
    Furthermore, to help ensure that studies are conducted in a manner 
that protects human subjects, the revised draft guidance contains 
recommendations for procedures sponsors can implement 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 revised 
draft guidance, FDA further recommends that the sponsor ensure that 
clinical investigators maintain complete and accurate records to 
account for receipt, use, and disposition of investigational tobacco 
products. FDA also recommends that the sponsor keep clinical 
investigators and any committee or group formally designated to oversee 
research involving human subjects informed of new information on the 
product, particularly adverse experience information.
    In addition, FDA recommends that if there are changes to the 
current investigational use, sponsors consult with the Office of 
Science, Center for Tobacco Products (CTP), and any committee or group 
formally designated to oversee research involving human subjects to 
ensure that the sponsor's use of an investigational tobacco product 
continues to appropriately account for the factors FDA intends to 
consider in determining enforcement priorities. FDA recommends that 
sponsors also notify FDA if they choose to terminate a study, withdraw 
or inactivate a protocol, or want to withdraw studies of a product 
before completion. This information is relevant for FDA to consider in 
making decisions relating to future investigations involving the 
tobacco product that was the subject of the terminated study. Moreover, 
in the revised draft guidance, FDA recommends that under certain 
circumstances, sponsors also 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 clinical investigations 
using investigational tobacco products conducted outside of the United 
States, but intended for submission to FDA, and refers to section 
801(e) of the FD&C Act (21 U.S.C. 381(e)) with respect to exported 
tobacco products intended for investigational use. The revised draft 
guidance also recommends that sponsors prepare and maintain certain 
records and reports for studies conducted outside of the United States 
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.
    Finally, in the revised draft guidance, FDA 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. The revised draft 
guidance recommends that records be maintained and available for 
inspection upon request for a period of at least 4 years after the date 
on which the investigation

[[Page 5451]]

is terminated or completed, or the date that the records are no longer 
considered necessary for supporting marketing of a product, or the 
later of the two dates if both apply.
    FDA estimates the burden of this collection of information as 
follows:

                                                       Table 1--Estimated Annual Reporting Burden
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                                                                                                                                            Capital and
Activity/FDA form for proposed use of     Number of       Number of     Total annual                                                       operating and
  an investigational tobacco product     respondents    responses per     responses       Average burden per response       Total hours     maintenance
                                                         respondent                                                                            costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Initial Submission...................              20               1              20  35...............................             700  ..............
Protocol Amendments..................              30               1              30  4................................             120  ..............
Information Amendments...............              20               1              20  15...............................             300  ..............
Administrative Amendments............               1             1.5             1.5  0.5 (30 minutes).................            0.75  ..............
Other Information....................               3               1               3  0.5 (30 minutes).................             1.5  ..............
Serious or Unexpected Adverse                      75               3              75  2................................             150  ..............
 Experience Reports.
First year, electronic setup safety                15               1              15  0.5 (30 minutes).................             7.5  ..............
 reporting portal.
First year, Electronic Gateway setup                2               1               2  42 \1\...........................              84          37,800
 and verification certificate (one-
 time burden).
First year, CTP Portal setup.........              18  ..............              18  3................................              54  ..............
Electronic Gateway Submission                       2               1               2  3................................               6           2,700
 (recurring).
                                      ------------------------------------------------------------------------------------------------------------------
    Total Reporting Burden Hours.....  ..............  ..............  ..............  .................................           1,424          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 
20 respondents will submit study information to FDA annually. FDA 
estimates that it will take each respondent approximately 35 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 intracompany edits and approvals, as 
well as the burden for assembling additional information, as described 
in the revised draft guidance.
    Since the initial publication of the September 2015 draft guidance, 
FDA has updated the estimated burden hours using current information. 
In addition, FDA has revised table 1 to clarify the types of 
submissions we anticipate receiving and to clarify what type of 
information may be included in the initial submission. Specifically, we 
now estimate that protocol submissions would be included with the 
initial submission. As such, the approximate burden on respondents is 
less than discussed in the original Notice of Availability (NOA) for 
the September 2015 draft guidance.
    In response to the original NOA, FDA received one PRA-related 
comment.
    (Comment) The comment stated that FDA has vastly underestimated the 
time and burden of preparing an initial submission. The comment 
contended that our estimate is not in line with the Agency's experience 
with respect to investigational new drug applications, which the 
comment also contends is an analogous context.
    (Response) FDA does not agree with this comment. The Agency based 
its estimates on its understanding of the submissions it has received 
to date. The revised draft guidance announced in this notice also 
attempts to clarify the Agency's proposed recommendations regarding 
submissions.
    Following the initial submission, sponsors may wish to provide 
protocol amendments to reflect certain changes to a protocol. FDA 
estimates that 30 respondents will submit a protocol amendment. The 
estimated time for submitting a protocol amendment is 4 hours per 
response. In addition, FDA estimates that 20 respondents will 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 respondents will infrequently need to report 
administrative amendments. The total number of respondents of this type 
of information is estimated to be one. FDA estimates administrative 
amendments taking around 30 minutes per response.
    FDA estimates that approximately three respondents will report 
other types of submissions. These submissions are estimated to take 30 
minutes per response.
    FDA estimates that it will receive 75 reports of serious or 
unexpected adverse experiences. This submission will take an average of 
2 hours per report. FDA further estimates that approximately 15 
respondents will set up an account in the safety reporting portal for 
purposes of submitting serious or unexpected adverse experiences. The 
first year setup of the safety reporting portal for this purpose will 
take 30 minutes per respondent.
    As referenced in the September 2015 draft guidance, FDA allows for 
three ways of submission. However, FDA strongly encourages the use of 
electronic format for submission because of its overall efficiency in 
transmitting information. To submit information through the Electronic 
Submissions Gateway (ESG), the submitter should first set up an account 
with WebTrader. FDA estimates from past experience with 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

[[Page 5452]]

Certification. In addition, to submit information through the ESG (or 
any other means of electronic submission), the submitter must package 
the information using the eSubmitter formatting software. FDA estimates 
that the gathering and scanning of information and related 
correspondence would take approximately 2 hours using the eSubmitter 
system.
    Therefore, the first year will include 40 hours for the WebTrader 
system plus 2 hours for the eSubmitter 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 process, resulting in 3 hours per response 
each year thereafter.
    In addition to the ESG system, an alternative electronic method for 
respondents to submit electronic information is through the CTP Portal. 
Respondents with access to an Industry Account Manager (IAM) may 
contact the IAM directly for establishment of an account and access to 
the CTP Portal. Respondents without access to an IAM will be required 
to identify and establish an IAM. To establish an IAM with the CTP 
Portal, respondents should contact the CTP Portal Helpdesk and submit 
required administrative information. FDA estimates that the first-year 
setup for the CTP Portal is approximately 1 hour per respondent. After 
receiving access to the CTP Portal, respondents will submit information 
through the CTP Portal using the eSubmitter system. FDA estimates the 
gathering, scanning, and submission of information and related 
correspondence would take approximately 2 hours using the ESG system.
    Additionally, there are capital and operating or maintenance costs 
associated with the ESG platform for the purpose of 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 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 1,424 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
 Activity records maintained     Number of      records per    Total annual     Average  burden     Total hours
                               recordkeepers   recordkeeper       records     per  recordkeeping
----------------------------------------------------------------------------------------------------------------
Records by Sponsors.........              20               1              20                  10             200
Records by Sponsor-                       10               1              10                  20             200
 Investigators..............
Records by Investigators and              15               1              15                  15             225
 CROs.......................
                             -----------------------------------------------------------------------------------
    Total Recordkeeping       ..............  ..............  ..............  ..................             625
     Burden 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 
has updated these numbers based on submissions received since the 
publication of the September 2015 draft guidance. Compared to FDA's 
original estimates, the recordkeeping burden has been decreased by 
1,025 hours. In addition, FDA has revised table 2 to reflect that we 
have clarified which records we are recommending should be maintained. 
Consequently, FDA now anticipates that 20 sponsors, 10 sponsor-
investigators, and 15 investigators and CROs (for a total of 45 
respondents) 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 per 
study annually to maintain these records. FDA further estimates that it 
will take each sponsor-investigator approximately 20 hours per study 
annually to maintain these records. Finally, FDA estimates that it will 
take investigators and CROs approximately 15 hours per study annually 
to maintain these records. The total reporting burden for recordkeeping 
is estimated to be 625 hours [200 hours for sponsors (20 x 10) + 200 
hours for sponsor-investigators (10 x 20) + 225 for investigators and 
CROs (15 x 15)].

                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                  Number of
                                                  Number of      disclosures    Total annual
                   Activity                      respondents         per         disclosures        Average  burden per  disclosure         Total hours
                                                                 respondent
--------------------------------------------------------------------------------------------------------------------------------------------------------
Disclosures to Investigators.................              50               1              50  1........................................              50
Disclosures to any Committee or Group........              50               1              50  0.17 (10 minutes)........................               9
Disclosure to Study Subjects.................              50               2             100  0.5 (30 minutes).........................              50
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................             109
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 increased the number of anticipated disclosures based on 
submissions received since publication of the September 2015 draft 
guidance. Additionally, FDA recognizes that sponsors will need to make 
third-party disclosures to multiple individuals and groups including 
investigators, study subjects, as well as any committee or group 
designated to oversee research. FDA estimates that disclosing

[[Page 5453]]

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 revised draft 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 
revised draft guidance is estimated to be approximately 2,158 hours.
    The revised draft guidance also refers to previously approved 
collections of information. The revised 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 CTP can be found in FDA's guidance 
``Meetings with Industry and Investigators on the Research and 
Development of Tobacco Products'' (https://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM305282.pdf).
    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.

IV. Electronic Access

    Persons with access to the internet may obtain an electronic 
version of the revised draft guidance at either https://www.regulations.gov or https://www.fda.gov/TobaccoProducts/Labeling/RulesRegulationsGuidance/default.htm.

    Dated: February 15, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-02971 Filed 2-20-19; 8:45 am]
BILLING CODE 4164-01-P