[Federal Register Volume 87, Number 201 (Wednesday, October 19, 2022)]
[Notices]
[Pages 63502-63505]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-22708]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-N-2854]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Premarket Tobacco 
Product Applications and Recordkeeping Requirements

AGENCY: Food and Drug Administration, Health and Human Services (HHS).

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by November 18, 2022.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The OMB control number for 
this information collection is 0910-0879.

FOR FURTHER INFORMATION CONTACT: JonnaLynn Capezzuto, Office of 
Operations, Food and Drug Administration, Three White Flint North, 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-3794, 
[email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Premarket Tobacco Product Applications and Recordkeeping Requirements--
21 CFR 1114

OMB Control Number 0910-0879--Extension

    This information collection supports the requirements for the 
content, format, submission recordkeeping, and postmarket reporting 
requirements of a premarket tobacco product application (PMTA). Section 
910(a) (21 U.S.C. 387j(a)) of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act) established requirements for premarket review of new tobacco 
products and the implementing regulations are found in part 1114 (21 
CFR part 1114), subchapter K.
    An applicant may submit a PMTA to demonstrate that a new tobacco 
product meets the requirements to receive a marketing granted order. A 
new tobacco product may not be introduced or delivered for introduction 
into interstate commerce under this part until FDA has issued a 
marketing granted order for the product (Sec.  1114.5). Further, Sec.  
1114.7 describes the required content and format of the PMTA. The PMTA 
must contain sufficient information for FDA to determine whether any of 
the grounds for denial specified in section 910(c)(2) of the FD&C Act 
apply. The application must contain the following sections: general 
information, descriptive information, product samples, labeling, a 
statement of compliance with 21 CFR part 25, a summary, product 
formulation, manufacturing, health risk investigations, effect on the 
population as a whole, and a certification statement.
    Submitters can visit the following web page which describes the 
process for submitting a PMTA (https://www.fda.gov/tobacco-products/market-and-distribute-tobacco-product/premarket-tobacco-product-applications).
    After submission of a PMTA, FDA may request, and an applicant may 
submit, an amendment to a pending PMTA. FDA generally expects that when 
an applicant submits a PMTA, the submission will include all 
information required by section 910(b)(1) of the FD&C Act and part 1114 
to enable FDA to determine whether it should authorize the marketing of 
a new tobacco product. However, FDA recognizes that additional 
information

[[Page 63503]]

may be needed to complete the review of a PMTA and, therefore FDA 
allows the submission of amendments to a pending application.
    An applicant may transfer ownership of its PMTA at any time, 
including when FDA has yet to act on it. Section 1114.13 describes the 
steps that an applicant would be required to take when it changes 
ownership of a PMTA. This section is intended to facilitate transfers 
of ownership and help ensure that FDA has current information regarding 
the ownership of a PMTA.
    A supplemental PMTA are an alternative format of submitting a PMTA 
(Sec.  1114.15). Applicants that have received a marketing granted 
order would be able to submit a supplemental PMTA to seek marketing 
authorization for a new tobacco product that results from a 
modification or modifications to the original tobacco product that 
received the marketing granted order. FDA restricts the use of 
supplemental PMTAs to only changes that require the submission of 
limited information or revisions to ensure that FDA can efficiently 
review the application.
    If an applicant receives a no marketing granted order, they may 
submit a resubmission to respond to the deficiencies outlined (Sec.  
1114.17). A resubmission may be submitted for the same tobacco product 
that received a marketing denial order or for a different new tobacco 
product that results from changes necessary to address the deficiencies 
outlined in a marketing denial order. This application format allows an 
applicant to address the deficiencies described in a marketing denial 
order without having to undertake the effort of submitting a standard 
PMTA. The resubmission format is not available for PMTAs that FDA 
refused to accept, refused to file, cancelled, or administratively 
closed, or that the applicant withdrew because FDA has not previously 
completed reviews of such applications upon which it can rely, and such 
applications may need significant changes to be successfully 
resubmitted.
    FDA requires applicants that receive a marketing granted order to 
submit postmarket reports. Postmarket reports determine or facilitate a 
determination of whether there may be grounds to withdraw or 
temporarily suspend a marketing granted order. Applicants are required 
to submit two types of postmarket reports after receiving a marketing 
granted order: periodic reports and adverse experience reports. 
Periodic reports are required to be submitted within 60 calendar days 
of the reporting date specified in the marketing granted order. 
Applicants would also be required to report all serious and unexpected 
adverse experiences associated with the tobacco product that have been 
reported to the applicant or of which the applicant is aware. The 
serious and unexpected adverse experience reports must be submitted to 
the Center for Tobacco Products' Office of Science through the HHS 
Safety Reporting Portal (https://www.safetyreporting.hhs.gov/) within 
15 calendar days after receiving or becoming aware of a serious or 
unexpected adverse experience. FDA's Safety Reporting Portal is 
approved under OMB control number 0910-0291.
    Applicants receiving a marketing granted order are required to 
maintain all records necessary to facilitate a determination of whether 
there are or may be grounds to withdraw or temporarily suspend the 
marketing granted order, including records related to both the 
application and postmarket reports, and ensure that such records remain 
readily available to the Agency upon request (Sec.  1114.45).
    The Consolidated Appropriations Act of 2022 (the Appropriations 
Act), enacted on March 15, 2022, amended the definition of the term 
``tobacco product'' in section 201(rr) (U.S.C. 321(rr)) of the FD&C Act 
to include products that contain nicotine from any source. As a result, 
non-tobacco nicotine (NTN) products that were not previously subject to 
the FD&C Act (e.g., products containing synthetic nicotine) are now 
subject to all of the tobacco product provisions in the FD&C Act 
beginning on April 14, 2022, including the requirement of premarket 
review for new tobacco products. The Appropriations Act also makes all 
rules and guidances applicable to tobacco products apply to NTN 
products on that same effective date, which includes the Premarket 
Tobacco Product Application and Recordkeeping Requirements final rule. 
Additionally, the Appropriations Act includes a transition period for 
premarket review requirements, directing companies to submit PMTAs for 
NTN products by May 14, 2022, to receive an additional 60-day period of 
marketing without being considered in violation of premarket review 
requirements. On April 14, 2022, OMB granted an emergency clearance 
under this collection to include NTN products and its associated 
burden. OMB granted a 6-month approval, and as such per the 
requirements of the PRA, the Agency is seeking comment on these new 
estimates.
    In the Federal Register of May 16, 2022 (87 FR 29749), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
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                                                   Number of
  21 CFR part; activity; form      Number of     responses per   Total annual    Average  burden    Total hours
             FDA #                respondents     respondent       responses      per  response
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1114.5; Submission of Standard               1               1               1  1,713...........           1,713
 Bundled PMTAs \2\.
PMTA Submission; Form FDA 4057              39               1              39  0.75 (45                      29
                                                                                 minutes).
PMTA Amendment and General                  39              14             546  0.16 (10                      87
 Correspondence Submission;                                                      minutes).
 Form FDA 4057a.
PMTA Grouping Submission; Form              39               1              39  0.75 (45                      29
 FDA 4057b.                                                                      minutes).
1114.41; Reporting                           4               1               4  50..............             200
 Requirements (periodic
 reports).
1114.9; Amendments............              24               2              48  188.............           9,024
1114.13; Change in Ownership..               1               1               1  1...............               1
1114.15; Supplemental                        2               1               2  428.............             856
 Applications.
1114.17; Resubmissions........               3               1               3  565.............           1,695
1114.41(a)(2); Adverse                       4               6              24  1...............              24
 Experience Reports.
1114.49(b) and (c); Waiver                   1               1               1  0.25 (15                    0.25
 from Electronic Submission.                                                     minutes).
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[[Page 63504]]

 
    Total.....................  ..............  ..............  ..............  ................          13,658
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.
\2\ FDA anticipates that applicants will submit bundled PMTAs, which are single submissions containing PMTAs for
  a number of similar or related products. We estimate that a bundle will contain on average between 6 and 11
  distinct products.

    Table 1 describes the estimated annual reporting burden. FDA has 
based these estimates on the full analysis of economic impacts and 
experience with current PMTA submissions received under OMB control 
number 0910-0768 (which covers the burden for electronic nicotine 
delivery system (ENDS) products PMTA submissions). This average 
represents a wide range of hours that will be required for these 
applications under different circumstances, with some requiring more 
hours (e.g., as many as 5,000 hours for early applications that involve 
complex products and for which the company has no experience conducting 
studies or preparing analysis of public health impacts, or for which 
reliance on master files is not possible) as well as many requiring 
fewer hours (e.g., as few as 50 hours for applications for products 
that are very similar to other new products). FDA estimates that it 
will take each respondent approximately 1,500 hours to prepare a PMTA 
seeking an order from FDA allowing the marketing of a new tobacco 
product. FDA also estimates that it would on average take an additional 
213 hours to prepare an environmental assessment (EA) in accordance 
with the requirements of 21 CFR 25.40, for a total of 1,713 hours per 
PMTA application.
    FDA assumes that firms will submit all applications as PMTA 
bundles. We also considered updated data on market consolidation that 
has occurred since the Deeming Rule published for originally regulated 
products that would receive marketing granted orders through the PMTA 
pathway. For originally regulated products we expect to receive one 
full PMTA submission for a total of 1,713 hours. We believe that 
bundling PMTAs results in efficiencies for applicants when compared to 
submitting standalone, full-text submissions for each product. We 
expect to receive bundled PMTAs where applicants can use the same 
evidence to support PMTAs for similar or related products. Bundling 
PMTAs into a single submission would eliminate the administrative 
burden of having to reproduce the same evidence in a standalone PMTA 
for each product.
    FDA has three forms for use when submitting PMTA information to the 
Agency. Form FDA 4057 for use when submitting PMTA single and bundled 
submissions. FDA estimates that 39 respondents will submit PMTA bundles 
using this form at 0.75 (45 minutes) per response. The number 39 is 
accounting for the bundles of ENDS products and includes 15 new 
expected bundles submitted for NTN products and the 1 bundle we expect 
to receive yearly for originally regulated products, for a total of 29 
hours.
    Form FDA 4057a for use when firms are submitting amendments and 
other general correspondence. FDA estimates that 39 respondents will 
submit amendments and other general correspondence using this form at 
0.16 (10 minutes) per response, including 15 new expected submissions 
related to applications submitted for NTN products. We estimate there 
will be at least 14 amendments per application for a total of 87 hours. 
With most applications being submitted toward the end of our 3-year 
range, we expect fewer amendments during this period. However, FDA 
expects correspondence from earlier applications to be submitted during 
this period.
    Form FDA 4057b assists industry and FDA in identifying the products 
that are the subject of a submission where an applicant groups multiple 
PMTAs into a single submission (referred to as a bundled submission or 
a grouped submission). FDA has previously stated that one approach to 
submitting PMTAs could be to group applications for products that are 
both from the same manufacturer or domestic importer and in the same 
product category and subcategory into a single submission. The form 
assists applicants in providing the unique identifying information for 
each product in a grouped submission of PMTAs. A respondent would 
utilize Form FDA 4057b once for each submission containing more than 
one PMTA. We assume the submitter could include from 2 to 2,000 
products in each Form FDA 4057b. Entering data for up to 2,000 rows can 
take approximately 4 hours on average per Form FDA 4057b for manual 
data entry. We reflect the average time of 45 minutes per response 
based on the assumption that we expect to receive an average of nine 
bundled products per submission. Assuming 45 minutes per Form FDA 4057b 
for 39 applications, we estimate a total burden of 29 hours for this 
activity. Included in this estimate are the 15 new expected submissions 
submitted from NTN products.
    FDA estimates under Sec.  1114.41 that four respondents will submit 
a periodic report. This number is based on the average number of 
periodic report submissions expected between 2020-2022 and the addition 
of NTN products. The Agency estimates that periodic reports will take 
on average of 50 hours per response for a total of 200 hours. Firms 
must also submit adverse experience reports (Sec.  1114.41(a)(2)) for 
tobacco products with marketing orders. We assume the same number of 
firms submitting periodic reports will submit adverse experience 
reports. Currently, firms may voluntarily submit adverse experience 
reports using Form FDA 3800 under OMB control number 0910-0645. We have 
based our estimates on this information collection which estimates that 
it takes 1 hour (for mandatory reporting) to complete this form for 
tobacco products for a total of 24 hours.
    Under Sec.  1114.9 firms will prepare amendments to PMTA bundles in 
response to deficiency letters. These amendments contain additional 
information that we need to complete substantive review. We anticipate 
2 responses back per bundle and therefore, we estimate that 24 
respondents will submit 48 amendments (24 x 2). Assuming 1,500 hours as 
the time to prepare and submit a full PMTA and amendments may on 
average take 10 percent to 15 percent of that time (150-225). We 
averaged this time out (12.5 percent of a full submission preparation 
time) and arrived at 188 hours per response. FDA estimates the total 
burden hours for preparing amendments is 9,024 hours.
    Section 1114.13 would allow an applicant to transfer ownership of a 
PMTA to a new owner. FDA believes this will be infrequent, so we have

[[Page 63505]]

assigned 1 hour acknowledging the requirement.
    Section 1114.15 is an alternative format of submitting a PMTA that 
meets the requirements of Sec.  1114.7 that would reduce the burden 
associated with the submission and review of an application. Our 
estimated number of 2 respondents is based on the number estimated for 
postmarket reports, which is 4 bundles (which is approximately 34 
products). Not all applicants will resubmit modifications to previously 
authorized products, so we estimate 2 bundles (which is approximately 
17 products). FDA estimates further that a supplemental PMTA will take 
25 percent of the time it takes to do an original submission (including 
EA hours) for 428 hours per response. We estimate a total of 856 burden 
hours for this activity.
    Under Sec.  1114.17 an applicant may utilize the resubmission 
format for the same tobacco product for which FDA issued a marketing 
denial order or for a new tobacco product that results from changes 
necessary to address the deficiencies described in a marketing denial 
order. We are estimating that out of all bundles received in 2020, 
2021, and 2022, that an average of three bundles are authorized. If we 
receive 24 amendments to bundles yearly, we estimate based on 
historical data, 58 percent fail at acceptance (down to 8 bundles 
remaining), 17 percent fail at filing (down to 7 bundles remaining), 
and 25 percent receive marketing orders (5 left). We also estimate that 
50 percent of the applications that receive marketing denial orders 
will try to resubmit in a year. Thus, this number of respondents is 
three (rounded up). FDA estimates that a resubmission will take 33 
percent of the time it takes to complete an original submission 
(including EA hours) at 565 hours per response for a total of 1,695 
hours.
    An applicant is required to submit a PMTA and all supporting and 
related documents to FDA in electronic format that FDA can process, 
review, and archive unless an applicant requests, and FDA grants, a 
waiver from this requirement. FDA does not believe we will receive many 
waivers, so we have assigned one respondent to acknowledge the option 
to submit a waiver. Consistent with our other application estimates for 
waivers, we believe it would take .25 hours (15 minutes) per waiver for 
a total of .25 hours.

                               Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                     Number of                    Average burden
      21 CFR part; activity          Number of      records per    Total annual         per         Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
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1114.45; PMTA Records...........              39               1              39               2              78
1100.204; Pre-existing Products                1               1               1               2               2
 Records........................
1107.3; Exemptions From                        1               1               1               2               2
 Substantial Equivalence (SE)
 Records........................
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    Total.......................  ..............  ..............  ..............  ..............              82
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Table 2 describes the annual recordkeeping burden. FDA estimates 
that 39 recordkeepers will maintain records at 2 hours per record. 
Included in this estimate are the 15 expected new recordkeepers of NTN 
products. Firms are also required to establish and maintain records 
related to SE exemption requests and pre-existing products (Sec.  
1100.200 states that subpart C of part 1100). We expect the burden 
hours to be negligible for SE exemption requests. Firms would have 
already established the required records when submitting the SE 
exemption request. Similarly, we expect the hours of to be negligible 
for any pre-existing tobacco products that have already submitted 
standalone pre-existing tobacco product submissions, because firms 
would have established the required records when submitting the 
standalone pre-existing tobacco product submissions. We believe this 
time is usual and customary for these firms. We estimate that it would 
take 2 hours per record to establish the required records for a total 
of 4 hours.
    Relative to the emergency approval by OMB our estimated burden for 
the information collection reflects an overall increase of 72 hours and 
a corresponding increase of 117 responses/records. We attribute this 
adjustment to the addition of NTN product submissions.

    Dated: October 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-22708 Filed 10-18-22; 8:45 am]
BILLING CODE 4164-01-P