[Federal Register Volume 88, Number 147 (Wednesday, August 2, 2023)]
[Notices]
[Pages 50876-50879]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-16434]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-N-2780]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Premarket Notification for a New Dietary Ingredient

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
an opportunity for public comment on the proposed collection of certain 
information by the Agency. Under the Paperwork Reduction Act of 1995 
(PRA), Federal Agencies are required to publish notice in the Federal 
Register concerning each proposed collection of information and to 
allow 60 days for public comment in response to the notice. This notice 
solicits comments on the procedure by which a manufacturer or 
distributor of a new dietary ingredient or of a dietary supplement 
containing a new dietary ingredient is to submit to FDA information 
upon which it has based its conclusion that a dietary supplement 
containing the new dietary ingredient will reasonably be expected to be 
safe.

DATES: Either electronic or written comments on the collection of 
information must be submitted by October 2, 2023.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of October 2, 2023. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are received on or before that date.

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-2023-N-2780 for ``Agency Information Collection Activities; 
Proposed Collection; Comment Request; Premarket Notification for a New

[[Page 50877]]

Dietary Ingredient.'' Received comments, those filed in a timely manner 
(see ADDRESSES), 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, 240-402-7500.
     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.govinfo.gov/content/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, 240-402-7500.

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: Under the PRA (44 U.S.C. 3501-3521), 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.

Premarket Notification for a New Dietary Ingredient--21 CFR 190.6

OMB Control Number 0910-0330--Revision

    This information collection supports Agency regulation, guidance, 
and associated Form FDA 3880. Under section 413(a)(2) of the Federal 
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 350b(a)(2)), the 
manufacturer or distributor of a new dietary ingredient (NDI) or a 
dietary supplement that contains the NDI, must submit an NDI 
notification (NDIN) to FDA (as delegate for the Secretary of Health and 
Human Services) at least 75 days before introducing the product into 
interstate commerce, unless the NDI and any other dietary ingredients 
in the dietary supplement ``have been present in the food supply as an 
article used for food in a form in which the food has not been 
chemically altered'' (21 U.S.C. 350b(a)(1)).
    The notification must contain the information, including any 
citation to published articles, which provides the basis on which the 
manufacturer or distributor of the NDI or dietary supplement (the 
notifier) has concluded that the dietary supplement containing the NDI 
will reasonably be expected to be safe (21 U.S.C. 350b(a)(2)). If the 
required premarket notification is not submitted to FDA, section 413(a) 
of the FD&C Act provides that the dietary supplement containing the NDI 
is deemed to be adulterated under section 402(f) of the FD&C Act (21 
U.S.C. 342(f)). Even if the notification is submitted as required, the 
dietary supplement containing the NDI is adulterated under section 
402(f) unless there is a history of use or other evidence of safety 
establishing that the NDI, when used under the conditions recommended 
or suggested in the labeling of the dietary supplement, will reasonably 
be expected to be safe.
    Section 190.6 (21 CFR 190.6) specifies the information a notifier 
must include in its NDIN and establishes the administrative procedures 
for these notifications. Section 190.6(a) requires each manufacturer or 
distributor of an NDI, or of a dietary supplement containing an NDI, to 
submit to the Center for Food Safety and Applied Nutrition's (CFSAN's) 
Office of Dietary Supplement Programs (ODSP) notification of the basis 
for their conclusion that said supplement or ingredient will reasonably 
be expected to be safe. Section 190.6(b) requires that the notification 
include the following: (1) the complete name and address of the 
manufacturer or distributor, (2) the name of the NDI, (3) a description 
of the dietary supplement(s) that contain the NDI, including the level 
of the new dietary ingredient in the dietary supplement and the dietary 
supplement's conditions of use, (4) the history of use or other 
evidence of safety establishing that the dietary ingredient will 
reasonably be expected to be safe when used under the conditions 
recommended or suggested in the labeling of the dietary supplement, and 
(5) the signature of a responsible person designated by the 
manufacturer or distributor.
    These NDIN requirements are designed to enable us to monitor the 
introduction into the marketplace of NDIs and dietary supplements that 
contain NDIs in order to protect consumers from ingredients and 
products whose safety is unknown. We use the information collected in 
the NDINs to evaluate more efficiently the safety of NDIs in dietary 
supplements and to support regulatory action against ingredients and 
products that are potentially unsafe.
    FDA developed guidance to further assist industry with NDINs. In 
the Federal Register of July 5, 2011 (76 FR

[[Page 50878]]

39111), we announced the availability of a draft guidance for industry 
entitled ``Dietary Supplements: New Dietary Ingredient Notifications 
and Related Issues'' (the 2011 draft guidance). We gave interested 
parties an opportunity to submit comments on the substance of the 
guidance by October 3, 2011. In the Federal Register of September 9, 
2011 (76 FR 55927), we extended the comment period to December 2, 2011. 
We received numerous comments on the 2011 draft guidance. Based on 
those comments and our meetings with industry and other stakeholders, 
we revised the 2011 draft guidance. In the Federal Register of August 
12, 2016 (81 FR 53486), we announced the availability of a revised 
draft guidance for industry with the same title (the 2016 revised draft 
guidance) that supersedes the 2011 draft guidance (available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/draft-guidance-industry-new-dietary-ingredient-notifications-and-related-issues). We gave interested parties another opportunity to 
submit comments on the substance of the guidance by October 11, 2016. 
In the Federal Register of October 4, 2016 (81 FR 68434), we extended 
the comment period to December 12, 2016. It is with this notice that we 
solicit comments on the information collection in the guidance.
    The 2016 revised draft guidance, when finalized, is intended to 
provide instruction and further assist industry in deciding when a 
premarket safety notification for a dietary supplement containing an 
NDI is necessary and in preparing an NDIN. The draft guidance discusses 
in question-and-answer format FDA's views on what qualifies as an NDI, 
when an NDIN is required, the types of data and information that 
manufacturers and distributors should consider when they evaluate the 
safety of a dietary supplement containing an NDI, and what should be 
included in an NDIN as well as other topics. We intend to divide the 
2016 revised draft guidance into discrete sections for ease of use, 
consistent with stakeholder requests (including from industry) 
submitted in the form of comments to the docket for the draft guidance, 
and issue a series of several guidances. These guidances will reflect, 
among other things, public comments submitted to the docket in response 
to the 2011 draft guidance and the 2016 revised draft guidance. 
Sections of the 2016 revised draft guidance that FDA is prioritizing to 
issue at this time address administrative procedures, identity, safety, 
and master files. Per our standard process, FDA will announce guidance 
documents we plan to issue within a calendar year via our FDA Foods 
Program Guidance Agenda, available at: https://www.fda.gov/food/guidance-documents-regulatory-information-topic-food-and-dietary-supplements/foods-program-guidance-under-development. The following 
sections discuss the various topics related to NDINs, all of which were 
previously referenced or discussed in the 2016 revised draft guidance.
1. Administrative Procedures
    The recommendations found in section V, NDI Notification Procedures 
and Timeframes, of the 2016 revised draft guidance and certain 
recommendations in section IV.C., Other Questions About When an NDI 
Notification Is Necessary, provide instruction for certain ways 
manufacturers and distributors can reduce the number of NDINs they must 
file and provide some clarification with regard to when data and 
information from a previous NDIN may be used in a notification. We 
recommend that certain information should be provided in list form for 
ease of reference and to help ensure completeness.
    Certain recommendations found in the 2016 revised draft guidance, 
section IV.C., Determining Whether a New Dietary Ingredient (NDI) 
Notification Is Required; Other Questions About When an NDI 
Notification Is Necessary, discusses information that should be 
included if referring to non-public information from a previous 
notification. Such information to include with a notification could 
involve written authorization to reference information from another 
firm. The option to reference certain information from a previous 
notification should reduce notifiers' burden for preparing and 
submitting identity, manufacturing, and safety information.
    We encourage manufacturers or distributors of NDIs to submit their 
NDINs electronically via the CFSAN Online Submission Module (COSM). 
Although we encourage electronic submission, notifiers also have the 
option of submitting a paper NDIN for us to review. The recommendations 
found in the 2016 revised draft guidance, section V, Recommended 
Template for Organizing an NDI Notification, recommends that 
information in a paper NDIN should be organized in a specific manner, 
and that some information should be provided in list form, for ease of 
reference and to ensure completeness. Doing so will help notifiers 
provide a complete, well-organized NDIN, which should facilitate an 
efficient and timely FDA review.
    These sections of the 2016 revised draft guidance provide 
instruction and help dietary supplement manufacturers and distributors 
understand what to expect when submitting an NDIN and enhance 
industry's ability to submit a complete notification that FDA can 
efficiently review.
2. Identity Information About the NDI and the Dietary Supplement
    Certain recommendations found in the 2016 revised draft guidance, 
section VI.A., What to Include in an NDI Notification; Identity 
Information About the NDI and the Dietary Supplement, provide 
instruction and discuss information that is important in describing the 
identity of an NDI and the dietary supplement containing the NDI. We 
will recommend that certain information should be provided in table 
form for ease of reference and to help ensure completeness.
3. History of Use or Other Evidence of Safety
    Certain recommendations in the 2016 revised draft guidance, 
sections VI.B., History of Use or Other Evidence of Safety, and VI.C, 
Summary of the Basis for Your Conclusion of Safety, as well as table 3, 
the Safety Testing Recommendations Matrix, provide instruction and 
discuss information that is important in describing the basis for which 
a dietary supplement containing the NDI will reasonably be expected to 
be safe. While the FD&C Act does not specify the type or amount of 
information that must be included in an NDIN, the notification should 
include a dietary supplement safety narrative containing the objective 
evaluation of the history of use or other evidence of safety cited in 
the notification, along with an explanation of how the evidence of 
safety provides a basis to conclude that the dietary supplement 
containing the NDI, when used under the conditions described in the 
NDIN, will reasonably be expected to be safe. Once finalized, the 
recommendations will instruct and help dietary supplement manufacturers 
and distributors understand what to consider when evaluating the safety 
of a dietary supplement containing an NDI and what should be included 
in an NDIN in this regard.
4. Electronic Submission
    We developed an electronic portal that respondents may use to 
electronically submit their notifications to ODSP via COSM. COSM 
assists respondents filing regulatory

[[Page 50879]]

submissions and is specifically designed to aid users wishing to file 
submissions with CFSAN. COSM allows safety and other information to be 
uploaded and submitted online via Form FDA 3880. This form provides a 
standard format to describe the history of use or other evidence of 
safety on which the manufacturer or distributor bases its conclusion 
that the NDI is reasonably expected to be safe under the conditions of 
use recommended or suggested in the labeling of the dietary supplement, 
as well as a description of the ingredient and other information. Firms 
that prefer to submit a paper notification in a format of their own 
choosing have the option to do so; however, Form FDA 3880 prompts a 
notifier to input the elements of an NDIN in a standard format that we 
will be able to review efficiently. Form FDA 3880 may be accessed at 
https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/how-submit-notifications-new-dietary-ingredient.
    Description of Respondents: The respondents to this collection of 
information are certain manufacturers and distributors in the dietary 
supplement industry.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                  Number of
    Activity; type of respondent; citation        Number of     responses per   Total annual          Average burden per response           Total hours
                                                 respondents     respondent       responses
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NDIN submission; Sec.   190.6................              55               1              55  20.......................................           1,100
List Form and Template; Administrative                      1               1               1  1........................................               1
 Procedures; Section V.
Written Authority; Master Files; Section                   10               1              10  0.4 (24 minutes).........................               4
 IV.C.1 and 4.
Table Form; Identity Specifications; Section               55               1              55  1........................................              55
 VI.A.
Manufacturing Process Information; Identity                55               1              55  5........................................             275
 Information; Section VI.B and C.
                                              ----------------------------------------------------------------------------------------------------------
    Total....................................  ..............  ..............  ..............  .........................................           1,435
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    Our estimate is based on our experience with information 
collections related to past NDIN submissions. The estimated burden also 
reflects an industry average, although burden associated with 
individual submissions may vary depending on the complexity of the 
notification. Due to a program change we are revising this information 
collection request to include recommendations found in the 2016 revised 
draft guidance. Therefore, we have increased our total burden hour 
estimate by 335. However, the number of respondents remains the same.
    We estimate that 55 respondents each submits 1 NDIN annually. We 
estimate that extracting and summarizing the relevant information from 
what exists in the company's files and presenting it in a format that 
meets the requirements of Sec.  190.6 will take approximately 20 hours 
of work per notification. We believe that the burden of the premarket 
notification requirement is reasonable because we are requesting only 
safety and identity information that the manufacturer or distributor 
should already have developed to satisfy itself that a dietary 
supplement containing the NDI is in compliance with the FD&C Act. If 
the required premarket notification is not submitted to FDA, section 
413(a) of the FD&C Act provides that the dietary supplement containing 
the NDI is deemed to be adulterated under section 402(f) of the FD&C 
Act. Even if the notification is submitted as required, the dietary 
supplement containing the NDI is adulterated under section 402(f) of 
the FD&C Act unless there is a history of use or other evidence of 
safety establishing that the NDI, when used under the conditions 
recommended or suggested in the labeling of the dietary supplement, 
will reasonably be expected to be safe. This requirement is separate 
from and additional to the requirement to submit a premarket 
notification for the NDI.
    FDA's regulation on NDINs, Sec.  190.6(a), requires the 
manufacturer or distributor of the NDI or dietary supplement containing 
the NDI to submit to FDA the information that forms the basis for its 
conclusion that the NDI, or dietary supplement containing the NDI, will 
reasonably be expected to be safe. Thus, Sec.  190.6 only requires the 
manufacturer or distributor to extract and summarize information that 
should have already been developed to meet the safety requirement in 
section 413(a)(2) of the FD&C Act.
    We estimate that 95 percent of respondents submit electronically, 
leaving about 3 who submit their NDIN in paper format (5% x 55 = 2.75, 
rounded up to 3). However, we have seen a trend of decreased paper 
submissions over the past 2 years and expect usage to remain low. Thus, 
we estimate only one NDIN will be submitted in paper format. We 
estimate that information in this NDIN regarding the table of contents, 
names of contacts, and reference lists will be provided in list form. 
Because the underlying information should be already readily available, 
we estimate that it will take about 60 minutes to prepare the 
information in list form, which would create a burden of 1 hour (1 x 1 
hour).
    We estimate that 10 notifiers will each reference information once 
from a previous notification and will provide written authorization to 
do so. We estimate that it will take about 24 minutes to prepare a 
written authorization. We calculate that the burden for this activity 
will be 4 hours annually (10 notifiers x 1 authorization x 0.4 hour).
    We estimate that 55 notifiers each will provide identity 
specifications in table form with their NDIN submissions. Because the 
underlining information should be already readily available, we 
estimate that it will take about 1 hour to prepare the information in 
table form, which would create a burden of 55 hours (55 tables x 1 
hour).
    We estimate that 55 notifiers each will provide information about 
the manufacturing process with their NDIN submissions. We estimate that 
it will take about 5 hours to prepare this information, which would 
create a burden of 275 hours (55 manufacturing process x 5 hours).

    Dated: July 28, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-16434 Filed 8-1-23; 8:45 am]
BILLING CODE 4164-01-P