[Federal Register Volume 91, Number 153 (Tuesday, August 11, 2026)]
[Proposed Rules]
[Pages 51834-51881]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2026-16296]
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Vol. 91
Tuesday,
No. 153
August 11, 2026
Part II
Department of Health and Human Services
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Food and Drug Administration
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21 Parts 170 and 570
Substances Generally Recognized as Safe; Proposed Rule
Federal Register / Vol. 91 , No. 153 / Tuesday, August 11, 2026 /
Proposed Rules
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 170 and 570
[Docket No. FDA-2025-N-3262]
RIN 0910-AJ02
Substances Generally Recognized as Safe
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA or we) is proposing to
require the submission of generally recognized as safe (GRAS) notices
for the use of a human or animal food substance purported to be GRAS
under the conditions of its intended use under the Federal Food, Drug,
and Cosmetic Act (FD&C Act).
DATES: Either electronic or written comments on the proposed rule must
be submitted by December 9, 2026. Submit comments (including
recommendations) on the collection of information under the Paperwork
Reduction Act of 1995 by December 9, 2026.
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 December 9, 2026. 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-2025-N-3262 for ``Substances Generally Recognized as Safe.''
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.'' We will review
this copy, including the claimed confidential information, in our
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, the
plain language summary of the proposed rule of not more than 100 words
as required by the ``Providing Accountability Through Transparency
Act,'' 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.
Under the Paperwork Reduction Act (PRA), comments on the
information collection provisions are best assured of consideration if
your comments are received by December 9, 2026. Submit your comments on
FDA's need for this information, the accuracy of the provided burden
estimates, and any suggested methods for minimizing respondent burden
to FDA using the docket identified at the beginning of this rulemaking.
FDA will respond to any information collection-related comments in the
final rule. You may also send your information collection-related
comments to OMB's Office of Information and Regulatory Affairs using
the interface at 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
title of this proposed collection is ``Substances Generally Recognized
as Safe: Notification Procedure.''
FOR FURTHER INFORMATION CONTACT:
With regard to substances that would be used in human food:
Paulette Gaynor or Christopher Kampmeyer, Office of Pre-Market Additive
Safety, Human Foods Program, Food and Drug Administration, 5001 Campus
Dr., College Park, MD 20740, 240-402-1200; Carrol Bascus or Alexandra
Beliveau, Office of Policy and International Engagement, Human Foods
Program, Food and Drug Administration, 5001 Campus Dr., College Park,
MD 20740, 240-402-2378.
With regard to substances that would be used in animal food:
Charlotte Conway, Tonia Bair, or Marla Keller, Office of Surveillance
and Compliance, Center for Veterinary Medicine, Food and Drug
Administration, 5001 Campus Dr., College Park, MD 20740, 240-402-6768.
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With regard to the information collection: Michael Ellison, Office
of Operations, Food and Drug Administration, Three White Flint North,
10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 240-402-2093,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose and Coverage of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Statutory and Regulatory History
B. The Need To Mandate GRAS Notifications
IV. Legal Authority
A. Statutory Framework
B. Legal Basis for the Proposal
V. Description of the Proposed Rule
A. Proposed Revisions to Sec. 170.3--Definitions
B. Proposed Revisions to Sec. 170.30--Eligibility for
Classification as GRAS
C. Proposed Revisions to Sec. 170.38--Determination of Food
Additive Status
D. Proposed Revisions to Sec. 170.39--Threshold of Regulation
(TOR) for Substances Used in Food or as a Food Contact Substance
E. Proposed Revisions to Sec. 170.203--Definitions Pertaining
to GRAS Notices
F. Proposed Sec. 170.205--Creation of a Mandatory GRAS
Notification Program
G. Proposed Revisions to Sec. 170.210--Mandatory Electronic
Submission of GRAS Notices to FDA
H. Proposed Revisions to Sec. 170.220--Requirement To Submit
English Translations of Material Included in a GRAS Notice
I. Proposed Revisions to Sec. 170.250--Identification of Data
and Information Exempt From Disclosure Under the Freedom of
Information Act
J. Proposed Revisions to Sec. 170.265--Circumstance Where FDA
Would Not Consider the Mandatory GRAS Notice Notification
Requirement To Be Met
K. Proposed Revisions to Sec. 170.275--Public Disclosure of a
GRAS Notice
L. Proposed Revocation of Sec. 170.285--Disposition of GRAS
Affirmation Petitions
M. Proposed Addition of Subpart F--Establishment of Definitions
and Pathway for Submission of Certain Information During Time-
Limited Option for Substances Introduced Into Interstate Commerce
Under the GRAS Provision of Section 201(s) of the FD&C Act Before
the Effective Date of A Final Rule
N. Proposed Revision to the Header of Part 170
O. Non-Substantive Edits to Part 170
P. Table Summarizing the Proposed Changes to Part 170
Q. Proposed Revisions to Part 570 for Food Substances Used in
Animal Food and Incorporation by Reference
VI. Request for Comments on Alternatives
VII. Proposed Effective/Compliance Dates
VIII. Preliminary Economic Analysis of Impacts
IX. Analysis of Environmental Impact
X. Paperwork Reduction Act of 1995
XI. Federalism
XII. Consultation and Coordination With Indian Tribal Governments
XIII. References
I. Executive Summary
A. Purpose and Coverage of the Proposed Rule
The proposed rule, if finalized, would amend our regulations at
parts 170 and 570 (21 CFR parts 170 and 570) to require the submission
of GRAS notices for the use of a human or animal food substance that is
purported to be GRAS under the conditions of its intended use under
section 201(s) of the FD&C Act (21 U.S.C. 321(s)). Food
substances include both ingredients and substances added indirectly,
such as from food packaging. The proposed rule would require any person
introducing a substance into interstate commerce under the GRAS
provision of section 201(s) of the FD&C Act to notify FDA of the basis
for their conclusion that the substance is GRAS under the conditions of
its intended use unless an exception to the requirement to submit a
GRAS notice applies. This change would provide greater transparency
about substances that are added to food (including substances already
in the food supply and those being introduced into interstate commerce
for use in food for the first time), so that FDA can more efficiently
determine if the use of a substance constitutes a food additive use
that is subject to FDA review and approval under the FD&C Act. This
change is expected to provide FDA with information to help identify the
use of potentially unsafe substances in food, thereby enabling FDA to
take action as appropriate and regulate the safety of food substances
more effectively.
B. Summary of the Major Provisions of the Proposed Rule
The proposed rule, if finalized, would:
Convert the voluntary GRAS notification program to a
mandatory GRAS notification program and explain that if the
notification requirement is not met for a substance's conditions of
intended use, FDA would consider such noncompliance as a factor in its
prioritization of food substances for post-market review;
Establish certain exceptions to the requirement to submit
a GRAS notice, including a time-limited option to make a streamlined
submission to FDA for certain intended uses of substances already in
interstate commerce instead of initially submitting a GRAS notice; and
Revise our procedural regulations for a threshold of
regulation (TOR) exemption for human food to reflect updated scientific
guidance and to include uses of substances in food and as a food
contact substance (FCS).
C. Legal Authority
We are issuing this proposed rule consistent with our authority in
sections 201, 402, 409, and 701 of the FD&C Act (21 U.S.C. 321, 342,
348, 371).
D. Costs and Benefits
This proposed rule would revise the procedures by which a person
introducing a human or animal food substance into interstate commerce
notifies FDA of a conclusion that the use of such substance is GRAS.
Specifically, the proposed rule would require the submission of GRAS
notices to FDA for certain uses of food substances. A substance that is
GRAS under the conditions of its intended use is not subject to FDA
premarket review and approval as a food additive for that particular
use (see sections 201(s) and 409 of the FD&C Act). Under our current
regulations, a person who concludes that the use of a substance is GRAS
under the conditions of its intended use may, but is not required to,
notify FDA of this conclusion. The submission of a GRAS notice is
therefore currently voluntary. If the proposed rule is finalized, GRAS
notices will be required for certain uses of substances in human and
animal food.
The primary benefits of the proposed rule, if finalized, would come
from increased information being made available to FDA and the public
regarding substances used in human and animal foods. This information
would enable us to more effectively determine if the use of a substance
constitutes a food additive use that is subject to premarket review and
approval under the FD&C Act. This information is also expected to
provide FDA with information to help identify the use of potentially
unsafe substances in food, thereby enabling FDA to take action as
appropriate and regulate the safety of food substances more
effectively. A mandatory GRAS notification program would allow FDA to
ensure that GRAS conclusions have a scientific basis and that
appropriate documentation supporting those conclusions exists. The
proposed rule, if finalized, is in part intended to help
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strengthen public confidence in FDA's ability to oversee the safety of
the U.S. food supply. One-time costs of the proposed rule to persons
who introduce a substance into interstate commerce under the GRAS
provision of section 201(s) of the FD&C Act include reading the rule
and revising standard operating procedures regarding GRAS notices.
Other one-time per manufacturer costs of the proposed rule are
preparing and submitting streamlined submissions related to uses of
substances introduced into interstate commerce under the GRAS provision
of section 201(s) of the FD&C Act before the effective date of a final
rule, for firms that choose to submit this information during the
window of availability for this time-limited option for such
submissions. Costs associated with these activities may include
translation costs for manufacturers in non-English speaking countries.
Recurring costs to affected manufacturers would include preparing and
submitting GRAS notices for new uses of substances introduced into
interstate commerce under the GRAS provision of section 201(s) of the
FD&C Act after the effective date of a final rule that would otherwise
have been the subject of an independent conclusion of GRAS status
(i.e., a GRAS conclusion has been reached without submitting a GRAS
notice) (see sections III and VII of this document for further
discussion of independent conclusion of GRAS status and effective and
compliance dates, respectively).
Costs to FDA would include one-time costs of reviewing streamlined
submissions related to uses of substances introduced into interstate
commerce under the GRAS provision of section 201(s) of the FD&C Act
before the effective date of a final rule during the time-limited
period for such submissions, and annual costs of evaluating ongoing
submissions of GRAS notices regarding uses of substances that would
otherwise have been the subject of an independent conclusion of GRAS
status.
Other effects of the proposed rule may include transfers of market
share and revenue between manufacturers of products with similar
ingredients. For example, the submission of a GRAS notice may lead to a
determination by FDA that there is an insufficient basis for concluding
that a substance that happens to be used in only certain of the
products was GRAS. We acknowledge the potential for such transfers if
the rule is finalized. We do not estimate the magnitude of such effects
because we cannot identify which substances may be the subject of an
insufficient basis letter, which products they are in, or the market
share of such products.
We estimate that the present value of the costs of the proposed
rule would be approximately $89.6 million, with a lower bound of $34.9
million and an upper bound of $210.0 million, discounted at 3 percent
at 10 years in 2024 dollars. At a 7 percent discount rate, the present
value of costs would be approximately $82.3 million, with a lower bound
of $31.5 million and an upper bound of $195.9 million. We estimate that
the annualized costs of the proposed rule would be approximately $10.5
million, with a lower bound of $4.1 million and an upper bound of $24.6
million, discounted at 3 percent over 10 years. At a 7 percent discount
rate, annualized costs would be approximately $11.7 million, with a
lower bound of $4.5 million and an upper bound of $27.9 million.
[GRAPHIC] [TIFF OMITTED] TP11AU26.043
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III. Background
On March 10, 2025, the Secretary of Health and Human Services,
Robert F. Kennedy Jr., directed FDA to explore rulemaking to eliminate
the pathway for firms to introduce purported GRAS uses of substances
into the market without notifying FDA of the basis for their GRAS
conclusions (Ref. 1). Secretary Kennedy's call for a reformed GRAS
notification process aligns with the Administration's Make America
Healthy Again initiative by providing increased transparency about the
substances being added to the nation's food supply (Ref. 2). A
mandatory GRAS notification program would require any person
introducing a substance into interstate commerce under the GRAS
provision of section 201(s) of the FD&C Act to notify FDA of the basis
for their conclusion that the substance is GRAS under the conditions of
its intended use. A mandatory program would enable FDA to more
effectively ensure the safety of the U.S. food supply--one that has
grown far more complex in recent years--by providing us with
information needed to help identify the use of potentially unsafe
substances in food or additives that require FDA's review and approval
to be lawfully marketed, so we can take action as appropriate. A
mandatory GRAS notification program would therefore address growing
concerns about the increasingly complex U.S. food supply. For example,
firms are introducing substances into food without publicly disclosing
the underlying safety information about the use of such ingredients and
FDA sometimes becomes aware of the need to take action regarding unsafe
substances in food only after adverse public health events occur.
Further, a mandatory program that includes the continued public
disclosure of information about GRAS uses of substances would
substantially increase the public's access to information concerning
the substances being added to human and animal food.
In 1958, Congress enacted the Food Additives Amendment to the FD&C
Act (the 1958 amendment) (Pub. L. 85-929, 72 Stat. 1784), which
expanded FDA's broad authority under the FD&C Act to ensure the safety
of the U.S. food supply. Among other things, the 1958 amendment created
a new framework for FDA's oversight of substances being added to food.
The 1958 amendment defined the term ``food additive'' and established a
premarket review and approval framework for these food substances
(sections 201(s) and 409 of the FD&C Act). Notably, in defining what
constitutes a food additive subject to premarket review and approval,
the 1958 amendment excluded substances that are GRAS under the
conditions of their intended use (section 201(s) of the FD&C Act).
Congress therefore exempted substances that are GRAS under the
conditions of their intended use from the premarket review and approval
requirements for food additives under the FD&C Act. However, as
discussed elsewhere in this document, Congress struck a balance:
although it exempted substances that are GRAS under the conditions of
their intended use from premarket review and approval, Congress granted
FDA the authority to review food substances on the market, including
new and existing substances introduced into food that are purported to
be GRAS under the conditions of their intended use, to assess whether
these substances meet the definition of a food additive that requires
premarket authorization (sections 409(a) and (d) of the FD&C Act).
In the over 60 years since the enactment of the 1958 amendment, FDA
has regulated GRAS uses of substances in food through various
mechanisms, including by: listing certain substances as GRAS under the
conditions of their intended use in our regulations; conducting a
comprehensive study of purported GRAS uses of substances to determine
whether certain uses of substances required FDA's review and approval
as food additive uses; and establishing a GRAS affirmation process,
through which interested parties could petition us to affirm the GRAS
status of a particular use of a substance.
Our current GRAS notification program was first proposed in 1997,
and under this program, parties can voluntarily notify us of a
conclusion that a substance is GRAS under the conditions of its
intended use. Through a GRAS notice, parties can share with us the
underlying data and other scientific information used to support their
conclusion that the use of a substance is GRAS under the conditions of
its intended use. A GRAS conclusion constitutes an assertion on the
part of the notifier (i.e., the person responsible for the GRAS notice;
see Sec. 170.203 (21 CFR 170.203) and Sec. 570.203 (21 CFR 570.203))
that the intended use of a substance is not a food additive use that is
subject to the premarket review and approval requirements of section
409 of the FD&C Act. Importantly, a person's conclusion that a
substance is GRAS under the conditions of its intended use (or similar
claims by a person that they have independently ``certified'' the use
of a substance as GRAS) does not necessarily mean that such a use is
GRAS or that the use is not an unapproved food additive use. For
example, FDA may determine, based on an assessment of evidence, that
the use of a substance is not GRAS or that it is otherwise an
unapproved food additive.
As part of our voluntary GRAS notification program, once we file a
GRAS notice, we conduct an evaluation to determine whether the data and
information presented, and other information available to FDA, provide
a sufficient basis for a conclusion that the substance is GRAS under
the conditions of its intended use. In general, FDA will respond to a
GRAS notice in one of three ways: (1) by indicating that we do not
question the basis for the GRAS conclusion contained in the notice
(``no questions'' letter); (2) by indicating that we have concluded
that the notice does not provide a sufficient basis for a GRAS
conclusion (e.g., because the notice does not include appropriate data
and information or because key data and information are not publicly
available); or (3) by stating that we have granted a request by the
notifier for us to cease our evaluation of the GRAS notice. There is no
requirement that a notifier must wait to receive a response from FDA
regarding their GRAS conclusion before introducing the substance into
interstate commerce. We provide information about GRAS notices and our
responses on our website (Refs. 3 and 4).
While the current GRAS notification program has been informative
and beneficial to our administration of the FD&C Act, our nearly 30
years of experience with the program, and particularly our experience
administering the program since it was finalized in 2016, has
highlighted several challenges.
The voluntary nature of the GRAS notification program has meant
that information gaps persist for both FDA and the public about
substances being added to food, an issue covered extensively in a 2010
U.S. Government Accountability Office (GAO) report (see section
III.B.1.c of this document for further discussion) (Ref. 5). Our lack
of complete information about what substances are being added to food
has, at times, prevented early engagement with industry about new uses
of substances in food and frustrated our ability to carry out our
public health and safety responsibilities under the FD&C Act (see
section III.B of this document for further discussion). At the same
time, recent changes in our country's food supply, such as evolving
consumer demand for different types of
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products and ongoing innovation in food manufacturing and ingredient
development, have resulted in a more diverse food supply. It was
estimated that, as of January 2011, more than 10,000 additives were
being used in food, including an estimated 1,000 human food substances
for which firms had claimed independent conclusions of GRAS status
(i.e., they had reached a GRAS conclusion without submitting a GRAS
notice) (Refs. 6 and 7).
In light of the issues we have identified with the voluntary GRAS
notification program, and the challenges we face due to ongoing food
innovation and evolving consumer demands, we find ourselves in a
situation much like the years before the 1958 amendment's enactment. At
that time, numerous substances with unknown safety profiles were being
added to or used in connection with food without sufficient FDA
oversight. Today, an unknown number of substances are being introduced
into the market under the GRAS provision of section 201(s) of the FD&C
Act. The proposed rule would address our current circumstances by
requiring the submission of GRAS notices. Mandatory submission of GRAS
notices would increase knowledge and improve the transparency about
substances in the U.S. food supply that are purported to be GRAS under
the conditions of their intended use. It would give FDA, state
regulators, consumers, industry, and consumer advocacy groups more
information about substances being used in human and animal food. Once
filed, information about all purported GRAS uses of substances is
expected to enable FDA to more efficiently determine whether the use of
a substance meets the definition of a food additive use under the FD&C
Act, and therefore whether the use of the substance requires FDA's
review and approval to be lawfully marketed. Further, mandatory
submission of GRAS notices would help FDA ensure that GRAS conclusions
have a scientific basis and are appropriately documented and
maintained. It would also provide an earlier opportunity for us to
engage with industry if questions arise regarding a conclusion that a
substance is GRAS under the conditions of its intended use. Mandatory
submission of GRAS notices would enable FDA to administer and enforce
the FD&C Act more effectively and efficiently.
A. Statutory and Regulatory History
1. The Food Additives Amendment of 1958
In 1950, to address emerging health concerns about the use of new
chemicals in food, the U.S. House of Representatives established a
committee chaired by Representative James Delaney of New York (the
Delaney Committee) to investigate the substances being added to or used
in connection with the nation's changing food supply. The Delaney
Committee issued a report in June 1952 summarizing its findings (Ref.
8). The report found, among other things, that food substances were
being used ``without adequate and sufficient testing of their possible
long-range injurious effects'' (id. at 27). The report further
concluded that the public was ``entitled to greater protection with
respect to the foods it must necessarily consume[,]'' and that ``such
protection [was] not afforded by existing legislation, under which the
Government may take no action until after the food has been placed upon
the market and injury may have occurred'' (id. at 27). The Delaney
Committee therefore recommended that the FD&C Act be amended to require
premarket safety reviews for ``chemicals employed in or on foods'' (id.
at 27).
In 1958, based in part on the Delaney Committee's report, as
referenced in the corresponding House Report (Ref. 9), Congress enacted
the Food Additives Amendment to the FD&C Act to strengthen government
oversight of substances being added to or used in connection with food.
``Food'' includes articles used for food or drink for humans or other
animals and articles used for components of such food (see section
201(f) of the FD&C Act); therefore, the 1958 amendment covered
additives in both human and animal foods. Echoing the Delaney
Committee's call for premarket oversight of food substances, Congress's
stated purpose in passing the 1958 amendment was ``[t]o protect the
public health by amending the [FD&C Act] to prohibit the use in food of
additives which have not been adequately tested to establish their
safety'' (Pub. L. 85-929, 72 Stat. 1784).
Specifically, the 1958 amendment requires that, before certain
substances may be added to food, FDA must authorize their use through a
premarket review and approval process (sections 409(b) through (e) of
the FD&C Act). Among other things, the 1958 amendment:
defines what constitutes a ``food additive'' subject to
premarket review and approval (now codified at section 201(s) of the
FD&C Act);
creates a detailed premarket authorization process for
food additives that can result in a food additive regulation
establishing the safety of a food additive for a particular use
(sections 409(a) through (e) of the FD&C Act);
enables any person to submit a food additive petition to
propose the issuance of a food additive regulation (section 409(b) of
the FD&C Act);
empowers the Secretary of the U.S. Department of Health
and Human Services (the Secretary) to at any time, on their own
initiative, propose the issuance of a food additive regulation (section
409(d) of the FD&C Act); and
deems adulterated any food that is, or bears or contains,
a ``food additive that is unsafe within the meaning of section 409 [of
the FD&C Act]'' (now section 402(a)(2)(C)(i) of the FD&C Act).
With some exceptions, section 409(a) of the FD&C Act provides that
food additives are deemed ``unsafe'' for purposes of the adulteration
provision of section 402(a)(2)(C)(i) of the FD&C Act unless their use
conforms with a food additive regulation issued pursuant to the
premarket review and approval process of section 409 of the FD&C Act.
Congress later added to this premarket authorization framework by
establishing a mandatory food contact notification program for human
foods (see section 409(h) of the FD&C Act) and certain requirements
specific to food additives intended for use in animal food (see section
409(k) of the FD&C Act).
2. Statutory Approach to Substances Generally Recognized as Safe (GRAS)
In enacting the 1958 amendment, Congress recognized that many
substances added to food would not need to go through formal premarket
review and approval to assure their safety, either because their safety
had been established by a long history of use in food or by virtue of
the nature of the substance, its customary or projected conditions of
use, and the information generally available to scientists about the
substance. Therefore, Congress adopted a two-step definition of ``food
additive'' (see section 201(s) of the FD&C Act). The first step broadly
includes any substance, the intended use of which results or may
reasonably be expected to result, directly or indirectly, in its
becoming a component or otherwise affecting the characteristics of
food. This includes substances added to food directly (i.e.,
ingredients) and indirectly (i.e., substances used in contact with
food). As such, substances that migrate or may reasonably be expected
to migrate into food from their intended use in contact with food
(e.g.,
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from conveyor belts, containers for shipping, packaging for food) would
be regulated as food additives unless such use is GRAS or otherwise
excepted from the definition of a food additive. Further information
about food contact substances is available on our website (see Ref.
10). The second step excludes from the definition of a ``food
additive'' substances that are generally recognized, among experts
qualified by scientific training and experience to evaluate their
safety, as having been adequately shown through scientific procedures
(or, in the case of substances used in food before January 1, 1958,
through either scientific procedures or through experience based on
common use in food) to be safe under the conditions of their intended
use. Under section 201(s) of the FD&C Act, the conditions of intended
use of a substance, rather than the substance itself, are eligible for
GRAS status. Similarly, food additives are deemed unsafe when their
conditions of use do not conform with a food additive regulation (see
section 409(a) of the FD&C Act).
The 1958 amendment created two distinct processes for the proposal
and creation of food additive regulations. First, under section 409(b)
of the FD&C Act, any person may propose the issuance of a food additive
regulation by filing a petition with the Secretary. Under section
409(c) of the FD&C Act, in response to a food additive petition, the
Secretary, and by delegation, FDA, will, by order, either: (1) deny the
petition; or (2) establish a food additive regulation prescribing the
conditions under which the food additive may be safely used. Second,
under section 409(d) of the FD&C Act, Congress specifically authorized
the Secretary, and by delegation, FDA, to at any time, upon the
Secretary's own initiative, propose the issuance of a food additive
regulation prescribing the conditions under which a particular food
additive may be safely used. After 30 days, the Secretary, and by
delegation, FDA, may issue an order establishing a food additive
regulation based upon the proposal (section 409(d) of the FD&C Act).
Section 409(d) of the FD&C Act thus authorizes us to propose food
additive regulations of our own accord. As discussed further in section
IV of this document, by granting FDA authority to propose food additive
regulations upon our own initiative and at any time, Congress intended
for FDA to play a critical role in determining whether a food substance
being introduced into interstate commerce, including one already being
added to food, meets the definition of a food additive and requires a
food additive regulation to be lawfully marketed.
3. FDA's Regulatory Approach to the GRAS Provision of Section 201(s) of
the FD&C Act
We have periodically revised our regulations to adapt our approach
to the GRAS provision of section 201(s) of the FD&C Act to the nation's
changing food supply and to address issues we identified after years of
experience under prior regulatory schemes. The revisions were intended
to help us better understand what substances are being added to or used
in connection with food under the GRAS provision of section 201(s) of
the FD&C Act. The goal of these regulations was to give us, and the
public, safety information about these substances and to enable us to
take appropriate actions to assure the safe use of these substances in
food. Shortly after Congress amended the FD&C Act in 1958, we clarified
the regulatory status of many substances that were added to food before
1958, and we ultimately amended our regulations to include a list of
food substances that, when used for the purposes indicated and in
accordance with good manufacturing practices, are GRAS. The list,
historically referred to as ``the GRAS list,'' can be found at part 182
(21 CFR part 182) for human food and part 582 (21 CFR part 582) for
animal food.
When creating the GRAS list, we acknowledged that it would be
impracticable for us to list all substances that are GRAS for their
intended use in our regulations (Sec. 121.101(a) (later renumbered as
Sec. 182.1(a) (21 CFR 182.1(a)) and Sec. 582.1(a) (21 CFR 582.1(a))).
Consequently, we did not include many substances considered GRAS under
the conditions of their intended use by the food industry in the GRAS
list. Despite the fact that a substance that is GRAS under the
conditions of its intended use is not subject to FDA premarket review
and approval as a food additive for that particular use (see sections
201(s) and 409 of the FD&C Act), firms who concluded on their own
initiative that a use of a substance qualified for GRAS status
frequently sought our opinion on whether their conclusion was
justified. Many firms requested an ``opinion letter,'' in which FDA
would render an informal opinion on the GRAS status of the conditions
of use of a substance. Although convenient and expedient, these
informal opinion letters were often available only to the requestor and
were not binding on us even at the time they were issued.
FDA updated the GRAS list over time. For example, in the Federal
Register of October 21, 1969 (34 FR 17063), we deleted from the GRAS
list various cyclamate salts, a family of nonnutritive sweeteners that
had been added to food under the GRAS provision of section 201(s) of
the FD&C Act, because they were implicated in the formation of bladder
tumors in rats (Ref. 11). Later, in response to concerns raised by the
new information on cyclamates, then-President Nixon directed FDA to
reexamine the safety of all substances included on the GRAS list (Ref.
12). We subsequently announced that we were conducting a comprehensive
study of these substances (35 FR 18623, December 8, 1970). The purpose
of the study was to evaluate the available safety information for
substances on the GRAS list. For substances determined safe under their
conditions of use, we would then repromulgate each substance in a new
(i.e., affirmed) GRAS list, a food additive regulation, or an interim
food additive regulation pending completion of additional studies. In
conjunction with this comprehensive study, we revoked informal GRAS
opinion letters issued before April 9, 1970, in part because many
letters no longer resided in FDA's files; thus, in the absence of
information concerning the names and uses of the substances in the
letters, the safety of all such substances and uses could not be
reexamined (35 FR 5810, April 9, 1970) (see Sec. 170.6 (21 CFR 170.6)
and Sec. 570.6 (21 CFR 570.6)).
In the notice announcing the comprehensive review of substances
included on the original GRAS list, we proposed criteria that could be
used to establish whether the use of these substances should be
included on a new GRAS list, become the subject of a food additive
regulation, or be listed in an interim food additive regulation pending
completion of additional studies (35 FR 18623). We incorporated these
criteria into our regulations as Sec. 121.3 (21 CFR 121.3) (36 FR
12093, June 25, 1971) (renumbered as Sec. 170.30 (21 CFR 170.30) for
human food and Sec. 570.30 (21 CFR 570.30) for animal food; see 41 FR
38618, September 10, 1976, and 42 FR 14302, March 15, 1977). We later
announced that we were conducting a study of certain GRAS substances
(36 FR 20546, October 23, 1971) and subsequently instituted a
rulemaking to establish procedures that we could use, on our own
initiative, to affirm the GRAS status of substances that were the
subject of that review and were found to satisfy the criteria
established in Sec. 121.3 (proposed rule, 37
[[Page 51840]]
FR 6207, March 25, 1972; final rule, 37 FR 25705, December 2, 1972). We
recodified these procedures at Sec. 170.35(a) and (b) (21 CFR
170.35(a) and (b)) for human food (42 FR 14302) and Sec. 570.35(a) and
(b) (21 CFR 570.35(a) and (b)) for animal food (41 FR 38618). Because
the GRAS review did not cover all GRAS substances (e.g., substances
that were marketed based on a firm's conclusion of GRAS status), the
1972 rulemaking included a mechanism (the GRAS affirmation petition
process) whereby an individual could petition us to review the GRAS
status of substances not being considered as part of our GRAS review.
If we agreed that the substance was GRAS under the conditions of its
intended use, we could affirm the use of the substance as GRAS in our
regulations. Our affirmations of GRAS status are currently codified in
parts 184 and 186 (21 CFR parts 184 and 186) for human food and part
584 (21 CFR part 584) for animal food.
Petitions submitted as part of the GRAS affirmation process
informed us, the domestic and international food industry, and the
public of conclusions of GRAS status. However, this framework proved to
be resource-intensive (e.g., FDA issued a rule proposing to affirm a
substance as GRAS under the conditions of its intended use and affirmed
the GRAS status in a final rule). Therefore, in the Federal Register of
April 17, 1997 (62 FR 18938), we proposed to: (1) clarify the criteria
for eligibility for classification as GRAS; and (2) replace the
voluntary GRAS affirmation petition process with a voluntary GRAS
notification procedure. In the Federal Register of August 17, 2016 (81
FR 54960) (the 2016 GRAS final rule), we finalized the voluntary GRAS
notification regulation in Subpart E of part 170 (21 CFR part 170) for
human food and Subpart E of part 570 (21 CFR part 570) for animal food.
The regulations provide that any person may notify FDA of a view that a
substance is not subject to the premarket review and approval
requirements of section 409 of the FD&C Act based on that person's
conclusion that the substance is GRAS under the conditions of its
intended use (see Sec. 170.205 (21 CFR 170.205) and Sec. 570.205 (21
CFR 570.205)). We explained that we would evaluate whether the data,
information, and narrative in a GRAS notice support that conclusion (81
FR 54960 at 55035; see also Sec. 170.265(b) (21 CFR 170.265(b)) and
Sec. 570.265(b) (21 CFR 570.265(b))).
B. The Need To Mandate GRAS Notifications
The voluntary GRAS notification program has improved our efficient
administration of the FD&C Act by providing us with more data and
information about uses of substances in food. GRAS notices have
informed us about new food substances entering the market, including
some substances into which we might not otherwise have insight. GRAS
notices have therefore provided us with information that improved our
understanding of the U.S. food supply and enhanced our ability to
protect public health by helping to identify the use of potentially
unsafe substances in food or additives that require FDA review and
approval to be lawfully marketed, so we can take action as appropriate.
As part of an interim pilot program created with the 1997 proposed
rule, parties began notifying us about their conclusions of GRAS status
(62 FR 18938 at 18954). FDA's former Center for Food Safety and Applied
Nutrition (now called the Human Foods Program (HFP)) filed its first
GRAS notice in 1998 under the interim pilot program. As of March 25,
2025, HFP has filed over 1,200 GRAS notices (Ref. 3). FDA's Center for
Veterinary Medicine (CVM) established its interim pilot program more
recently (75 FR 31800, June 4, 2010) and filed its first GRAS notice in
December 2010. As of March 28, 2025, CVM has filed 75 GRAS notices
(Ref. 4).
In addition to providing us with more information about uses of
substances in food, the voluntary GRAS notification program has
improved our administration of the FD&C Act in other ways. For example,
the voluntary GRAS notification program created new opportunities for
us to engage with industry to learn more about the U.S. markets for
human and animal food. Under the voluntary GRAS notification program,
FDA routinely engages with industry through pre-submission meetings and
related consultations. We also work with industry to improve GRAS
notice submissions and recommend the necessary data and other
information to facilitate a successful evaluation of a GRAS notice.
These opportunities to engage with stakeholders provide us with more
information about human and animal food substances, and they enable us
to better achieve our ultimate goal of helping to identify the use of
potentially unsafe substances in food or additives that require FDA
review and approval to be lawfully marketed, so we can take action as
appropriate.
Despite the benefits of our GRAS notification program, we have
identified challenges with our current voluntary approach to GRAS
notifications. These challenges, which we describe in the sections that
follow, have created obstacles to fulfilling our statutory
responsibility to determine if the use of a substance constitutes a
food additive use that is subject to the premarket review and approval
requirements of section 409 of the FD&C Act. We are, therefore,
proposing a mandatory approach to GRAS notifications to better serve
these purposes.
1. Issues Identified Over the Course of the Voluntary GRAS Notification
Program
After nearly 30 years of receiving and evaluating GRAS notices, and
after filing more than 1,200 GRAS notices, FDA has identified several
issues with the current voluntary approach to GRAS notifications. We
describe some issues we have identified with a voluntary approach to
GRAS notifications in greater detail in the following sections.
a. Issue #1: Inadequate analyses to support independent conclusions
of GRAS status can result in unapproved food additive uses. Due to the
voluntary nature of the GRAS notification program, we have periodically
learned about the continued use of substances in food that we have
publicly indicated constitute unapproved food additive uses. It may be
unclear whether such substances are being used based on a new
independent conclusion of GRAS status and, if so, what data and
information a firm may be relying on to substantiate that conclusion.
The continued use of stevia leaves and crude extracts of stevia
leaves provide one such example. We first issued an import alert in
1991 for crude extracts of stevia leaves and foods containing stevia
leaves or stevia extracts to prevent the importation of unsafe stevia
products into the United States. We have updated the import alert to
add firms subject to the import alert and to account for uses of
purified extracts for which FDA does not have questions following the
review of a GRAS notice. The most recent update issued in 2025
continues to recommend detention without physical examination of stevia
leaves, crude extracts of stevia leaves, or foods containing these
substances (Ref. 13). The import alert states that, when used in
conventional foods, stevia leaf, or its crude extract, is not an
approved food additive and is not considered GRAS due to inadequate
toxicological information necessary to demonstrate safety. In contrast,
the safety of high purity (greater than or equal to 95 percent pure)
steviol glycosides, the sweetening molecules found in stevia leaves, is
well-established, and FDA has evaluated and issued ``no questions''
letters in response to multiple GRAS notices
[[Page 51841]]
regarding highly purified forms of steviol glycosides. Notwithstanding
these developments regarding high purity steviol glycosides, FDA's
position on stevia leaves and their crude extracts has remained clear
and consistent since the 1991 import alert--their use is not considered
GRAS and constitutes an unapproved food additive use. Despite our
unambiguous position regarding stevia leaves and stevia leaf crude
extracts since 1991, we continue to find products containing these
substances. In 2022, for instance, FDA issued a warning letter about
the use of an unapproved food additive--stevia leaf--in several green
tea products (Ref. 14).
Our experience under the voluntary GRAS notification program has
further demonstrated that some firms may not be conducting sufficient
analyses of whether their use of a substance in food is GRAS. FDA
advises firms that preserving the applicable data and information that
forms the basis of an independent conclusion of GRAS status represents
prudent practice for those who assert that the statutory premarket
review and approval requirements for food additives do not apply to the
use of a substance in food (81 FR 54960 at 55028; see also 62 FR 18938
at 18947). We encourage firms to maintain the data and information that
support the independent conclusion of GRAS status in the form of a GRAS
notice (81 FR 54960 at 55027; see also Ref. 14). We also recommend that
a firm make public the basis for its independent conclusion of GRAS
status, as that aligns with FDA's practice to make GRAS notices
publicly available (Ref. 15) and our goal of increasing transparency.
Notwithstanding these recommendations, we have learned that some
firms may not conduct an evaluation that is sufficient to establish
that a substance is GRAS under the conditions of its intended use.
Firms also may not have the data and information that adequately
support the basis for an independent conclusion of GRAS status. These
observations are troubling given that firms are responsible for the
safe manufacture of food being introduced into interstate commerce,
including assuring the safety of substances used in making a food
product.
Several examples illustrate the real-life consequences of these
trends. In 2009, we received a letter from 18 Attorneys General and one
city attorney expressing concerns about caffeinated alcoholic beverages
(Ref. 16). FDA advised manufacturers that we were considering whether
caffeine could lawfully be added to alcoholic beverages (Ref. 17). We
informed these firms that there are no food additive regulations
authorizing the use of added caffeine in alcoholic beverages, that such
use was not prior sanctioned, and that we had not determined the use to
be GRAS (id.). We gave them 30 days to submit their rationale,
supporting data, and information for their conclusion that the use of
caffeine in alcoholic beverages was GRAS or prior sanctioned. One firm
said that it would prepare and submit a GRAS notice to us (Ref. 18),
but it took more than 7 months for us to receive their GRAS notice. We
identified several questions for the submitted notice, and in the end,
we granted the firm's request to cease to evaluate the GRAS notice
(Ref. 19).
During our evaluation of the GRAS notice, we issued four warning
letters to firms marketing caffeinated alcoholic beverage products,
including the firm that submitted the GRAS notice (Ref. 20). We stated
in the letters that, based on the publicly available literature, a
number of qualified experts have concerns about the safety of
caffeinated alcoholic beverages. We further stated that FDA is not
aware of data or other information to establish the safety of caffeine
as used in these products. We informed firms marketing these
caffeinated alcoholic beverages that caffeine, as used in the firms'
products, is an unsafe food additive, and that the products are thus
adulterated under section 402(a)(2)(C) of the FD&C Act. The firms
subsequently ceased distribution of these products. This experience
yielded a valuable insight into our GRAS notification program--had the
firms marketing caffeinated alcoholic beverages been required to submit
GRAS notices, we could have reviewed the information provided and
informed firms much earlier that this use of caffeine rendered the
substance a food additive requiring premarket review and approval.
We have drawn similar insight from our more recent experience
involving human food products containing Delta-8 tetrahydrocannabinol
(THC). In 2024, we sent warning letters to several firms for selling
human food products that were represented as containing Delta-8 THC
(Ref. 21). We stated that no food additive regulation authorizes the
use of Delta-8 THC and that the use of the substance was not prior
sanctioned. The warning letters went on to explain that available data
raise serious concerns about the potential harm from Delta 8-THC,
including adverse effects on the central nervous and cardiopulmonary
systems and that some studies in animals suggested gestational exposure
can interfere with neurodevelopment. The warning letters also cited
adverse event reports related to ingestion by children and adults of
edible products containing Delta-8 THC. The letters concluded that,
based on FDA's review, the use of Delta-8 THC in conventional foods did
not meet the criteria for GRAS status in FDA's regulations and that
these products contained an unsafe food additive rendering them
adulterated under section 402(a)(2)(C)(i) of the FD&C Act.
When we are not aware of an independent conclusion of GRAS status,
we do not know what data and other information a firm uses to support
their GRAS conclusion. Thus, there may be independent GRAS conclusions
for currently marketed uses of substances for which we would typically
have questions about their GRAS status. Without data and information,
we cannot follow up on these questions as we would if we received a
deficient voluntary GRAS notice. Moreover, in the case of independent
conclusions of GRAS status, we may not become aware of a firm's poorly
supported GRAS conclusion until after a product becomes available to
consumers and, in some cases, only after an adverse event occurs.
For example, in 2022, a firm that used tara flour as an ingredient
in a human food product initiated a voluntary recall of that product
after it was associated with roughly 400 adverse event reports that
detailed, among other things, gastrointestinal distress,
hepatotoxicity, and hospitalization (Ref. 22). The firm conducted its
own root cause analysis and identified tara flour as a possible
contributor to the illnesses. We requested, but the firm did not share
with FDA any records or other indication that demonstrated that they
had reached a GRAS conclusion regarding the use of tara flour in human
food. FDA evaluated the regulatory status of tara flour, which had not
been the subject of any prior GRAS notice or a GRAS pre-submission
meeting. We determined that there are not enough data on the use of
tara flour in food, or a history of its safe use in food before 1958,
to consider it GRAS, and there is also no food additive regulation
authorizing the use of tara flour in food (id.). We posted our
assessment of tara flour to FDA's ``Post-market Determinations that the
Use of a Substance is Not GRAS'' website (Ref. 23). If we had received
information from the firm through a GRAS notice earlier, we could have
advised them of the need for information and studies to establish
safety.
In addition to posting ``not GRAS'' memos to our website, we also
issue import alerts or warning letters in
[[Page 51842]]
situations where we have first evaluated the regulatory status of an
ingredient, such as following inspection activities. For example, in
2023 FDA placed ashwagandha, an evergreen shrub whose extracts were
identified in some human food products, on Import Alert 99-45 after FDA
inspectors raised questions about its regulatory status and deemed it
to be an unsafe food additive (Ref. 24). As a result, FDA may detain,
without physical examination, shipments of certain identified food
products containing ashwagandha from firms on the Red List of Import
Alert 99-45. Ashwagandha has not been the subject of a voluntary GRAS
notice.
These examples demonstrate that, under the current voluntary GRAS
notification program, firms sometimes lack a sufficient basis for GRAS
conclusions, resulting in the use of unapproved food additives in our
food supply. In some cases, we become aware of the need to take action
regarding unsafe additives in food only after learning of adverse
public health events. Mandating the submission of GRAS notifications
would enable us to better address concerns regarding the potential use
of unapproved food additives in foods by providing us with information
about independent conclusions of GRAS status. It would also further
improve our administration of the FD&C Act by providing more
opportunities for us to engage with industry to understand the basis
for these GRAS conclusions.
b. Issue #2: Substances introduced into the marketplace after we
cease to evaluate a GRAS notice at a notifier's request. The voluntary
GRAS notification program provides that notifiers may request that FDA
cease to evaluate a GRAS notice (see Sec. 170.260(b) (21 CFR
170.260(b)) and Sec. 570.260(b) (21 CFR 570.260(b))). We noted in the
2016 GRAS final rule that a cease to evaluate letter signals that a
GRAS notice does not provide an adequate basis for a conclusion that
the notified substance is GRAS under the conditions of its intended
use, even though we do not issue an insufficient basis letter regarding
the notified substance (81 FR 54960 at 55010).
In current practice, notifiers request that we cease to evaluate a
GRAS notice for a variety of reasons. For example, if we have questions
about a GRAS notice that cannot be addressed by a timely amendment, a
notifier may ask us to cease evaluating their GRAS notice so that they
can later submit a new GRAS notice that addresses our questions. During
our evaluation of a GRAS notice, we also may raise issues regarding the
data and information used to support the GRAS conclusion. If our
questions about the underlying support for a GRAS conclusion cannot be
easily resolved, notifiers may request that we cease reviewing the
notice while they develop or compile additional data to address the
issues raised. For GRAS notices pertaining to substances used in animal
food, notifiers have sometimes sent us cease to evaluate requests after
we have raised questions about proposed contaminant limits in their
GRAS notices.
In some cases, a notifier who received a cease to evaluate letter
submits a new GRAS notice for the use of the notified substance after
addressing our questions, and we respond to the new GRAS notice with a
no questions letter. Alternately, after receiving a cease to evaluate
letter from FDA, some notifiers may decide not to submit a new GRAS
notice and instead to make an independent conclusion of GRAS status and
market the substance or food containing the substance. If a notifier
does not submit a new GRAS notice to FDA after receiving a cease to
evaluate letter, we have no information about whether the previously
notified substance later entered the market based on an independent
conclusion of GRAS status. We also do not have insight into whether any
questions we raised about the notified substance were adequately
addressed. In such cases, this could cause confusion about whether the
use of a substance meets the definition of a food additive use under
the FD&C Act, and therefore whether the use of the substance requires
FDA review and approval to be lawfully marketed. Our existing voluntary
GRAS notification program creates the opportunity for a notifier to
introduce a substance about which we had safety questions into the
market without providing transparency to FDA and the public regarding
the basis of their GRAS conclusion.
c. Issue #3: Insufficient information hinders FDA's efficient
administration of the FD&C Act. Due to the voluntary nature of our
current GRAS notification program, a firm can market a substance that
it has concluded is GRAS under the conditions of its intended use
without submitting a notice to FDA. This prevents us and the public
from having knowledge about, and insight into, these purported GRAS
uses of substances. Our lack of a complete understanding of what
substances are being used in the food supply impedes our ability to
efficiently carry out our role under the FD&C Act to prohibit the use
of unsafe additives in food and protect public health.
In GAO's 2010 report entitled ``Food Safety: FDA Should Strengthen
Its Oversight of Food Ingredients Determined to be Generally Recognized
as Safe (GRAS),'' GAO noted that FDA generally has no information about
GRAS determinations that are not submitted to the voluntary
notification program (Ref. 5 at page 12). (We use the terms ``GRAS
conclusion'' or ``conclusion of GRAS status'' instead of ``GRAS
determination''; see 81 FR 54960 at 54969.) The GAO report included one
example of a firm indicating that it ``makes about 5 GRAS
determinations each year without notifying FDA'' (Ref. 5 at page 12).
These GRAS determinations usually pertained to ``new uses of substances
that have been deemed GRAS for other uses'' (id. at page 12). The GAO
report further stated that FDA is less informed about the U.S. food
supply and consumers' cumulative dietary exposure to GRAS substances
because we do not oversee all GRAS determinations (id. at page 13). GAO
recommended that we develop a strategy to require any firm that
conducts a GRAS determination to provide FDA with basic information
about the identity and use of the substance (id. at page 34).
As discussed in our response to the GAO Report, we share the
transparency goal underlying GAO's recommendation to require the
submission of basic information about GRAS uses of substances (Ref. 5).
In the 2016 GRAS final rule, we said that a voluntary approach to GRAS
notifications would mitigate many issues GAO raised in its report. For
instance, we noted that a voluntary GRAS notification program would
enable us to evaluate more, and higher priority, substances (81 FR
54960 at 54961). We also discussed the increasing use of the voluntary
GRAS notification program throughout the interim pilot program (id. at
54980). However, after nearly a decade of additional experience
administering the voluntary GRAS notification program, and in light of
the ongoing changes to the nation's food supply discussed in greater
detail below, the risks of not requiring GRAS notifications have become
more evident.
As of January 2011, some sources estimate that there were 1,000
substances in use in human food for which firms had claimed independent
conclusions of GRAS status (Refs. 6 and 7). However, given that the
current GRAS notification program is voluntary, we have little, if any,
information on independent conclusions of GRAS status, including the
identity of the substance and its intended use(s).
Regarding food contact substances, specifically, we operate two
programs (the infant formula notification program and the food contact
substance
[[Page 51843]]
formulation review program) where food packaging producers submit their
packaging product formulations to us to verify compliance with FDA
regulations. These programs provide FDA with limited opportunities to
obtain information on independent conclusions of GRAS status. Through
these programs, FDA has reviewed submissions where the inclusion of
certain food contact product components is based on claims that the
component is GRAS under the conditions of its intended use. While these
programs provide us with some insight into independent GRAS conclusions
made about those components, we lack a complete understanding of the
number of substances currently on the market based on an independent
conclusion of GRAS status.
In addition, our lack of a complete understanding of the substances
added to food prevents us from efficiently sharing knowledge and
providing transparency to others, such as state regulators, food
manufacturers, and consumers, about substances in interstate commerce
that are purported to be GRAS under the conditions of their intended
use. For example, both HFP and CVM receive questions from state
regulators, the regulated industry, and consumers about the regulatory
status of such substances in human and animal food. Responding to these
inquiries can often be challenging, as the lack of information we have
on many substances impedes FDA's ability to effectively provide
oversight in partnership with state regulators.
We are also aware that confidence in the federal government's
ability to ensure the safety of the U.S. food supply, generally, has
declined. The percentage of U.S. adults who say they have a ``great
deal'' or ``fair amount'' of confidence in the government to keep the
food supply safe fell from 68 percent in 2019 to 57 percent in 2024
(Ref. 25). Consumers indicate they would have more confidence in the
safety of the U.S. food supply if they better understood how the
federal government and industry work together to ensure food safety or
if the federal government's regulations on food safety were stricter
(Ref. 26). This general lack of consumer confidence speaks to an
overarching need for the federal government to work to strengthen
public confidence in the safety of the U.S. food supply--this proposed
rule would be one example of a way to strengthen public confidence
through increased transparency about the substances being added to the
nation's food supply.
Unless a voluntary GRAS notice has been filed, we may not have
insight into whether a given substance is GRAS under the conditions of
its intended use without expending significant FDA resources to
identify whether publicly available data supports the safe use of the
substance. Aside from our GRAS notice inventory, which does not cover
independent conclusions of GRAS status, no publicly available list
exists where we or interested parties can verify the use in interstate
commerce of all substances purported to be GRAS under the conditions of
their intended use. Our inability to proactively share knowledge and
provide transparency regarding all such substances may undermine public
confidence regarding FDA's ability to protect public health. It also
impedes our ability to effectively and efficiently regulate the U.S.
food supply.
2. The Changing Food Supply in the United States
The country's continually evolving food supply also presents new
challenges to our efficient administration of the FD&C Act. As
referenced elsewhere in this document, some sources estimate that, as
of January 2011, there were more than 10,000 additives in use in food,
including an estimated 1,000 human food substances for which firms had
claimed independent conclusions of GRAS status (Refs. 6 and 7).
Although we cannot verify the accuracy of these estimates, these
figures, and the statistics from our voluntary GRAS notification
programs for both human and animal food, describe a food supply that is
markedly different from the one FDA regulated when it first began to
implement the 1958 amendment.
The Delaney Committee, for instance, stated in its 1952 report that
FDA representatives testified during a 1950 hearing that there were in
total ``704 chemicals employed in food use'' at that time (Ref. 8), of
which ``428 [were] definitely known to be safe'' (id.). In contrast,
HFP and CVM combined have filed over 670 GRAS notices since January
2016 and more than 1,200 GRAS notices in total since 1998 when FDA
began filing GRAS notices under the interim pilot program. (We note
that multiple GRAS notices may pertain to the same substance (i.e.,
they describe different conditions of intended use).) Information from
GRAS notices we have filed also highlights the increasingly complex and
globalized nature of our food supply. Of the more than 1,200 filed GRAS
notices, 617 were submitted by foreign firms, and 503 of these were
submitted by foreign firms located in countries where English is not
the primary language.
An additional challenge is that, for certain nutrients, dietary
exposure estimates are approaching the tolerable upper intake level
(UL) established by the Institute of Medicine (IOM) (now the National
Academies of Sciences, Engineering, and Medicine). A nutrient's UL is
the highest level of daily intake that is likely to pose no risk of
adverse health effects (Ref. 27). A UL may differ for individuals at
different life stages (e.g., children ages 9 through 13 years, adults
over 70 years) and is determined using a risk assessment approach
developed specifically for nutrients (id.). Notably, whether a
substance in food is contributing to dietary exposure approaching a
nutrient's UL is information that is critical to our assessment of both
whether a given use of a substance renders it a food additive use, and
whether the use of a food additive is safe.
A case study of calcium demonstrates the importance of such
information. Calcium is an essential nutrient necessary for numerous
physiological processes, including formation/metabolism of bone, and
intracellular signaling related to muscular function, vascular
contraction/dilation, nerve transmission, and hormonal secretion (Ref.
28). Maintenance of calcium balance is essential for the body's normal
function (Id.). The IOM established ULs between 2,000 and 3,000
milligrams per day for different life stage groups among the population
aged 4 years and older (Ref. 29). However, excessive supplemental
calcium intake can lead to certain health complications, such as an
increased risk for kidney stones (Refs. 29 and 30).
To assess the safety of calcium, which we would do when we are
evaluating a submission for a calcium salt, such as a food additive
petition, color additive petition, or GRAS notice, we consider the IOM
ULs relative to the cumulative dietary exposure estimates. Since 2017,
our evaluations regarding uses of calcium salts for human foods have
shown that cumulative dietary exposure estimates to calcium have been
increasing (see 82 FR 51554, November 7, 2017; and 87 FR 58445,
September 27, 2022). In 2024, we noted that the dietary exposure
estimate for calcium at the 90th percentile was approaching the IOM's
upper limit for calcium of 2000 mg for population groups 51-70 and 71
years and older (Ref. 31). We also noted that the National Cancer
Institute (NCI) developed a validated model to estimate the usual
dietary intakes of episodically consumed foods and dietary
[[Page 51844]]
supplements (NCI usual dietary intakes method) (id.).
In a recent final order listing calcium phosphate (a calcium salt)
as a color additive in ready-to-eat chicken products, white candy
melts, doughnut sugar, and sugar for coated candies, we stated our
literature search identified no new publications relevant to the safe
use of calcium in food, and therefore, the current state of the science
supports the continued use of the IOM UL for calcium as a dietary
reference value to support public health (90 FR 20097, May 12, 2025).
During our review, and in consultation with us, the petitioner amended
the intended uses of calcium phosphate to remove the use in icing and
reduce the use level in sugar for coated candies to reduce overall
dietary exposure to calcium (id. at 20098). Using 2015-2020 National
Health and Nutrition Examination Survey food consumption data combined
with the NCI usual dietary intakes method, we estimated the cumulative
dietary exposure to calcium from the background dietary sources,
including dietary supplements and drugs, and the petitioned uses to be
1,195 mg/p/d at the mean and 1,789 mg/p/d at the 90th percentile for
the U.S. population ages 2 years and older (id.). If the petitioner had
not amended the intended uses of calcium phosphate, then overall
dietary exposure to calcium would have exceeded the UL for certain life
stage groups.
We anticipate continuing to see nutrients approaching, and
potentially exceeding, the UL, which, in certain cases, would present
questions about the safe use of such ingredients and raise health
concerns that we would want to address. Ongoing consumption of
substances that are purported to be GRAS under the conditions of their
intended use, as well as consumption of new substances that are
purported to be GRAS under the conditions of their intended use, may be
contributing to these trends. Without a mandatory GRAS notification
requirement, FDA will not always be aware of what uses of substances
are contributing to nutrient consumption approaching the UL, nor will
FDA always be provided with sufficient information to engage with firms
to address questions and concerns about such issues.
Another facet of the changes we are seeing to the nation's food
supply is the increase in individually packaged single-serving foods
along with the growing awareness both by food manufacturers and
consumers about the environmental impact of disposable food packaging
(Ref. 32). This has resulted in initiatives to substitute certain food
packaging materials, in particular plastics made from petroleum
sources, with alternative packaging materials thought to have lower
environmental impacts (id.). Many of these alternative packaging
materials are bio-based (i.e., derived from raw materials such as
plants), which may be perceived as less toxic than petroleum-based
plastics (Ref. 33). In some cases, users of these alternative materials
may consider them to be GRAS under the conditions of their intended use
and may choose not to go through FDA's review programs prior to
bringing their products to market. As stated elsewhere in this
document, due to the voluntary nature of our current GRAS notification
program, a firm can market a substance that it has concluded is GRAS
under the conditions of its intended use without submitting a notice to
FDA. The Food and Drug Administration Modernization Act amended section
409 of the FD&C Act to establish the food contact notification program
for food contact substances that are food additives, as an alternative
to food additive petitions. Food contact notifications (FCNs) or food
additive petitions are not required for food contact substances that
are GRAS. Therefore, companies use the GRAS provision of the statute to
conclude that a food contact substance is GRAS and that a food contact
notification or a food additive petition is not required. This prevents
us and the public from having knowledge about, and insight into, these
purported GRAS uses of substances. This proposed rule would provide
flexibility to companies to submit an FCN instead of a GRAS notice for
food contact substances if they prefer to use the FCN process. Note, in
contrast to GRAS notices, food contact notifications and the intended
use are specific to the listed manufacturer or supplier for the
effective FCN.
Our lack of a complete understanding of what substances are being
used in the food supply impedes or delays our ability to efficiently
carry out our role under the FD&C Act to prohibit the use of unsafe
additives in food and protect public health.
For example, we recently evaluated, on our own initiative,
dinnerware (i.e., bowls, plates, cups, cutlery) manufactured from the
sheath of leaves from the Areca catechu (A. catechu) plant (Ref. 34)
after inquiries from industry as to whether this use would require
premarket authorization. Our research shows that naturally occurring
toxins in these products migrate into food at levels that may pose a
potential safety concern to consumers (Ref. 35). Therefore, the use of
the sheath of A. catechu palm leaves in food contact articles such as
dinnerware does not meet the statutory criteria for GRAS, and no
authorizations exist for its use in food (Ref. 34). We issued a letter
informing retailers, distributors, and importers of dinnerware
manufactured from the sheath of leaves from the A. catechu plant that
such dinnerware may not be lawfully offered for sale in the U.S. (Ref.
36), and we added palm leaf dinnerware to Import Alert 23-15 (Ref. 37).
3. How a Mandatory GRAS Notification Program Would Address These Issues
and Challenges
A mandatory GRAS notification program would provide FDA with
information, in the form of a GRAS notice, on the uses of substances
that would otherwise be marketed under an independent conclusion of
GRAS status. The proposed amendments to convert our current voluntary
GRAS notification program to a mandatory program would increase the
level of knowledge and transparency about substances in the U.S. food
supply that are purported to be GRAS under the conditions of their
intended use. This would provide FDA, state regulators, consumers, and
industry with more information about substances being added to human
and animal food and enable FDA to establish a more comprehensive
catalog of what substances are being added to food. These proposed
changes would help ensure that GRAS conclusions have a scientific basis
and that sufficient documentation supporting those conclusions is
developed and shared with FDA. This information would be accessible to
the public within a few weeks of filing through FDA's GRAS Notice
Inventory, which is available on our website and where we currently
maintain this information (Refs. 3 and 4), thereby increasing
transparency about purported GRAS uses of substances (see section V.K
of this document for further discussion). These proposed changes would
also enhance our ability to efficiently carry out our role under the
FD&C Act to prohibit the use of unsafe additives in food and protect
public health. Therefore, the proposed rule, if finalized, is in part
intended to help strengthen public confidence in FDA's ability to
oversee the safety of the U.S. food supply.
A mandatory GRAS notification program would also help ensure that
human food safety, as well as target animal safety in the case of
animal food GRAS notices, is fully assessed as part of a notifier's
GRAS conclusion. This information would help us to more efficiently
determine whether the use of
[[Page 51845]]
a substance meets the definition of a food additive use under the FD&C
Act, and therefore whether the use of the substance requires FDA review
and approval to be lawfully marketed. A mandatory GRAS notification
program would also respond to GAO's recommendation to develop a
strategy to require any firm that conducts a GRAS determination to
provide FDA with basic information about the identity and use of the
substance.
In addition, a mandatory GRAS notification program would provide us
with insight into any current uses of substances that were the subject
of a cease to evaluate letter. Only some notified substances that were
the subject of a cease to evaluate letter were later the subject of a
new GRAS notice for the same intended use. While our existing voluntary
GRAS notification program does not prohibit a notifier from making an
independent conclusion of GRAS status and entering the market with a
use of a substance that was the subject of a cease to evaluate letter,
this, in practice, leads to the same lack of knowledge that we have
when it comes to other independent conclusions of GRAS status. Unless
we receive a voluntary GRAS notice or there is a public health concern
prompting us to evaluate the use of an ingredient, we do not always
know how such substances are being used. Making GRAS notice submissions
mandatory would eliminate much of the confusion over whether a
substance is GRAS under the conditions of its intended use, because
these GRAS conclusions and their underlying data would be publicly
available along with our response letters.
Information about levels of added nutrients, such as calcium, would
help FDA evaluate the uses of nutrients across the food supply to
accurately evaluate dietary exposure. Mandatory GRAS notices would
provide more transparency about the ingredients, such as calcium salts,
being used in the food supply, including how they are being used and at
what levels. Such information would give us greater insight into
whether these ingredients pose safety concerns under certain conditions
of use, which might render them food additives subject to premarket
review and approval for those uses.
Ultimately, the proposed rule would help us better carry out our
statutory responsibility to prohibit the use of unsafe additives in
food. The proposed rule, if finalized, would create a framework whereby
firms would still be able to render their own GRAS conclusions, but
they would be required to submit these GRAS conclusions to FDA in
accordance with subpart E of parts 170 and 570. Mandatory GRAS notices
would provide us with safety information about substances that are
purportedly GRAS under the conditions of their intended use, helping us
to carry out our statutorily-defined role under sections 409(a) and (d)
of the FD&C Act of determining whether uses of substances introduced
into interstate commerce constitute food additive uses that are subject
to premarket review and approval. The proposed rule would, therefore,
aid in our effective and efficient administration of the FD&C Act.
IV. Legal Authority
We are proposing to amend parts 170 and 570 to require submission
of GRAS notices for certain substances added to or used in connection
with human or animal food under our authority in sections 201, 402,
409, and 701 of the FD&C Act. Specifically, the proposed rule would
require any person introducing a substance into interstate commerce
under the GRAS provision of section 201(s) of the FD&C Act, for which
the conditions of intended use of such substance are not covered by one
of several exceptions listed in the rule, to notify FDA of the basis
for a conclusion that the conditions of intended use of the substance
are GRAS.
A. Statutory Framework
As discussed in section III.A.1 of this document, in 1958 Congress
amended the FD&C Act to address growing concerns about the increasing
number of chemicals being added to the nation's food supply. As
amended, the FD&C Act requires that all food additives (as defined by
section 201(s) of the FD&C Act) be approved by FDA before they are
marketed or used in food (sections 402(a)(2)(C)(i) and 409 of the FD&C
Act). Sections 409(a) through (h), and also (k) for animal food, of the
FD&C Act authorize FDA to approve a food additive by issuing an order
establishing a regulation regarding the food additive's safety for a
particular use. In particular, sections 409(b) and (d) of the FD&C Act
set out in detail the two types of processes that may result in orders
establishing food additive regulations: (1) under section 409(b) of the
FD&C Act, any person may file with the Secretary a petition proposing
the issuance of a food additive regulation; and (2) under section
409(d) of the FD&C Act, the Secretary (or his delegate) may propose the
issuance of a food additive regulation at any time, upon his own
initiative. In addition, section 409(h) of the FD&C Act provides for a
process through which the intended use of a food additive that is an
FCS becomes authorized through a notification submitted by the
manufacturer or supplier. With some exceptions, food additives are
deemed unsafe food additives under section 409(a) of the FD&C Act
unless their use conforms with a food additive regulation. Foods that
are, or bear or contain, unsafe food additives are deemed adulterated
under section 402(a)(2)(C)(i) of the FD&C Act, rendering them potential
targets for enforcement actions under the FD&C Act (e.g., sections 302
and 304 of the FD&C Act).
Section 201(s) of the FD&C Act excludes from the definition of a
food additive a substance generally recognized, among experts qualified
by scientific training and experience to evaluate its safety, as having
been adequately shown through scientific procedures (or, in the case of
a substance used in food before January 1, 1958, through either
scientific procedures or experience based on common use in food) to be
safe under the conditions of its intended use. Thus, substances that
are GRAS under the conditions of their intended use are not subject to
the food additive premarket review and approval requirements of section
409 of the FD&C Act.
B. Legal Basis for the Proposal
The proposed rule would provide FDA with information about
substances being introduced into interstate commerce under the GRAS
provision of section 201(s) of the FD&C Act. Specifically, the proposed
rule would require the submission of information about the intended use
of such substances and the data and information supporting the
conclusion that the substance is GRAS under the conditions of its
intended use. Because the conditions of intended use of these
substances, together with available safety data, may render them food
additives subject to premarket review and approval, requiring the
submission of information about these substances and their intended
uses would help FDA efficiently carry out its responsibilities under
sections 409(a) and (d) of the FD&C Act to propose and establish food
additive regulations.
When read together, sections 409(a) and (d) of the FD&C Act task
the Secretary, and by delegation, FDA, with identifying food substances
that have not been the subject of a food additive petition or an FCN
and with initiating review of the safety of such substances for
particular uses. See Se. Minerals, Inc. v. Harris, 622 F.2d 758, 767
(5th
[[Page 51846]]
Cir. 1980) (citing, inter alia, section 409(d) of the FD&C Act and
Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 624
(1973)) (``The FDA has the authority to determine whether a particular
product requires an approved food additive regulation in order to be
marketed in interstate commerce.''). Thus, sections 409(a) and (d) of
the FD&C Act authorize FDA to review substances on the market,
including new and existing substances introduced into food that are
purportedly GRAS under the conditions of their intended use, to assess
whether these uses constitute food additive uses that require a food
additive regulation to be lawfully marketed. The proposed rule, which
would require persons introducing certain substances into interstate
commerce under the GRAS provision of section 201(s) of the FD&C Act to
notify FDA of the basis for their conclusion that the use of a
substance is GRAS, would help FDA to efficiently carry out these
statutory responsibilities.
Specifically, requiring the submission of GRAS notifications would
better enable us to monitor what substances are being added to or used
in connection with food by alerting us to substances on the market that
we might not otherwise know exist. This includes uses of substances in
food that were the subject of independent conclusions of GRAS status,
and thus uses of substances that FDA otherwise may learn about only
after public health concerns are raised. Further, requiring the
submission of GRAS notices would provide us with safety information
about substances that are purportedly GRAS under the conditions of
their intended use, which would help us to determine whether such uses
of substances actually constitute food additive uses that are subject
to the premarket review and approval requirements of the FD&C Act. See,
e.g., Se. Minerals, Inc., 622 F.2d at 767 (``FDA, as the administrative
agency created by Congress to administer the [FD&C Act], cannot
intelligently and rationally perform its regulatory duties unless it
determines what products are `food additives' . . . and what products,
because of their GRAS status, are exempt from regulation.''). This
information would also support FDA's compliance and enforcement
activities related to the use of unapproved food additives, such as the
issuance of warning letters and seizure of adulterated foods. A
mandatory GRAS notification program would therefore help us to fulfill
the underlying purpose of sections 409(a) and (d) and related
provisions of the FD&C Act by providing us with information that better
enables us ``[t]o prohibit the use in food of additives which have not
been adequately tested to establish their safety.'' See Public Law 85-
929, 72 Stat. 1784 (1958).
The proposed rule, if finalized, would thus facilitate FDA's
efficient administration and enforcement of sections 409(a) and (d) of
the FD&C Act. Section 701(a) of the FD&C Act authorizes the Secretary
to issue regulations for the efficient enforcement of the FD&C Act;
under section 1003(d) of the FD&C Act (21 U.S.C. 393(d)), the Secretary
is responsible for executing the FD&C Act, including section 701(a) of
the FD&C Act, through the Commissioner of Food and Drugs.
V. Description of the Proposed Rule
As discussed in section III.B.1 of this document, in light of the
issues we have identified with the voluntary GRAS notification program,
and the challenges posed by the changing U.S. food supply, we are
proposing to require the submission of GRAS notices for the use of a
human or animal food substance that is purported to be GRAS under the
conditions of its intended use. Food substances include both
ingredients (i.e., substances added directly to food) and food contact
substances (i.e., substances added indirectly to food, such as
migration from food packaging). In proposing these changes, FDA is (1)
converting the current GRAS notification program from voluntary to
mandatory; (2) identifying certain categories of exceptions from the
requirement to submit a GRAS notice, including a time-limited option to
make a streamlined submission to FDA for certain substances already in
use in interstate commerce; and (3) identifying uses of substances that
are not eligible to be the subject of a GRAS notice.
We are also proposing to make conforming edits throughout part 170
to reflect the change to a mandatory program; changes to our procedural
regulations for a TOR exemption to reflect updated scientific guidance
and to expand the scope of this exemption to cover uses of substances
in food and FCSs generally, in addition to FCSs used in food contact
articles; and other changes to make non-substantive edits. Several of
these changes would support the Administration's goal of modernizing
Federal regulations to eliminate outdated or unnecessary requirements
and ensure there is flexibility to, for example, leverage new
technology in the future to more efficiently fulfill regulatory
requirements. In addition, we are proposing new definitions to help in
the administration of a mandatory GRAS notification program and
updating other definitions for clarity.
A. Proposed Revisions to Sec. 170.3--Definitions
Our regulations, at Sec. 170.3 (21 CFR 170.3), define certain
terms for use throughout part 170. Specifically, Sec. 170.3(m) defines
food as including human food, substances migrating to food from food-
contact articles, pet food, and animal feed. Proposed Sec. 170.3(m)
would revise the definition of food to include human food, substances
migrating to food from food-contact articles, and animal food. The term
``animal food'' would update ``pet food, and animal feed'' and would
align with the use of the term ``animal food'' within our regulations
in part 507 (21 CFR part 507) (see Sec. 507.3) and proposed changes to
part 570 (see section V.Q of this document).
Proposed Sec. 170.3(p) would define ``We, our, us, and FDA'' to
mean the Food and Drug Administration. While our regulations, at Sec.
170.203, define ``We, our, and us'' as the ``United States Food and
Drug Administration'' for use in Subpart E--Generally Recognized as
Safe (GRAS) Notice, these terms are not defined in Sec. 170.3 to apply
more generally to part 170. We propose adding ``FDA'' to the list of
terms that would mean the Food and Drug Administration. This change
would establish these terms for use throughout part 170.
B. Proposed Revisions to Sec. 170.30--Eligibility for Classification
as GRAS
Our regulations, at Sec. 170.30, describe the criteria for
determining if a substance is eligible to be classified as GRAS.
Specifically, Sec. 170.30(a) outlines the general criteria for GRAS
status, in accordance with section 201(s) of the FD&C Act, and provides
that general recognition of safety may be based only on the views of
experts qualified by scientific training and experience to evaluate the
safety of substances directly or indirectly added to food. GRAS status
may be based on scientific procedures (see Sec. 170.30(a)(1)) or for a
substance used in food before January 1, 1958, through experience based
on common use in food (see Sec. 170.30(a)(2)). Our regulations, at
Sec. 170.30(b) and (c), further explain the elements of the general
criteria for GRAS status, and Sec. 170.30(d) through (l) discuss
specific situations in relation to GRAS status.
We are proposing revisions to Sec. 170.30(c), (e), and (i). Our
regulations, at Sec. 170.30(c)(2), recommend that a person notify FDA
if they conclude that
[[Page 51847]]
a use of a substance is GRAS through experience based on its common use
in food outside of the U.S. Proposed Sec. 170.30(c)(2) would remove
this recommendation, because the proposed rule would require a person
to notify FDA about the purported GRAS status of a substance used in
food before January 1, 1958, if that conclusion is through experience
based on the substance's common use in food outside of the United
States.
Our regulations, at Sec. 170.30(e), provide some historical
context for substances listed or affirmed as GRAS in parts 182, 184, or
186 of this chapter and mention of the systematic review of such
substances that FDA conducted beginning in 1969. Proposed Sec.
170.30(e) would remove those discussions because they are no longer
necessary.
Our regulations, at Sec. 170.30(i), state that if a substance is
affirmed as GRAS in part 184 or part 186 with no limitation other than
good manufacturing practice, then it is regarded as GRAS if its
conditions of use are not significantly different from those reported
in the regulation as the basis on which the GRAS status of the
substance was affirmed. If the conditions of use are significantly
different, then the use of the substance may not be GRAS, and a
manufacturer may not rely on the regulation as authorizing the use but
must independently establish that the use is GRAS or must use the
substance in accordance with a food additive regulation. Proposed Sec.
170.30(i) would divide the provision into Sec. 170.30(i)(1) and (i)(2)
for clarity, as these provisions cover different circumstances.
Proposed Sec. 170.30(i)(1) would contain the concept that a substance
will be regarded as GRAS if the conditions of use are not significantly
different from those reported in the regulation (i.e., part 184 or part
186). A mandatory GRAS notice would not be required for substances that
fall within the scope of proposed Sec. 170.30(i)(1) (see proposed
Sec. 170.205(b)(3)). Proposed Sec. 170.30(i)(2) would contain the
concept that if the conditions of use of a substance are significantly
different, the regulation in part 184 or part 186 may not be relied on
as authorizing such use. In this latter situation, a GRAS notice would
need to be submitted to FDA that covers the conclusion that a substance
is GRAS under the conditions of its intended use if relevant safety
information is generally available or a food additive petition could be
submitted if there is not an existing food additive regulation to cover
such use. Together, proposed Sec. 170.30(i)(1) and (i)(2) would
clarify the circumstances when our regulations in part 184 or part 186
can be relied on to regard a substance as GRAS under the conditions of
its intended use.
C. Proposed Revisions to Sec. 170.38--Determination of Food Additive
Status
The proposed rule would amend Sec. 170.38 (21 CFR 170.38) to
remove unnecessary provisions and add new provisions to clarify the
steps we may take when we determine that a substance is not GRAS under
the conditions of its intended use.
Our regulations, at Sec. 170.38(a), provide for the Commissioner
to publish a notice in the Federal Register determining that a
substance is not GRAS under the conditions of its intended use if,
after proposing that a substance is entitled to affirmation as GRAS
under the conditions of its intended use, the Commissioner evaluates
the comments and concludes that there is a lack of convincing evidence
that the substance is GRAS under the conditions of its intended use
(see Sec. 170.35). The proposal would amend Sec. 170.38(a) to remove
the reference to publishing a notice in the Federal Register because
FDA does not necessarily publish a notice when making such a
determination. However, even though we may not publish a notice in the
Federal Register, we would still make public the basis for our
determination that the substance is not GRAS under the conditions of
its intended use and is a food additive subject to section 409 of the
FD&C Act. Proposed Sec. 170.38(a) would retain the concept that when a
substance is determined to not be GRAS under the conditions of its
intended use and would instead be a food additive, the substance and
its use or intended use are subject to section 409 of the FD&C Act. A
substance subject to section 409 of the FD&C Act would require the
issuance of a food additive regulation, or an effective FCN in the case
of an FCS, for its use as a food additive to be authorized.
Our regulations, at Sec. 170.38(b), provide for the Commissioner,
on his own initiative or on the petition of any person pursuant to part
10 of this chapter, to issue a notice in the Federal Register proposing
that a substance is not GRAS under the conditions of its intended use
and is a food additive subject to section 409 of the FD&C Act; receive
comments; and, upon evaluation of all comments, publish a notice in the
Federal Register as to whether the substance's conditions of intended
use are GRAS. Proposed Sec. 170.38(b) would clarify that this
paragraph applies to substances listed or affirmed as GRAS in parts
182, 184, or 186. We also propose other non-substantive edits for Sec.
170.38(b)(1) and (b)(2) (see section V.O of this document for further
discussion). Proposed Sec. 170.38(b)(3) would also provide that if FDA
concludes that there is a lack of convincing evidence that the
substance is GRAS under the conditions of its intended uses, FDA will
amend or repeal the relevant regulation. We propose removing language
stating that we will evaluate all comments received. As we would
consider comments in response to a published proposal, this language is
unnecessary.
Our regulations, at Sec. 170.38(c), state that a Federal Register
notice determining that a substance is a food additive must provide the
use of the food additive in food or food contact substances and that we
may promulgate a food additive regulation governing the additive's use,
an interim food additive regulation governing the additive's use,
require discontinuation of the additive's use, or adopt any combination
of the above for different uses or levels of use of the additive.
Proposed Sec. 170.38(c) would replace the discussion of what a Federal
Register notice must contain (because the discussion is unnecessary as
sections 409(c) and (d) of the FD&C Act already describe the contents
of a food additive regulation) and would provide that, for uses of a
substance for which FDA has issued a no questions letter (see proposed
Sec. 170.203 and section V.E of this document for further discussion)
in response to a GRAS notice, FDA may send the notifier questions about
their GRAS conclusion in accordance with Sec. 170.265(c). Under
proposed Sec. 170.38(c), if we determine that a substance is not GRAS
under the conditions of its intended use (e.g., we receive information
that calls into question a notifier's GRAS conclusion), FDA would make
public the basis for this determination and update or rescind the no
questions letter. This provision would pertain to GRAS conclusions
received through the current voluntary GRAS notification program and
the proposed mandatory GRAS notification program, if finalized.
Our regulations, at Sec. 170.38(d), provide that if we are aware
of a prior sanction for use of a substance, FDA will concurrently
propose a separate regulation for such use. We propose to replace Sec.
170.38(d), because the proposal of a regulation based on prior sanction
for use of the substance would be covered by proposed Sec. 170.30(e).
Instead, the proposed rule would create a new paragraph (d) to cover
uses of substances not covered by proposed paragraphs (b) or (c) (i.e.,
uses of substances not covered by a regulation or a GRAS notice but
which exist in
[[Page 51848]]
interstate commerce). If FDA makes a determination that uses of such
substances are not GRAS, we would make public the basis for this
determination. The fact that FDA has not made such a determination for
a specific substance does not mean that the substance is GRAS under the
conditions of its intended use.
D. Proposed Revisions to Sec. 170.39--Threshold of Regulation (TOR)
for Substances Used in Food or as a Food Contact Substance
Our regulations, at Sec. 170.39 (21 CFR 170.39), allow for an
exemption from regulation for a substance used in food contact articles
(e.g., food packaging or food processing equipment) that migrates or,
that may be expected to migrate, into food if such substance meets the
TOR criteria, as outlined in Sec. 170.39(a)(1) through (a)(4). These
criteria include that the substance has not been shown to be a
carcinogen and data supporting the resultant dietary concentration will
be below 0.5 parts per billion.
FDA established the TOR exemption process for food contact uses
where migration is so trivial there are no concerns for safety. TOR
submissions to FDA only require minimal data (e.g., identity, dietary
exposure) to demonstrate the safe use of a substance. A full safety
narrative is not required for a TOR submission. The scientific basis
for the TOR is FDA's determination that very low dietary exposure
presents no meaningful safety concern. Analysis of existing
toxicological data allows FDA to identify a dietary exposure threshold
for safety under certain criteria (see 60 FR 36582, July 17, 1995).
We propose revising the title of Sec. 170.39 to ``Threshold of
regulation for substances used in food or as a food contact
substance.'' We propose amending Sec. 170.39(a) to provide that any
substance used in food (both directly or indirectly added to food) will
be exempted from regulation as a food additive or from the GRAS
notification requirement under Sec. 170.205, if it meets the TOR
criteria (see proposed 170.39(a)(1) through (a)(3)), which demonstrate
safe use (i.e., the substance is present in foods at levels that result
in no appreciable risk to human health). This would be true regardless
of whether the use of the substance directly or indirectly resulted in
it becoming a component of food. Therefore, both direct and indirect
uses of a substance would be appropriately handled through the TOR
process.
We propose other changes throughout Sec. 170.39 to consistently
reflect the expansion of the TOR exemption program to include
substances used in food or as food contact substances and remove
language specific to food contact articles (see proposed Sec.
170.39(c)(2), (c)(3), (c)(4)(i) through (c)(4)(iv), (e), and (g)).
Additionally, in several provisions, we propose amendments to reference
GRAS substances, the GRAS notification requirement, and the GRAS notice
program, given the proposed expansion of the TOR provisions to cover
uses in food and as FCSs generally, that fall under the GRAS exception
to the food additive definition of section 201(s) of the FD&C Act, as
well as the FCN program, where applicable (see proposed Sec.
170.39(b), (c), and (e)). We note that a substance that meets the TOR
criteria can fall outside the definition of a food additive as defined
by section 201(s) of the FD&C Act if such substance, under the
conditions of its intended use, is GRAS. In such situations, a
manufacturer or supplier may submit a TOR request as specified under
proposed Sec. 170.39 and, if the intended use of a substance is the
subject of a granted TOR exemption under Sec. 170.39, would meet an
exception to submitting a mandatory GRAS notice under proposed Sec.
170.205(b)(5). The TOR process is specifically tailored to handle the
submission of data related to the use of substances that meet the TOR
criteria, and we therefore recommend that industry use the TOR process
for the intended use of a food substance that is purported to be GRAS
and meets the TOR criteria.
We propose revising Sec. 170.39(a) to update scientific
terminology and reflect updated approaches to account for the
assessment of cancer risk of carcinogenic compounds. Our regulation, at
Sec. 170.39(a)(2)(i), states that the use in question must result in a
dietary concentration of the FCS at or below 0.5 parts per billion
corresponding to dietary exposure levels at or below 1.5 micrograms per
person per day (based on a diet of 1,500 grams of solid food and 1,500
grams of liquid food per person per day). Proposed Sec.
170.39(a)(2)(i) would reflect updated approaches to determining
exposure that accounts for differences in total dietary consumption and
body weight of different subpopulations; the proposed revision from the
dietary concentration of 0.5 parts per billion currently specified in
our regulations to an estimated daily intake of 0.025 micrograms per
kilogram bodyweight per day normalizes exposure across subpopulations,
ensuring an equivalent level of safety for all subpopulations (Ref.
38). We would make corresponding edits in proposed Sec. 170.39(a)(1),
(c)(3) through (c)(5), (e), and (g).
Additionally, our regulations at Sec. 170.39(a)(1) state that a
substance must not contain a carcinogenic impurity or, if it does, it
must not contain a carcinogenic impurity with a TD50 value
of less than 6.25 milligrams per kilogram bodyweight per day. Proposed
Sec. 170.39(a)(1) would update this requirement to reflect equivalent
updated approaches to assessment of cancer risk and scientific
terminology and state that the substance, if it contains a carcinogenic
impurity, must not contain a carcinogenic impurity with a lifetime
cancer risk greater than one in one million, when calculated using a
TD50 value or another approach based on chronic feeding
studies reported in the scientific literature or otherwise available to
FDA, when present in the diet at 0.025 micrograms per kilogram
bodyweight per day. In the parenthesis that follows, we propose
clarifying that a TD50 of 6.25 milligrams per kilogram
bodyweight per day equates to a lifetime cancer risk of less than one
in one million when the impurity is present in the diet at 0.025
micrograms per kilogram bodyweight per day. This demonstrates that the
proposed revision results in an equivalent level of safety to that
currently specified in our regulations. We would make corresponding
edits in proposed Sec. 170.39(c)(5).
Our regulations, at Sec. 170.39(a)(3), state that a substance used
in a food contact article that migrates, or that may be expected to
migrate, into food will be exempted from regulation as a food additive
because it becomes a component of food at levels that are below the
threshold of regulation if the substance has no technical effect in or
on the food to which it migrates. We propose removing Sec.
170.39(a)(3) because it is focused on food contact articles and would
thus be inconsistent with our proposed change to expand the regulation
to include substances added to food, and FCSs generally, that meet the
criteria for exemption. We would also renumber existing Sec.
170.39(a)(4) as Sec. 170.39(a)(3).
Our regulations, at Sec. 170.39(b), state that we reserve the
right to decline to grant an exemption in those cases in which
available information establishes that the proposed use may pose a
public health risk. The rule also states that we will provide the
reasons for our decision to decline to grant an exemption in our
response to the ``requestor.'' Proposed Sec. 170.39(b) would clarify
that the ``requestor'' is the person who submits the request to exempt
a use of a
[[Page 51849]]
substance from regulation as a food additive or from the GRAS
notification requirement. These proposed changes align with the
proposed expansion of TOR and the proposed changes to the GRAS
notification program (see proposed Sec. 170.205).
Our regulations, at Sec. 170.39(c), describe the contents of a
request to exempt a use of a substance from regulation as a food
additive. For example, under Sec. 170.39(c), the request must include
three copies. Under Sec. 170.39(c)(1), the request must contain the
chemical composition of the substance for which the request is being
made, including, whenever possible, the chemical's name in accordance
with the current Chemical Abstract Service (CAS) nomenclature
guidelines and a CAS registry number if available. Proposed Sec.
170.39(c) would clarify that a request under this section may be for
FDA to exempt a use of a substance from regulation as a food additive
or from the proposed GRAS notification requirement under Sec. 170.205.
The proposed change would expand the provision to include the proposed
mandatory GRAS notification requirement (see proposed Sec. 170.205(a))
and remove the requirement to submit three copies of the request, as
submission in triplicate is no longer efficient or necessary.
Our regulations, at Sec. 170.39(d), specify where data to be
reviewed under this section must be submitted. Proposed Sec. 170.39(d)
would require electronic submission of the data through HFP's
Centralized Online Submission Module (COSM). Electronic submission of
the data would make our administration of the TOR exemption process
more efficient. Proposed Sec. 170.39(d) would also include an
opportunity to request a waiver from the requirement to electronically
submit the data through COSM. We are aware that electronic submission
may not be available to every requestor, and thus, we are proposing
that a requestor may request a waiver from the electronic data
submission requirement from HFP's Office of Pre-Market Additive Safety.
Our regulations, at Sec. 170.39(e), state that FDA will inform the
requestor by letter whether the specific use is exempt from regulation
as a food additive and that FDA will maintain a list of substances
exempt from regulation as food additives on display at the Dockets
Management Staff. Such list would include the name of the company that
made the request, the chemical name of the substance, the specific use
for which it has received an exemption from regulation as a food
additive, and any appropriate limitations on its use, but it will not
include trade names. Proposed Sec. 170.39(e) would remove reference to
informing the requestor ``by letter'' whether the use is exempt or not
from regulation as a food additive or from the GRAS notification
requirement under Sec. 170.205. This change would provide flexibility
to ensure we can leverage current and future technology to communicate
information to the requestor and the public. Proposed Sec. 170.39(e)
would also state that FDA will maintain a ``publicly available'' list
of substances and their uses that are exempted from regulation as food
additives or from the GRAS notification requirement under Sec.
170.205. The proposed revision would remove language which provides
that the list of substances and their use will be on display at the
Dockets Management Staff and what the list will include. We are
proposing these changes to maintain flexibility in how we provide
information to a requestor and the public.
We propose removing Sec. 170.39(f) which provides that if a
request for an exemption from regulation as a food additive is not
granted, the requestor may submit a petition for reconsideration to FDA
in accordance with Sec. 10.33 (21 CFR 10.33). Paragraph (f) is
unnecessary because our existing regulations at Sec. 10.33,
``Administrative reconsideration of action,'' establish a process for
interested persons to request reconsideration. Although it would no
longer be specified in Sec. 170.39, under Sec. 10.33 the opportunity
to seek reconsideration is available to a requestor that is denied a
request for an exemption from regulation. We would renumber existing
Sec. 170.39(g) as Sec. 170.39(f).
Our regulations, at Sec. 170.39(h), state that guidance documents
to help a requestor prepare a submission seeking exemption from the
food additive regulations are available from FDA's Office of Food
Additive Safety. The rule also encourages interested persons to obtain
specific guidance from FDA on protocols to be used for obtaining
migration data, on validation of analytical methods used to quantify
migration levels, on procedures used to relate migration data to
dietary exposures, and on any other issue. The proposed rule would
remove Sec. 170.39(h) because FDA guidance documents are publicly
available online, as well as through HFP, generally. As such guidance
and recommendation language is not information we usually include in
our regulations, removing it would streamline the provision.
E. Proposed Revisions to Sec. 170.203--Definitions Pertaining to GRAS
Notices
Our regulations, at Sec. 170.203, provide definitions that are
applicable throughout Subpart E--Generally Recognized as Safe (GRAS)
Notice. Proposed Sec. 170.203 would remove introductory language, as
well as the definition of ``We, our, and us;'' amend the definitions of
``GRAS'' and ``GRAS notice'' with clarifying edits; and establish
definitions for ``Inventory'' and ``No questions letter.'' We propose
removing the introductory language, which states ``The definitions and
interpretations of terms in Sec. 170.3 apply to such terms when used
in this subpart. The following definitions also apply.'' This language
is unnecessary, as the introductory language of Sec. 170.3 makes clear
that the definitions listed in Sec. 170.3 apply throughout part 170.
The definitions in proposed Sec. 170.3 would continue to apply to
subpart E of part 170, as well as to the other subparts. As discussed
in section V.A of this document, we propose moving the definition of
``We, our, and us'' to Sec. 170.3 so that these terms can apply
throughout part 170.
In the definition of ``GRAS,'' we propose adding a cross-reference
to Sec. 170.3(i), which defines ``safe or safety.'' Our regulations,
at Sec. 170.203, explain the acronym ``GRAS,'' but they do not provide
a tie to how we define ``safe.'' Providing a cross-reference to Sec.
170.3(i) would connect the explanation of the GRAS acronym with the
definition of ``safe or safety'' in our regulations.
In the definition of ``GRAS notice,'' we propose to cross-reference
Sec. 170.205, ``Opportunity to submit a GRAS notice,'' in relation to
``a submission'' and to revise ``not subject to the premarket approval
requirements'' to read ``not subject to the premarket review and
approval requirements for food additives under section 409 of the Act''
for clarity.
We propose establishing definitions for ``Inventory'' and ``No
questions letter,'' as we use these terms in proposed Sec. 170.275 (21
CFR 170.275) and Sec. 170.205, respectively. ``Inventory'' would mean
an online repository where FDA makes public certain information related
to GRAS notices. In proposed Sec. 170.275(b) (see section V.K of this
document for further discussion), we state that we will make the
information included in Sec. 170.275(b)(1) through (3) available to
the public through its inclusion in the inventory. We propose keeping
the term ``inventory'' generic to allow for flexibility, because the
name of the inventory or the location where
[[Page 51850]]
we house the inventory might evolve over time. This information is
currently housed in a searchable database entitled ``GRAS Notices''
(Ref. 3).
As discussed in the 2016 GRAS final rule, we established at least
three categories of response letters during the interim pilot program,
with ``No questions letter'' being one category (81 FR 54960 at 55014).
We stated that the content of these categories of response letters has
evolved over time and may continue to evolve; therefore, we did not
specify any detail about the nature of our responses in our regulations
(id.). Under the current voluntary GRAS notification program, a typical
no questions letter makes clear that: (1) It is the information that is
provided by the notifier that forms the basis for our response, and
that the notifier (rather than FDA) is responsible for the conclusion
of GRAS status; (2) our response must be considered in context based on
the knowledge and information available to us at a point in time,
because scientific knowledge and information about a particular
ingredient can evolve and sometimes change; and (3) our response is not
an affirmation of GRAS status of the notified substance under the
conditions of its intended use in accordance with Sec. 170.35.
Proposed Sec. 170.203 would define ``No questions letter'' as a
letter from FDA, sent in response to a GRAS notice, which states that,
based on the information the notifier provided, as well as other
information available to us, we have no questions at this time
regarding the notifier's conclusion that the notified substance is GRAS
under the conditions of its intended use. We also propose including
language to clarify that a no questions letter is neither an
affirmation by FDA that the notified substance is GRAS for its intended
conditions of use under Sec. 170.35, nor a published finding under
section 721(b)(4) of the FD&C Act, which pertains to the premarket
review and approval process for color additives, declaring the use of
such substance exempt from the term ``food additive'' because of its
being GRAS. Establishing a definition in our regulations for the no
questions letter would be appropriate and necessary, as we propose to
include an exception to the proposed requirement to submit a GRAS
notice that is based off the existence of a no questions letter (see
proposed Sec. 170.205 and section V.F of this document for further
discussion).
We also discussed two other categories of response letters in the
2016 GRAS final rule (81 FR 54960 at 55014 through 55015). We noted
that it is possible that in the future a response to a GRAS notice may
not fit squarely within one of the current categories of response
letters. In addition to the proposed definition for no questions
letter, we also propose establishing definitions for cease to evaluate
letter and insufficient basis letter (see section V.M.1 of this
document). However, we are not proposing to establish these categories
of response letters as the only response letters FDA might send in
response to a GRAS notice.
F. Proposed Sec. 170.205--Creation of a Mandatory GRAS Notification
Program
Our regulations, at Sec. 170.205, provide that any person may
voluntarily notify FDA of a view that a substance is not subject to the
premarket review and approval requirements of section 409 of the FD&C
Act based on that person's conclusion that the substance is GRAS under
the conditions of its intended use. As discussed in section III of this
document, we propose moving from the current voluntary GRAS
notification program to a framework under which GRAS notices would be
mandatory with certain limited exceptions. This change would lead to
increased transparency about substances that are added to food,
enabling FDA to regulate the safety of food substances more effectively
and efficiently; determine if the use of a substance constitutes a food
additive use that is subject to the premarket review and approval
requirements of section 409 of the FD&C Act; and possibly identify
instances where a potentially unsafe food additive is used in food, so
we can take action as appropriate. Therefore, we propose revising the
title of Sec. 170.205 from ``Opportunity to submit a GRAS notice'' to
``Submission of a GRAS notice.''
1. Mandatory GRAS Notice Submission
The proposed rule would create a new Sec. 170.205(a) to provide
that any person introducing a substance into interstate commerce under
the GRAS provision of section 201(s) of the FD&C Act must notify FDA of
the basis for their conclusion that the substance is GRAS under the
conditions of its intended use. This would include substances already
in the food supply and those being marketed for food use for the first
time. Proposed Sec. 170.205(a) would replace the current voluntary
GRAS notification program, under which any person may, but is not
required to, notify FDA of a view that a substance is GRAS under the
conditions of its intended use. As discussed elsewhere in this
document, our experience administering the voluntary GRAS notification
program, particularly in the last decade, has demonstrated a need for
us to require the submission of GRAS notices to provide FDA with
information to help us to better identify potentially unsafe substances
used in food, thereby enabling FDA to take action as appropriate and
regulate the safety of food substances more effectively. Changes in our
country's food supply during this same period further support the need
to require the submission of GRAS notices. Among other things,
requiring the submission of GRAS notices would increase transparency
about substances in the U.S. food supply that are purported to be GRAS
under the conditions of their intended use.
Uses of substances that are excepted from the definition of a food
additive under section 201(s)(1) through (6) of the FD&C Act cannot be
the subject of a GRAS notice. Specifically, the term ``food additive''
does not include: (1) A pesticide chemical residue in or on a raw
agricultural commodity or processed food; (2) a pesticide chemical; (3)
a color additive; (4) any substance used in accordance with a sanction
or approval granted prior to September 6, 1958, pursuant to the FD&C
Act, the Poultry Products Inspection Act (Pub. L. 85-172, 71 Stat. 441)
or the Federal Meat Inspection Act (Pub. L. 59-382, 34 Stat. 669); (5)
a new animal drug; or (6) an ingredient described in section 201(ff) of
the FD&C Act in, or intended for use in, a dietary supplement (section
201(s)(1) through (6) of the FD&C Act). As such categories are excepted
from the definition of ``food additive'' in section 201(s) of the FD&C
Act, they are not eligible for classification as GRAS under the GRAS
provision included in the definition of ``food additive'' (see proposed
Sec. 170.205(c)).
Proposed Sec. 170.205(a) would also provide that if the conditions
of use meet the definition of an FCS in accordance with Sec.
170.3(e)(3), then a manufacturer or supplier may submit an FCN as
specified under Sec. 170.100 (21 CFR 170.100) instead of a GRAS
notice. An FCN refers to a premarket notification for an FCS. Section
409(h)(3)(A) of the FD&C Act states that the FCN process shall be
utilized for authorizing the marketing of food additives that are FCSs,
except where the Secretary determines that the submission and review of
a food additive petition is necessary to provide adequate assurance of
safety, or where FDA and any manufacturer or supplier agree that a
petition may be submitted (see S. Rept. No. 105-43, 105th Cong., 1st
sess. 46 (1997); H. Rept. 105-306, 105th Cong., 1st sess. 19 (1997)).
FCNs are required only for those FCSs that are
[[Page 51851]]
food additives as defined by section 201(s) of the FD&C Act (21 U.S.C.
321(s)) and that are not otherwise authorized under section 409 of the
FD&C Act. We note, however, that an FCS can fall outside the definition
of a food additive as defined by section 201(s) of the FD&C Act if such
substance, under the conditions of its intended use, is GRAS. In such
situations, a manufacturer or supplier may submit either an FCN as
specified under Sec. 170.100 or a mandatory GRAS notice under proposed
Sec. 170.205. However, we recognize that the FCN process is
specifically tailored to handle the submission of data related to FCSs,
and we therefore recommend that industry use the FCN process for an FCS
that is purported to be GRAS under the conditions of its intended use.
For uses of substances that are required to be the subject of a
GRAS notice, FDA would consider as a factor in its prioritization of
food substances for post-market review whether the notification
requirement has been met concerning the substance's conditions of
intended use pursuant to Sec. 170.265(a) (which relates to what FDA
will do with a GRAS notice). As discussed in section II.B.3 of this
document, we are proposing the GRAS notification requirement to gain
information about purported GRAS uses of substances on the market,
including some substances and uses into which we might not otherwise
have insight. Because the failure to comply with the proposed GRAS
notification requirement would impede FDA's efforts in this regard, as
well as our ability to carry out our statutory responsibility to
prohibit the use of unsafe additives in food, noncompliance with
proposed Sec. 170.205(a) for uses of substances that are required to
be the subject of a GRAS notice would be a factor in FDA's
prioritization of food substances for post-market review.
As we have received a significant number of submissions during the
voluntary GRAS notification program that we did not file as GRAS
notices (e.g., because the submission did not contain all parts of a
GRAS notice that are required by our regulations), we are proposing
that the mere submission of materials for a GRAS notice to FDA would
not be sufficient to meet the notification requirement. Rather, under
proposed Sec. 170.265(a)(2), FDA would consider the notification
requirement of proposed Sec. 170.205 to be met upon FDA's filing of a
submission as a GRAS notice, except as provided for in proposed Sec.
170.265(b)(3).
Upon receipt of a submission, we would continue to follow our
existing procedures to conduct an initial evaluation of the submission
before determining whether to file it as a GRAS notice, but we are
proposing that this initial evaluation will be completed within 45 days
(see proposed Sec. 170.265(a)(1)). During this preliminary assessment
to determine whether the submission is adequate to file, FDA is not
evaluating the GRAS status of the substance's conditions of intended
use, and the filing of a GRAS notice does not mean that the substance
that is the subject of the GRAS notice is GRAS under the conditions of
its intended use. Upon the filing of a GRAS notice, we will then
evaluate the notifier's basis for concluding that the criteria for GRAS
status are satisfied.
Importantly, the proposed GRAS notification program generally, and
proposed Sec. 170.205(a), do not establish a premarket review program
for purportedly GRAS substances. As explained elsewhere in this
document, the FD&C Act allows a person to introduce a substance into
interstate commerce if the substance is GRAS under the conditions of
its intended use (see sections 201(s) and 409 of the FD&C Act). Thus, a
company may continue marketing a purported GRAS substance before
submitting a GRAS notice or after submitting a GRAS notice before it is
filed by FDA. Similarly, a company may reach a GRAS conclusion about a
new use of a substance and introduce the substance into interstate
commerce before submitting a GRAS notice. However, the proposed GRAS
notification program would assist FDA's post-market review of purported
GRAS substances, enabling FDA to determine whether these substances are
not GRAS and therefore require FDA review and approval under section
409 of the FD&C Act.
2. Exceptions From Mandatory GRAS Notice Submission
There may be circumstances where requiring the submission of a GRAS
notice would be unnecessary or unwarranted.
a. No questions letter. Proposed Sec. 170.205(b)(1) would create
an exception from the GRAS notice submission requirement when an
existing no questions letter covers the substance under the conditions
of its intended use. There is no provision in the FD&C Act providing a
notifier exclusivity for the use of a substance on the basis that it is
GRAS under the conditions of its intended use. As discussed in section
V.E of this document, a no questions letter is a category of response
letter that FDA may send to the notifier in response to a GRAS notice
(see also 81 FR 54960 at 55014). When a no questions letter exists and
covers a substance under the conditions of its intended use, that means
that we previously received a GRAS notice pertaining to the conditions
of use of the substance, conducted a substantive evaluation of the GRAS
notice, and had no questions at that time regarding the notifier's
conclusion that the notified substance is GRAS under the conditions of
its intended use (see proposed Sec. 170.203). Given this prior
evaluation and assessment, if the conditions of use of a substance are
the same as those that were the subject of a GRAS notice that received
a no questions letter, we would not need to evaluate the GRAS status of
the use of such substance.
We note that a GRAS conclusion within a GRAS notice for which we
issued a no questions letter may not apply to a use of a substance if
the identity of, manufacturing process for, or the conditions of use
(e.g., food categories, use levels, technical effect, specifications)
of that substance are significantly different from those discussed in
the GRAS notice that received the no questions letter response. For
example, a substance may not be food grade following a manufacturing
process change that introduces impurities into the substance.
Therefore, a change in manufacturing process may alter the composition,
and perhaps the toxicity, of the substance. If the use of a substance
differs from the uses discussed in a GRAS notice that received a no
questions letter response, it is the obligation of the manufacturer to
demonstrate whether the substance is GRAS under the conditions of its
intended use. The manufacturer may consult with FDA regarding this
issue.
In addition, we note that proposed Sec. 170.205(b)(1) would
require that a no questions letter cover the conditions of use of a
substance in order for the exception to apply. Thus, proposed Sec.
170.205(b)(1) would not apply, and a GRAS notice would be required for
the use of the substance, if pursuant to proposed Sec. 170.38(c), FDA
later rescinded the no questions letter that pertained to the
conditions of use of the substance.
We considered whether to provide for an alternate procedure (e.g.,
abbreviated GRAS notice submission) for substances that exist in our
GRAS notice inventory--e.g., when the use of a substance differs from
the uses discussed in an existing GRAS notice that received a no
questions letter or when there is a change in manufacturing process
related to the
[[Page 51852]]
uses of a substance discussed in an existing GRAS notice that received
a no questions letter. We have tentatively concluded that an alternate
procedure is unnecessary, as notifiers currently are able to
incorporate into a new GRAS notice data and information previously
submitted to FDA (see 21 CFR 170.215). As we stated in the 2016 GRAS
final rule (81 FR 54960 at 54988), we expect a notifier to provide a
specific file number (e.g., for a GRAS notice) that contains the
referenced data and information, and to identify the specific data and
information in that file (rather than to broadly incorporate into a
GRAS notice the entire file without explaining which data and
information to incorporate). However, we invite comment on additional
ways in which we could facilitate or make more efficient a notifier's
ability to incorporate data and information already submitted to FDA
into a new GRAS notice. We also invite comment on other specific
scenarios for which FDA could consider providing an alternate procedure
(e.g., abbreviated GRAS notice submission) or that FDA could consider
to be covered by an existing no questions letter. Furthermore, as
discussed in section V.Q of this document, we invite comment on this
topic as it relates to substances that exist in our animal food GRAS
notice inventory.
b. Substance listed or affirmed as GRAS under the conditions of its
intended use in parts 182, 184, or 186. Proposed Sec. 170.205(b)(2)
would create an exception from the GRAS notice submission requirement
for a substance that is listed or affirmed as GRAS under the conditions
of its intended use in parts 182, 184, or 186. Where FDA has conducted
rulemaking to list or affirm a substance as GRAS under the conditions
of its intended use, we have already determined that such substance is
GRAS for its intended use. Therefore, a GRAS notice would be
unnecessary. If, pursuant to proposed Sec. 170.38(b), we later repeal
the relevant regulation in parts 182, 184, or 186 that covered the
conditions of use of a substance, or amended the relevant regulation
such that it no longer covered the conditions of use of the substance,
a GRAS notice would be required if the substance is introduced into
interstate commerce under the GRAS provision of section 201(s) of the
FD&C Act.
c. Substance considered GRAS under the conditions of its intended
use in accordance with Sec. 170.30(d) or proposed Sec. 170.30(i)(1).
Proposed Sec. 170.205(b)(3) would create an exception from the GRAS
notice submission requirement for a substance considered GRAS under the
conditions of its intended use in accordance with Sec. 170.30(d) or
proposed Sec. 170.30(i)(1). Our regulations, at Sec. 170.30(d),
provide that a food ingredient of natural biological origin that has
been widely consumed for its nutrient properties in the United States
before January 1, 1958, without known detrimental effects, which is
subject only to conventional processing as practiced before January 1,
1958, and for which no known safety hazard exists, will ordinarily be
regarded as GRAS without specific inclusion in parts 182, 184, or 186.
Our regulations, at Sec. 170.30(i) (see proposed Sec. 170.30(i)(1)),
provide that a substance that is affirmed as GRAS under the conditions
of its intended use in part 184 or part 186 with no limitation other
than good manufacturing practice shall be regarded as GRAS if its
conditions of use are not significantly different from those reported
in the regulation as the basis on which the GRAS status of the
substance was affirmed. While such substances are not explicitly listed
or affirmed as GRAS under the conditions of their intended use in our
regulations, both provisions provide that such substances are generally
to be regarded as GRAS if certain conditions are met. Requiring a GRAS
notice for uses of substances already covered by Sec. 170.30(d) and
proposed Sec. 170.30(i)(1) would similarly be unnecessary.
d. Established FDA process. Proposed Sec. 170.205(b)(4) would
create an exception from the GRAS notice submission requirement where
we have considered the intended use of the substance through an
established FDA process to evaluate the potential presence of
unapproved food additives and documentation made publicly available by
FDA through that process does not recommend or otherwise identify the
need to submit a GRAS notice.
FDA operates three processes for evaluating foods developed using
innovative technologies to help developers ensure that resulting foods
are safe and lawful prior to marketing. For foods from new plant
varieties developed through biotechnology, HFP and CVM jointly offer
Voluntary Premarket Consultations and Voluntary Premarket Meetings. For
foods from cultured animal cells, HFP offers Animal Cell Culture
Consultations. These processes are standardized, science-based, and
provide transparency--we post information about the subjects of
Voluntary Premarket Consultations, Voluntary Premarket Meetings, and
Animal Cell Culture Consultations to FDA's website (Refs. 39 to 41).
During these processes, we consider whether the food under
consideration may require further review because it contains a
substance that would be subject to the premarket review and approval
requirements for food additives under section 409 of the FD&C Act or
those for color additives under section 721 of the FD&C Act.
A possible outcome is a recommendation that a substance undergo
evaluation through a separate program (e.g., GRAS notification, FCN,
food additive petition, or color additive petition). If the process
concludes without FDA recommending or otherwise identifying the need
for evaluation through a GRAS notice, we propose that a GRAS notice
would not be required for anyone marketing the substance for the
particular use that was reviewed because FDA was able to examine the
intended use of the substance in food before it is introduced into
interstate commerce. We note that if we were to recommend or otherwise
identify the need for evaluation through a premarket review and
approval program (e.g., FCN, food additive petition, or color additive
petition), it would not be appropriate to introduce such a substance
into the food supply under the GRAS provision of section 201(s) of the
FD&C Act.
FDA routinely conducts informal consultations with firms and
advises on the regulatory status of substances added to food. Informal
written statements, such as technical assistance, would not qualify for
the exception in proposed Sec. 170.205(b)(4), because such
documentation does not necessarily reflect the conclusion of a formal,
standardized evaluation process providing for transparency. FDA also
offers the Early Food Safety Evaluation Program for new non-pesticidal
proteins produced by new plant varieties not intended to enter the food
supply, but that might occur in food unintentionally at intermittent,
low levels. This program would similarly not qualify for the exception
in proposed Sec. 170.205(b)(4), because this process was developed to
manage instances of unintended, low-level presence in food, not to
resolve regulatory issues about the potential presence of unapproved
food additives.
e. TOR exemption. Proposed Sec. 170.205(b)(5) would create an
exception from the GRAS notice submission requirement where the
intended use of a substance is the subject of an exemption under the
TOR process in Sec. 170.39. If the intended use of a substance is a
subject of an exemption under the TOR process as proposed in Sec.
170.39, it means that the substance is in foods or migrates into foods
at levels that result in no
[[Page 51853]]
appreciable risk to human health. As such, the substance used in food
or as a food contact substance is present in the diet at levels that
are below the TOR. The TOR process allows these substances to undergo
an abbreviated review process where we determine whether the specific
use of the substance meets criteria ensuring that the intended use
would pose no more than a negligible health risk. If we evaluated the
specific use of a substance under TOR and granted an exemption, a
mandatory GRAS notice would be redundant and unnecessary. Providing an
exception in this circumstance would enable us to devote more time and
resources to reviewing GRAS notices for uses of substances where there
could be more pressing public health concerns.
f. Effective premarket notification for an FCS. Proposed Sec.
170.205(b)(6) would create an exception from the GRAS notice submission
requirement where there is an effective premarket notification for an
FCS which covers the substance under the conditions of its intended use
and the substance in interstate commerce originates from the
manufacturer or supplier listed in the effective FCN. As discussed
elsewhere in this document, the FCN program may receive submissions
that cover a food contact substance that is GRAS under the conditions
of its intended use. If there is an effective FCN which covers the
substance under the conditions of its intended use, a GRAS notice is
not required. However, as the FCN program is limited to the use of a
specific food contact-substance and to the specific manufacturer or
supplier listed in the FCN (see section 409(h)(2)(C) of the FD&C Act
and Sec. 170.100(a)), this exception from a mandatory GRAS notice
submission would apply only for the manufacturer or supplier listed in
the FCN. Therefore, if the substance under the conditions of its
intended use is in interstate commerce through a different manufacturer
or supplier than is listed in the FCN, this exception would not apply,
and a GRAS notice submission would be required for the substance under
the conditions of its intended use.
g. Time-limited option to submit certain information to FDA.
Proposed Sec. 170.205(b)(7) would create an exception from the GRAS
notice submission requirement if certain information about the
conditions of use of the substance is submitted to FDA (see proposed
Sec. 170.305 (21 CFR 170.305), discussed in section V.M of this
document) and the submission is included on a public list maintained by
FDA, unless we issue a determination that a GRAS notice or a food
additive petition must be submitted for the intended use of a
substance. Thus, inclusion on the list would not represent a
determination by FDA that the use of the substance is GRAS or does not
require a food additive petition (see proposed Sec. 170.305(d) (21 CFR
170.305(d))).
This proposed exception from having to submit a GRAS notice, in
conjunction with proposed Sec. 170.305, provides a pathway, for a
time-limited period, to submit certain information to FDA for a
substance that was introduced into interstate commerce before the
effective date of any final rule resulting from this rulemaking based
on an independent conclusion of GRAS status. As many persons have
relied on section 201(s) of the FD&C Act and our existing regulations
to market these substances and given the considerable resources it
takes us to evaluate and respond to a GRAS notice, providing this
alternate streamlined submission pathway would enable FDA to gather
information about these substances and their conditions of use while
not overly burdening our administrative resources. We would use the
information we gather to evaluate through post-market activities
whether the use of substances should be re-evaluated, including whether
a GRAS notice regarding the conditions of use of a substance must be
submitted (see proposed Sec. 170.305(d) and section V.M. of this
document for further discussion).
G. Proposed Revisions to Sec. 170.210--Mandatory Electronic Submission
of GRAS Notices to FDA
Our regulations, at Sec. 170.210 (21 CFR 170.210), specify where a
GRAS notice is to be submitted, the format, and the organization of a
GRAS notice. Proposed Sec. 170.210 would require electronic submission
of GRAS notices through HFP's Centralized Online Submission Module
(COSM). Requiring the electronic submission of GRAS notices would make
our administration of the GRAS notification program more efficient.
Requiring electronic submission of GRAS notices would reduce the
resources needed to disseminate a submission among FDA staff, decrease
the likelihood of poor-quality paper scans or lost documents, and
ensure submissions are transmitted in a timely fashion, thus making our
administration of the GRAS notification procedure more efficient.
We propose the use of COSM for submission of mandatory GRAS
notices. COSM is used to transmit not only voluntary GRAS notices, but
also food and color additive petitions, FCNs, final biotechnology
consultations, and more. COSM provides a real-time user interface to
assist users in making submissions to HFP's program offices. FDA has
worked with industry on transmitting the submission of GRAS notices in
electronic format since 2010.
Proposed Sec. 170.210 would also include the opportunity to
request a waiver from the requirement to electronically submit a GRAS
notice through COSM. We are aware that electronic submission may not be
available to every notifier, and, thus, we are proposing that a
notifier could send a request for a waiver from the requirement to
submit a GRAS notice electronically to the Office of Pre-Market
Additive Safety. If granted, a waiver would allow the notifier to
submit a GRAS notice on paper.
H. Proposed Revisions to Sec. 170.220--Requirement To Submit English
Translations of Material Included in a GRAS Notice
Our regulations, at Sec. 170.220 (21 CFR 170.220), cover general
requirements applicable to a GRAS notice. Proposed Sec. 170.220(c)
would add a requirement that any material submitted in or referenced by
a GRAS notice that is in a foreign language must be accompanied by an
accurate and complete English translation. This requirement is
comparable to the requirements in Sec. 170.100 and Sec. 171.1(a) (21
CFR 171.1(a)) for data submitted in a premarket notification for an FCS
and a food additive petition, respectively, and would facilitate our
review of GRAS notice submissions.
I. Proposed Revisions to Sec. 170.250--Identification of Data and
Information Exempt From Disclosure Under the Freedom of Information Act
Our regulations, at Sec. 170.250 (21 CFR 170.250), describe what
is to be included in Part 6 of a GRAS notice: Narrative. Specifically,
Sec. 170.250(d) tells notifiers that they must, at the time of their
submission, identify specific data and information that they view as
exempt from disclosure under the Freedom of Information Act (FOIA; 5
U.S.C. 552). Proposed Sec. 170.250(d) would clarify how we intend to
handle data and information that is not identified as exempt under FOIA
by stating that if a notifier's narrative does not identify data and
information as exempt from disclosure under FOIA, we will consider such
data and information to not be exempt from disclosure or that you have
waived any claim of confidentiality. This proposed change would provide
transparency to notifiers as to what data and information will be
considered not exempt and subject to
[[Page 51854]]
public disclosure in accordance with part 20 (21 CFR part 20).
Proposed Sec. 170.250(e) would require the notifier to explain how
there could be a basis for a conclusion of GRAS status for any non-
public, safety related data and information that the notifier
identifies as exempt from disclosure under FOIA despite the fact that
qualified experts do not have access to such data and information. The
proposed change would more clearly connect the explanation required by
Sec. 170.250(e) with the data and information identified as exempt
from disclosure under FOIA in Sec. 170.250(d).
J. Proposed Revisions to Sec. 170.265--Circumstance Where FDA Would
Not Consider the Mandatory GRAS Notice Notification Requirement To Be
Met
Our regulations, at Sec. 170.265, outline what FDA does with a
GRAS notice. Currently, we conduct an initial evaluation of a
notifier's submission to determine whether to file it as a GRAS notice.
There are no timing parameters for how long this initial evaluation
takes. Proposed Sec. 170.265(a)(1) would add a 45-day timeframe to
this initial evaluation of a submission to determine whether to file it
as a GRAS notice. We recognize that, under the current voluntary GRAS
notification program, the initial evaluation of a submission can be
lengthy. Including timing parameters around our initial pre-filing
evaluation would alleviate concerns about potential delays that might
occur for these steps and provide more certainty about FDA's GRAS
notification program. As we are proposing that the notification
requirement of Sec. 170.205 will be met when we file a submission as a
GRAS notice, we request comment on this proposed 45-day pre-filing
period and other ways to reduce potential delays between receipt of a
submission and filing of a GRAS notice.
Our regulations, at Sec. 170.265(a)(2), provide that if FDA files
a submission as a GRAS notice, we will send the notifier a letter that
informs them of the date of filing; alternately, Sec. 170.265(a)(3)
provides that if FDA does not file a submission as a GRAS notice, we
will send the notifier a letter that informs them of this fact and
provides our reasons for not filing the submission as a GRAS notice. We
propose to amend Sec. 170.265(a)(2) and (a)(3) to state that we will
send these letters within two business days of FDA making the decision
to file or not file the submission as a GRAS notice. Including timing
parameters around our sending of these filing decision letters would
similarly alleviate potential concerns and provide more certainty about
FDA's GRAS notification program. Proposed Sec. 170.265(a)(2) would
also state that if we file a submission as a GRAS notice, we will
consider the notification requirement of Sec. 170.205 to be met,
except as provided by Sec. 170.265(b)(3). Proposed Sec. 170.265(a)(5)
would clarify that we may contact a notifier with questions related to
the notice, including about the data and information used to support a
GRAS conclusion, during our evaluation of a GRAS notice. This new
provision would help prevent confusion with the response that we send
to a notifier based on our evaluation of a GRAS notice under Sec.
170.265(b)(1).
Our regulations, at Sec. 170.265(b)(1), state that, within 180
days of filing plus an additional 90 days if needed, we will respond to
a notifier based on our evaluation of a GRAS notice. If we need to
extend the timeframe, we inform a notifier in writing of the extension
as soon as practicable but no later than within 180 days of filing (see
Sec. 170.265(b)(2)). Proposed Sec. 170.265(b)(1) would add a second
90-day extension period, if necessary, and proposed Sec. 170.265(b)(2)
would clarify that we will inform a notifier in writing of this second
extension as soon as practicable but no later than the end of the
initial 90-day extension. Given the expected increase in the number of
GRAS notices if this rule is finalized, a second 90-day extension would
provide FDA with the opportunity to complete timely evaluations. It
would give us the time needed to consider amendments to a filed notice
or any other information received from a notifier related to a GRAS
submission. Further, allowing for a second 90-day extension may
increase the potential for a successful evaluation outcome (i.e.,
issuance of a no questions letter). Informing the notifier about the
need for a second extension by no later than the end of the initial 90-
day extension aligns with the current notification procedure for an
extension of the 180-day evaluation period. We invite comment on the
addition of a second 90-day extension to the 180-day evaluation period.
Our regulations, at Sec. 170.265(b)(3), state that if a notifier
asks us to cease to evaluate a GRAS notice, we will send the notifier a
letter informing them of our decision regarding the request. Proposed
Sec. 170.265(b)(3) would clarify that if FDA ceases to evaluate a GRAS
notice, we will not consider the mandatory GRAS notification
requirement under proposed Sec. 170.205 to be met. A GRAS notice for
which we grant a cease to evaluate request for has the same effect as
if we never received a GRAS notice for the intended use of a substance.
Therefore, a notifier would not meet their obligation under proposed
Sec. 170.205 to submit a mandatory GRAS notice if they: submit a GRAS
notice, later request that FDA cease to evaluate their GRAS notice, and
we grant such request. In such a case, the use of the substance that
was the subject of the GRAS notice that we ceased to evaluate would not
comply with the GRAS notification requirement until we filed a new GRAS
notice pertaining to the substance's use.
In other situations, after completing our review of a GRAS notice,
we may not issue a no questions letter, and may instead issue a
different response, for example, a letter stating that the notice does
not provide sufficient information in support of a GRAS conclusion. A
response stating that there is an insufficient basis for a GRAS
conclusion would not mean that a notifier has failed to meet their
obligation under Sec. 170.205 to submit a mandatory GRAS notice.
However, such a response would be relevant to our determination of
whether a food substance is an unapproved food additive under its
conditions of use and would inform any post-market action against such
a substance added to food.
K. Proposed Revisions to Sec. 170.275--Public Disclosure of a GRAS
Notice
Our regulations, at Sec. 170.275, cover public disclosure of GRAS
notices. Specifically, Sec. 170.275(a)(1) states that even though
submission of a GRAS notice is voluntary, it is considered a mandatory
submission for purposes of its status under FOIA and FDA's public
information requirements in part 20. Section 170.275(a)(2) states that
the information is available for public disclosure in accordance with
part 20 as of the date that we receive the GRAS notice. Proposed Sec.
170.275(a) would reflect the change from a voluntary to a mandatory
submission requirement for GRAS notices and combine the information in
a single paragraph (a), thus eliminating the need for subparagraphs
(a)(1) and (2).
Our regulations, at Sec. 170.275(b), outline what information we
will make readily accessible to the public. However, we do not specify
a location where we make this information public. Proposed Sec.
170.275(b) would clarify that we will make the information listed in
Sec. 170.275(b)(1) through (3) accessible to the public through the
inventory (as defined in proposed Sec. 170.203). We currently maintain
this information in FDA's GRAS Notice Inventory, which is available on
our website (Refs. 3 and 4). We intend to continue using this web page
to share: (1) filed GRAS notices; (2)
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any letters sent based on our evaluation of the notice (Sec.
170.265(b)(1)) or subsequent letters regarding the notice (Sec.
170.265(c)); and (3) any letters granting a cease to evaluate request
(Sec. 170.265(b)(3)).
We propose removing Sec. 170.275(c), which states that we will
disclose all remaining data and information that are not exempt from
public disclosure in accordance with part 20, because this language
would be covered by proposed Sec. 170.275(a). Data and information
which falls within the definitions of a trade secret or confidential
commercial or financial information are not available for public
disclosure (see part 20).
L. Proposed Revocation of Sec. 170.285--Disposition of GRAS
Affirmation Petitions
Our regulations, at Sec. 170.285 (21 CFR 170.285), cover how we
handled filed GRAS affirmation petitions that were pending as of
October 17, 2016 (the effective date of the GRAS final rule) as we
transitioned to the current voluntary GRAS notification program. As
there are no longer any pending GRAS affirmation petitions, and we have
replaced the GRAS affirmation process with the voluntary GRAS
notification program, this section is outdated. We propose removing
Sec. 170.285 consistent with Executive Order 13563, ``Improving
Regulation and Regulatory Review'' (76 FR 3821, Jan. 21, 2011), which
requires agencies to periodically conduct retrospective analyses of
existing regulations to identify those ``that may be outmoded,
ineffective, insufficient, or excessively burdensome, and to modify,
streamline, expand, or repeal them,'' accordingly.
M. Proposed Addition of Subpart F--Establishment of Definitions and
Pathway for Submission of Certain Information During Time-Limited
Option for Substances Introduced Into Interstate Commerce Under the
GRAS Provision of Section 201(s) of the FD&C Act Before the Effective
Date of a Final Rule
We propose establishing a new subpart F, ``Submissions for
Substances Introduced into Interstate Commerce Under the GRAS Provision
of Section 201(s) of the Act Before [EFFECTIVE DATE OF THE FINAL
RULE].'' The proposed subpart F would provide definitions that would
apply only to subpart F (see proposed Sec. 170.303 (21 CFR 170.303))
and describe the time-limited option that firms can choose to
participate in to qualify for an exception from the GRAS notice
submission requirement under proposed Sec. 170.205(b)(7) (see proposed
Sec. 170.305).
1. Definitions Applicable for Proposed Subpart F
Proposed Sec. 170.303 would define ``Cease to evaluate letter,''
``GRAS,'' ``GRAS notice,'' ``Insufficient basis letter,'' and
``Submitter.'' Our regulations reference that FDA may grant a
notifier's request that we cease to evaluate a GRAS notice by sending a
letter informing the notifier of our decision (Sec. 170.265(b)(3)).
While we refer to these as cease to evaluate letters (see, e.g., 81 FR
54960 at 55015), our regulations have not codified this term. Because
proposed Sec. 170.305 would use this term (see section V.M.2 of this
document), we propose to define ``Cease to evaluate letter'' to mean a
letter from FDA granting a request to cease to evaluate a GRAS notice
under Sec. 170.265(b)(3).
We propose using the terms ``GRAS'' and ``GRAS notice'' in subpart
F in the same way as we use these terms in subpart E; however, the
definitions in Sec. 170.203 only apply to subpart E. Therefore, we
propose including the same definitions for ``GRAS'' and ``GRAS notice''
in Sec. 170.303 so that these terms are defined for use in subpart F
of part 170 and align with subpart E of part 170.
Our regulations, at Sec. 170.265(b)(1), state that within 180 days
of filing a GRAS notice, we will respond to a notifier by letter based
on our evaluation of the notice. As discussed in the 2016 GRAS final
rule, we established at least three categories of response letters
during the interim pilot program--``Insufficient basis letter'' was one
category (81 FR 54960 at 55014). The content of these categories of
response letters has evolved over time and may continue to evolve;
therefore, we did not specify any detail about the nature of our
responses in our regulations (Id.). We propose in Sec. 170.303 to
define ``Insufficient basis letter'' to mean a letter from FDA, sent in
response to a GRAS notice, which states that, based on the data and
information provided, as well as other available information, the
notice does not provide a sufficient basis for a conclusion that the
notified substance (as defined in Sec. 170.203) is GRAS under the
conditions of its intended use. Establishing this definition is
necessary because we propose that a submission under Sec. 170.305 is
not allowed for any conditions of use of a substance that are the
subject of an insufficient basis letter (see proposed Sec. 170.305(b)
and section V.M.2 of this document for further discussion).
Proposed Sec. 170.303 would define ``Submitter'' to mean a person
(e.g., an individual, partnership, corporation, association, or other
legal entity) who is responsible for the submission under subpart F,
even if another person (such as an attorney, agent, or qualified
expert) prepares or submits the information. This definition would
parallel the definition of ``Notifier'' for a GRAS notice (see Sec.
170.203), while also differentiating the people responsible for a GRAS
notice (``notifiers'') from those who are responsible for this
information in accordance with proposed Sec. 170.303 (``submitters'').
2. Specific Requirements Proposed for the Option To Submit Information
To Be Excepted From Mandatory GRAS Notice Submission
As discussed in section V.F of this document, we are proposing a
limited number of exceptions to the proposed GRAS notice submission
requirement. One exception would state that a GRAS notice does not need
to be submitted if certain information about the conditions of use of a
substance is submitted to FDA in accordance with proposed Sec. 170.305
and the submission is included on a public list maintained by FDA,
unless we issue a determination that a GRAS notice or a food additive
petition must be submitted for the intended use of a substance (see
proposed Sec. 170.205(b)(7)). Any person could rely on the inclusion
of the submission on a public list maintained by FDA for the same
conditions of use of a substance.
Proposed Sec. 170.305 would provide a streamlined way for us to
gain insight into substances already in use in the market under the
GRAS provision of section 201(s) of the FD&C Act. We are proposing this
exception because we recognize that many persons have relied on section
201(s) of the FD&C Act and our existing regulations to market uses of
substances based on an independent conclusion of GRAS status. Requiring
GRAS notices for all such uses of substances would likely overburden
the administrative resources we have to evaluate and respond to GRAS
notices. This exception will enable us to administer the proposed
mandatory GRAS notification program more effectively and efficiently.
Proposed Sec. 170.305(a) would describe the substances that could
be the subject of these streamlined submissions, i.e., substances that
have been introduced into interstate commerce before the effective date
of any final rule resulting from this rulemaking based on a conclusion
that the substance is GRAS
[[Page 51856]]
under the conditions of its intended use. Proposed Sec. 170.305(a)
would state that, for a substance that has been introduced into
interstate commerce before the effective date of any final rule under
the GRAS provision of section 201(s) of the FD&C Act, a person may
submit information regarding the substance and its conditions of use in
accordance with subpart F instead of submitting a GRAS notice under
proposed Sec. 170.205. Obtaining this information for substances
already in use in food would better inform our oversight of the food
supply and help us prioritize our post-market review of substances used
in food.
Proposed Sec. 170.305(b) would not allow a submission under this
subpart in two circumstances, even if a substance would otherwise
qualify under Sec. 170.305(a). First, a submission would not be
allowed under this subpart if the submission concerned any conditions
of use of a substance that are the subject of an insufficient basis
letter (proposed Sec. 170.305(b)(1)). If the conditions of use of a
substance are the subject of an insufficient basis letter, this means
that we have evaluated the data and information in a prior GRAS notice
for the substance under the conditions of its intended use and
determined that the GRAS notice does not provide a sufficient basis for
a conclusion that the notified substance is GRAS under the conditions
of intended use. Under these circumstances, a new GRAS notice would
have to be submitted that covers the substance purported to be GRAS
under the conditions of its intended use to enable us to re-evaluate
whether data and information provides a sufficient basis for a GRAS
conclusion (and whether the insufficient basis should be revised or
rescinded), or whether the use of the substance should be the subject
of a food additive petition.
Second, a submission would not be allowed under this subpart if the
submission concerned any conditions of use of a substance that are the
subject of a determination by FDA that the substance is not GRAS under
the conditions of its intended use (proposed Sec. 170.305(b)(2)). If
the conditions of use of a substance are the subject of such a
determination by FDA, this means we have evaluated data and information
relating to a substance and determined that such conditions of use of a
substance are not GRAS. As explained in section III.B.1.a of this
document, we post our determinations that the conditions of use of a
substance are not GRAS on a public inventory (see Ref. 20). Under these
circumstances, we would expect to receive a food additive petition for
the substance's conditions of use. However, if a person believes that
there are data or information supporting the conclusion that the
substance is GRAS under these conditions of use, we would require the
submission of a GRAS notice so that we can adequately evaluate that
GRAS conclusion.
Proposed Sec. 170.305(c) would detail what a submission must
include (proposed Sec. 170.305(c)(1)), additional information that it
may include (proposed Sec. 170.305(c)(2)), and how the submission must
be made and by when (proposed Sec. 170.305(c)(3)).
Proposed Sec. 170.305(c)(1)(i) would require the submission to
include the name and address of the submitter. This is necessary for
full identification of the person who accepts responsibility for the
submission. This is also necessary so that we can ask a submitter
questions about their submission (proposed Sec. 170.305(d)(2)).
Proposed Sec. 170.305(c)(1)(ii) would require the submission to
include the name of the substance, using an appropriately descriptive
term. This is necessary to identify the substance to both FDA and the
public. Proposed Sec. 170.305(c)(1)(iii) would require the submission
to include the conditions of intended use of the substance, including
the foods in which the substance is used or is in contact with, the
levels of use, and the purposes for which the substance is used.
Information describing the conditions of intended use is necessary to
delineate the boundaries of the submission under this subpart and the
GRAS provision of section 201(s) of the FD&C Act. The information that
would be required to be submitted under proposed Sec. 170.305(c)(1)(i)
through (iii) aligns with information submitted as part of a GRAS
notice (see Sec. 170.225(c)(2) through (4)). We are not proposing to
require that submissions under proposed subpart F include underlying
data or information pertaining to a conclusion of GRAS status.
Proposed Sec. 170.305(c)(1)(iv) would require the submission to
include evidence of presence of the substance under the conditions of
its intended use in interstate commerce before the effective date of
any final rule resulting from this rulemaking. Evidence of presence in
interstate commerce before the effective date of any final rule
resulting from this rulemaking would be necessary, as only those
substances that have been introduced into interstate commerce before
this time can take advantage of the option to submit under proposed
subpart F of part 170. We would offer this alternative to submitting a
GRAS notice only for substances already in interstate commerce under
the GRAS provision of section 201(s) of the FD&C Act so that we can
gather information on all purported GRAS uses of substances and not
just for new uses moving forward. Uses of substances that are excepted
from the definition of a food additive under section 201(s)(1) through
(6) of the FD&C Act cannot be the subject of a GRAS notice. Likewise,
uses of substances that are excepted from the definition of a food
additive under section 201(s)(1) through (6) of the FD&C Act would be
ineligible for this alternative to submitting a GRAS notice for uses of
substances already in interstate commerce. As this option is available
as an exception to the proposed requirement to submit a GRAS notice, it
would be available only for uses of substances that can properly be the
subject of a GRAS notice.
Proposed Sec. 170.305(c)(1)(v) would require the submitter to
include a GRAS notice file number (GRN No.) if FDA sent a cease to
evaluate letter in response to a submitter's previous GRAS notice for
the same conditions of intended use of a substance. Information about a
submitter's previous GRAS notice in the form of submitting to us the
GRN No. is necessary, as safety issues raised during our evaluation of
a GRAS notice that we ceased to evaluate may warrant consideration as a
higher priority.
Proposed Sec. 170.305(c)(2) would provide that a submission may
inform us of the statutory basis for the conclusion of GRAS status for
the conditions of intended use of the substance (i.e., through
scientific procedures or through experience based on common use in food
(section 201(s) of the FD&C Act; see also Sec. 170.30(a) through
(c))), but this information would not be a required element of the
submission. This information is not necessary to establish the presence
of a substance already in interstate commerce under the GRAS provision
of section 201(s) of the FD&C Act, but we recommend its inclusion
because it would help us understand the basis for the GRAS conclusion.
Proposed Sec. 170.305(c)(3) would require that a submission under
this section be submitted to us electronically through COSM within one
year after the effective date of any final rule, unless provided with a
waiver to submit on paper. This would align with our proposed
requirement for electronic submission of GRAS notices (see proposed
Sec. 170.210). The proposed one-year deadline to make these
submissions would enable us to obtain information on many substances
already
[[Page 51857]]
in use in food, informing our oversight of the food supply and helping
us prioritize our post-market review of these substances. The one-year
deadline would also allow many affected parties to efficiently comply
with new proposed regulatory requirements, while helping us to more
effectively administer the proposed mandatory GRAS notification
program.
Proposed Sec. 170.305(c)(3) would provide that submissions under
subpart F of part 170 will not be accepted beyond one year after the
effective date of any final rule resulting from this rulemaking. This
would provide a clear cutoff for submissions under this subpart.
Proposed Sec. 170.305(d) would outline what we will do with these
submissions. Proposed Sec. 170.305(d)(1) would state that we will post
the information we receive (i.e., information listed in proposed Sec.
170.305(c)(1) and (2)) in a publicly available list in accordance with
part 20 and clarify that the posting of this information does not mean
that we have reviewed the GRAS status of the substance's conditions of
intended use. This would provide transparency into the substances that
are purported to be GRAS under the conditions of their intended use,
and it would enable us to develop a more comprehensive catalog of food
substances in use in the market under the GRAS provision of section
201(s) of the FD&C Act.
Proposed Sec. 170.305(d)(2) would enable us to ask a submitter
questions about their submission. This is necessary for us to ask
clarifying questions about any information provided or to help us
determine whether we need more information about the use of a
substance.
Proposed Sec. 170.305(d)(3) would state that we may issue a
determination that a GRAS notice or food additive petition must be
submitted for the intended use of a substance in accordance with
subpart E of part 170 or section 409 of the FD&C Act, respectively.
This would mean that the conditions of use of the substance would not
qualify for the exception from the GRAS notice submission requirement
under proposed Sec. 170.205(b)(7). The submitter would have to submit
a GRAS notice in accordance with subpart E of part 170 or, under
certain circumstances, a food additive petition in accordance with
section 409 of the FD&C Act. Proposed Sec. 170.305(d)(3) would also
state that we would make such a determination publicly available. This
would provide transparency into the substances that were purported to
be GRAS under the conditions of their intended use but no longer
qualify for the exception from the GRAS notice submission requirement
under proposed Sec. 170.205(b)(7).
While we are not proposing to require that submissions under
proposed subpart F include underlying data or information pertaining to
a conclusion of GRAS status, FDA is proposing that we may issue a
determination that a GRAS notice must be submitted for the intended use
of a substance that is the subject of a proposed subpart F submission.
Thus, proposed subpart F would provide a streamlined way for us to gain
insight into substances already in use in the market under the GRAS
provision of section 201(s) of the FD&C Act, while still enabling us to
require that additional information (in the form of a GRAS notice) be
submitted for certain uses of these substances.
N. Proposed Revision to the Header of Part 170
Part 170 of Title 21 is titled ``Part 170--Food Additives;''
however, it not only covers food additives but also our GRAS
regulations. Therefore, to reflect the subject matter of this part more
accurately, we propose renaming part 170 to ``Part 170--Food Additives
and Generally Recognized as Safe (GRAS) Substances.''
O. Non-Substantive Edits to Part 170
We propose several non-substantive edits throughout part 170 to
align with federal plain language guidelines (Ref. 42). We propose
revising ``prior to'' to ``before''; ``shall'' to ``must,'' ``will,''
or ``are''; ``assist'' to ``help''; and ``agency'' to ``FDA'' (see
proposed Sec. Sec. 170.30(c)(2), (d), (e), (i)(1), 170.38(b)(1) and
(b)(2), and 170.39(b), (c), (d), (e), and (f)).
We propose other non-substantive edits to update terms and improve
clarity. We propose changing ``company'' to ``requestor,'' ``part 182,
part 184, or part 186 of this chapter'' to ``parts 182, 184, or 186 of
this chapter,'' and ``Federal Food, Drug, and Cosmetic Act'' to ``the
Act'' (as defined in Sec. 170.3(d) for use throughout part 170) (see
proposed Sec. Sec. 170.30(c)(2) and (d), 170.38(b)(3), 170.39(e),
170.203, and 170.225(c)(6)). We propose changing ``Commissioner'' and
``he'' or ``his'' to ``FDA'' and ``its,'' respectively, adding ``of
this chapter'' after ``Sec. 171.130(b),'' and adding ``under the
conditions of its intended use'' after ``substance is GRAS'' (see
proposed Sec. 170.38(a), (b)(1), and (b)(3)).
Proposed Sec. Sec. 170.203 and 170.225(c)(6) would clarify that
``premarket approval requirements of the Federal Food, Drug, and
Cosmetic Act'' means ``premarket review and approval requirements for
food additives under section 409 of the Act.'' As defined in Sec.
170.3(d), ``the Act'' means the FD&C Act and as discussed in the prior
paragraph, we propose using this term throughout part 170 consistent
with this definition. In creating the premarket approval requirement
for food additives in the 1958 amendment, Congress excluded a substance
that is GRAS under the conditions of its intended use from the
definition of food additive. The creation of the GRAS provision
reflected Congress' determination that many substances intentionally
added to food for a specific use do not need premarket review by FDA to
ensure their safety, either because their safety has been established
by a long history of use in food, or because their safety has been
established by information that is generally available to and accepted
by qualified experts, regarding the intended conditions of use of a
substance in food. This revision would help avoid any confusion with
the mandatory GRAS notification submission and with other premarket
submissions (e.g., new dietary ingredient notifications).
P. Table Summarizing the Proposed Changes to Part 170
In table 1, we briefly summarize the proposed changes to part 170
and how they would impact the existing GRAS regulations at part 170.
Table 1 provides the current section citation in part 170, the
corresponding proposed section citation in part 170, and a summary of
the proposed revision which includes a cross-reference to the section
of this document that discusses the reasons for the proposed revision.
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Q. Proposed Revisions to Part 570 for Food Substances Used in Animal
Food and Incorporation by Reference
FDA is also proposing to amend certain provisions of part 570. The
proposed revisions to the animal food regulations in part 570 largely
track the proposed revisions to the human food regulations in part 170
because parts 170 and 570 implement the same statutory provisions, and
the rationale for proposing these revisions is the same. However, there
are some proposed revisions to part 570 that are different from the
proposed revisions to their counterpart regulation in part 170, some
proposed revisions to part 570 that have no counterpart in part 170,
and some proposed revisions to part 170 that have no counterpart in
part 570.
1. Proposed Revisions to Part 570 That Parallel the Proposed Revisions
to Part 170
See table 2 for a summary of the proposed revisions to part 570
that are parallel to the proposed revisions to part 170. Table 2
provides the proposed revision section in part 570, the parallel
proposed revision section in part 170, and a summary of the proposed
revision which includes a cross-reference to the section of this
document that discusses the reasons for the proposed revision.
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Related to proposed Sec. 570.205(b)(1), we are seeking comment on
our tentative conclusion that, in light of existing regulations
providing for the incorporation of data and information previously
submitted to FDA into a new GRAS notice (see 21 CFR 570.215), it is
unnecessary to provide for an alternate procedure (e.g., abbreviated
animal food GRAS notice submission) for substances that exist in our
animal food GRAS notice inventory. For example, this would involve
situations where the use of an animal food substance differs from the
uses discussed in an existing animal food GRAS notice that received a
no questions letter or when there is a change in manufacturing process
related to the uses of an animal food substance discussed in an
existing animal food GRAS notice that received a no questions letter.
We also invite comment on additional ways in which we could facilitate
or make more efficient a notifier's ability to incorporate data and
information already submitted to FDA into a new animal food GRAS
notice, as well as on other specific animal food scenarios for which
FDA could consider providing an alternate procedure (e.g., abbreviated
GRAS notice submission) or that FDA could consider to be covered by an
existing no questions letter. Refer to section V.F.2 of this document
for additional discussion of this tentative conclusion and these
requests for comment.
Our regulations, at Sec. 570.38(d), provide that if we are aware
of a prior sanction for use of a substance, FDA will concurrently
propose a separate regulation for such use. This proposed rule would
remove Sec. 507.38(d). Prior sanctioned uses of substances for human
food use are almost all for use in manufacturing food packaging
materials (see 21 CFR part 181, subpart B). The prior sanctioned
substances for human food use were placed in the then-new part 181 in
1977 (42 FR 14302, 14638-40, March 15, 1977). At the same time, FDA
amended part 570 to include Sec. 570.13, which incorporates the
regulations in part 181 for use in the manufacture of animal food-
packaging materials (42 FR 14091, March 15, 1977). Since then, the only
prior sanctioned uses of a substance for animal food that we are aware
of are menadione and menadione sodium bisulfite complex (certain
vitamin K active substances) for use in poultry feed (48 FR 16748,
April 19, 1983). A person wishing to assert that an animal food use of
a substance is prior sanctioned should contact CVM at [email protected] to discuss their situation.
2. Proposed Revisions to Part 570 That Are Different From Parallel
Proposed Revisions to Part 170
The proposed changes to parts 170 and 570 also differ slightly
regarding the administration of the mandatory GRAS notification
program. Where proposed Sec. 170.205(a) would reference FCNs as an
alternate pathway for conditions of use of a substance that meet the
definition of an FCS in accordance with Sec. 170.3(e)(3), proposed
Sec. 570.205(a) would not include this language because the FCN
program is specific to human foods.
Our regulations, at Sec. 570.210, specify where a GRAS notice is
to be submitted. Proposed Sec. 570.210 would be revised to include a
technical change to replace ``Division of Animal Feeds (HFV-220)'' with
``Division of Animal Food Ingredients'' to bring our regulations up to
date with FDA's current structure. The proposed changes would also
instruct notifiers to contact CVM's Division of Animal Food Ingredients
by email prior to submitting a GRAS notice for the most current
instructions on submission, while we consolidate our physical location,
including our mailing address, and transition from paper submissions to
online submissions. If the proposed rule is finalized, we also
anticipate making additional information on how to submit an animal
food GRAS notice available on our website.
In proposed subpart F of part 570, in which we would provide
definitions that would apply only to this subpart (see proposed Sec.
570.303) and describe the time-limited option that firms can choose to
participate in to qualify for an exception to the GRAS notice
submission requirement (see Sec. 507.305), the definitions and
requirements are identical to those applicable to human food under
proposed subpart F of part 170, with the exception of proposed Sec.
570.305(c)(1)(iii) and (iv).
Proposed Sec. 570.305(c)(1)(iii) would specify that submissions
must include: the intended conditions of use of the substance,
including the target animal species; foods in which the substance is
used; the levels of use in such foods; the purposes for which the
substance is used; and, when the intended use is in food for food-
producing animals, the quantities of any residues that humans may be
exposed to in edible animal tissues. Therefore, we propose limiting
these submissions, when applicable, to substances for which the
submitter had data or information to support human food safety related
to such use.
Proposed Sec. 570.305(c)(1)(iv) would require that the submission
include evidence of presence of the substance under the conditions of
its intended use
[[Page 51866]]
in interstate commerce before the effective date of any final rule
resulting from this rulemaking. The conditions of intended use include,
when applicable, being marketed for a particular target animal species
and use.
Proposed Sec. 570.305(c)(3) would detail how the submission must
be made and by when. We propose that a submission under this section
must be submitted to CVM by email within one year after the effective
date of any final rule.
3. Proposed Revisions to Part 570 That Have No Counterpart in Part 170
We are proposing an exception in Sec. 570.205(b)(5) from the
requirement to submit a GRAS notice if the intended use of the
substance has been the subject of an established animal food ingredient
consultation process with FDA and a summary document made publicly
available by FDA through the consultation process indicates that FDA
has no questions or concerns about the safety of the substance for the
intended use.
An example of such a consultation process is the Animal Food
Ingredient Consultation (AFIC), described in our Guidance for Industry
(GFI) #294 (Ref. 43). This guidance describes an interim, voluntary
process that helps FDA become aware of some new animal food ingredients
that are marketed in interstate commerce and any potential safety
concerns associated with them. Upon completion of a consultation under
AFIC, FDA intends to provide a letter summarizing the information that
FDA reviewed in order to conclude whether the agency has questions
about the safe use of the ingredient, and to post the letter to an FDA
web page. The consultation provides FDA with the opportunity to express
our concerns to a person regarding their plan to market an animal food
ingredient without further evaluation through a GRAS notice or an
animal food additive petition when we have questions about the public
health impact. Because AFIC enables FDA to examine intended uses of
substances in animal food, we propose that a GRAS notice would not be
required for anyone marketing a substance for a particular use that was
reviewed by FDA under AFIC, so long as FDA provided a publicly
available summary that indicates it has no questions or concerns about
the safety of the substance for the intended use.
In addition, for animal food ingredients that are listed in and
used in accordance with Chapter 6 ``Official Feed Terms, Common or
Usual Ingredient Names and Ingredient Definitions'' of the ``Official
Publication'' (OP) of the Association of American Feed Control
Officials, Inc. (AAFCO), 2024 ed., (Ref. 44) and for which FDA has not
publicly expressed a concern about the GRAS status of the use of the
ingredient, we provide an exception in proposed Sec. 570.205(b)(6)
from the requirement to submit a GRAS notice. This exception would be
applicable if the ingredient is introduced in interstate commerce for
use in animal food under the GRAS provision of section 201(s) of the
FD&C Act and may overlap with other exceptions (e.g., inclusion in part
582, coverage by a GRAS notification that has received a no questions
letter from FDA).
We are proposing to except these ingredients from the requirement
to submit a GRAS notice because we are aware of their use given their
listing in AAFCO's 2024 OP, and we have reviewed many of them for
safety for their intended use in animal food through our former
participation in the AAFCO ingredient definition request process under
a memorandum of understanding (MOU) that expired in October 2024 (Ref.
45). Moreover, for ingredients that were reviewed as part of the AAFCO
ingredient definition request process but that we did not specifically
review as part of the MOU process, we are not aware of any safety
issues concerning them and many have a long history of use in animal
food. For animal food ingredients listed and used in accordance with
editions of the AAFCO OP other than the 2024 edition, and for animal
food ingredients that are used in accordance with the AAFCO 2024 OP but
that are the subject of a public FDA statement of concern regarding
their GRAS status, the exception in Sec. 570.205(b)(6) would not
apply, and proposed Sec. 570.205(a) would require a GRAS notice if the
substance is being introduced into interstate commerce under the GRAS
provision of section 201(s) of the FD&C Act.
Proposed Sec. 570.205(b)(5) and proposed Sec. 570.205(b)(6) have
therefore been added to structure a mandatory GRAS notification program
for animal food ingredients that takes into account the unique
circumstances of how animal food has historically been regulated by
States and FDA, as well as how we anticipate we will continue to
regulate animal food ingredients.
4. Proposed Revisions to Part 170 That Have No Counterpart in Part 570
Proposed Sec. 170.39 would expand the scope of the TOR exemption
to include uses in human food and FCSs generally, not just food contact
articles. There is no TOR exemption for animal food, and we do not
propose one at this time because we are unaware that there is a need
for such a regulation for animal food and because of the complexities
involved in determining appropriate TOR criteria for animal species
with differing body sizes, diets, feeding practices, and physiologies.
As there is no TOR provision or FCN program for animal food, the
exceptions we are proposing in Sec. 170.205(b)(5) and (b)(6) would not
apply to animal food GRAS notices. The changes we are proposing to
Sec. 570.205(b) would therefore not contain these two exceptions.
5. Incorporation by Reference
In Sec. 570.205(b)(6), FDA is proposing to incorporate by
reference the ``Official Common or Usual Names and Definitions of Food
Ingredients'' section of Chapter 6 of the ``Official Publication'' of
AAFCO, 2024 edition, pages 367-549.
You may obtain a free copy of the material from the Docket for GFI
#293, FDA Enforcement Policy for AAFCO-Defined Animal Feed Ingredients,
at https://www.regulations.gov/document/FDA-2024-D-2977-0003 or you may
inspect a copy at the Dockets Management Staff (HFA-306), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville MD 20852; phone
240-402-7500, between 9 a.m. and 4 p.m., Monday through Friday. You may
also purchase a copy from AAFCO, 1800 S Oak Street, Suite 100,
Champaign, IL, 61820-6974; phone: 217-356-4221; website (including
links for purchasing AAFCO publications): https://www.aafco.org.
Chapter 6 of the 2024 edition of the ``Official Publication''
contains a comprehensive list of animal food ingredients, many of which
include definitions established through AAFCO's ingredient definition
request process. Because most States adopt the ingredient definitions
listed in the ``Official Publication'' under their State laws, the
publication facilitates the marketing of animal food ingredients under
those State laws. As explained above, for animal food ingredients that
are listed in and used in accordance with Chapter 6 of the 2024 edition
of AAFCO's ``Official Publication,'' we are proposing an exception in
proposed Sec. 570.205(b)(6) from the requirement to submit a GRAS
notice, as long as FDA has not publicly expressed a concern about the
GRAS status of the use of the ingredient.
We are proposing to incorporate by reference the ``Official Common
or Usual Names and Definitions of Feed Ingredients'' section of Chapter
6 of the 2024 edition of AAFCO's ``Official Publication,'' pages 367-
549, for the
[[Page 51867]]
sole purpose of providing a list of ingredients that would be covered
by proposed Sec. 570.205(b)(6).
VI. Request for Comments on Alternatives
In addition to seeking comments on the overall proposed rule, FDA
is specifically seeking comments on potential alternatives to the
proposed rule that could reduce regulatory burdens (e.g., allowing
streamlined submissions for all substances purported to be GRAS under
the conditions of their intended use under section 201(s) of the FD&C
Act). FDA is seeking comments on any alternatives that would still meet
our goals of helping FDA fulfill its statutory responsibility to
prohibit the use of unsafe additives in food and of increasing
transparency about the substances being added to the U.S. food supply.
In addition, FDA is interested in comments on whether such alternatives
would enhance our ability to protect public health by helping FDA
identify the use of potentially unsafe substances in food or additives
that require FDA review and approval to be lawfully marketed, so we can
take action as appropriate. FDA is seeking data and other information
to support any suggested alternatives, including how such an
alternative would meet FDA's goals of protecting public health and
increasing transparency.
VII. Proposed Effective/Compliance Dates
We intend that any final rule resulting from this rulemaking become
effective 60 days after the date of the final rule's publication in the
Federal Register.
We also propose that Sec. Sec. 170.205 and 570.205, if finalized,
have a compliance date of 18 months after the effective date of the
final rule. Based on our experience reviewing GRAS notices under the
voluntary GRAS notification program, we think that a compliance period
of 18 months would provide industry with sufficient time to come into
compliance with these proposed requirements and for FDA to make
available on a public list the information that is submitted under the
time-limited option to make a streamlined submission to FDA for certain
substances already in interstate commerce in proposed Subpart F that
has a period of one year from the effective date. The availability of
this information on a public list would be necessary to inform industry
whether the exception in proposed Sec. Sec. 170.205(b)(7) and
570.205(b)(7) applies.
VIII. Preliminary Economic Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, Executive Order 14192, the
Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded
Mandates Reform Act of 1995 (Pub. L. 104-4).
Executive Orders 12866 and 13563 direct us to assess all benefits
and costs of available regulatory alternatives and, when regulation is
necessary, to select regulatory approaches that maximize net benefits.
Rules are economically significant under Executive Order 12866 if they
have an annual effect on the economy of $100 million or more; or
adversely affect in a material way the economy, a sector of the
economy, productivity, competition, jobs, the environment, public
health or safety, or State, local, or tribal governments or
communities. The Office of Information and Regulatory Affairs (OIRA)
has determined that this proposed rule is an economically significant
regulatory action under section 3(f)(1) of Executive Order 12866.
Executive Order 14192 requires that any new incremental costs
associated with certain significant regulatory actions ``shall, to the
extent permitted by law, be offset by the elimination of existing costs
associated with at least 10 prior regulations.'' This proposed rule, if
finalized as proposed, is expected to be an Executive Order 14192
regulatory action.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because we estimate that the economic impact of this proposed
rule is more than 3 percent of annual revenue for small entities, we
find that the proposed rule would have a significant economic impact on
a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (Section 202(a)) requires
us to prepare a written statement, which includes estimates of
anticipated impacts, before proposing ``any rule that includes any
Federal mandate that may result in the expenditure by State, local, and
tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted annually for inflation) in any one
year.'' The current threshold after adjustment for inflation is $193
million, using the most current (2025) Implicit Price Deflator for the
Gross Domestic Product. This proposed rule would result in an
expenditure in at least one year that meets or exceeds this amount.
The primary benefits of the proposed rule, if finalized, would come
from increased information being made available to FDA and the public
regarding substances used in human and animal foods. A mandatory GRAS
notification program would allow FDA to ensure that GRAS conclusions
have a scientific basis and that appropriate documentation supporting
those conclusions exists. The proposed rule, if finalized, is in part
intended to help strengthen public confidence in FDA's ability to
oversee the safety of the U.S. food supply.
One-time costs of the proposed rule to persons who introduce a
substance into interstate commerce under the GRAS provision of section
201(s) of the FD&C Act include reading the rule and revising standard
operating procedures regarding GRAS notices. Other one-time costs of
the proposed rule are preparing and submitting streamlined submissions
related to uses of substances introduced into interstate commerce under
the GRAS provision of section 201(s) of the FD&C Act before the
effective date of a final rule, for firms that choose to submit this
information during the window of availability for this time-limited
option for such submissions. Costs associated with these activities may
include translation costs for manufacturers in non-English speaking
countries. Recurring costs to affected manufacturers include preparing
and submitting GRAS notices for new uses of substances introduced into
interstate commerce under the GRAS provision of section 201(s) of the
FD&C Act after the effective date of a final rule that would otherwise
have been the subject of an independent conclusion of GRAS status.
Costs to FDA would include one-time costs of reviewing streamlined
submissions related to uses of substances introduced into interstate
commerce under the GRAS provision of section 201(s) of the FD&C Act
before the effective date of a final rule during the time-limited
period for such submissions and annual costs of evaluating ongoing
submissions of GRAS notices regarding uses of substances that would
otherwise have been the subject of an independent conclusion of GRAS
status.
We estimate that the present value of the costs of the proposed
rule would be approximately $89.6 million, with a lower bound of $34.9
million and an upper bound of $210.0 million, discounted at 3 percent
at 10 years in 2024 dollars. At a 7 percent discount rate, the present
value of costs would be approximately $82.3 million, with a lower bound
of $31.5 million and an upper bound of $195.9 million. We
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estimate that the annualized costs of the proposed rule would be
approximately $10.5 million, with a lower bound of $4.1 million and an
upper bound of $24.6 million, discounted at 3 percent over 10 years. At
a 7 percent discount rate, annualized costs would be approximately
$11.7 million, with a lower bound of $4.5 million and an upper bound of
$27.9 million. The estimated benefits and costs of the proposed rule
are summarized in table 3.
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In line with Executive Order 14192, we estimate present and
annualized values of costs, cost savings, and net costs over an
infinite time horizon in table 4. The net present value of the costs of
the proposed rule are approximately $86.0 million, with a lower bound
of $37.8 million and an upper bound of $189.7 million, discounted at 7
percent over an infinite time horizon in 2024 dollars. The annualized
costs of the proposed rule are approximately $6.0 million, with a lower
bound of $2.6 million with an upper bound of $13.3 million.
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We have developed a Preliminary Economic Analysis of Impacts that
assesses the impacts of the proposed rule. The full preliminary
analysis of economic impacts is available in the docket for this
proposed rule (Ref. 46) and at https://www.fda.gov/economics-staff/regulatory-impact-analyses-ria.
IX. Analysis of Environmental Impact
We have determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
[[Page 51869]]
X. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by OMB under the Paperwork Reduction Act of 1995
(44 U.S.C. 3501-3521). A description of these provisions is given in
the Description section below with an estimate of the annual reporting.
Included in the estimate is the time for reviewing instructions,
searching existing data sources, gathering, and maintaining the data
needed, and completing and reviewing each 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.
Title: Substances Generally Recognized as Safe: Notification
Procedure; OMB Control Number 0910-0342--Revision.
Description: The FD&C Act requires that all food additives (as
defined by section 201(s) of the FD&C Act) be reviewed and approved by
FDA before they are marketed. Section 409 of the FD&C Act establishes a
premarket review and approval requirement for ``food additives.''
Section 201(s) of the FD&C Act provides an exclusion to the definition
of food additive, and thus from the food additive premarket review and
approval requirement, for uses of substances that are GRAS by qualified
experts. The GRAS provision of section 201(s) of the FD&C Act is
implemented in parts 170 and 570 for human food and animal food,
respectively. The provisions include an administrative procedure for a
person to voluntarily notify FDA about a conclusion that a substance is
GRAS under the conditions of its intended use in food for humans or
animals.
A GRAS notice will include the following information:
signed statements and a certification;
the identity, method of manufacture, specifications, and
physical or technical effect of the notified substance;
dietary exposure to the notified substance (and human
exposures when used in food for food-producing animals);
self-limiting levels of use in circumstances where the
amount of the notified substance that can be added to human food or
animal food is limited because the food containing levels of the
notified substance above a particular level would become unpalatable or
technologically impractical;
evidence of substantial history of consumption of the
substance for food use by a significant number of consumers (or animals
in the case of animal food) prior to January 1, 1958, if a conclusion
of GRAS status is based on common use of the substance in food prior to
1958;
a narrative that provides the basis for the notifier's
conclusion of GRAS status, including why the data, information,
methods, and principles described in the notice provide a basis for the
conclusion that the notified substance is generally recognized, among
qualified experts, to be safe under the conditions of its intended use;
and
a list of the data and information the notifier cites in
the GRAS notice.
This proposed rule, if finalized, would amend our regulations in
parts 170 and 570 to require the submission of GRAS notices for the use
of a human or animal food substance that is purported to be GRAS under
the conditions of its intended use under section 201(s) of the FD&C
Act. This proposed rule would require any person introducing a
substance into interstate commerce under the GRAS provision of section
201(s) of the FD&C Act to notify FDA of the basis for their conclusion
that the substance is GRAS under the conditions of its intended use
unless an exception to the requirement to submit a GRAS notice applies.
In short, the proposed rule would convert the voluntary GRAS
notification program to a mandatory GRAS notification program. This
change would provide greater transparency about substances that are
added to food (including substances already in the food supply and
those being introduced into interstate commerce for use in food for the
first time) so that FDA can more efficiently determine if the use of a
substance constitutes a food additive use that is subject to the
premarket review and approval requirements of the FD&C Act. This will
therefore enable FDA to more effectively regulate the safety of food
substances and ultimately help identify the use of potentially unsafe
substances in food, so we can take action as appropriate.
The proposed rule would establish certain exceptions to the
requirement to submit a GRAS notice, including a time-limited option to
make a streamlined submission to FDA for certain substances already in
interstate commerce under the GRAS provision of the FD&C Act instead of
initially submitting a GRAS notice. The submission must include: (1)
the name and address of the submitter; (2) the name of the substance,
using an appropriately descriptive term; (3) the intended conditions of
use of the substance, including the foods in which the substance is
used or is in contact with, the levels of use, and the purposes for
which the substance is used (and the target animal species for animal
food as well as human exposures when used in food for food-producing
animals); (4) evidence of presence in interstate commerce before the
effective date of the final rule; and (5) if applicable, where FDA sent
a cease to evaluate letter in response to a notifier's previous GRAS
notice (GRN or AGRN), provide that file number (GRN No. or AGRN No.) as
part of the submission.
The proposed rule would revise our procedural regulations for a TOR
exemption for human food to reflect updated scientific guidance and to
include substances used in food and as an FCS. FDA has an existing
information collection for information submitted in support of a TOR
exemption for a food contact substance under OMB control number 0910-
0495 (Food Additives; Food Contact Substances Notification System). The
proposed rule would allow manufacturers and suppliers to also seek the
TOR exemption for substances used in food. A request for a TOR
exemption will include: (1) the chemical composition of the substance
for which the request is made; (2) detailed information on the
conditions of use of the substance; (3) a clear statement of the basis
for the request for exemption from regulation as a food additive; (4)
data that will enable FDA to estimate the daily dietary concentration
resulting from the proposed use of the substance; (5) results of a
literature search for toxicological data on the substance and its
impurities; and (6) information on the environmental impact that would
result from the proposed use.
HFP would require notifiers or submitters to submit data
electronically using the Centralized Online Submission Module (COSM)
(Form FDA 3667) (https://www.fda.gov/food/registration-food-facilities-and-other-submissions/centralized-online-submission-module-cosm) for
GRAS
[[Page 51870]]
notices, the time-limited option to submit information for certain
substances already in interstate commerce, and requests for a TOR
exemption. Notifiers may request a waiver from HFP to submit on paper
at Office of Pre-Market Additive Safety, Human Foods Program, Food and
Drug Administration, 5001 Campus Dr., College Park, MD 20740. CVM would
require notifiers to contact CVM by email at [email protected] before submitting a GRAS notice. For the time-
limited option to submit information for certain substances already in
interstate commerce, CVM would require submitters to send data by email
at [email protected].
Description of Respondents: Respondents to the collection of
information are manufacturers of substances used in food for humans and
animals.
We estimate the burden of this collection of information as
follows:
[GRAPHIC] [TIFF OMITTED] TP11AU26.053
The burden estimates in tables 5 and 6 are consistent with the
estimates found in the Preliminary Regulatory Impact Analysis (PRIA)
(Ref. 46). The existing information collection for annual voluntary
GRAS notices, OMB control number 0910-0342 (Substances Generally
Recognized as Safe: Notification Procedure), estimates 100 firms for
human foods and 12 firms for animal food that voluntarily submitted
GRAS notices for a total of 112 firms. These annual estimates are based
on our experience with the voluntary GRAS notice program, and we
include with them our annual estimates for additional firms that will
submit GRAS notices to comply with the proposed rule, if finalized.
In table 15 of the PRIA, we estimate that a total of approximately
98 additional firms, including GRAS substance producers and food
manufacturers, will submit a GRAS notice annually. Of the new firms, we
estimate that 94 produce human food, and 4 produce animal food. For
this analysis, we estimate that 194 firms (100 voluntarily submitting +
94 due to rulemaking) annually will submit a GRAS notice for human
food, and 16 firms (12 voluntarily submitting + 4 due to rulemaking)
will submit a GRAS notice for animal food. In table 14 of the PRIA, we
estimate that it will take 180 hours to prepare and submit a GRAS
notice for either human or animal food. Accordingly, we estimate the
annual burden for submitting a GRAS notice to be 34,920 hours for human
food (194 notices x 180 hours) and 2,880 hours for animal food (16
notices x 180 hours).
We estimate that approximately 58 respondents will request a waiver
to submit in paper format either a GRAS notice, TOR exemption, or the
time-limited option to submit information for certain substances
already in interstate commerce for human food. This annual estimate is
based on our experience with the voluntary GRAS notice program and the
annual estimate in the existing information collection approved under
OMB control number 0910-0342, where we estimate that approximately 30
percent of submissions are in paper format annually. For this analysis,
we will assume approximately 30 percent of firms will choose to submit
in paper format. Thus, 30 percent of the estimated 194 firms for human
food is about 58 (194 firms x 0.30). We believe respondents will need
no longer than an hour to prepare such a request as respondents should
already have any information needed to request a waiver. Accordingly,
we estimate the annual burden to request a waiver to submit a GRAS
notice for human food in paper format to be 58 hours.
The existing information collection for food contact substances
covers TOR exemption under OMB control number 0910-0495 (Food
Additives; Food Contact Substances Notification System). For this
analysis, we will use the same annual estimates for TOR exemption from
that information collection to apply to the TOR exemption for food
substances. Thus, we estimate that 7 respondents annually will each
submit 1 request for a TOR exemption, which will take approximately 48
hours to prepare and submit. Accordingly, we estimate the annual burden
to request a TOR exemption for a food substance will be 336 hours (7
requests x 48 hours).
[[Page 51871]]
[GRAPHIC] [TIFF OMITTED] TP11AU26.054
In table 7 of the PRIA, we estimate that there are 1,028 unique
firms with independent conclusions of GRAS status. Based on table 6 of
the PRIA, we calculate that 94 percent of the independent conclusions
of GRAS status are for human foods (1,885 human food independent
conclusions of GRAS status / 2,000 total human and animal independent
conclusions of GRAS status). We assume the same distribution for the
number of unique firms preparing a submission for certain substances
purported to be GRAS based on an independent conclusion of GRAS status.
Accordingly, we calculate the number of respondents preparing a
submission for certain substances purported to be GRAS based on an
independent conclusion of GRAS status for human food to be 966 (1,028 x
0.94).
In table 10 of the PRIA, we estimate that each respondent will
prepare approximately 2.5 submissions for certain substances purported
to be GRAS based on an independent conclusion of GRAS status that were
already introduced into interstate commerce before the effective date
of a final rule. In table 10 of the PRIA, we estimate that there are
1,740 association expert panel-concluded GRAS substances. As discussed
in the PRIA, this category includes substances evaluated by the Flavor
and Extract Manufacturers Association and introduced into interstate
commerce under section 201(s) of the FD&C Act but can include other
independent conclusions of GRAS status made by other expert panels
selected and convened by associations. For efficiency purposes, we
assume that there will be one submission by one respondent to cover all
submissions for certain substances purported to be GRAS based on an
association expert panel GRAS conclusion that were already introduced
into interstate commerce before the effective date of a final rule.
Accordingly, we calculate the total number of respondents to be 967
(966 respondents preparing a submission for certain substances
purported to be GRAS based on an independent conclusion of GRAS status
+ 1 respondent preparing a submission for certain substances purported
to be GRAS based on an association expert panel GRAS conclusion).
Although we believe that one respondent will have one submission for
1,740 substances, we estimate that on average each respondent will
submit 2.5 responses. Thus, we calculate that 2,418 submissions
(rounded up from 2,417.5) will be submitted for certain substances
purported to be GRAS based on an association expert panel GRAS
conclusion that were already introduced into interstate commerce before
the effective date of a final rule (967 respondents x 2.5 responses).
In table 10 of the PRIA, we estimate that it will take
approximately 32 hours (rounded up from 31.5) to prepare a submission
for certain substances purported to be GRAS under section 201(s) of the
FD&C Act that were already introduced into interstate commerce before
the effective date of a final rule (we assume, in the PRIA, that a
streamlined submission would require between 10 percent and 25 percent
of the time expenditure of a GRAS notice (180 hours), with a central
estimate of 17.5 percent to arrive at the estimate of 31.5 hours to
prepare a streamlined submission (180 hours x 17.5 percent).
Accordingly, we calculate the burden for this activity to be 77,376
hours (2,418 submissions x 32 hours). We believe that this will be a
one-time burden because these streamlined submissions are time-limited
and would only be available for 1 year after the effective date of a
final rule.
We estimate the remaining 62 respondents would be preparing a
submission for certain substances purported to be GRAS based on an
independent conclusion of GRAS status for animal food (1,028 unique
firms with independent conclusions of GRAS status--966 respondents
preparing a submission for certain substances purported to be GRAS
based on an independent conclusion of GRAS status for human food). In
table 10 of the PRIA, we estimate that each respondent will prepare
approximately 2.5 submissions for certain substances purported to be
GRAS based on an independent conclusion of GRAS status that were
already introduced into interstate commerce before the effective date
of the final rule. Provided that each respondent will prepare 2.5
submissions, we calculated that there will be 155 responses (62
respondents x 2.5 submissions per respondent). In table 10 of the PRIA,
we estimate that it will take approximately 32 hours (rounded up from
31.5) to prepare a submission for certain substances purported to be
GRAS based on an independent conclusion of GRAS status that were
already introduced into interstate commerce before the effective date
of a final rule. Accordingly, we estimate the burden for this activity
to be 4,960 hours (155 submissions x 32 hours). We believe that this
will be a one-time burden because the option to make streamlined
submissions would only be available for 1 year after the effective date
of a final rule.
To ensure that comments on information collection are received, OMB
recommends that written comments be submitted through reginfo.gov (see
ADDRESSES). All
[[Page 51872]]
comments should be identified with the title of the information
collection.
In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C.
3407(d)), we have submitted the information collection provisions of
this proposed rule to OMB for review. These information collection
requirements will not be effective until FDA publishes a final rule,
OMB approves the information collection requirements, and the rule goes
into effect. FDA will announce OMB approval of these requirements in
the Federal Register.
XI. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
the proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the rule does not contain policies that have
federalism implications as defined in the Executive order and,
consequently, a federalism summary impact statement is not required.
XII. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, or the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian Tribes. FDA invites comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.
XIII. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. Although FDA verified the website addresses
in this document, please note that websites are subject to change over
time.
* 1. U.S. Food and Drug Administration. ``HHS Secretary Kennedy
Directs FDA to Explore Rulemaking to Eliminate Pathway for Companies
to Self-Affirm Food Ingredients Are Safe.'' March 2025. Accessed
April 8, 2026. Available at https://www.hhs.gov/press-room/revising-gras-pathway.html.
* 2. U.S. Food and Drug Administration. ``The MAHA Report.'' May
2025. Accessed April 8, 2026. Available at https://www.whitehouse.gov/maha/.
* 3. U.S. Food and Drug Administration. ``GRAS Notices.'' Accessed
April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices.
* 4. U.S. Food and Drug Administration. ``Current Animal Food GRAS
Notices Inventory.'' Accessed April 8, 2026. Available at https://www.fda.gov/animal-veterinary/generally-recognized-safe-gras-notification-program/current-animal-food-gras-notices-inventory.
* 5. U.S. Government Accountability Office. ``FDA Should Strengthen
Its Oversight of Food Ingredients Determined to Be Generally
Recognized as Safe (GRAS).'' March 2010. Accessed April 8, 2026.
Available at https://www.gao.gov/products/gao-10-246.
6. The PEW Charitable Trusts. ``Fixing the Oversight of Chemicals
Added to our Food.'' November 2013. Accessed April 8, 2026.
Available at https://www.pew.org/en/research-and-analysis/reports/2013/11/07/fixing-the-oversight-of-chemicals-added-to-our-food.
7. Neltner, T.G., N.R. Kulkarni, H.M. Alger, et al. ``Navigating the
U.S. Food Additive Regulatory Program.'' Comprehensive Reviews in
Food Science and Food Safety, 10:342-368, 2011. Accessed April 8,
2026. Available at https://doi.org/10.1111/j.1541-4337.2011.00166.x.
* 8. U.S. Congress. House. House Select Committee to Investigate the
Use of Chemicals in Food Products. House Report No. 82-2356, 82nd
Cong., 2d sess., June 30, 1952. Accessed April 8, 2026. Available at
https://www.govinfo.gov/app/details/SERIALSET-11578_00_00-071-2356-0000.
* 9. U.S. Congress. House. Committee on Interstate and Foreign
Commerce. House Report No. 85-2284, 85th Cong., 2d sess., July 28,
1958.
* 10. U.S. Food and Drug Administration. ``Understanding How the FDA
Regulates Substances That Come into Contact with Food.'' Accessed
May 27, 2026. Available at https://www.fda.gov/food/food-packaging-other-substances-come-contact-food-information-consumers/understanding-how-fda-regulates-substances-come-contact-food.
11. Price, J.M., C.G. Biava, B.L. Oser, et al., ``Bladder Tumors in
Rats Fed Cyclohexylamine or High Doses of a Mixture of Cyclamate and
Saccharin.'' Science, 167:1131-1132, 1970. Available at https://doi.org/10.1126/science.167.3921.1131.
12. New York Times. ``Text of President Nixon's Message to Congress
on Proposals to Help Consumers.'' October 1969. Accessed April 8,
2026. Available at https://timesmachine.nytimes.com/timesmachine/1969/10/31/issue.html.
* 13. U.S. Food and Drug Administration. ``Import Alert 45-06
Detention without Physical Examination of Stevia Leaves, Crude
Extracts of Stevia Leaves and Foods Containing Stevia Leaves and/or
Stevia Extracts.'' May 2025. Accessed April 8, 2026. Available at
https://www.accessdata.fda.gov/cms_ia/importalert_119.html.
* 14. U.S. Food and Drug Administration. ``Warning Letter H2
Beverages, Inc., CMS 622917.'' June 2022. Accessed April 8, 2026.
Available at https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/h2-beverages-inc-622917-06142022.
* 15. U.S. Food and Drug Administration. ``Guidance for Industry:
Regulatory Framework for Substances Intended for Use in Human Food
or Animal Food on the Basis of the Generally Recognized as Safe
(GRAS) Provision of the Federal Food, Drug, and Cosmetic Act.''
November 2017. Accessed April 8, 2026. Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-regulatory-framework-substances-intended-use-human-food-or-animal-food-basis.
* 16. Chief Legal Officers of The State of Connecticut, The State of
Utah, and The Territory of Guam. Letter to FDA re Caffeinated
Alcoholic Beverages. September 25, 2009.
* 17. U.S. Food and Drug Administration. Letter from FDA to Phusion
Projects LLC re Caffeinated Alcoholic Beverages. November 12, 2009.
18. Diane C. McEnroe, Sidley Austin LLP, to Dr. Cheeseman, Acting
Director, Office of Food Additive Safety, Center for Food Safety and
Applied Nutrition, FDA. Letter re Caffeinated Alcoholic Beverages--
Phusion Projects, LLC. December 10, 2009.
* 19. U.S. Food and Drug Administration. ``GRN No. 347 Caffeine.''
Accessed April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=347&sort=GRN_No&order=DESC&startrow=1&ty
pe=basic&search=caffeine.
* 20. U.S. Food and Drug Administration. ``Update on Caffeinated
Coffee Beverages--FDA Announces Progress on Removal of Certain
Caffeinated Alcoholic Beverages from the Market.'' November 2010.
Accessed April 8, 2026. Available at https://wayback.archive-it.org/7993/20161024020218/https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm234900.htm.
* 21. U.S. Food and Drug Administration. ``FDA, FTC Continue Joint
Effort to Protect Consumers Against Companies
[[Page 51873]]
Illegally Selling Copycat Delta-8 THC Food Products.'' July 2024.
Accessed April 8, 2026. Available at https://www.fda.gov/news-events/press-announcements/fda-ftc-continue-joint-effort-protect-consumers-against-companies-illegally-selling-copycat-delta-8.
* 22. U.S. Food and Drug Administration. ``Post-market
Determinations That the Use of a Substance Is not GRAS: Tara
Flour.'' Accessed April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=Postmarket&id=taraflour&sort=Sortterm_ID&order=ASC&star
trow=1&type=basic&search=tara%20flour.
* 23. U.S. Food and Drug Administration. ``Post-market
Determinations That the Use of a Substance Is not GRAS.'' Accessed
April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=Postmarket.
* 24. U.S. Food and Drug Administration. ``Import Alert 99-45
Detention Without Physical Examination of Food Products That Are or
Contain an Unsafe Food Additive.'' August and October 2023. Accessed
April 8, 2026. Available at https://www.accessdata.fda.gov/CMS_IA/importalert_1173.html.
25. Gallup. ``Trust in Government Assurance of Food Safety Hits
Records Low.'' September 6, 2024. Accessed April 8, 2026. Available
at https://news.gallup.com/poll/650024/trust-government-assurance-food-safety-hits-record-low.aspx.
26. International Food Information Council. ``IFIC Food & Health
Survey: A Focus on Food & Ingredient Safety.'' 2025. Accessed April
8, 2026. Available at https://ific.org/wp-content/uploads/2025/07/2025-IFIC-Food-Health-Survey-Food-Ingredient-Safety.pdf.
* 27. Institute of Medicine. ``DRI Dietary Reference Intakes:
Applications in Dietary Assessment.'' Washington, DC: National
Academies Press, 2000. Accessed April 8, 2026. Available at https://www.ncbi.nlm.nih.gov/books/NBK222879.
* 28. Institute of Medicine. ``Dietary Reference Intakes for Calcium
and Vitamin D.'' Washington, DC: National Academies Press, 2011.
Accessed April 8, 2026. Available at https://www.ncbi.nlm.nih.gov/books/NBK56060.
* 29. Institute of Medicine. ``Dietary Reference Intakes for Calcium
and Vitamin D Report Brief.'' Washington, DC: National Academies
Press, 2011. Accessed April 8, 2026. Available at https://nap.nationalacademies.org/resource/13050/Vitamin-D-and-Calcium-2010-Report-Brief.pdf.
* 30. National Institutes of Health. ``Calcium: Fact Sheet for
Health Professionals.'' ODS.OD.NIH.GOV. July 2025. Accessed April 8,
2026. Available at https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/.
* 31. U.S. Food and Drug Administration. ``GRN No. 1126 Calcium
Acetate.'' Accessed April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GRASNotices&id=1126.
32. Lacourt C., K. Mukherjee, J. Garthoff, et al. ``Recent and
Emerging Food Packaging Alternatives: Chemical Safety Risks, Current
Regulations, and Analytical Challenges.'' Comprehensive Reviews in
Food Science and Food Safety, 23(6), 2024. Accessed April 8, 2026.
Available at https://doi.org/10.1111/1541-4337.70059.
33. Zimmermann L., A. Dombrowski, C. Volker, et al. ``Are
Bioplastics and Plant-Based Materials Safer Than Conventional
Plastics? In Vitro Toxicity and Chemical Composition.'' Environment
International, 145, 2020. Accessed April 8, 2026. Available at
https://doi.org/10.1016/j.envint.2020.106066.
* 34. U.S. Food and Drug Administration Memorandum, ``Regulatory
Status and Review of Available Information Pertaining to the Sheath
of Areca Catechu Palm Tree Leaves in Food Contact Articles: Lack of
General Recognition of Safety for Its Use as a Food Contact
Substance.'' HHS, FDA, Human Foods Program. April 2025. Available at
https://www.fda.gov/media/186355/download?attachment.
35. Mangrum, J.B., L. DeJager, and T. Begley. ``Investigation into
the Presence of Alkaloids in Areca Catechu-Based Single-Use Food-
Contact Articles (FCA).'' Food Additives & Contaminants: Part A,
42(4), 526-538, 2025. Available at https://doi.org/10.1080/19440049.2025.2469271.
* 36. U.S. Food and Drug Administration. ``Letter to Retailers,
Distributors, and Importers of Dinnerware.'' May 2025. Accessed
April 8, 2026. Available at https://www.fda.gov/food/post-market-determinations-use-substance-not-gras/letter-retailers-distributors-and-importers-dinnerware.
* 37. U.S. Food and Drug Administration. ``Import Alert 23-15
Detention Without Physical Examination of Food Products Including
Finished Dietary Supplements and Bulk Dietary Ingredients, That Are,
or That Contain, Areca (Betel) Nuts, and Foodware Made from Areca
Catechu Palm Leaves.'' May 2025. Accessed April 8, 2026. Available
at https://www.accessdata.fda.gov/CMS_IA/importalert_1139.html.
* 38. U.S. Food and Drug Administration. ``Guidance for Industry:
Preparation of Food Contact Notifications for Food Contact
Substances in Contact with Infant Formula and/or Human Milk.'' May
2019. Accessed April 8, 2026. Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-preparation-food-contact-notifications-food-contact-substances-contact-infant.
* 39. U.S. Food and Drug Administration. ``New Plant Variety
Consultations.'' Accessed April 8, 2026. Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=NewPlantVarietyConsultations.
* 40. U.S. Food and Drug Administration. ``Premarket Meetings
Regarding Food from Genome Edited Plants.'' Accessed April 8, 2026.
Available at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=GenomeEditedPlants.
* 41. U.S. Food and Drug Administration. ``Human Food Made with
Cultured Animal Cells Inventory.'' Accessed April 8, 2026. Available
at https://www.hfpappexternal.fda.gov/scripts/fdcc/index.cfm?set=AnimalCellCultureFoods.
* 42. U.S. General Services Administration. ``Federal Plain Language
Guidelines.'' Accessed April 8, 2026. Available at https://www.plainlanguage.gov/guidelines/.
* 43. U.S. Food and Drug Administration. ``Animal Food Ingredient
Consultation (AFIC): Guidance for Industry #294.'' July 2025.
Accessed April 8, 2026. Available at https://www.fda.gov/media/180442/download.
* 44. U.S. Food and Drug Administration. ``FDA Enforcement Policy
for AAFCO--Defined Animal Feed Ingredients: Guidance for Industry
#293.'' October 2024. Accessed April 8, 2026. Available at https://www.fda.gov/media/180441/download.
* 45. U.S. Food and Drug Administration. ``Memorandum of
Understanding Between the United States Food and Drug Administration
and the Association of American Feed Control Official.'' HHS, FDA,
Center for Veterinary Medicine. June 2019. Available at https://www.fda.gov/about-fda/domestic-mous/mou-225-07-7001.
* 46. U.S. Food and Drug Administration. ``Substances Generally
Recognized as Safe Preliminary Regulatory Impact Analysis, Initial
Regulatory Flexibility Analysis, Unfunded Mandates Reform Act
Analysis. Available at https://www.fda.gov/economics-staff/regulatory-impact-analyses-ria.
List of Subjects
21 CFR Part 170
Administrative practice and procedure, Food additives, Reporting
and recordkeeping requirements.
21 CFR Part 570
Animal feeds, Animal foods, Food additives, Incorporation by
reference.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, FDA proposes
that 21 CFR parts 170 and 570 be amended as follows:
PART 170--FOOD ADDITIVES
0
1. The authority citation for part 170 continues to read as follows:
Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.
0
2. Revise the heading to read as follows:
[[Page 51874]]
PART 170--FOOD ADDITIVES AND GENERALLY RECOGNIZED AS SAFE (GRAS)
SUBSTANCES
0
3. Amend Sec. 170.3 by:
0
a. Revising paragraph (m); and
0
b. Adding paragraph (p).
The revision and addition read as follows:
Sec. 170.3 Definitions.
* * * * *
(m) Food includes human food, substances migrating to food from
food contact articles, and animal food.
* * * * *
(p) We, our, us, and FDA refer to the United States Food and Drug
Administration.
0
4. Amend Sec. 170.30 by:
0
a. Revising paragraph (c)(2);
0
b. Revising paragraph (d);
0
c. Revising paragraph (e);
0
d. Revising paragraph (i); and
0
e. Adding paragraphs (i)(1) and (2).
The revisions and additions read as follows:
Sec. 170.30 Eligibility for classification as generally recognized as
safe (GRAS).
* * * * *
(c) * * *
(2) A substance used in food before January 1, 1958, may be
generally recognized as safe through experience based on its common use
in food when that use occurred exclusively or primarily outside of the
United States if the information about the experience establishes that
the substance is safe under the conditions of its intended use within
the meaning of section 201(u) of the Act (see also Sec. 170.3(i)).
Common use in food before January 1, 1958, that occurred outside of the
United States must be documented by published or other information and
must be corroborated by information from a second, independent source
that confirms the history and circumstances of use of the substance.
The information used to document and to corroborate the history and
circumstances of use of the substance must be generally available; that
is, it must be widely available in the country in which the history of
use has occurred and readily available to interested qualified experts
in the United States.
(d) The food ingredients listed as GRAS in part 182 of this chapter
or affirmed as GRAS in part 184 or part 186 of this chapter do not
include all substances that are generally recognized as safe for their
intended use in food. Because of the large number of substances, the
intended use of which results or may reasonably be expected to result,
directly or indirectly, in their becoming a component or otherwise
affecting the characteristics of food, it is impracticable to list in
part 182 of this chapter or affirm in part 184 or part 186 of this
chapter all such substances that are GRAS. A food ingredient of natural
biological origin that has been widely consumed for its nutrient
properties in the United States before January 1, 1958, without known
detrimental effects, which is subject only to conventional processing
as practiced before January 1, 1958, and for which no known safety
hazards exists, will ordinarily be regarded as GRAS without specific
inclusion in parts 182, 184, or 186 of this chapter.
(e) All affirmations of GRAS status or determinations of food
additive status or prior sanction status must be handled pursuant to
Sec. Sec. 170.35, 170.38, 180.1, and 181.1 of this chapter.
Affirmation of GRAS status must be announced in part 184 or part 186 of
this chapter.
* * * * *
(i) If a substance is affirmed as GRAS in part 184 or part 186 of
this chapter with no limitation other than good manufacturing practice:
(1) It will be regarded as GRAS if its conditions of use are not
significantly different from those reported in the regulation as the
basis on which the GRAS status of the substance was affirmed; or
(2) If the conditions of use are significantly different, the
regulation may not be relied on as authorizing such use.
* * * * *
0
5. Amend Sec. 170.38 by:
0
a. Revising paragraph (a);
0
b. Adding introductory text to paragraph (b);
0
c. Revising paragraphs (b)(1) through (3); and
0
d. Revising paragraphs (c) and (d).
The revisions and addition read as follows:
Sec. 170.38 Determination of food additive status.
(a) FDA may determine that a substance is not GRAS under the
conditions of its intended use and is not otherwise excepted from the
definition of a food additive. If FDA determines that a substance is a
food additive under the conditions of intended use, the substance and
its use or intended use are subject to section 409 of the Act.
(b) For substances listed or affirmed as GRAS in parts 182, 184, or
186 of this chapter:
(1) FDA, on its own initiative or on the petition of any person,
pursuant to part 10 of this chapter, may issue a notice in the Federal
Register proposing to determine that a substance is not GRAS under the
conditions of its intended use and is a food additive subject to
section 409 of the Act. Any petition must include all relevant data and
information of the type described in Sec. 171.130(b) of this chapter.
FDA will place all the data and information on which it relies on
public file in the office of the Dockets Management Staff and will
include in the Federal Register notice the name of the substance, its
known uses, and a summary of the basis for the determination.
(2) The Federal Register notice will allow a period of 60 days
during which any interested person may review the data and information
and/or file comments with the Dockets Management Staff. Copies of all
comments are available for examination in the Dockets Management
Staff's office.
(3) If FDA concludes that there is a lack of convincing evidence
that the substance is GRAS under the conditions of its intended use,
FDA will amend or repeal the relevant regulation in parts 182, 184, or
186 of this chapter, as appropriate.
(c) For a use of a substance for which FDA has issued a no
questions letter as defined in Sec. 170.203 in response to a GRAS
notice, FDA may send the notifier (see Sec. 170.203) questions about
their GRAS conclusion in accordance with Sec. 170.265(c). If FDA later
determines that such substance is not GRAS under the conditions of its
intended use, FDA will make public the basis for this determination and
update or rescind the no questions letter.
(d) For a use of a substance not covered by paragraphs (b) or (c)
of this section, if FDA determines that such substance is not GRAS
under the conditions of its intended use, FDA will make public the
basis for this determination. The fact that FDA has not made such a
determination does not mean that a substance is GRAS under the
conditions of its intended use.
0
6. Amend Sec. 170.39 by:
0
a. Revising the section heading;
0
b. Revising the introductory text of paragraph (a);
0
c. Revising paragraphs (a)(1), (a)(2)(i) and(ii);
0
d. Removing paragraph (a)(3);
0
e. Redesignating paragraph (a)(4) as paragraph (a)(3);
0
f. Revising paragraph (b);
0
g. Revising the introductory text of paragraph (c);
0
h. Revising paragraphs (c)(2) through (5);
0
i. Revising paragraphs (d) and (e);
0
j. Removing paragraph (f);
0
k. Redesignating paragraph (g) as paragraph (f); and
[[Page 51875]]
0
l. Removing paragraph (h).
The revisions read as follows:
Sec. 170.39 Threshold of regulation for substances used in food or as
a food-contact substance.
(a) A substance used in food or as a food-contact substance will be
exempted from regulation as a food additive or from the GRAS
notification requirement under Sec. 170.205 because the substance
becomes a component of food at levels that are below the threshold of
regulation if:
(1) The substance has not been shown to be a carcinogen in humans
or animals, and there is no reason, based on the chemical structure of
the substance, to suspect that the substance is a carcinogen. The
substance must also not contain a carcinogenic impurity or, if it does,
must not contain a carcinogenic impurity with a lifetime cancer risk
greater than one in one million, when calculated using a
TD50 value or another approach based on chronic feeding
studies reported in the scientific literature or otherwise available to
FDA, when present in the diet at 0.025 micrograms per kilogram
bodyweight per day. (The TD50, for purposes of this section,
is the feeding dose that causes cancer in 50 percent of the test
animals when corrected for tumors found in control animals. A
TD50 of 6.25 milligrams per kilogram bodyweight per day
equates to a lifetime cancer risk of less than one in one million when
present in the diet at 0.025 micrograms per kilogram bodyweight per
day. If more than one TD50 value has been reported in the
scientific literature for a substance, FDA will use the lowest
appropriate TD50 value in its review.);
(2) The substance presents no other health or safety concerns
because:
(i) The use in question has been shown to result in or may be
expected to result in dietary exposure levels at or below 0.025
micrograms per kilogram bodyweight per day; or
(ii) The substance is currently regulated for direct addition into
food, and the dietary exposure to the substance resulting from the
proposed use is at or below 1 percent of the acceptable daily intake as
determined by safety data in FDA's files or from other appropriate
sources; and
(3) The substance use has no significant adverse impact on the
environment.
(b) Notwithstanding paragraph (a) of this section, FDA may decline
to grant an exemption in those cases in which available information
establishes that the proposed use may pose a public health risk. The
reasons for FDA's decision to decline to grant an exemption will be
explained in FDA's response to the person who submitted the request
(the requestor) to exempt a use of a substance from regulation as a
food additive or from the GRAS notification requirement under Sec.
170.205.
(c) A request for FDA to exempt a use of a substance from
regulation as a food additive or from the GRAS notification requirement
under Sec. 170.205 must include the following information (if part of
the submitted material is in a foreign language, it must be accompanied
by an English translation verified to be complete and accurate in
accordance with Sec. 10.20(c)(2) of this chapter):
(1) * * *
(2) Detailed information on the conditions of use of the substance;
(3) A clear statement as to whether the request for exemption from
regulation as a food additive is based on the fact that the use of the
substance results in a dietary exposure level at or below 0.025
micrograms per kilogram bodyweight per day, or on the fact that it
involves the use of a regulated direct food additive for which the
dietary exposure is at or below 1 percent of the acceptable dietary
intake (ADI);
(4) Data that will enable FDA to estimate the dietary exposure
resulting from the proposed use of the substance;
(5) The results of an analysis of existing toxicological
information on the substance and its impurities. This information on
the substance is needed to show whether an animal carcinogen bioassay
has been carried out, or whether there is some other basis for
suspecting that the substance is a carcinogen or potent toxin. This
type of information on the impurities is needed to show whether any of
them are carcinogenic, and, if carcinogenic, whether their lifetime
cancer risk is less than one in one million when present in the diet at
0.025 micrograms per kilogram bodyweight per day in accordance with
paragraph (a)(1) of this section; and
(6) * * *
(d) Data to be reviewed under this section must be submitted
electronically through the Centralized Online Submission Module, unless
provided with a waiver to submit on paper. Send a request for a waiver
to the Office of Pre-market Additive Safety, Human Foods Program, Food
and Drug Administration, 5001 Campus Dr., College Park, MD 20740.
(e) FDA will inform the requestor whether the use is exempt from
regulation as a food additive or from the GRAS notification requirement
under Sec. 170.205. Although a use that results in a dietary exposure
at or below the threshold of regulation will not be the subject of a
regulation published in the Federal Register and will not appear in the
Code of Federal Regulations, FDA will maintain a publicly available
list of substances and their use exempted from regulation as food
additives or from the GRAS notification requirement under Sec.
170.205. The list will not include any trade names. The list will
enable interested persons to see the types of uses being exempted under
the regulation. Interested persons may also obtain a copy of the list
of exempted substances by contacting the Food and Drug Administration's
Office of Food Additive Safety (HFS-200), 5001 Campus Dr., College
Park, MD 20740. For actions requiring an environmental assessment,
FDA's finding of no significant impact and the evidence supporting that
finding, contained in the petitioner's environmental assessment, also
will be available for public inspection at the Dockets Management Staff
in accordance with Sec. 25.51(b)(2) of this chapter. Requests for
copies of releasable information contained in submissions requesting
exemptions from the food additive regulations or from the GRAS
notification requirement under Sec. 170.205 will be handled in
accordance with the Freedom of Information Act procedures in part 20 of
this chapter. Data and information that fall within the definitions of
a trade secret or confidential commercial or financial information are
not available for public disclosure in accordance with Sec. 20.61(c)
of this chapter.
(f) If FDA receives significant new information that raises
questions about the dietary exposure or the safety of a substance that
FDA has exempted from regulation, FDA may reevaluate the substance. If
FDA tentatively concludes that the information that is available about
the substance no longer supports an exemption for the proposed use of
the substance from the GRAS or food additive regulations, FDA will
notify any persons that requested an exemption for the substance of its
tentative decision. FDA will give the requestor an opportunity to show
why the use of the substance should not be regulated under the food
additive provisions of the Act. If the requestor fails to respond
adequately to the new evidence, FDA will notify them that further use
of the substance in question for the particular use will require a food
additive regulation, an effective premarket notification for a food-
contact substance, or a GRAS notice. This
[[Page 51876]]
notification will be made publicly available. FDA recognizes that
manufacturers other than those that made a request for exemption may
also be using exempted substance under conditions of use that are
similar to those for which the exemption was issued. Because only the
requestor will be notified as part of the revocation process described
in this section, FDA plans to notify other manufacturers by means of a
notice published in the Federal Register of its decision to revoke an
exemption issued for a specific use of a substance in food or as a
food-contact substance.
0
7. Amend Sec. 170.203 by:
0
a. Removing the introductory text;
0
b. Revising the definition of ``GRAS'';
0
c. Revising the definition of ``GRAS notice'';
0
d. Adding the definition of ``Inventory'';
0
e. Adding the definition of ``No questions letter''; and
0
f. Removing the definition of ``We, our and us''.
The revisions and additions read as follows:
Sec. 170.203 Definitions.
* * * * *
GRAS means generally recognized as safe (see Sec. 170.3(i)).
GRAS notice means a submission under Sec. 170.205 that informs us
of your view that a substance is not subject to the premarket review
and approval requirements for food additives under section 409 of the
Act based on your conclusion that the substance is GRAS under the
conditions of its intended use in accordance with Sec. 170.30.
Inventory means an online repository where FDA makes public certain
information related to GRAS notices.
No questions letter means a letter from FDA, sent in response to a
GRAS notice, which states that, based on the information you provided,
as well as other information available to FDA, we have no questions at
this time regarding your conclusion that the notified substance is GRAS
under the conditions of its intended use. A no questions letter is
neither an affirmation by FDA that the notified substance is GRAS for
its intended conditions of use under Sec. 170.35, nor a published
finding under section 721(b)(4) of the Act declaring the use of such
substance exempt from the term ``food additive'' because of its being
GRAS.
* * * * *
0
8. Amend Sec. 170.205 by:
0
a. Revising the section header; and
0
b. Adding paragraphs (a) through (c).
The revision and additions read as follows:
Sec. 170.205 Submission of a GRAS notice.
(a) Any person introducing a substance into interstate commerce
under the GRAS provision of section 201(s) of the Act must notify FDA
of the basis for their conclusion that the substance is GRAS under the
conditions of its intended use, except as provided under paragraph (b)
of this section. For the conditions of use that meet the definition of
a food-contact substance in accordance with Sec. 170.3(e)(3), a
manufacturer or supplier may alternatively submit a food-contact
notification as specified under Sec. 170.100.
(b) A GRAS notice is not required when:
(1) A no questions letter covers the substance under the conditions
of its intended use;
(2) The substance is listed or affirmed as GRAS under the
conditions of its intended use in parts 182, 184, or 186 of this
chapter;
(3) The substance is considered GRAS under the conditions of its
intended use in accordance with Sec. 170.30(d) or (i)(1);
(4) The intended use of the substance has been considered by FDA
through an established FDA process to evaluate the potential presence
of unapproved food additives, and documentation made publicly available
by FDA through that process does not recommend or otherwise identify
the need to submit a GRAS notice;
(5) The intended use of the substance is the subject of an
exemption under the threshold of regulation process described in Sec.
170.39;
(6) There is an effective premarket notification for a food-contact
substance (FCN) which covered the substance under conditions of its
intended use, and the substance in interstate commerce originates from
the manufacturer or supplier listed in the effective FCN; or
(7) Information about the conditions of use of the substance has
been submitted in accordance with Sec. 170.305 and the submission is
included on a public list maintained by FDA, unless FDA issues a
determination that a GRAS notice or food additive petition must be
submitted for the intended use of a substance.
(c) Uses of substances that are excluded from the definition of a
food additive in section 201(s)(1) through (6) of the Act cannot be the
subject of a GRAS notice.
0
9. Revise Sec. 170.210 to read as follows:
Sec. 170.210 How to send your GRAS notice to FDA.
You must submit your GRAS notice electronically through the
Centralized Online Submission Module unless you seek a waiver to submit
your GRAS notice on paper. Send a request for a waiver to the Office of
Pre-market Additive Safety, Human Foods Program, Food and Drug
Administration, 5001 Campus Dr., College Park, MD 20740.
0
10. Amend Sec. 170.220 by adding paragraph (c) to read as follows:
Sec. 170.220 General requirements applicable to a GRAS notice.
* * * * *
(c) Any material submitted in or referenced by a GRAS notice that
is in a foreign language must be accompanied by an accurate and
complete English translation.
0
11. Amend Sec. 170.225 by revising paragraph (c)(6) to read as
follows:
Sec. 170.225 Part 1 of a GRAS notice: Signed statements and
certification.
* * * * *
(c) * * *
(6) State your view that the notified substance is not subject to
the premarket review and approval requirements for food additives under
section 409 of the Act based on your conclusion that the notified
substance is GRAS under the conditions of its intended use;
* * * * *
0
12. Amend Sec. 170.250 by revising paragraphs (d) and (e) to read as
follows:
Sec. 170.250 Part 6 of a GRAS notice: Narrative.
* * * * *
(d) If you view any data and information in your notice as exempt
from disclosure under the Freedom of Information Act, you must identify
the specific data and information at the time of submission. If you do
not, we will consider such data and information to not be exempt from
disclosure or that you have waived any claim of confidentiality; and
(e) For any non-public, safety-related data and information
considered in reaching a conclusion of GRAS status that you identify,
under paragraph (d) of this section, as exempt from disclosure under
the Freedom of Information Act, you must explain how there could be a
basis for a conclusion of GRAS status despite the fact that qualified
experts do not have access to such data and information.
0
13. Amend Sec. 170.265 by:
0
a. Revising paragraphs (a)(1) through (3);
0
b. Adding paragraph (a)(5);
0
c. Revising paragraphs (b)(1) and (2); and
0
d. Adding a sentence to the end of paragraph (b)(3).
The revisions and additions read as follows:
[[Page 51877]]
Sec. 170.265 What FDA will do with a GRAS notice.
(a) * * *
(1) Within 45 days of receiving your submission, we will conduct an
initial evaluation to determine whether to file it as a GRAS notice for
evaluation of your view that the notified substance is GRAS under the
conditions of its intended use.
(2) If we file your submission as a GRAS notice, we will send you a
letter within two business days that informs you of the date of filing.
If we file your submission as a GRAS notice, we will consider the
notification requirement of Sec. 170.205 to be met, except as provided
by Sec. 170.265(b)(3).
(3) If we do not file your submission as a GRAS notice, we will
send you a letter within two business days that informs you of that
fact and provides our reasons for not filing the submission as a GRAS
notice.
* * * * *
(5) During our evaluation of a GRAS notice, we may contact you with
questions related to the notice, including the data and information
used to support your GRAS conclusion.
(b) * * *
(1) Within 180 days of filing, we will respond to you by letter
based on our evaluation of your notice. We may extend the 180-day
timeframe by 90 days up to two times on an as needed basis.
(2) If we extend the timeframe, we will inform you in writing of an
initial extension as soon as practicable but no later than within 180
days of filing. If a second extension is needed, we will inform you in
writing as soon as practicable but no later than the end of the initial
90-day extension.
(3) * * * If we cease to evaluate your GRAS notice, we will not
consider the notification requirement of Sec. 170.205 to be met.
* * * * *
0
14. Amend Sec. 170.275 by:
0
a. Revising paragraph (a);
0
b. Revising the introductory text of paragraph (b); and
0
c. Removing paragraph (c).
The revisions read as follows:
Sec. 170.275 Public disclosure of a GRAS notice.
(a) The data and information in a GRAS notice (including data and
information submitted in any amendment or supplement to your GRAS
notice or incorporated into your GRAS notice) are available for public
disclosure as of the date that we receive your GRAS notice, in
accordance with part 20 of this chapter.
(b) We will make the following readily accessible to the public
through inclusion in the inventory:
* * * * *
Sec. 170.285 [Removed]
0
15. Remove Sec. 170.285.
0
16. Add subpart F to part 170 to read as follows:
Subpart F--Submissions for Substances Introduced into Interstate
Commerce Under the GRAS Provision of Section 201(s) of the Act
Before [EFFECTIVE DATE OF THE FINAL RULE]
Sec.
170.303 Definitions.
170.305 Option for Submissions for Pre-[EFFECTIVE DATE OF THE FINAL
RULE] Substances.
Sec. 170.303 Definitions.
Cease to evaluate letter means a letter from FDA granting a request
to cease to evaluate a GRAS notice (see Sec. 170.265(b)(3)).
GRAS means generally recognized as safe (see Sec. 170.3(i)).
GRAS notice means a submission under Sec. 170.205 that informs us
of the view that a substance is not subject to the premarket review and
approval requirements for food additives under section 409 of the Act
based on a conclusion that the substance is GRAS under the conditions
of its intended use in accordance with Sec. 170.30.
Insufficient basis letter means a letter from FDA, sent in response
to a GRAS notice, which states that, based on the data and information
provided, as well as other available information, the notice does not
provide a sufficient basis for a conclusion that the notified substance
(as defined in Sec. 170.203) is GRAS under the conditions of its
intended use.
Submitter means the person (e.g., an individual, partnership,
corporation, association, or other legal entity) who is responsible for
the submission under this subpart, even if another person (such as an
attorney, agent, or qualified expert) prepares or submits the
information.
Sec. 170.305 Option for Submissions for Pre-[EFFECTIVE DATE OF THE
FINAL RULE] Substances.
(a) Submissions for pre-[EFFECTIVE DATE OF THE FINAL RULE]
substances. For a substance introduced into interstate commerce before
[EFFECTIVE DATE OF THE FINAL RULE] under the GRAS provision of section
201(s) of the Act, a person may submit information regarding the
substance and its conditions of use in accordance with this subpart
instead of submitting a GRAS notice under Sec. 170.205.
(b) When a submission is not allowed. A submission under this
subpart may not concern any conditions of use of a substance that are
the subject of:
(1) An insufficient basis letter (see Sec. 170.303); or
(2) A determination by FDA that the substance is not GRAS under the
conditions of its intended use.
(c) Parts of a submission and how to submit.
(1) A submission must include the following:
(i) The name and address of the submitter;
(ii) The name of the substance, using an appropriately descriptive
term;
(iii) The intended conditions of use of the substance, including
the foods in which the substance is used or is in contact with, the
levels of use, and the purposes for which the substance is used;
(iv) Evidence of presence in interstate commerce before [EFFECTIVE
DATE OF THE FINAL RULE]; and
(v) If applicable, where FDA sent a cease to evaluate letter in
response to a submitter's previous GRAS notice (GRN), provide that file
number (GRN No.) as part of the submission.
(2) A submission may inform us of the statutory basis for the
conclusion of GRAS status (i.e., through scientific procedures in
accordance with Sec. 170.30(a) and (b) or through experience based on
common use in food in accordance with Sec. 170.30(a) and (c)).
(3) This information must be submitted to FDA electronically
through the Centralized Online Submission Module by [DATE 1 YEAR AFTER
EFFECTIVE DATE OF THE FINAL RULE], unless provided with a waiver to
submit on paper. Send a request for a waiver to the Office of Pre-
market Additive Safety, Human Foods Program, Food and Drug
Administration, 5001 Campus Dr., College Park, MD 20740. Submissions
under this subpart will not be accepted after [DATE 1 YEAR AFTER
EFFECTIVE DATE OF THE FINAL RULE].
(d) What FDA will do with a submission.
(1) FDA will post information that meets the requirements for a
submission as specified in Sec. 170.305(c)(1) and (c)(2) in a publicly
available list in accordance with part 20 of this chapter. The posting
of this information does not mean that FDA has reviewed the GRAS status
of the substance's conditions of intended use.
[[Page 51878]]
(2) FDA may ask the submitter questions about their submission.
(3) FDA may issue a determination that a GRAS notice or food
additive petition must be submitted for the intended use of a substance
in accordance with subpart E of this part or section 409 of the Act.
Such a determination will be made publicly available.
PART 570--FOOD ADDITIVES
0
17. The authority citation for part 570 continues to read as follows:
Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.
0
18. Revise the part heading to read as follows:
PART 570--FOOD ADDITIVES AND GENERALLY RECOGNIZED AS SAFE (GRAS)
SUBSTANCES
0
19. Amend Sec. 570.3 by revising paragraph (m) and adding paragraph
(o) to read as follows:
Sec. 570.3 Definitions.
* * * * *
(m) Food includes human food, substances migrating to food from
food contact articles, and animal food.
* * * * *
(o) We, our, us, and FDA refer to the United States Food and Drug
Administration.
0
20. Amend Sec. 570.30 by:
0
a. Revising paragraph (c)(2);
0
b. Revising paragraphs (d) and (h); and
0
c. Adding paragraphs (h)(1) and (2).
The revisions and addition read as follows:
Sec. 570.30 Eligibility for classification as generally recognized as
safe (GRAS).
* * * * *
(c) * * *
(2) A substance used in food before January 1, 1958, may be
generally recognized as safe through experience based on its common use
in food when that use occurred exclusively or primarily outside of the
United States if the information about the experience establishes that
the substance is safe under the conditions of its intended use within
the meaning of section 201(u) of the Act (see also Sec. 570.3(i)) for
both the target animal and for humans consuming human food derived from
food-producing animals. Common use in food before January 1, 1958, that
occurred outside of the United States must be documented by published
or other information and must be corroborated by information from a
second, independent source that confirms the history and circumstances
of use of the substance. The information used to document and to
corroborate the history and circumstances of use of the substance must
be generally available; that is, it must be widely available in the
country in which the history of use has occurred and readily available
to interested qualified experts in the United States.
(d) The food ingredients listed as GRAS in part 582 of this chapter
or affirmed as GRAS in part 584 of this chapter do not include all
substances that are generally recognized as safe for their intended use
in food. Because of the large number of substances, the intended use of
which results or may reasonably be expected to result, directly or
indirectly, in their becoming a component or otherwise affecting the
characteristics of food, it is impracticable to list in part 582 of
this chapter or affirm in part 584 of this chapter all such substances
that are GRAS. A food ingredient of natural biological origin that has
been widely consumed for its nutrient properties in the United States
before January 1, 1958, without known detrimental effects, which is
subject only to conventional processing as practiced before January 1,
1958, and for which no known safety hazard exists, will ordinarily be
regarded as GRAS without specific inclusion in parts 582 or 584 of this
chapter.
* * * * *
(h) If a substance is affirmed as GRAS in part 584 of this chapter
with no limitation other than good manufacturing practice:
(1) It will be regarded as GRAS if its conditions of use are not
significantly different from those reported in the regulation as the
basis on which the GRAS status of the substance was affirmed; or
(2) If the conditions of use are significantly different, the
regulation may not be relied on as authorizing such use.
* * * * *
0
21. Amend Sec. 570.38 by:
0
a. Revising paragraph (a);
0
b. Adding introductory text to paragraph (b);
0
c. Revising paragraphs (b)(1) through (3); and
0
d. Revising paragraphs (c) and (d).
The revisions and addition read as follows:
Sec. 570.38 Determination of food additive status.
(a) FDA may determine that a substance is not GRAS under the
conditions of its intended use and is not otherwise excepted from the
definition of a food additive. If FDA determines that a substance is a
food additive under the conditions of intended use, the substance and
its use or intended use are subject to section 409 of the Act.
(b) For substances listed or affirmed as GRAS in parts 582 or 584
of this chapter:
(1) FDA, on its own initiative or on the petition of any interested
person, pursuant to part 10 of this chapter, may issue a notice in the
Federal Register proposing to determine that a substance is not GRAS
under the conditions of its intended use and is a food additive subject
to section 409 of the Act. Any petition must include all relevant data
and information of the type described in Sec. 571.130(b) of this
chapter. FDA will place all the data and information on which it relies
on public file in the office of the Dockets Management Staff and will
include in the Federal Register notice the name of the substance, its
known uses, and a summary of the basis for the determination.
(2) The Federal Register notice will allow a period of 60 days
during which any interested person may review the data and information
and/or file comments with the Dockets Management Staff. Copies of all
comments are available for examination in the Dockets Management
Staff's office.
(3) If FDA concludes that there is a lack of convincing evidence
that the substance is GRAS under the conditions of its intended use,
FDA will amend or repeal the relevant regulation in part 582 or 584 of
this chapter, as appropriate.
(c) For a use of a substance for which FDA has issued a no
questions letter as defined in Sec. 570.203 in response to a GRAS
notice, FDA may send the notifier (see Sec. 570.203) questions about
their GRAS conclusion in accordance with Sec. 570.265(c). If FDA later
determines that such substance is not GRAS under the conditions of its
intended use, FDA will make public the basis for this determination and
update or rescind the no questions letter.
(d) For a use of a substance not covered by paragraphs (b) or (c)
of this section, if FDA determines that such substance is not GRAS
under the conditions of its intended use, FDA will make public the
basis for this determination. The fact that FDA has not made such a
determination does not mean that a substance is GRAS under the
conditions of its intended use.
0
22. Amend Sec. 570.203 by:
0
a. Removing the introductory text;
0
b. Revising the definition of ``GRAS'';
0
c. Revising the definition of ``GRAS notice'';
0
d. Adding the definition of ``Inventory'';
[[Page 51879]]
0
e. Adding the definition of ``No questions letter''; and
0
f. Removing the definition of ``We, our and us''.
The revisions and additions, read as follows:
Sec. 570.203 Definitions.
* * * * *
GRAS means generally recognized as safe (see Sec. 570.3(i)).
GRAS notice means a submission under Sec. 570.205 that informs us
of your view that a substance is not subject to the premarket review
and approval requirements for food additives under section 409 of the
Act based on your conclusion that the substance is GRAS under the
conditions of its intended use in accordance with Sec. 570.30.
Inventory means an online repository where FDA makes public certain
information related to GRAS notices.
No questions letter means a letter from FDA, sent in response to a
GRAS notice, which states that, based on the information you provided,
as well as other information available to FDA, we have no questions at
this time regarding your conclusion that the notified substance is GRAS
under the conditions of its intended use. A no questions letter is
neither an affirmation by FDA that the notified substance is GRAS for
its intended conditions of use under Sec. 570.35, nor a published
finding under section 721(b)(4) of the Act declaring the use of such
substance exempt from the term ``food additive'' because of its being
GRAS.
* * * * *
0
23. Amend Sec. 570.205 by:
0
a. Revising the section heading and removing the existing text; and
0
b . Adding paragraphs (a) through (c).
The revision and additions read as follows:
Sec. 570.205 Submission of a GRAS notice.
(a) Any person introducing a substance into interstate commerce
under the GRAS provision of section 201(s) of the Act must notify FDA
of the basis for their conclusion that the substance is GRAS under the
conditions of its intended use, except as provided under paragraph (b)
of this section.
(b) A GRAS notice is not required when:
(1) A no questions letter covers the substance under the conditions
of its intended use;
(2) The substance is listed or affirmed as GRAS under the
conditions of its intended use in part 582 or 584 of this chapter;
(3) The substance is considered GRAS under the conditions of its
intended use in accordance with Sec. 570.30(d) or (h)(1);
(4) The intended use of the substance has been considered by FDA
through an established FDA process to evaluate the potential presence
of unapproved food additives, and documentation made publicly available
by FDA through that process does not recommend or otherwise identify
the need to submit a GRAS notice;
(5) The intended use of the substance has been the subject of an
established animal food ingredient consultation process with FDA, and a
summary document made publicly available by FDA through the
consultation process indicates FDA has no questions or concerns about
the safety of the substance for the intended use;
(6)
(i) The substance is listed in and used in accordance with the
``Official Common or Usual Names and Definitions of Feed Ingredients''
section of Chapter 6 of the ``Official Publication'' of the Association
of American Feed Control Officials (AAFCO), Inc., 2024 ed., pp. 354-
549, which is incorporated by reference into this section, with the
approval of the Director of the Federal Register under 5 U.S.C. 552(a)
and 1 CFR part 51. This incorporation by reference (IBR) material is
available for inspection at FDA and at the National Archives and
Records Administration (NARA). Contact FDA at: Dockets Management Staff
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, between 9 a.m. and 4 p.m. Monday through Friday;
phone: 240-402-7500; email: [email protected]. For
information on the availability of this material at NARA, visit https://www.archives.gov/federal-register/cfr/ibr-locations.html or email
[email protected]. The material may be obtained from AAFCO, 1800
S. Oak Street, Suite 100, Champaign, IL 61820-6974; phone: 217-356-
4221; website: https://www.aafco.org; and
(ii) The use of the substance is not the subject of a public FDA
statement of concern regarding its GRAS status; or
(7) Information about the conditions of use of the substance has
been submitted in accordance with Sec. 570.305 and the submission is
included on a public list maintained by FDA, unless FDA issues a
determination that a GRAS notice or food additive petition must be
submitted for the intended use of a substance.
(c) Uses of substances that are excluded from the definition of a
food additive in section 201(s)(1) through (6) of the Act cannot be the
subject of a GRAS notice.
0
24. Revise Sec. 570.210 to read as follows:
Sec. 570.210 How to send your GRAS notice to FDA.
Contact the Division of Animal Food Ingredients by email at
[email protected] prior to sending your GRAS notice.
0
25. Amend Sec. 570.220 by adding paragraph (c) to read as follows:
Sec. 570.220 General requirements applicable to a GRAS notice.
* * * * *
(c) Any material submitted in or referenced by a GRAS notice that
is in a foreign language must be accompanied by an accurate and
complete English translation.
0
26. Amend Sec. 570.225 by revising paragraph (c)(6) as follows:
Sec. 570.225 Part 1 of GRAS notice: Signed statements and
certification.
* * * * *
(c) * * *
(6) State your view that the notified substance is not subject to
the premarket review and approval requirements for food additives under
section 409 of the Act based on your conclusion that the notified
substance is GRAS under the conditions of its intended use;
* * * * *
0
27. Amend Sec. 570.250 by revising paragraphs (d) and (e) to read as
follows:
Sec. 570.250 Part 6 of a GRAS notice: Narrative.
* * * * *
(d) If you view any data and information in your notice as exempt
from disclosure under the Freedom of Information Act, you must identify
the specific data and information at the time of submission. If you do
not, we will consider such data and information to not be exempt from
disclosure or that you have waived any claim of confidentiality; and
(e) For any non-public, safety-related data and information
considered in reaching a conclusion of GRAS status that you identify,
under paragraph (d) of this section, as exempt from disclosure under
the Freedom of Information Act, you must explain how there could be a
basis for a conclusion of GRAS status despite the fact that qualified
experts do not have access to such data and information.
0
28. Amend Sec. 570.265 by:
0
a. Revising paragraphs (a)(1) through (3);
0
b. Adding paragraph (a)(5);
0
c. Revising paragraphs (b)(1) and(2); and
0
d. Adding a sentence to the end of paragraph (b)(3).
[[Page 51880]]
The revisions and additions read as follows:
Sec. 570.265 What FDA will do with a GRAS notice.
(a) * * *
(1) Within 45 days of receiving your submission, we will conduct an
initial evaluation to determine whether to file it as a GRAS notice for
evaluation of your view that the notified substance is GRAS under the
conditions of its intended use.
(2) If we file your submission as a GRAS notice, we will send you a
letter within two business days that informs you of the date of filing.
If we file your submission as a GRAS notice, we will consider the
notification requirement of Sec. 570.205 to be met, except as provided
by Sec. 570.265(b)(3).
(3) If we do not file your submission as a GRAS notice, we will
send you a letter within two business days that informs you of that
fact and provides our reasons for not filing the submission as a GRAS
notice.
* * * * *
(5) During our evaluation of a GRAS notice, we may contact you with
questions related to the notice, including the data and information
used to support your GRAS conclusion.
(b) * * *
(1) Within 180 days of filing, we will respond to you by letter
based on our evaluation of your notice. We may extend the 180-day
timeframe by 90 days up to two times on an as needed basis.
(2) If we extend the timeframe, we will inform you in writing of an
initial extension as soon as practicable but no later than within 180
days of filing. If a second extension is needed, we will inform you in
writing as soon as practicable but no later than the end of the initial
90-day extension.
(3) * * * If we cease to evaluate your GRAS notice, we will not
consider the notification requirement of Sec. 570.205 to be met.
* * * * *
0
29. Amend Sec. 570.275 by:
0
a. Revising paragraph (a);
0
b. Revising the introductory text of paragraph (b); and
0
c. Removing paragraph (c).
The revisions read as follows:
Sec. 570.275 Public disclosure of a GRAS notice.
(a) The data and information in a GRAS notice (including data and
information submitted in any amendment or supplement to your GRAS
notice, or incorporated into your GRAS notice) are available for public
disclosure as of the date that we receive your GRAS notice, in
accordance with part 20 of this chapter.
(b) We will make the following readily accessible to the public
through inclusion in the inventory:
* * * * *
0
30. Add subpart F to part 570 to read as follows:
Subpart F--Submissions for Substances Introduced into Interstate
Commerce Under the GRAS Provision of Section 201(s) of the Act
Before [EFFECTIVE DATE OF THE FINAL RULE]
Sec.
570.303 Definitions.
570.305 Option for Submissions for Pre-[EFFECTIVE DATE OF THE FINAL
RULE] Substances.
Sec. 570.303 Definitions.
Cease to evaluate letter means a letter from FDA granting a request
to cease to evaluate a GRAS notice (see Sec. 570.265(b)(3)).
GRAS means generally recognized as safe (see Sec. 570.3(i)).
GRAS notice means a submission under Sec. 570.205 that informs us
of the view that a substance is not subject to the premarket review and
approval requirements for food additives under section 409 of the Act
based on a conclusion that the substance is GRAS under the conditions
of its intended use in accordance with Sec. 570.30.
Insufficient basis letter means a letter from FDA, sent in response
to a GRAS notice, which states that, based on the data and information
provided, as well as other available information, the notice does not
provide a sufficient basis for a conclusion that the notified substance
(as defined in Sec. 570.203) is GRAS under the conditions of its
intended use.
Submitter means the person (e.g., an individual, partnership,
corporation, association, or other legal entity) who is responsible for
the submission under this subpart, even if another person (such as an
attorney, agent, or qualified expert) prepares or submits the
information.
Sec. 570.305 Option for Submissions for Pre-[EFFECTIVE DATE OF THE
FINAL RULE] Substances.
(a) Submissions for pre-[EFFECTIVE DATE OF THE FINAL RULE]
substances. For a substance introduced into interstate commerce before
[EFFECTIVE DATE OF THE FINAL RULE] under the GRAS provision of section
201(s) of the Act, a person may submit information regarding the
substance and its conditions of use in accordance with this subpart
instead of submitting a GRAS notice under Sec. 570.205.
(b) When a submission is not allowed. A submission under this
subpart may not concern any conditions of use of a substance that are
the subject of:
(1) An insufficient basis letter (see Sec. 570.303); or
(2) A determination by FDA that the substance is not GRAS under the
conditions of its intended use.
(c) Parts of a submission and how to submit.
(1) A submission must include the following:
(i) The name and address of the submitter;
(ii) The name of the substance, using an appropriately descriptive
term;
(iii) The intended conditions of use of the substance, including
the target animal species, foods in which the substance is used, the
levels of use in such foods, the purposes for which the substance is
used, and, when the intended use is in food for food-producing animals,
the quantities of any residues that humans may be exposed to in edible
animal tissues;
(iv) Evidence of presence in interstate commerce before [EFFECTIVE
DATE OF THE FINAL RULE]; and
(v) If applicable, where FDA sent a cease to evaluate letter in
response to a submitter's previous GRAS notice (AGRN), provide that
file number (AGRN No.) as part of the submission.
(2) A submission may inform us of the statutory basis for the
conclusion of GRAS status (i.e., through scientific procedures in
accordance with Sec. 570.30(a) and (b) or through experience based on
common use in food in accordance with Sec. 570.30(a) and (c)).
(3) This information must be submitted to Center for Veterinary
Medicine, Food and Drug Administration, by email at [email protected] by [DATE 1 YEAR AFTER EFFECTIVE DATE OF THE FINAL
RULE]. Submissions under this subpart will not be accepted after [DATE
1 YEAR AFTER EFFECTIVE DATE OF THE FINAL RULE].
(d) What FDA will do with a submission.
(1) FDA will post information that meets the requirements for a
submission as specified in Sec. 570.305(c)(1) and (c)(2) in a publicly
available list in accordance with part 20 of this chapter. The posting
of this information does not mean that FDA has reviewed the GRAS status
of the substance's conditions of intended use.
(2) FDA may ask the submitter questions about their submission.
(3) FDA may issue a determination that a GRAS notice or food
additive
[[Page 51881]]
petition must be submitted for the intended use of a substance in
accordance with subpart E of this part or section 409 of the Act. Such
a determination will be made publicly available.
Robert F. Kennedy, Jr.,
Secretary, Department of Health and Human Services.
[FR Doc. 2026-16296 Filed 8-10-26; 11:15 am]
BILLING CODE 4164-01-P