``under the           language in section
                               intended conditions   201(s) ``under the
                               of use'' with         conditions of its
                               ``under the           intended use''
                               conditions of its     rather than
                               intended use''.       variations (such as
                                                     under the intended
                                                     conditions of use).
Sec.   170.3(k).............  Replace ``General     Conforming change.
                               recognition of        See Response 41.
                               safety shall be
                               determined in
                               accordance with
                               170.30'' with
                               ``General
                               recognition of
                               safety shall be in
                               accordance with
                               Sec.   170.30''.
Throughout Sec.   170.30....  Replace ``Sec.        Correction to
                               186.1'' with ``part   clarify that the
                               186''.                provision applies
                                                     to all of part 186,
                                                     not just Sec.
                                                     186.1.
Sec.   170.30(a)............  Replace the proposed  Conforming change to
                               regulatory text       consistently use
                               ``there is            the exact statutory
                               reasonable            language in section
                               certainty that the    201(s) ``under the
                               substance is not      conditions of its
                               harmful under the     intended use''
                               intended conditions   rather than
                               of use'' with         variations (such as
                               ``there is            under the intended
                               reasonable            conditions of use).
                               certainty that the
                               substance is not
                               harmful under the
                               conditions of its
                               intended use''.
Sec.   170.30(b), Sec.        Replace ``General      Clarify
 570.30(b).                    recognition of        that FDA approves a
                               safety based upon     food additive, not
                               scientific            a ``food additive
                               procedures shall      regulation''.
                               require the same      Clarify
                               quantity and          that the same
                               quality of            quantity and
                               scientific evidence   quality of
                               as is required to     scientific evidence
                               obtain approval of    is required
                               a food additive       regardless of
                               regulation for the    whether the
                               ingredient'' with     substance is
                               ``General             intended for use as
                               recognition of        an ``ingredient''.
                               safety based upon
                               scientific
                               procedures shall
                               require the same
                               quantity and
                               quality of
                               scientific evidence
                               as is required to
                               obtain approval of
                               a food additive''.
Sec.   170.30(c)(1), Sec.     Replace ``General      Conforming
 570.30(c)(1).                 recognition of        change. See
                               safety through        Response 41.
                               experience based on   Clarify
                               common use in food    that FDA approves a
                               prior to January 1,   food additive, not
                               1958, may be          a ``food additive
                               determined without    regulation''.
                               the quantity or
                               quality of
                               scientific
                               procedures required
                               for approval of a
                               food additive
                               regulation'' with
                               ``General
                               recognition of
                               safety through
                               experience based on
                               common use in food
                               prior to January 1,
                               1958, may be
                               achieved without
                               the quantity or
                               quality of
                               scientific
                               procedures required
                               for approval of a
                               food additive''.
Sec.   170.30(c)(2).........   Replace       Conforming
                               ``if the              change to
                               information about     consistently use
                               the experience        the exact statutory
                               establishes that      language in section
                               the use of the        201(s) ``under the
                               substance is safe     conditions of its
                               within the meaning    intended use''
                               of the act (see       rather than
                               Sec.   170.3(i))''    variations (such as
                               with ``if the         ``the use of the
                               information about     substance'').
                               the experience        Clarify
                               establishes that      that the applicable
                               the substance is      section of the FD&C
                               safe under the        Act is section
                               conditions of its     201(u). Section
                               intended use within   170.3(i) is in our
                               the meaning of        regulations, not in
                               section 201(u) of     the FD&C Act.
                               the Federal Food,     Editorial
                               Drug, and Cosmetic    change to include
                               Act (see also Sec.    the full name of
                                170.3(i))''.         the statute.
                               Replace       Editorial
                               ``in this country''   change to be
                               with ``in the         specific that
                               United States''.      ``this country''
                                                     means ``the United
                                                     States''.
170.30(c)(2), 170.38(a),      Replace ``the act''   Editorial. It is now
 570.38(a).                    with ``the Federal    our practice to
                               Food, Drug, and       include the full
                               Cosmetic Act'' in     name of this
                               any provision that    statute when we
                               we otherwise          refer to it.
                               revised.
Sec.   170.30(e)............   Replace       See
                               ``Beginning in        Response 41.
                               1969, the Food and    Include
                               Drug Administration   statutory language
                               has undertaken a      from section 201(s)
                               systematic review     of the FD&C Act to
                               of the status of      clarify that GRAS
                               all ingredients       status applies to
                               used in food on the   the intended
                               determination that    conditions of use
                               they are GRAS or      of a substance, not
                               subject to a prior    the substance
                               sanction'' with       itself.
                               ``Beginning in        Clarify
                               1969, the Food and    that GRAS status
                               Drug Administration   pursuant to parts
                               has undertaken a      184 and 186 is
                               systematic review     affirmed by FDA.
                               of the status of
                               all ingredients
                               used in food based
                               on the view that
                               they are GRAS under
                               the conditions of
                               their intended use
                               or subject to a
                               prior sanction''.
                               Replace
                               ``All
                               determinations of
                               GRAS status or food
                               additive status or
                               prior sanction
                               status pursuant to
                               this review shall
                               be handled pursuant
                               to Sec.  Sec.
                               170.35, 170.38, and
                               180.1 of this
                               chapter.
                               Affirmation of GRAS
                               status shall be
                               announced in part
                               184 or Sec.   186.1
                               of this chapter''
                               with ``All
                               affirmations of
                               GRAS status or
                               determinations of
                               food additive
                               status or prior
                               sanction status
                               pursuant to this
                               review shall be
                               handled pursuant to
                               Sec.  Sec.
                               170.35, 170.38, and
                               180.1 of this
                               chapter.
                               Affirmation of GRAS
                               status shall be
                               announced in part
                               184 or part 186 of
                               this chapter''.

Sec.   170.30(l)............  Replace ``Any change  Clarify the
                               in part 182, part     applicability of
                               184, or Sec.          the requirement.
                               186.1 of this
                               chapter shall be
                               accomplished
                               pursuant to Sec.
                               170.38'' with ``Any
                               change to the GRAS
                               status of a food
                               ingredient in part
                               182, part 184, or
                               part 186 of this
                               chapter shall be
                               accomplished
                               pursuant to Sec.
                               170.38''.
Sec.   170.35(a), Sec.        Replace ``may affirm   Editorial
 570.35(a).                    the GRAS status of    change to use the
                               substances'' with     singular.
                               ``may affirm that a   Include
                               substance that        statutory language
                               directly or           from section 201(s)
                               indirectly becomes    of the FD&C Act to
                               a component of food   clarify that GRAS
                               is GRAS under the     affirmation applies
                               conditions of its     to the intended
                               intended use''.       conditions of use
                                                     of a substance, not
                                                     the substance
                                                     itself.
Sec.   170.35(b)(1), Sec.     Replace ``If the      Include statutory
 570.35(b)(1).                 Commissioner          language from
                               proposes on his own   section 201(s) of
                               initiative that a     the FD&C Act to
                               substance is          clarify that GRAS
                               entitled to           affirmation applies
                               affirmation as        to the intended
                               GRAS'' with ``If      conditions of use
                               the Commissioner      of a substance, not
                               proposes on his own   the substance
                               initiative that a     itself.
                               substance is
                               entitled to
                               affirmation as GRAS
                               under the
                               conditions of its
                               intended use''.
Sec.   170.35(b)(3), Sec.      Replace       Include
 570.35(b)(3).                 ``convincing          statutory language
                               evidence that the     from section 201(s)
                               substance is GRAS''   of the FD&C Act to
                               with ``convincing     clarify that GRAS
                               evidence that the     affirmation applies
                               substance is GRAS     to the intended
                               under the             conditions of use
                               conditions of its     of a substance, not
                               intended use''.       the substance
                               Replace       itself.
                               ``listing the         Deleted
                               substance as GRAS     reference to parts
                               in part 182, part     182 and 582. If FDA
                               184, or part 186 of   affirms GRAS
                               this chapter'' with   status, the
                               ``listing the GRAS    affirmation
                               conditions of use     regulation would
                               of the substance in   appear in part 184
                               part 184 or part      or 186.
                               186 of this
                               chapter''.
Sec.   170.35(b)(4), Sec.     Replace ``there is a  Include statutory
 570.35(b)(4).                 lack of convincing    language from
                               evidence that the     section 201(s) of
                               substance is GRAS''   the FD&C Act to
                               with ``there is a     clarify that GRAS
                               lack of convincing    affirmation applies
                               evidence that the     to the intended
                               substance is GRAS     conditions of use
                               under the             of a substance, not
                               conditions of its     the substance
                               intended use''.       itself.
Sec.   170.38(a), Sec.         Replace       See
 570.38(a).                    ``may, in             Response 41.
                               accordance with       Conforming
                               Sec.   170.35(b)(4)   change in light of
                               or (c)(5), publish    the deletion of the
                               a notice in the       GRAS affirmation
                               Federal Register      petition process.
                               determining that a    Include
                               substance is not      statutory language
                               GRAS'' with ``may,    from section 201(s)
                               in accordance with    of the FD&C Act to
                               Sec.                  clarify that GRAS
                               170.35(b)(4),         affirmation applies
                               publish a notice in   to the intended
                               the Federal           conditions of use
                               Register              of a substance, not
                               determining that a    the substance
                               substance is not      itself.
                               GRAS under the
                               conditions of its
                               intended use''.
                               Replace
                               ``may, in
                               accordance with
                               Sec.   570.35(b)(4)
                               or (c)(5), publish
                               a notice in the
                               Federal Register
                               determining that a
                               substance is not
                               GRAS'' with ``may,
                               in accordance with
                               Sec.
                               570.35(b)(4),
                               publish a notice in
                               the Federal
                               Register
                               determining that a
                               substance is not
                               GRAS under the
                               conditions of its
                               intended use''.
 Throughout part      Replace variations    Editorial change.
 170, subpart E.               of ``data or other    Although data is a
 Throughout part       information'' with    type of
 570, subpart E.               ``data and            ``information,'' it
                               information''.        is simpler and
                                                     clearer to say
                                                     ``data and
                                                     information.''
 Throughout part      Replace variations    See Response 41.
 170, subpart E.               of ``determine''
 Throughout part       and
 570, subpart E.               ``determination''
                               with ``conclude''
                               and ``conclusion''.
 Throughout part       Replace      See Response 42.
 170, subpart E.               ``exempt'' with
 Throughout part       ``not subject to:.
 570, subpart E.               Replace
                               ``claim'' with
                               ``view''.
Sec.   170.203, Sec.          In the definition of  Clarification by
 570.203.                      ``notifier,'' add a   including text from
                               parenthetical with    the definition of
                               examples of what we   ``person'' in Sec.
                               mean by ``person''     10.3.
                               (e.g., an
                               individual,
                               partnership,
                               corporation,
                               association, or
                               other legal entity).
Sec.   170.225(c)(4)........  Replace the proposed  Clarifying change to
                               phrase ``applicable   use the statutory
                               conditions of use''   term ``intended''
                               with ``intended       in place of
                               conditions of use''.  ``applicable''.
Sec.   184.1(a).............  Replace ``The direct  Clarify that the
                               human food            GRAS status of the
                               ingredients listed    uses of substances
                               in this part have     listed in part 184
                               been reviewed by      has been affirmed
                               the Food and Drug     by FDA, either on
                               Administration and    FDA's initiative or
                               determined to be      in response to a
                               generally             GRAS affirmation
                               recognized as safe    petition.
                               (GRAS) for the
                               purposes and
                               conditions
                               prescribed'' with
                               ``The direct human
                               food ingredients
                               listed in this part
                               have been reviewed
                               by the Food and
                               Drug Administration
                               and affirmed to be
                               generally
                               recognized as safe
                               (GRAS) for the
                               purposes and under
                               the conditions
                               prescribed''.

Sec.   184.1(b)(1)..........   Replace       Conforming
                               ``shall               change to reflect
                               independently         ``conclusions'' of
                               establish'' with      GRAS status.
                               ``shall have a        Conforming
                               basis to conclude''.  change in light of
                               Remove the    the deletion of the
                               last sentence,        GRAS affirmation
                               i.e., ``Persons       petition process.
                               seeking FDA
                               approval of an
                               independent
                               determination that
                               a use of an
                               ingredient is GRAS
                               may submit a GRAS
                               petition in
                               accordance with
                               170.35 of this
                               chapter.''.
Sec.   186.1(a).............  Replace ``The         Clarify that the
                               indirect human food   GRAS status of the
                               ingredients listed    uses of substances
                               in this part have     listed in part 186
                               been reviewed by      has been affirmed
                               the Food and Drug     by FDA, either on
                               Administration and    FDA's initiative or
                               determined to be      in response to a
                               generally             GRAS affirmation
                               recognized as safe    petition.
                               (GRAS)'' with ``The
                               indirect human food
                               ingredients listed
                               in this part have
                               been reviewed by
                               the Food and Drug
                               Administration and
                               affirmed to be
                               generally
                               recognized as safe
                               (GRAS)''.
Sec.   186.1(b)(1)..........   Replace      Conforming change in
                               ``shall               light of the
                               independently         deletion of the
                               establish'' with      GRAS affirmation
                               ``shall have a        petition process.
                               basis to conclude''.
                               Remove the
                               last sentence,
                               i.e., ``Persons
                               seeking FDA
                               approval of an
                               independent
                               determination that
                               a use of an
                               ingredient is GRAS
                               may submit a GRAS
                               petition in
                               accordance with
                               170.35 of this
                               chapter.''.
Sec.   570.3(f).............   Add ``of     Changes to
                               the species to        Conform
                               which the substance   with revisions to
                               is intended to be     Sec.   570.30(a)
                               fed'' in describing   and (c)
                               the animals           Conform
                               consuming the         with the
                               substance.            corresponding
                               Delete ``in   definition for
                               the United States''.  human food in Sec.
                               Add ``(and,    170.3(f), which
                               for food-producing    does not specify
                               animals fed with      ``in the United
                               such substance,       States.''
                               also means a          Clarify
                               substantial history   that substantial
                               of consumption by     history of
                               humans consuming      consumption should
                               human foods derived   be demonstrated by
                               from those food-      the same animal
                               producing animals)    species as the
                               prior to January 1,   species intended to
                               1958.                 be fed to conform
                                                     with the submission
                                                     requirements in
                                                     part 5 of a GRAS
                                                     notice when the
                                                     basis for the
                                                     conclusion of GRAS
                                                     status is through
                                                     experience based on
                                                     common use in food
                                                     (Sec.   570.245).
                                                     Clarify
                                                     that substantial
                                                     history of
                                                     consumption for
                                                     food-producing
                                                     animals also should
                                                     be demonstrated by
                                                     a substantial
                                                     history of
                                                     consumption by
                                                     humans consuming
                                                     human foods derived
                                                     from those food-
                                                     producing animals
                                                     prior to January 1,
                                                     1958 to conform
                                                     with the submission
                                                     requirements in
                                                     part 5 of a GRAS
                                                     notice.
Sec.   570.3(k).............  Replace ``General     Conforming change.
                               recognition of        The GRAS
                               safety shall be       notification
                               determined in         procedure does not
                               accordance with       use the term
                               Sec.   570.30''       ``determine.''
                               with ``General
                               recognition of
                               safety shall be in
                               accordance with
                               Sec.   570.30''.
Sec.   570.3................  Define ``food-        Clarify the meaning
                               producing animal''    of this term for
                               to mean an animal     the purpose of part
                               used to produce       570, subpart E in
                               human food.           light of provisions
                                                     that address the
                                                     safety of a
                                                     substance for
                                                     humans consuming
                                                     human food derived
                                                     from an animal used
                                                     to produce human
                                                     food.
Sec.   570.30(c)............  Replace ``General      Conforming
                               recognition of        change. The GRAS
                               safety through        notification
                               experience based on   procedure does not
                               common use in food    use the term
                               prior to January 1,   ``determine.''
                               1958, may be          Clarify
                               determined without    that FDA approves a
                               the quantity or       food additive, not
                               quality of            a ``food additive
                               scientific            regulation''.
                               procedures required
                               for approval of a
                               food additive
                               regulation'' with
                               ``General
                               recognition of
                               safety through
                               experience based on
                               common use in food
                               prior to January 1,
                               1958, may be
                               achieved without
                               the quantity or
                               quality of
                               scientific
                               procedures required
                               for approval of a
                               food additive''.
Sec.   570.30(d)............   Replace      Clarify that the
                               ``ingredients         provisions apply
                               listed as GRAS in     regardless of
                               part 582 of this      whether an
                               chapter'' with        ingredient is
                               ``ingredients         listed as GRAS in
                               listed as GRAS in     part 582 or
                               part 582 of this      affirmed as GRAS in
                               chapter or affirmed   part 584.
                               as GRAS in part 584
                               of this chapter''.
                               Replace
                               ``without specific
                               inclusion in part
                               582 of this
                               chapter'' with
                               ``without specific
                               inclusion in part
                               582 or part 584 of
                               this chapter''.
Sec.   570.30(i)............  Replace ``Any use of  Editorial correction
                               such and              of ``and'' to
                               ingredient'' with     ``an''.
                               ``Any use of such
                               an ingredient''.
570.225(c)(4),                Replace ``food''      Clarification for
 570.225(c)(5), 570.230(c),    with ``animal         part 570.
 570.235, 570.240, 570.245.    food''.
------------------------------------------------------------------------

XXVII. Economic Analysis of Impacts

    We have examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, 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 costs
and benefits of available regulatory alternatives and, when regulation
is necessary, to select regulatory approaches that maximize net
benefits (including potential economic, environmental, public health
and safety, and other advantages; distributive impacts; and equity). We
have developed a comprehensive Economic Analysis of Impacts that
assesses the impacts of the final rule. We believe that this final rule
is not a significant regulatory action as defined by Executive Order
12866.
    The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. The final rule replaces the voluntary GRAS affirmation
petition process with a voluntary GRAS notification procedure. Similar
to the petition process, we expect that profit-maximizing firms will
only submit the GRAS notice when the private benefits equal or exceed
the costs of the GRAS notice, regardless of the size of the firm.
Because small firms face the same voluntary business decision as large
firms, we certify that the final rule will not 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 an assessment of
anticipated costs and benefits, before issuing ``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 $146
million, using the most current (2015) Implicit Price Deflator for the
Gross Domestic Product. This final rule will not result in an
expenditure in any year that meets or exceeds this amount.
    The final rule will eliminate the petition process to affirm a
substance is GRAS and replace the petition process with a GRAS
notification procedure. The level of effort required by a firm to reach
a conclusion that a substance is GRAS for its intended use remains
unchanged by the final rule. However, the rule will require that firms
submit some additional information to support their conclusion with
their notices. Although uncertain, we estimate that notifiers will
spend between 5 more hours and 20 more hours to prepare and submit each
notice. We estimate that this will cost notifiers less than $0.1
million each year.
    For all affected notifiers, we expect that they will spend time
reading and understanding the requirements of the final rule and
revising standard operating procedures for preparing and submitting
GRAS notices. We estimate that it will take from 20 hours to 80 hours
for notifiers to perform this action. Firms with outstanding GRAS
affirmation petitions may choose to submit GRAS notices and incorporate
the information included in their petition. To account for the
additional effort by these firms, we include the one-time cost to
prepare and submit a GRAS notice for all outstanding petitions. We
estimate that notifiers will spend between 170 and 190 hours to submit
GRAS notices for each outstanding petition. The total one-time costs of
the final rule range from $0.8 million to $2.7 million.
    We estimate that over 10 years with a 7 percent discount rate, the
present value of the total costs of the final rule range from $0.9
million to $3.3 million; with a 3 percent discount rate, the present
value of the total costs range from $0.9 million to $3.4 million. The
annualized costs of the rule range from $0.1 million to $0.4 million
with a 7 percent discount rate and range from $0.1 million to $0.5
million with a 3 percent discount rate.
    We do not quantify the benefits of the final rule. However, based
on the differences in review time between the GRAS petition process and
the GRAS notification procedure, we anticipate that industry will
benefit from the more speedy notification procedure. For example, we
have filed more than 600 GRAS notices for human food substances since
1998. During this time, it took an average of 200 days for us to
respond to 588 GRAS notices; it took an average of 7.9 years to
complete 24 previous GRAS affirmation petitions. We began to accept
GRAS notices for animal food substances in 2010 and we have filed 18
GRAS notices for animal food substances since that time. It took an
average of 294 days for us to respond to 12 GRAS notices with a ``no
questions letter'' or ``insufficient basis letter''; it took an average
of 4.9 years to respond to the three previous GRAS affirmation
petitions. With the GRAS notification procedure, we can complete our
evaluation within the timelines specified in the final rule.
    The Economic Analysis of Impacts of the final rule performed in
accordance with Executive Order 12866, Executive Order 13563, the
Regulatory Flexibility Act, and the Unfunded Mandates Reform Act (Ref.
51) is available at http://www.regulations.gov under the docket number
for this final rule and at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm.

XXVIII. Analysis of Environmental Impact

    We have carefully considered the potential environmental effects of
this action. We have concluded 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.

XXIX. Paperwork Reduction Act of 1995

    This final rule contains information collection provisions that are
subject to review by OMB under the PRA (44 U.S.C. 3501-3520). The
title, description, and respondent description of the information
collection provisions are shown in the following paragraphs with an
estimate of the one-time and annual reporting burdens. 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.
    Title: Substances Generally Recognized as Safe Notification
Procedure (21 CFR parts 170 and 570) (OMB Control No. 0910-0342)--
Revision.
    Description: The FD&C Act requires that all food additives (as
defined by section 201(s)) be approved by FDA before they are marketed
(sections 402(a)(2)(C) and 409 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 prior to 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.'' This final rule amends our regulations in parts
170 and 570 and revises the information collection provisions regarding
the notification procedures for GRAS substances. The

regulations implement the GRAS provision of section 201(s) of the FD&C
Act in part 170 and part 570 for human food and animal food,
respectively.
    Description of Respondents: Respondents to the collection of
information are manufacturers of substances used in human food and
animal food. We estimate there are 480 such respondents. As estimated
in the Final Regulatory Impact Analysis (Ref. 51), approximately 340 to
460 notifiers (for human food) and approximately 10 to 20 notifiers
(for animal food) will be affected by the final rule. The Final
Regulatory Impact Analysis reflects an overall increase in respondents
to the program and we have therefore adjusted our respondent numbers
accordingly.
    As discussed in section II.B of the preamble to this final rule,
previously manufacturers were invited to submit notices of their
independent GRAS determinations for review under the framework of the
proposed rule during the period between issuance of the proposed rule
and any final rule based on the proposed rule. The proposed regulations
provided a standard format for the voluntary submission of a notice. To
date, the GRAS program has been administered under these proposed
procedures. Comments regarding the information collection topics
solicited in the proposed rule and subsequent 2010 notice are discussed
in the preamble in sections IV, VII, and X through XVIII. While none of
the comments suggested we modify the estimated annual burden associated
with the information collection, we have revised the underlying
notification procedures and, consequently, have revised the underlying
information collection provisions consistent with the final rule.
    Specifically the final rule establishes a voluntary administrative
procedure for notifying FDA about a conclusion that a substance is GRAS
under the conditions of its intended use in human food or animal food.
The final rule explains that a GRAS notice must include the following
seven parts:

   Table 30--Information To Be Included in Each Part of a GRAS Notice
------------------------------------------------------------------------
             Part No.                    Information to be included
------------------------------------------------------------------------
Part 1............................  Signed statements and a
                                     certification.
Part 2............................  The identity, method of manufacture,
                                     specifications, and physical or
                                     technical effect of the notified
                                     substance.
Part 3............................  Dietary exposure to the notified
                                     substance.
Part 4............................  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.
Part 5............................  The 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.
Part 6............................  A narrative that provides the basis
                                     for the notifier's conclusion of
                                     GRAS status, including why the
                                     scientific 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.
Part 7............................  A list of the generally available
                                     data, information, and methods the
                                     notifier cites in the GRAS notice.
------------------------------------------------------------------------

    The information submitted to us in a GRAS notice is necessary to
allow us to administer efficiently the FD&C Act's various provisions
that apply to the use of substances added to food, specifically with
regard to whether a substance is GRAS under the conditions of its
intended use or is a food additive subject to premarket review. We will
use the information collected through the GRAS notification procedure
to complete our evaluation within the timelines specified in the final
rule.
One-Time Reporting Burden
    Table 31 shows the estimated one-time reporting burden associated
with the final rule. We expect that all respondents to the information
collection will spend time reading and understanding the requirements
of the final rule and revising standard operating procedures for
preparing and submitting GRAS notices. As noted, we estimate that
approximately 340 to 460 notifiers (for human food) and approximately
10 to 20 notifiers (for animal food) will be affected by the final
rule. We use the upper-bound estimates of 460 and 20 respondents as
shown in rows 1 and 2. We estimate that it will take from 20 to 80
hours for respondents to perform this action. We use the upper-bound
estimate of 80 hours as shown in rows 1 and 2. Of the 480 affected
respondents, some will have outstanding GRAS petitions. Firms with
outstanding GRAS petitions regarding substances intended for use in
human food may choose to submit GRAS notices and incorporate the
information included in their petition. As estimated in the Final
Regulatory Impact Analysis (Ref. 51), up to 45 petitions (for human
food) will be submitted as GRAS notices and incorporated. We use the
upper-bound estimate of 45 as shown in row 3. To account for the
additional effort by these firms, we include the one-time burden to
prepare and submit a GRAS notice for all outstanding petitions. Because
there are no outstanding GRAS petitions regarding substances intended
for use in animal food, we do not account for any burden for the
submission of a GRAS notice that incorporates a GRAS petition regarding
a substance intended for use in animal food. We estimate that
respondents will spend between 170 and 190 hours to submit GRAS notices
for each outstanding petition and have used, therefore, an average
estimate of 185 hours as shown in row 3.

                                Table 31--Estimated One-Time Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
     Activity/21 CFR section         Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
Notifier's review of final rule              460               1             460              80          36,800
 and revision of procedures for
 preparing and submitting GRAS
 notices for human food, 170.210
 through 170.270................
Notifier's review of final rule               20               1              20              80           1,600
 and revision of procedures for
 preparing and submitting GRAS
 notices for animal food,
 570.210 through 570.270........
Prepare and submit GRAS notice                45               1              45             185           8,325
 for an outstanding GRAS
 petition, 170.285..............
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          46,725
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

Recurring Reporting Burden

    Table 32 shows the estimated recurring annual reporting burden
associated with the final rule. As previously discussed, the final rule
replaces the petition process with a GRAS notification procedure. The
level of effort required by a firm to reach a conclusion that a
substance is GRAS for its intended use remains unchanged by the final
rule. However, the final rule requires that firms submit some
additional information to support the conclusions found within their
notices. The additional information might include an amendment
(Sec. Sec.  170.260 and 570.260); a supplement (Sec. Sec.  170.280 and
570.280); a request for FDA to cease to evaluate a GRAS notice
(Sec. Sec.  170.260 and 570.260); an incorporation into a GRAS notice
(Sec. Sec.  170.215 and 570.215); and, information required when the
intended conditions of use of a notified substance includes use in a
product subject to regulation by FSIS, including authorization to us to
share any trade secrets with FSIS (Sec.  170.270). Because the amount
of additional information may vary, we estimate that respondents will
spend between 155 and 170 hours to prepare and submit each notice.
Using the upper-bound figure of 170 hours, we therefore estimate that
the 50 notifiers for human food and 25 notifiers for animal food will
expend 12,750 hours annually as shown, respectively, in rows 1 and 2.

                                 Table 32--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of
     Activity/21 CFR section         Number of     responses per   Total annual   Average burden    Total hours
                                    respondents     respondent       responses     per response
----------------------------------------------------------------------------------------------------------------
GRAS notification procedure for               50               1              50             170           8,500
 human food, 170.210 through
 170.270........................
GRAS notification procedure for               25               1              25             170           4,250
 animal food, 570.210 through
 570.270........................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          12,750
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

Recordkeeping
    The final rule does not contain recordkeeping requirements. We
believe that documentation used by respondents in support of a
conclusion of GRAS status is information that is collected and retained
as a part of usual and customary business practices for a firm engaged
in the manufacture of substances used in human food and animal food. We
have, therefore, not provided an estimate for these activities (5 CFR
1320.3(b)(2)).
    This final rule also refers to other currently approved collections
of information found in our regulations. These collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR 25.32(i) are approved under OMB control number
0910-0541. The collections of information in 21 CFR 10.33 are approved
under OMB control number 0910-0191.
    The information collection provisions of this final rule have been
submitted to OMB for review as required by section 3507(d) of the PRA.
Before the effective date of this final rule, FDA will publish a notice
in the Federal Register announcing OMB's decision to approve, modify,
or disapprove the information collection provisions in this final rule.
An Agency may not conduct or sponsor, and a person is not required to
respond to, a collection of information unless it displays a currently
valid OMB control number.

XXX. Federalism

    We have analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has determined that the 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 have concluded 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.

XXXI. References

    The following references are on display in the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 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 http://

www.regulations.gov. FDA has verified the Web site addresses, as of the
date this document publishes in the Federal Register, but Web sites are
subject to change over time.

1. House Report No. 2284, July 28, 1958. See Reference 1 to the
proposed rule.
2. 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. See Reference 2 to the
proposed rule.
3. New York Times, p. 22, October 31, 1969. See Reference 3 to the
proposed rule.
4. United States Government Accountability Office, ``Report to
Congressional Requestors on Food Safety: FDA Should Strengthen Its
Oversight of Food Ingredients Determined to Be Generally Recognized
as Safe (GRAS),'' Report No. GAO-10-246, (http://www.gao.gov/new.items/d10246.pdf), February 2010. Accessed and printed on May 3,
2010. See Reference 2 to the 2010 notice.
5. FDA, ``Draft Guidance for Industry: Assessing the Effects of
Significant Manufacturing Process Changes, Including Emerging
Technologies, on the Safety and Regulatory Status of Food
Ingredients and Food Contact Substances, Including Food Ingredients
that Are Color Additives,'' (http://www.regulations.gov in Docket
No. FDA-2011-D-0490), 2012. Accessed and printed on February 19,
2016.
6. FDA, ``Guidance for Industry: Assessing the Effects of
Significant Manufacturing Process Changes, Including Emerging
Technologies, on the Safety and Regulatory Status of Food
Ingredients and Food Contact Substances, Including Food Ingredients
that Are Color Additives,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm300661.htm), 2014. Accessed and printed on January 15, 2016.
7. FDA, ``Draft Guidance for Industry: Considering Whether an FDA-
Regulated Product Involves the Application of Nanotechnology,''
(http://www.regulations.gov in Docket No. FDA-2010-D-0530), 2011.
Accessed and printed on February 19, 2016.
8. FDA, ``Guidance for Industry: Considering Whether an FDA-
Regulated Product Involves the Application of Nanotechnology,''
(http://www.fda.gov/RegulatoryInformation/Guidances/ucm257698.htm),
2014. Accessed and printed on January 15, 2016.
9. The Pew Charitable Trusts, ``Fixing the Oversight of Chemicals
Added to Our Food,'' (http://www.pewtrusts.org/~/media/legacy/
uploadedfiles/phg/content_level_pages/reports/
foodadditivescapstonereportpdf.pdf), 2013. Accessed and printed on
February 19, 2016.
10. Letter dated November 17, 2010, from Joann M. Givens of FDA to
Mr. Tim Baggs, Charge Beverages Corporation, (http://www.fda.gov/iceci/enforcementactions/warningletters/2010/ucm233990.htm).
Accessed and printed on January 31, 2016.
11. Letter dated November 17, 2010, from Joann M. Givens of FDA to
Rhonda Kallman of New Century Brewing Company, (http://www.fda.gov/iceci/enforcementactions/warningletters/2010/ucm234028.htm).
Accessed and printed on January 31, 2016.
12. Letter dated November 17, 2010, from Joann M. Givens of FDA to
Jaisen Freeman, Chris Hunter, and Jeff Wright of Phusion Projects,
(http://www.fda.gov/iceci/enforcementactions/warningletters/2010/ucm234023.htm). Accessed and printed on January 31, 2016.
13. Letter dated November 17, 2010, from Joann M. Givens of FDA to
Michael Michail of United Brands Company, (http://www.fda.gov/iceci/enforcementactions/warningletters/2010/ucm234002.htm). Accessed and
printed on January 31, 2016.
14. TTB, Industry Circular 2010-8, (http://www.ttb.gov/industry_circulars/archives/2010/10-08.html), 2010. Accessed and
printed on January 21, 2016.
15. The National Academies of Sciences, Health and Medicine
Division, ``Caffeine in Food and Dietary Supplements: Examining
Safety--Workshop Summary,'' (http://www.nationalacademies.org/hmd/Reports/2014/Caffeine-in-Food-and-Dietary-Supplements-Examining-Safety.aspx), 2014. Accessed and printed on May 27, 2016.
16. Memorandum of Meeting Held on December 11, 2014, between
Representatives of FDA and Representatives of the Caffeine Technical
Working Group on the American Beverage Association (ABA) Caffeine
Technical Working Group (CTWG) Research Plans.
17. International Life Sciences Institute (ILSI North America),
``Caffeine Working Group,'' (http://ilsina.org/our-work/food-safety/caffeine/), 2015. Accessed and printed on June 8, 2016.
18. Experience With GRAS Notices Under the 1997 Proposed Rule,
Memorandum Dated November 4, 2010, from Linda S. Kahl of FDA to
Docket No. FDA-1997-N-0020. See Reference 1 to the 2010 notice.
19. ``Substances that Are Generally Recognized as Safe (GRAS);
Updated Experience With GRAS Notices,'' Memorandum Dated June 1,
2016, from Paulette M. Gaynor of FDA to Docket No. FDA-1997-N-0020.
20. ``Experience With GRAS Notices Under CVM's Interim Pilot
Program,'' Memorandum Dated June 10, 2016, from David Edwards of FDA
to Docket No. FDA-1997-N-0020.
21. Memorandum for the Heads of Executive Departments and Agencies,
Dated June 1, 1998, Signed by President William J. Clinton, (http://www.plainlanguage.gov/whatisPL/govmandates/memo.cfm). Accessed and
printed on July 14, 2008. See Reference 3 to the 2010 notice.
22. eRulemaking Program, ``Improving Electronic Dockets on
Regulations.gov and the Federal Docket Management System: Best
Practices for Federal Agencies,'' (http://www.regulations.gov/docs/FactSheet_eRulemaking_Best_Practices.pdf), 2010. Accessed and
printed on January 15, 2016.
23. Dictionary.com. Dictionary.com Unabridged. Random House, Inc.
(http://dictionary.reference.com/browse/corroborate), 2016. Accessed
and printed on February 23, 2016.
24. Food and Agriculture Organization of the United Nations and the
World Health Organization, ``Chapter 6, Dietary Exposure Assessment
of Chemicals in Food'' in Environmental Health Criteria 240.
Principles and Methods for the Risk Assessment of Chemicals in Food,
(http://apps.who.int/iris/bitstream/10665/44065/9/WHO_EHC_240_9_eng_Chapter6.pdf), 2009. Accessed and printed on
February 13, 2006.
25. FDA, ``Guidance for Industry: Estimating Dietary Intake of
Substances in Food,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm074725.htm), 2006.
Accessed and printed on January 15, 2016.
26. Renwick, A.G., ``The Use of a Sweetener Substitution Method to
Predict Dietary Exposures for the Intense Sweetener Rebaudioside
A.,'' Food and Chemical Toxicology, 46:S61-S69, 2008.
27. Mitchell, D.C., C.A. Knight, J. Hockenberry, et al., ``Beverage
Caffeine Intakes in the U.S.,'' Food and Chemical Toxicology,
63:136-142, 2014.
28. Fulgoni, V.L., D.R. Keast, and H.R. Lieberman, ``Trends in
Intake and Sources of Caffeine in the Diets of US Adults: 2001-
2010,'' The American Journal of Clinical Nutrition, 101:1081-1087,
2015.
29. Branum, A.M., L.M. Rossen, and K.C. Schoendorf, ``Trends in
Caffeine Intake Among U.S. Children and Adolescents,'' Pediatrics,
133(3):386-393, 2014.
30. Food and Agriculture Organization and World Health Organization,
``Joint FAO/WHO Expert Consultation on Biotechnology and Food
Safety,'' (ftp://ftp.fao.org/es/esn/food/biotechnology.pdf), 1996.
See Reference 6 to the proposed rule.
31. FDA, ``Guidance for Industry: Recommendations for Submission of
Chemical and Technological Data for Direct Food Additive
Petitions,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm124917.htm), 2009.
Accessed and printed on January 15, 2016.
32. FDA, ``Guidance for Industry: Microbiological Considerations for
Antimicrobial Food Additive Submissions,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm230417.htm), 2008. Accessed and printed on January 15, 2016.
33. FDA, ``Guidance for Industry: Enzyme Preparations:
Recommendations for Submission of Chemical and Technological Data
for Food Additive

Petitions and GRAS Notices,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm217685.htm), 2010. Accessed and
printed on January 15, 2016.
34. FDA, ``Guidance for Industry: Summary Table of Recommended
Toxicological Testing for Additives Used in Food,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ucm054658.htm), 2006.
Accessed and printed on January 15, 2016.
35. FDA, ``Guidance for Industry and Other Stakeholders:
Toxicological Principles for the Safety Assessment of Food
Ingredients. Redbook 2000,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm2006826.htm), 2007. Accessed
and printed on January 15, 2016.
36. 225-00-2000 ``Amendment 1: Memorandum of Understanding Between
the United States Department of Agriculture Food Safety Inspection
Service and the United States Department of Health and Human
Services Food and Drug Administration, (http://www.fda.gov/AboutFDA/PartnershipsCollaborations/MemorandaofUnderstandingMOUs/DomesticMOUs/ucm441552.htm), 2000. Accessed and printed on November
25, 2015.
37. FDA, ``Guidance for Industry: Providing Regulatory Submissions
in Electronic or Paper Format to the Office of Food Additive Safety;
Draft Guidance,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm2021277.htm), 2010. Accessed
and printed on January 15, 2016.
38. Form FDA 3667. ``Generally Recognized As Safe (GRAS) Notice,''
(http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM350015.pdf), 2016. Accessed and printed on June 1, 2016.
39. Form FDA 3480. ``Food Contact Substance: Notification for New
Use, Pre-Notification Consultation, Food Master File'', (http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM076880.pdf), 2016. Accessed and printed on June 1, 2016.
40. Form FDA 3537. ``DHHS/FDA Food Facility Registration,'' (http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/forms/ucm071977.pdf), 2014. Accessed and printed on January 15, 2016.
41. FSIS, ``Contact Us,'' (http://www.fsis.usda.gov/wps/portal/informational/contactus). Accessed and printed on January 28, 2016.
42. Pariza, M.W. and M. Cook, ``Determining the Safety of Enzymes
Used in Animal Feed,'' Regulatory Toxicology and Pharmacology,
56:332-342, 2010.
43. Olempska-Beer Z.S., R.I Merker, M.D. Ditto, and M.J. DiNovi,
``Food-Processing Enzymes From Recombinant Microorganisms--A
Review,'' Regulatory Toxicology and Pharmacology, 45(2):144-158,
2006.
44. ``Guidance for Industry: Use of Nanomaterials in Food for
Animals (# 220),'' (http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM401508.pdf),
2015. Accessed and printed on January 15, 2016.
45. ``GRAS Notices, Search Results, Common Use in Food,'' 2016.
46. GRAS Notice Inventory, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm),
2016. Accessed and printed on January 15, 2016.
47. Current Animal Food GRAS Notices Inventory, (http://www.fda.gov/AnimalVeterinary/Products/AnimalFoodFeeds/GenerallyRecognizedasSafeGRASNotifications/ucm243845.htm), 2016.
Accessed and printed on February 23, 2016.
48. FDA, List of Pending GRAS Affirmation Petitions as of December
31, 2015.
49. FDA, ``Guidance for Industry: Frequently Asked Questions About
GRAS,'' (http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGRASPackaging/ucm061846.htm), 2004. Accessed and
printed on October 13, 2010. See Reference 6 to the 2010 notice.
50. FDA, Memorandum of Telephone Conference Held on May 19, 1998,
between Linda S. Kahl and Gloria Overholser of FDA and Carlton
Kempter and Jonathan Fleuchaus, U.S. Environmental Protection
Agency.
51. FDA, ``Substances Generally Recognized as Safe Final Rule: Final
Regulatory Impact Analysis, Final Regulatory Flexibility Analysis,
Final Unfunded Mandates Reform Act Analysis,'' 2016.
52. FDA, ``Compliance Policy Guide CPG Sec. 665.100 Common or Usual
Names for Animal Feed Ingredients,'' (http://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm074687.htm),
1995. Accessed and printed on January 7, 2016.
53. Selle, P.H. and V. Ravindran, ``Microbial Phytase in Poultry
Nutrition,'' Animal Feed Science and Technology, 135:1-41, 2007.
54. Hatten., L.F., D.R. Ingram., and S.T. Pittman, ``Effect of
Phytase on Production Parameters and Nutrient Availability in
Broilers and Laying Hens: A Review,'' The Journal of Applied Poultry
Research, 10(3):274-278, 2001.
55. Angel, C.R., W. Saylor, S.L. Vieira, and N. Ward, ``Effects of a
Monocomponent Protease on Performance and Protein Utilization in 7-
to 22-Day-Old Broiler Chickens,'' Poultry Science, 90:2281-2286,
2011.
56. FDA, ``Guidance for Industry: Recommendations for Preparation
and Submission of Animal Food Additive Petitions (# 221),'' (http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM367746.pdf),
2015. Accessed and printed on January 15, 2016.
57. National Research Council, ``General Considerations in
Determining Safety of Animal Dietary Supplements,'' in Safety of
Dietary Supplements for Horses, Dogs, and Cats, Washington, DC,
Chapter 9, pp. 169-175, The National Academies Press, 2009.
58. FDA, ``Compliance Policy Guide CPG Sec. 527.400. Whole Milk,
Lowfat Milk, Skim Milk--Aflatoxin M1,'' (http://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm074482.htm),
2005. Accessed and printed on January 15, 2016.

List of Subjects

21 CFR Part 20

    Confidential business information, Courts, Freedom of information,
Government employees.

21 CFR Part 25

    Environmental impact statements, Foreign relations, Reporting and
recordkeeping requirements.

21 CFR Part 170

    Administrative practice and procedure, Food additives, Reporting
and recordkeeping requirements.

21 CFR Part 184

    Food additives.

21 CFR Part 186

    Food additives, Food packaging.

21 CFR Part 570

    Animal feeds, Animal foods, Food additives.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR
chapter I is amended as follows:

PART 20--PUBLIC INFORMATION

0
1. The authority citation for part 20 continues to read as follows:

    Authority:  5 U.S.C. 552; 18 U.S.C. 1905; 19 U.S.C. 2531-2582;
21 U.S.C. 321-393, 1401-1403; 42 U.S.C. 241, 242, 242a, 242l, 242n,
243, 262, 263, 263b-263n, 264, 265, 300u-300u-5, 300aa-1.

0
2. In Sec.  20.100, add paragraph (c)(46) to read as follows:

Sec.  20.100   Applicability; cross-reference to other regulations.

* * * * *
    (c) * * *
    (46) Generally recognized as safe (GRAS) notices, in part 170,
subpart E and part 570, subpart E of this chapter.

PART 25--ENVIRONMENTAL IMPACT CONSIDERATIONS

0
3. The authority citation for part 25 continues to read as follows:

    Authority:  21 U.S.C. 321-393; 42 U.S.C. 262, 263b-264; 42
U.S.C. 4321, 4332; 40 CFR parts 1500-1508; E.O. 11514, 35 FR 4247, 3
CFR, 1971 Comp., p. 531-533 as amended by E.O. 11991, 42 FR 26967, 3
CFR, 1978 Comp., p. 123-124 and E.O. 12114, 44 FR 1957, 3 CFR, 1980
Comp., p. 356-360.

0
4. In Sec.  25.20, revise paragraph (k) to read as follows:

Sec.  25.20  Actions requiring preparation of an environmental
assessment.

* * * * *
    (k) Establishment or amendment of a regulation for a food substance
as GRAS under the conditions of its intended use for humans or animals
under parts 182, 184, 186, 582, or 584 of this chapter, or
establishment or amendment of a regulation for a prior-sanctioned food
ingredient, as defined in Sec. Sec.  170.3(l) and 181.5(a) of this
chapter, unless categorically excluded in Sec.  25.32(f), (i), (j),
(k), or (r).
* * * * *

0
5. In Sec.  25.32, revise paragraphs (f), (i), (j), (k), and (r) to
read as follows:

Sec.  25.32  Foods, food additives, and color additives.

* * * * *
    (f) Establishment or amendment of a regulation for a food substance
as GRAS under the conditions of its intended use for humans or animals
under parts 182, 184, 186, 582, or 584 of this chapter, and
establishment or amendment of a regulation for a prior-sanctioned food
ingredient, as defined in Sec. Sec.  170.3(l) and 181.5(a) of this
chapter, if the substance or food ingredient is already marketed in the
United States for the proposed use.
* * * * *
    (i) Approval of a food additive petition, establishment or
amendment of a regulation for a food substance as GRAS under the
conditions of its intended use for humans or animals under parts 182,
184, 186, 582, or 584 of this chapter, the granting of a request for
exemption from regulation as a food additive under Sec.  170.39 of this
chapter, or allowing a notification submitted under 21 U.S.C. 348(h) to
become effective, when the substance is present in finished food-
packaging material at not greater than 5 percent-by-weight and is
expected to remain with finished food-packaging material through use by
consumers or when the substance is a component of a coating of a
finished food-packaging material.
    (j) Approval of a food additive petition, establishment or
amendment of a regulation for a food substance as GRAS under the
conditions of its intended use for humans or animals under parts 182,
184, 186, 582, or 584 of this chapter, the granting of a request for
exemption from regulation as a food additive under Sec.  170.39 of this
chapter, or allowing a notification submitted under 21 U.S.C. 348(h) to
become effective, when the substance is to be used as a component of a
food-contact surface of permanent or semipermanent equipment or of
another food-contact article intended for repeated use.
    (k) Approval of a food additive petition or color additive
petition, establishment or amendment of a regulation for a food
substance as GRAS under the conditions of its intended use for humans
or animals under parts 182, 184, 186, 582, or 584 of this chapter, or
allowing a notification submitted under 21 U.S.C. 348(h) to become
effective, for substances added directly to food that are intended to
remain in food through ingestion by consumers and that are not intended
to replace macronutrients in food.
* * * * *
    (r) Approval of a food additive petition or color additive
petition, establishment or amendment of a regulation for a food
substance as GRAS under the conditions of its intended use for humans
or animals under parts 182, 184, 186, 582, or 584 of this chapter, or
allowing a notification submitted under 21 U.S.C. 348(h) to become
effective for a substance that occurs naturally in the environment,
when the action does not alter significantly the concentration or
distribution of the substance, its metabolites, or degradation products
in the environment.

PART 170--FOOD ADDITIVES

0
6. The authority citation for part 170 continues to read as follows:

    Authority:  21 U.S.C. 321, 341, 342, 346a, 348, 371.

0
7. In Sec.  170.3, revise paragraph (h), the first sentence of
paragraph (i), and paragraph (k), to read as follows:

Sec.  170.3  Definitions.

* * * * *
    (h) Scientific procedures include the application of scientific
data (including, as appropriate, data from human, animal, analytical,
or other scientific studies), information, and methods, whether
published or unpublished, as well as the application of scientific
principles, appropriate to establish the safety of a substance under
the conditions of its intended use.
    (i) Safe or safety means that there is a reasonable certainty in
the minds of competent scientists that the substance is not harmful
under the conditions of its intended use. * * *
* * * * *
    (k) General recognition of safety shall be in accordance with Sec.
170.30.
* * * * *

0
8. Amend Sec.  170.30 as follows:
0
a. Revise the last sentence of paragraph (a);
0
b. Revise paragraph (b).
0
c. Revise the the first sentence of paragraph (c)(1) and revise
paragraph (c)(2);
0
d. Remove ``Sec.  186.1'' and add in its place ``part 186'' wherever it
appears in paragraph (d);
0
e. Revise paragraph (e);
0
f. Remove and reserve paragraph (f);
0
g. Remove ``Sec.  186.1'' and add in its place ``part 186'' in
paragraphs (h) introductory text, (h)(1), (i), (j), and (k); and
0
h. Revise the last sentence of paragraph (l).
    The revisions read as follows:

Sec.  170.30   Eligibility for classification as generally recognized
as safe (GRAS).

    (a) * * * General recognition of safety requires common knowledge
throughout the scientific community knowledgeable about the safety of
substances directly or indirectly added to food that there is
reasonable certainty that the substance is not harmful under the
conditions of its intended use (see Sec.  170.3(i)).
    (b) General recognition of safety based upon scientific procedures
shall require the same quantity and quality of scientific evidence as
is required to obtain approval of a food additive. General recognition
of safety through scientific procedures shall be based upon the
application of generally available and accepted scientific data,
information, or methods, which ordinarily are published, as well as the
application of scientific principles, and may be corroborated by the
application of unpublished scientific data, information, or methods.
    (c)(1) General recognition of safety through experience based on
common use in food prior to January 1, 1958, may be achieved without
the quantity or quality of scientific procedures required for approval
of a food additive. * * *
    (2) A substance used in food prior to 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 Federal Food, Drug, and Cosmetic Act (see also
Sec.  170.3(i)). Common use in food prior to January 1, 1958, that
occurred outside of the United States shall be documented by published
or other information and shall 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. A person who
concludes that a use of a substance is GRAS through experience based on
its common use in food outside of the United States should notify FDA
of that view in accordance with subpart E of this part.
* * * * *
    (e) Food ingredients were listed as GRAS in part 182 of this
chapter during 1958-1962 without a detailed scientific review of all
available data and information relating to their safety. Beginning in
1969, the Food and Drug Administration has undertaken a systematic
review of the status of all ingredients used in food based on the view
that they are GRAS under the conditions of their intended use or
subject to a prior sanction. All affirmations of GRAS status or
determinations of food additive status or prior sanction status
pursuant to this review shall be handled pursuant to Sec. Sec.  170.35,
170.38, and 180.1 of this chapter. Affirmation of GRAS status shall be
announced in part 184 or part 186 of this chapter.
* * * * *
    (l) * * * Any change to the GRAS status of a food ingredient in
parts 182, 184, or 186 of this chapter shall be accomplished pursuant
to Sec.  170.38.

0
9. In Sec.  170.35, revise paragraphs (a), (b)(1), (3), and (4), and
remove paragraph (c) to read as follows:

Sec.  170.35  Affirmation of generally recognized as safe (GRAS)
status.

    (a) The Commissioner, on his own initiative, may affirm that a
substance that directly or indirectly becomes a component of food is
GRAS under the conditions of its intended use.
    (b)(1) If the Commissioner proposes on his own initiative that a
substance is entitled to affirmation as GRAS under the conditions of
its intended use, he will place all of the data and information on
which he relies on public file in the office of the Division of Dockets
Management and will publish in the Federal Register a notice giving the
name of the substance, its proposed uses, and any limitations proposed
for purposes other than safety.
* * * * *
    (3) The Commissioner will evaluate all comments received. If he
concludes that there is convincing evidence that the substance is GRAS
under the conditions of its intended use as described in Sec.  170.30,
he will publish a notice in the Federal Register listing the GRAS
conditions of use of the substance in part 184 or part 186 of this
chapter, as appropriate.
    (4) If, after evaluation of the comments, the Commissioner
concludes that there is a lack of convincing evidence that a substance
is GRAS under the conditions of its intended use and that it should be
considered a food additive subject to section 409 of the Federal Food,
Drug, and Cosmetic Act, he shall publish a notice thereof in the
Federal Register in accordance with Sec.  170.38.

0
10. In Sec.  170.38, revise paragraph (a) to read as follows:

Sec.  170.38   Determination of food additive status.

    (a) The Commissioner may, in accordance with Sec.  170.35(b)(4),
publish a notice in the Federal Register determining that a substance
is not GRAS under the conditions of its intended use and is a food
additive subject to section 409 of the Federal Food, Drug, and Cosmetic
Act.
* * * * *

0
11. Add subpart E, consisting of Sec. Sec.  170.203 through 170.285, to
read as follows:

Subpart E--Generally Recognized as Safe (GRAS) Notice

Sec.
170.203 Definitions.
170.205 Opportunity to submit a GRAS notice.
170.210 How to send your GRAS notice to FDA.
170.215 Incorporation into a GRAS notice.
170.220 General requirements applicable to a GRAS notice.
170.225 Part 1 of a GRAS notice: Signed statements and
certification.
170.230 Part 2 of a GRAS notice: Identity, method of manufacture,
specifications, and physical or technical effect.
170.235 Part 3 of a GRAS notice: Dietary exposure.
170.240 Part 4 of a GRAS notice: Self-limiting levels of use.
170.245 Part 5 of a GRAS notice: Experience based on common use in
food before 1958.
170.250 Part 6 of a GRAS notice: Narrative.
170.255 Part 7 of a GRAS notice: List of supporting data and
information in your GRAS notice.
170.260 Steps you may take before FDA responds to your GRAS notice.
170.265 What FDA will do with a GRAS notice.
170.270 Procedures that apply when the intended conditions of use of
a notified substance include use in a product or products subject to
regulation by the Food Safety and Inspection Service (FSIS) of the
United States Department of Agriculture.
170.275 Public disclosure of a GRAS notice.
170.280 Submission of a supplement.
170.285 Disposition of pending GRAS affirmation petitions.

Subpart E--Generally Recognized as Safe (GRAS) Notice

Sec.  170.203  Definitions.

    The definitions and interpretations of terms in Sec.  170.3 apply
to such terms when used in this subpart. The following definitions also
apply:
    Amendment means any data and information that you submit regarding
a filed GRAS notice before we respond to your notice by letter in
accordance with Sec.  170.265(b)(1) or cease to evaluate your notice in
accordance with Sec.  170.265(b)(3).
    GRAS means generally recognized as safe.
    GRAS notice means a submission that informs us of your view that a
substance is not subject to the premarket approval requirements of the
Federal Food, Drug, and Cosmetic Act based on your conclusion that the
substance is GRAS under the conditions of its intended use in
accordance with Sec.  170.30.
    Notified substance means the substance that is the subject of your
GRAS notice.
    Notifier means the person (e.g., an individual, partnership,
corporation, association, or other legal entity) who is responsible for
the GRAS notice, even if another person (such as an attorney, agent, or
qualified expert) prepares or submits the notice or provides an opinion
about the basis for a conclusion of GRAS status.
    Qualified expert means an individual who is qualified by scientific
training and experience to evaluate the safety of substances under the
conditions of their intended use in food.
    Supplement means any data and information that you submit regarding
a filed GRAS notice after we respond to your notice by letter in
accordance with Sec.  170.265(b)(1) or cease to evaluate your

notice in accordance with Sec.  170.265(b)(3).
    We, our, and us refer to the United States Food and Drug
Administration (FDA).
    You and your refer to a notifier.

Sec.  170.205  Opportunity to submit a GRAS notice.

    Any person may notify FDA of a view that a substance is not subject
to the premarket approval requirements of section 409 of the Federal
Food, Drug, and Cosmetic Act based on that person's conclusion that the
substance is GRAS under the conditions of its intended use.

Sec.  170.210  How to send your GRAS notice to FDA.

    (a) Send your GRAS notice to the Office of Food Additive Safety
(HFS-200), Center for Food Safety and Applied Nutrition, Food and Drug
Administration, 5001 Campus Drive, College Park, MD 20740.
    (b) When you submit your GRAS notice, you may do so either in an
electronic format that is accessible for our evaluation or on paper. If
you send your GRAS notice on paper, a single paper copy is sufficient.

Sec.  170.215  Incorporation into a GRAS notice.

    You may incorporate into your GRAS notice either specifically
identified data and information that you previously submitted to the
Center for Food Safety and Applied Nutrition (CFSAN), or specifically
identified publicly available data and information submitted by another
party, when such data and information remain in CFSAN's records, such
as data and information contained in a previous GRAS notice or a food
additive petition.

Sec.  170.220  General requirements applicable to a GRAS notice.

    (a) A GRAS notice has seven parts as required by Sec. Sec.  170.225
through 170.255. You must submit the data and information specified in
each of these parts on separate pages or sets of pages.
    (b) You must include each of the seven parts in your GRAS notice.
If you do not include a part, you must include with your GRAS notice an
explanation of why that part does not apply to your GRAS notice.

Sec.  170.225  Part 1 of a GRAS notice: Signed statements and
certification.

    (a) Part 1 of your GRAS notice must be dated and signed by a
responsible official of your organization, or by your attorney or
agent.
    (b) Except as required by paragraph (c)(8) of this section, you
must not include any information that is trade secret or confidential
commercial information in Part 1 of your GRAS notice.
    (c) In Part 1 of your GRAS notice, you must:
    (1) Inform us that you are submitting a GRAS notice in accordance
with this subpart;
    (2) Provide the name and address of your organization;
    (3) Provide the name of the notified substance, using an
appropriately descriptive term;
    (4) Describe the intended conditions of use of the notified
substance, including the foods in which the substance will be used, the
levels of use in such foods, and the purposes for which the substance
will be used, including, when appropriate, a description of a
subpopulation expected to consume the notified substance;
    (5) Inform us of the statutory basis for your 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));
    (6) State your view that the notified substance is not subject to
the premarket approval requirements of the Federal Food, Drug, and
Cosmetic Act based on your conclusion that the notified substance is
GRAS under the conditions of its intended use;
    (7) State that, if we ask to see the data and information that are
the basis for your conclusion of GRAS status, either during or after
our evaluation of your notice, you will:
    (i) Agree to make the data and information available to us; and
    (ii) Agree to both of the following procedures for making the data
and information available to us:
    (A) Upon our request, you will allow us to review and copy the data
and information during customary business hours at the address you
specify for where these data and information will be available to us;
and
    (B) Upon our request, you will provide us with a complete copy of
the data and information either in an electronic format that is
accessible for our evaluation or on paper;
    (8) State your view as to whether any of the data and information
in Parts 2 through 7 of your GRAS notice are exempt from disclosure
under the Freedom of Information Act, 5 U.S.C. 552 (e.g., as trade
secret or as commercial or financial information that is privileged or
confidential).
    (9) Certify that, to the best of your knowledge, your GRAS notice
is a complete, representative, and balanced submission that includes
unfavorable information, as well as favorable information, known to you
and pertinent to the evaluation of the safety and GRAS status of the
use of the substance;
    (10) State both the name and position or title of the person who
signs the GRAS notice; and
    (11) When applicable, state as required by Sec.  170.270 whether
you:
    (i) Authorize us to send any trade secrets to the Food Safety and
Inspection Service (FSIS) of the U.S. Department of Agriculture; or
    (ii) Ask us to exclude any trade secrets from the copy of the GRAS
notice that we will send to FSIS.

Sec.  170.230  Part 2 of a GRAS notice: Identity, method of
manufacture, specifications, and physical or technical effect.

    In Part 2 of your GRAS notice, you must include:
    (a) Scientific data and information that identifies the notified
substance.
    (1) Examples of appropriate data and information include the
chemical name, applicable registry numbers (such as a Chemical
Abstracts Service (CAS) registry number or an Enzyme Commission (EC)
number), empirical formula, structural formula, quantitative
composition, and characteristic properties.
    (2) When the source of a notified substance is a biological
material, you must include data and information sufficient to identify:
    (i) The taxonomic source (e.g., genus, species) including, as
applicable, data and information at the sub-species level (e.g.,
variety, strain);
    (ii) The part of any plant or animal used as the source; and
    (iii) Any known toxicants that could be in the source;
    (b) A description of the method of manufacture of the notified
substance in sufficient detail to evaluate the safety of the notified
substance as manufactured;
    (c) Specifications for food-grade material; and
    (d) When necessary to demonstrate safety, relevant data and
information bearing on the physical or other technical effect the
notified substance is intended to produce, including the quantity of
the notified substance required to produce such effect.

Sec.  170.235   Part 3 of a GRAS notice: Dietary exposure.

    In part 3 of your GRAS notice, you must provide data and
information about dietary exposure (i.e., the amount of relevant
substances that consumers are likely to eat or drink as part of a total
diet), regardless of whether your conclusion of GRAS status is through

scientific procedures or through experience based on common use in
food, as follows:
    (a) You must provide an estimate of dietary exposure to the
notified substance that includes exposure from its intended use and all
sources in the diet; and
    (b) When applicable, you must provide an estimate of dietary
exposure to any other substance that is expected to be formed in or on
food because of the use of the notified substance (e.g., hydrolytic
products or reaction products);
    (c) When applicable, you must provide an estimate of dietary
exposure to any other substance that is present with the notified
substance either naturally or due to its manufacture (e.g.,
contaminants or by-products);
    (d) You must describe the source of any food consumption data that
you use to estimate dietary exposure in accordance with paragraphs (a)
through (c) of this section; and
    (e) You must explain any assumptions you made to estimate dietary
exposure in accordance with paragraphs (a) through (c) of this section.

Sec.  170.240  Part 4 of a GRAS notice: Self-limiting levels of use.

    In circumstances where the amount of the notified substance that
can be added to food is limited because food containing levels of the
notified substance above a particular level would become unpalatable or
technologically impractical, in Part 4 of your GRAS notice you must
include data and information on such self-limiting levels of use.

Sec.  170.245  Part 5 of a GRAS notice: Experience based on common use
in food before 1958.

    If the statutory basis for your conclusion of GRAS status is
through experience based on common use in food, in Part 5 of your GRAS
notice you must include evidence of a substantial history of
consumption of the notified substance for food use by a significant
number of consumers prior to January 1, 1958.

Sec.  170.250   Part 6 of a GRAS notice: Narrative.

    In Part 6 of your GRAS notice, you must include a narrative that
provides the basis for your conclusion of GRAS status, in which:
    (a)(1) You must explain why the data and information in your notice
provide a basis for your view that the notified substance is safe under
the conditions of its intended use. In your explanation, you must
address the safety of the notified substance, considering all dietary
sources and taking into account any chemically or pharmacologically
related substances in such diet;
    (2) In your explanation, you must identify what specific data and
information that you discuss in accordance with paragraph (a)(1) of
this section are generally available, and what specific data and
information that you discuss in accordance with paragraph (a)(1) of
this section are not generally available, by providing citations to the
list of data and information that you include in Part 7 of your GRAS
notice in accordance with Sec.  170.255;
    (b) You must explain how the generally available data and
information that you rely on to establish safety in accordance with
paragraph (a) of this section provide a basis for your conclusion that
the notified substance is generally recognized, among qualified
experts, to be safe under the conditions of its intended use;
    (c) You must either:
    (1) Identify, discuss, and place in context, data and information
that are, or may appear to be, inconsistent with your conclusion of
GRAS status, regardless of whether those data and information are
generally available; or
    (2) State that you have reviewed the available data and information
and are not aware of any data and information that are, or may appear
to be, inconsistent with your conclusion of GRAS status;
    (d) If you view any of the data and information in your notice as
exempt from disclosure under the Freedom of Information Act, you must
identify the specific data and information; and
    (e) For non-public, safety-related data and information considered
in reaching a conclusion of GRAS status, you must explain how there
could be a basis for a conclusion of GRAS status if qualified experts
do not have access to such data and information.

Sec.  170.255  Part 7 of a GRAS notice: List of supporting data and
information in your GRAS notice.

    (a) In part 7 of your GRAS notice, you must include a list of all
of the data and information that you discuss in Part 6 of your GRAS
notice to provide a basis for your view that the notified substance is
safe under the conditions of its intended use as described in
accordance with Sec.  170.250(a)(1).
    (b) You must specify which data and information that you list in
accordance with paragraph (a) of this section are generally available,
and which data and information are not generally available.

Sec.  170.260  Steps you may take before FDA responds to your GRAS
notice.

    (a) You may submit a timely amendment to your filed GRAS notice, to
update your GRAS notice or in response to a question from us, before we
respond to your notice by letter in accordance with Sec.  170.265(b)(1)
or cease to evaluate your notice in accordance with Sec.
170.265(b)(3).
    (b) At any time before we respond to your GRAS notice in accordance
with Sec.  170.265(b)(1), you may request in writing that we cease to
evaluate your GRAS notice. Your request does not preclude you from
submitting a future GRAS notice in accordance with this subpart with
respect to the notified substance.

Sec.  170.265  What FDA will do with a GRAS notice.

    (a)(1) We will conduct an initial evaluation of your submission 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 that informs you of the date of filing.
    (3) If we do not file your submission as a GRAS notice, we will
send you a letter that informs you of that fact and provides our
reasons for not filing the submission as a GRAS notice.
    (4) We will consider any timely amendment that you submit to a
filed GRAS notice, to update your GRAS notice or in response to a
question from us, before we respond to you by letter in accordance with
paragraph (b)(1) of this section, if we deem that doing so is feasible
within the timeframes established in paragraph (b) of this section. If
we deem that considering your amendment is not feasible within the
timeframes established in paragraph (b) of this section or if we have
granted your request to cease to evaluate your notice, we will inform
you that we are not considering your amendment.
    (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 on an as needed basis.
    (2) If we extend the timeframe, we will inform you in writing of
the extension as soon as practicable but no later than within 180 days
of filing.
    (3) If you ask us to cease to evaluate your GRAS notice in
accordance with Sec.  170.260(b), we will send you a letter informing
you of our decision regarding your request.
    (c) If circumstances warrant, we will send you a subsequent letter
about the notice.

Sec.  170.270  Procedures that apply when the intended conditions of
use of a notified substance include use in a product or products
subject to regulation by the Food Safety and Inspection Service (FSIS)
of the United States Department of Agriculture.

    If the intended conditions of use of the notified substance include
use in a product or products subject to regulation by FSIS under
statutes that it administers:
    (a) When applicable, you must include in your GRAS notice a
statement as to whether you:
    (1) Authorize us to send any trade secrets to FSIS; or
    (2) Ask us to exclude any trade secrets from the copy of the GRAS
notice that we will send to FSIS.
    (b)(1) We will forward a copy of a GRAS notice or relevant portions
thereof to FSIS;
    (2) We will exclude any trade secrets unless you have authorized us
to do so in accordance with paragraph (a)(1) of this section; and
    (c) We will ask FSIS to advise whether the intended conditions of
use comply with applicable statutes and regulations, or, if not,
whether the use of the substance would be permitted in products under
FSIS' jurisdiction under specified conditions or restrictions.
    (d) As appropriate, we will inform you of the advice we receive
from FSIS in the letter we send you in accordance with Sec.
170.265(b)(1).

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:
    (1) Considered a mandatory, rather than voluntary, submission for
purposes of their status under the Freedom of Information Act and our
public information requirements in part 20 of this chapter; and
    (2) Available for public disclosure in accordance with part 20 of
this chapter as of the date that we receive your GRAS notice.
    (b) We will make the following readily accessible to the public:
    (1) A list of filed GRAS notices, including the information
described in Sec.  170.225(c)(2) through (c)(5);
    (2) The text of any letter that we issue under Sec.  170.265(b)(1)
or (c); and
    (3) The text of any letter that we issue under Sec.  170.265(b)(3)
if we grant your request that we cease to evaluate your notice.
    (c) We will disclose all remaining data and information that are
not exempt from public disclosure in accordance with part 20 of this
chapter.

Sec.  170.280   Submission of a supplement.

    If circumstances warrant, you may submit a supplement to a filed
GRAS notice after we respond to your notice by letter in accordance
with Sec.  170.265(b)(1) or cease to evaluate your notice in accordance
with Sec.  170.265(b)(3).

Sec.  170.285  Disposition of pending GRAS affirmation petitions.

    Because the procedure to submit a GRAS notice is replacing the
former process to submit a GRAS affirmation petition, the following
will happen to a filed GRAS affirmation petition that is pending on
October 17, 2016.
    (a) On October 17, 2016, we will close the docket for any GRAS
affirmation petition that is still pending as of October 17, 2016.
    (b) Any person who submitted a GRAS affirmation petition described
in this section may submit a GRAS notice as described in this subpart
and request that we incorporate the GRAS affirmation petition as
described in Sec.  170.215.

PART 184--DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED
AS SAFE

0
12. The authority citation for part 184 continues to read as follows:

    Authority: 21 U.S.C. 321, 342, 348, 371.

0
13. In Sec.  184.1, revise the first sentence of paragraph (a), and
revise the fifth sentence and remove the last sentence of paragraph
(b)(1) to read as follows.

Sec.  184.1  Substances added directly to human food affirmed as
generally recognized as safe (GRAS).

    (a) The direct human food ingredients listed in this part have been
reviewed by the Food and Drug Administration and affirmed to be
generally recognized as safe (GRAS) for the purposes and under the
conditions prescribed. * * *
    (b) * * *
    (1) * * * In such a case, a manufacturer may not rely on the
regulation as authorizing that use but shall have a basis to conclude
that that use is GRAS or shall use the ingredient in accordance with a
food additive regulation. * * *
* * * * *

PART 186--INDIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED
AS SAFE

0
14. The authority citation for part 186 continues to read as follows:

    Authority:  21 U.S.C. 321, 342, 348, 371.

0
15. In Sec.  186.1, revise the first sentence of paragraph (a), and
revise the fifth sentence and remove the last sentence of paragraph
(b)(1) to read as follows.

Sec.  186.1  Substances added indirectly to human food affirmed as
generally recognized as safe (GRAS).

    (a) The indirect human food ingredients listed in this part have
been reviewed by the Food and Drug Administration and affirmed to be
generally recognized as safe (GRAS) for the purposes and under the
conditions prescribed, providing they comply with the purity
specifications listed in this part or, in the absence of purity
specifications, are of a purity suitable for their intended use in
accordance with Sec.  170.30(h)(1) of this chapter. * * *
    (b) * * *
    (1) * * * In such a case, a manufacturer may not rely on the
regulation as authorizing that use but shall have a basis to conclude
that the use is GRAS or shall use the ingredient in accordance with a
food additive regulation. * * *
* * * * *

PART 570--FOOD ADDITIVES

0
16. The authority citation for part 570 continues to read as follows:

    Authority: 21 U.S.C. 321, 341, 342, 346a, 348, 371.

0
17. In Sec.  570.3, revise paragraphs (f), (h), the first sentence of
(i), and (k), and add paragraph (n) to read as follows:

Sec.  570.3  Definitions.

* * * * *
    (f) Common use in food means a substantial history of consumption
of a substance by a significant number of animals of the species to
which the substance is intended to be fed (and, for food-producing
animals fed with such substance, also means a substantial history of
consumption by humans consuming human foods derived from those food-
producing animals), prior to January 1, 1958.
* * * * *
    (h) Scientific procedures include the application of scientific
data (including, as appropriate, data from human, animal, analytical,
or other scientific studies), information, and methods, whether
published or unpublished, as well as the application of scientific
principles, appropriate to establish the safety of a substance under
the conditions of its intended use.
    (i) Safe or safety means that there is a reasonable certainty in
the minds of

competent scientists that the substance is not harmful under the
conditions of its intended use. * * *
* * * * *
    (k) General recognition of safety shall be in accordance with Sec.
570.30.
* * * * *
    (n) Food-producing animal means an animal used to produce human
food.
0
18. In Sec.  570.30, revise the last sentence of paragraph; (a); revise
paragraphs (b) through (d); and revise the last sentence in paragraph
(i) to read as follows:

Sec.  570.30   Eligibility for classification as generally recognized
as safe (GRAS).

    (a) * * * General recognition of safety requires common knowledge
throughout the scientific community knowledgeable about the safety of
substances directly or indirectly added to food that there is
reasonable certainty that the substance is not harmful to either the
target animal or to humans consuming human food derived from food-
producing animals under the conditions of its intended use (see Sec.
570.3(i)).
    (b) General recognition of safety based upon scientific procedures
shall require the same quantity and quality of scientific evidence as
is required to obtain approval of a food additive. General recognition
of safety through scientific procedures shall address safety for both
the target animal and for humans consuming human food derived from
food-producing animals and shall be based upon the application of
generally available and accepted scientific data, information, or
methods, which ordinarily are published, as well as the application of
scientific principles, and may be corroborated by the application of
unpublished scientific data, information, or methods.
    (c)(1) General recognition of safety through experience based on
common use in food prior to January 1, 1958, shall address safety for
both the target animal and for humans consuming human food derived from
food-producing animals and may be achieved without the quantity or
quality of scientific procedures required for approval of a food
additive. General recognition of safety through experience based on
common use in food prior to January 1, 1958, shall be based solely on
food use of the substance in the same animal species prior to January
1, 1958, and shall ordinarily be based upon generally available data
and information. An ingredient not in common use in food prior to
January 1, 1958, may achieve general recognition of safety only through
scientific procedures.
    (2) A substance used in food prior to 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 Federal Food, Drug, and Cosmetic
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 prior to January 1, 1958, that occurred outside of the United
States shall be documented by published or other information and shall
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. A person who concludes that a use of a substance
is GRAS through experience based on its common use in food outside of
the United States should notify FDA of that view in accordance with
subpart E of this part.
    (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 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 prior to January 1, 1958, without known detrimental
effects, which is subject only to conventional processing as practiced
prior to January 1, 1958, and for which no known safety hazard exists,
will ordinarily be regarded as GRAS without specific inclusion in part
582 or part 584 of this chapter.
* * * * *
    (i) * * * Any use of such an ingredient not in full compliance with
each such established limitation shall require a food additive
regulation.
* * * * *

0
19. In Sec.  570.35, revise paragraphs (a), (b)(1), (3), and (4), and
remove paragraph (c) to read as follows:

Sec.  570.35  Affirmation of generally recognized as safe (GRAS)
status.

    (a) The Commissioner, on his own initiative, may affirm that a
substance that directly or indirectly becomes a component of food is
GRAS under the conditions of its intended use.
    (b)(1) If the Commissioner proposes on his own initiative that a
substance is entitled to affirmation as GRAS under the conditions of
its intended use, he will place all of the data and information on
which he relies on public file in the office of the Division of Dockets
Management and will publish in the Federal Register a notice giving the
name of the substance, its proposed uses, and any limitations proposed
for purposes other than safety.
* * * * *
    (3) The Commissioner will evaluate all comments received. If he
concludes that there is convincing evidence that the substance is GRAS
under the conditions of its intended use as described in Sec.  570.30,
he will publish a notice in the Federal Register listing the GRAS
conditions of use in this subchapter E.
    (4) If, after evaluation of the comments, the Commissioner
concludes that there is a lack of convincing evidence that the
substance is GRAS under the conditions of its intended use and that it
should be considered a food additive subject to section 409 of the
Federal Food, Drug, and Cosmetic Act, he shall publish a notice thereof
in the Federal Register in accordance with Sec.  570.38.

0
20. In Sec.  570.38, revise paragraph (a) to read as follows:

Sec.  570.38  Determination of food additive status.

    (a) The Commissioner may, in accordance with Sec.  570.35(b)(4),
publish a notice in the Federal Register determining that a substance
is not GRAS under the conditions of its intended use and is a food
additive subject to section 409 of the Federal Food, Drug, and Cosmetic
Act.
* * * * *

0
21. Add and reserve subparts C and D.

0
22. Add subpart E, consisting of Sec. Sec.  570.203 through 570.280, to
read as follows:

Subpart E--Generally Recognized as Safe (GRAS) Notice

Sec.
570.203 Definitions.
570.205 Opportunity to submit a GRAS notice.

570.210 How to send your GRAS notice to FDA.
570.215 Incorporation into a GRAS notice.
570.220 General requirements applicable to a GRAS notice.
570.225 Part 1 of a GRAS notice: Signed statements and
certification.
570.230 Part 2 of a GRAS notice: Identity, method of manufacture,
specifications, and physical or technical effect.
570.235 Part 3 of a GRAS notice: Target animal and human exposures.
570.240 Part 4 of a GRAS notice: Self-limiting levels of use.
570.245 Part 5 of a GRAS notice: Experience based on common use in
food before 1958.
570.250 Part 6 of a GRAS notice: Narrative.
570.255 Part 7 of a GRAS notice: List of supporting data and
information in your GRAS notice.
570.260 Steps you may take before FDA responds to your GRAS notice.
570.265 What FDA will do with a GRAS notice.
570.275 Public disclosure of a GRAS notice.
570.280 Submission of a supplement.

Subpart E--Generally Recognized as Safe (GRAS) Notice

Sec.  570.203  Definitions.

    The definitions and interpretations of terms in Sec.  570.3 apply
to such terms when used in this subpart. The following definitions also
apply:
    Amendment means any data and information that you submit regarding
a filed GRAS notice before we respond to your notice by letter in
accordance with Sec.  570.265(b)(1) or cease to evaluate your notice in
accordance with Sec.  570.265(b)(3).
    GRAS means generally recognized as safe.
    GRAS notice means a submission that informs us of your view that a
substance is not subject to the premarket approval requirements of the
Federal Food, Drug, and Cosmetic Act based on your conclusion that the
substance is GRAS under the conditions of its intended use in
accordance with Sec.  570.30.
    Notified substance means the substance that is the subject of your
GRAS notice.
    Notifier means the person (e.g., an individual, partnership,
corporation, association, or other legal entity) who is responsible for
the GRAS notice, even if another person (such as an attorney, agent, or
qualified expert) prepares or submits the notice or provides an opinion
about the basis for a conclusion of GRAS status.
    Qualified expert means an individual who is qualified by scientific
training and experience to evaluate the safety of substances under the
conditions of their intended use in animal food.
    Supplement means any data and information that you submit regarding
a filed GRAS notice after we respond to your notice by letter in
accordance with Sec.  570.265(b)(1) or cease to evaluate your notice in
accordance with Sec.  570.265(b)(3).
    We, our, and us refer to the United States Food and Drug
Administration (FDA).
    You and your refer to a notifier.

Sec.  570.205  Opportunity to submit a GRAS notice.

    Any person may notify FDA of a view that a substance is not subject
to the premarket approval requirements of section 409 of the Federal
Food, Drug, and Cosmetic Act based on that person's conclusion that the
substance is GRAS under the conditions of its intended use.

Sec.  570.210   How to send your GRAS notice to FDA.

    (a) Send your GRAS notice to the Division of Animal Feeds (HFV-
220), Center for Veterinary Medicine, Food and Drug Administration,
7519 Standish Pl., Rockville, MD 20855.
    (b) When you submit your GRAS notice, you may do so either in an
electronic format that is accessible for our evaluation or on paper. If
you send your GRAS notice on paper, a single paper copy is sufficient.

Sec.  570.215  Incorporation into a GRAS notice.

    You may incorporate into your GRAS notice either specifically
identified data and information that you previously submitted to the
Center for Veterinary Medicine (CVM), or specifically identified
publicly available data and information submitted by another party,
when such data and information remain in CVM's records, such as data
and information contained in a previous GRAS notice or a food additive
petition.

Sec.  570.220  General requirements applicable to a GRAS notice.

    (a) A GRAS notice has seven parts as required by Sec. Sec.  570.225
through 570.255. You must submit the data and information specified in
each of these parts on separate pages or sets of pages.
    (b) You must include each of the seven parts in your GRAS notice.
If you do not include a part, you must include with your GRAS notice an
explanation of why that part does not apply to your GRAS notice.

Sec.  570.225  Part 1 of a GRAS notice: Signed statements and
certification.

    (a) Part 1 of your GRAS notice must be dated and signed by a
responsible official of your organization, or by your attorney or
agent.
    (b) Except as required by paragraph (c)(8) of this section, you
must not include any information that is trade secret or confidential
commercial information in Part 1 of your GRAS notice.
    (c) In Part 1 of your GRAS notice, you must:
    (1) Inform us that you are submitting a GRAS notice in accordance
with this subpart;
    (2) Provide the name and address of your organization;
    (3) Provide the name of the notified substance, using an
appropriately descriptive term;
    (4) Describe the intended conditions of use of the notified
substance, including stating whether the substance will be added to
food (including drinking water) for animals in which the substance will
be used; identifying the foods to which it will be added, the levels of
use in such foods, and the animal species for which these foods are
intended (including, when appropriate, a description of a subpopulation
expected to consume the notified substance); and the purposes for which
the substance will be used;
    (5) Inform us of the statutory basis for your 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 animal
food in accordance with Sec.  570.30(a) and (c));
    (6) State your view that the notified substance is not subject to
the premarket approval requirements of the Federal Food, Drug, and
Cosmetic Act based on your conclusion that the notified substance is
GRAS under the conditions of its intended use;
    (7) State that, if we ask to see the data and information that are
the basis for your conclusion of GRAS status, either during or after
our evaluation of your notice, you will:
    (i) Agree to make the data and information available to us; and
    (ii) Agree to both of the following procedures for making the data
and information available to us:
    (A) Upon our request, you will allow us to review and copy the data
and information during customary business hours at the address you
specify for where these data and information will be available to us;
and
    (B) Upon our request, you will provide us with a complete copy of
the data and information either in an electronic format that is
accessible for our evaluation or on paper;
    (8) State your view as to whether any of the data and information
in Parts 2 through 7 of your GRAS notice are exempt from disclosure
under the

Freedom of Information Act, 5 U.S.C. 552 (e.g., as trade secret or as
commercial or financial information that is privileged or
confidential);
    (9) Certify that, to the best of your knowledge, the GRAS notice is
a complete, representative, and balanced submission that includes
unfavorable information, as well as favorable information, known to you
and pertinent to the evaluation of the safety and GRAS status of the
use of the substance; and
    (10) State both the name and the position or title of the person
who signs the GRAS notice.

Sec.  570.230  Part 2 of a GRAS notice: Identity, method of
manufacture, specifications, and physical or technical effect.

    In Part 2 of your GRAS notice, you must include:
    (a) Scientific data and information that identifies the notified
substance.
    (1) Examples of appropriate data and information include the
chemical name, applicable registry numbers (such as a Chemical
Abstracts Service (CAS) registry number or an Enzyme Commission (EC)
number), empirical formula, structural formula, quantitative
composition, and characteristic properties.
    (2) When the source of a notified substance is a biological
material, you must include data and information sufficient to identify:
    (i) The taxonomic source (e.g., genus, species), including as
applicable data and information at the sub-species level (e.g.,
variety, strain);
    (ii) The part of any plant or animal used as the source; and
    (iii) Any known toxicants that could be in the source;
    (b) A description of the method of manufacture of the notified
substance in sufficient detail to evaluate the safety of the notified
substance as manufactured;
    (c) Specifications for material that is of appropriate grade for
use in animal food; and
    (d) When necessary to demonstrate safety, relevant data and
information bearing on the physical or other technical effect the
notified substance is intended to produce, including the quantity of
the notified substance required to produce such effect.

Sec.  570.235  Part 3 of a GRAS notice: Target animal and human
exposures.

    In part 3 of your GRAS notice, you must provide data and
information about exposure to the target animal and to humans consuming
human food derived from food-producing animals, regardless of whether
your conclusion of GRAS status is through scientific procedures or
through experience based on common use in food, as follows:
    (a) For exposure to the target animal, you must provide:
    (1) The amount of the notified substance that different target
animal species are likely to consume in the animal food (including
drinking water) as part of the animal's total diet, including the
intended use and all other sources in the total diet; and
    (2) When applicable, the amount of any other substance that is
expected to be formed in or on food because of the use of the notified
substance (e.g., hydrolytic products or reaction products);
    (3) When applicable, the amount of any other substance that is
present with the notified substance either naturally or due to its
manufacture (e.g., contaminants or by-products);
    (4) The data and information you rely on to establish the amount of
the notified substance and the amounts of any other substance in
accordance with paragraphs (a)(1) through (a)(3) of this section that
different target animal species are likely to consume in the animal
food (including drinking water) as part of the animal's total diet; and
    (b) When the intended use is in food for food-producing animals,
you must provide:
    (1) The potential quantities of any residues that humans may be
exposed to in edible animal tissues, including:
    (i) Residues of the notified substance;
    (ii) Residues of any other substance that is expected to be formed
in or on the animal food because of the use of the notified substance;
and
    (iii) Residues from any other substance that is present with the
notified substance whether naturally, due to its manufacture (e.g.,
contaminants or by-products), or produced as a metabolite in edible
animal tissues when the notified substance is consumed by a food-
producing animal; and
    (2) The data and information you rely on to establish, in
accordance with paragraph (b)(1) of this section, the potential
quantities of any residues that humans may be exposed to in edible
animal tissues.

Sec.  570.240  Part 4 of a GRAS notice: Self-limiting levels of use.

    In circumstances where the amount of the notified substance that
can be added to animal food is limited because animal food containing
levels of the notified substance above a particular level would become
unpalatable or technologically impractical, in Part 4 of your GRAS
notice you must include data and information on such self-limiting
levels of use.

Sec.  570.245  Part 5 of a GRAS notice: Experience based on common use
in food before 1958.

    If the statutory basis for your conclusion of GRAS status is
through experience based on common use in animal food, in Part 5 of
your GRAS notice you must include evidence of a substantial history of
consumption of the notified substance for food use by a significant
number of animals of the species to which the substance is intended to
be fed prior to January 1, 1958, and evidence of a substantial history
of consumption by humans consuming human foods derived from food-
producing animals prior to January 1, 1958.

Sec.  570.250  Part 6 of a GRAS notice: Narrative.

    In Part 6 of your GRAS notice, you must include a narrative that
provides the basis for your conclusion of GRAS status, in which:
    (a)(1) You must explain why the data and information in your notice
provide a basis for your view that the notified substance is safe under
the conditions of its intended use for both the target animal and for
humans consuming human food derived from food-producing animals. In
your explanation, you must address the safety of the notified
substance, considering all animal food (including drinking water) as
part of the animal's total diet, taking into account any chemically or
pharmacologically related substances in such diet. In your explanation,
you must also address the safety of the notified substance in regard to
human exposure, considering all dietary sources and taking into account
any chemically or pharmacologically related substances;
    (2) In your explanation, you must identify what specific data and
information that you discuss in accordance with paragraph (a)(1) of
this section are generally available, and what specific data and
information that you discuss in accordance with paragraph (a)(1) of
this section are not generally available, by providing citations to the
list of data and information that you include in Part 7 of your GRAS
notice in accordance with Sec.  570.255;
    (b) You must explain how the generally available data and
information that you rely on to establish safety in accordance with
paragraph (a) of this section provide a basis for your conclusion that
the notified substance is generally recognized, among qualified
experts, to be safe under the conditions of its intended use for both
the target animal and for humans consuming human food derived from
food-producing animals;

    (c) You must either:
    (1) Identify, discuss, and place in context, data and information
that are, or may appear to be, inconsistent with your conclusion of
GRAS status, regardless of whether those data and information are
generally available; or
    (2) State that you have reviewed the available data and information
and are not aware of any data and information that are, or may appear