assessment of the substance being evaluated, we strongly encourage any
person who intends to rely on data and information regarding a class of
substances, or a specific substance related to the substance that would
be added to food, to submit any conclusion of GRAS status to FDA via
the GRAS notification procedure.
    (Comment 18) One comment states that the use of an approved food
additive can, through the passage of time, become GRAS as the substance
becomes widely used and as information about the substance becomes
publicly available.
    (Response 18) We disagree that widespread use of an approved food
additive as time passes has any bearing on the eligibility of this use
for classification as GRAS. Eligibility for classification as GRAS
through scientific procedures would depend on the status of the
information--as generally available and generally accepted--rather than
on the amount of time that a food additive has been used in food.
However, in general, much of the data submitted for our review of a
food additive contains unpublished data and trade secret or
confidential information that is neither published nor otherwise
generally available. Although the safety data are available for public
disclosure under 21 CFR 171.1(h)(1), they typically are based on
unpublished studies sponsored by the petitioner.
    See also the discussion in Response 19 regarding the impact of the
passage of time and the discussion in Response 79 that the qualified
experts who evaluate the basis for a conclusion that the notified
substance is safe under the conditions of its intended use must not
exclusively be ``FDA's experts.''
    (Comment 19) One comment asks us to exclude uses of ``novel''
substances from consideration for eligibility for classification as
GRAS. The comment asserts that novel or newly discovered uses of
substances that are the subject of a conclusion of GRAS status are in
conflict with the original intent of the 1958 amendment and the plain
meaning of ``generally recognized,'' because there is no history of
safe use for these substances. The comment also states that similar
``general recognition'' provisions for new drugs are not interpreted to
allow industry-made safety determinations for new or novel drugs.
    (Response 19) We do not have a regulatory definition for a
``novel'' substance. As a general matter, section 201(s) of the FD&C
Act provides two alternatives for general recognition of safety--
through scientific procedures, or through experience based on common
use in food. Section 201(s) does not limit eligibility, or otherwise
exclude, the use of a substance from classification as GRAS through
scientific procedures if there is no history of use. Likewise, section
201(s) does not limit eligibility, or otherwise exclude, the use of a
substance from classification as GRAS through scientific procedures
based on other criteria, such as whether a substance or its use in food
is ``novel'' or ``newly discovered.'' Unlike the definition of a ``new
drug'' in section 201(p) of the FD&C Act, section 201(s) does not
require that a food ingredient be used ``to a material extent or for a
material time under such conditions'' before it can become GRAS.
Rather, the criteria for eligibility for classification as GRAS depend
on whether generally available and accepted data and information
establish that the substance is safe under the conditions of its
intended use.
    However, a conclusion of GRAS status must be based on common
knowledge throughout the scientific community knowledgeable about the
safety of substances added to food that there is reasonable certainty
that the substance is not harmful under the conditions of its intended
use (Sec.  170.30(a)), and a substance cannot be considered GRAS when
its characteristics are known to only a few experts (Final rule
establishing GRAS criteria, 41 FR 53600, December 7, 1976). In
addition, the passage of time is relevant in an evaluation of whether a
substance is GRAS under the conditions of its intended use. In our 1974
proposed rule on general recognition of safety and prior sanctions for
food ingredients, we acknowledged that there would be at least some gap
between the gathering of the scientific knowledge necessary to provide
the toxicological underpinning for general recognition of safety and
the dissemination to and assimilation by the scientific community of
this material that is necessary for general recognition of safety to
exist.'' (39 FR 34194 at 34194, September 23, 1974). More recently, the
discussions in sections III.A.4 and IV.K of CFSAN's 2010 experience
document (Ref. 18) show our approach to the time gap between the
publication of safety data and the use of the published safety data to
support a conclusion of GRAS status during the Interim Pilot program.
See also Response 67 regarding nanotechnology applications in food
substances.
    (Comment 20) One comment asserts that we must define the extent of
agreement needed to establish a consensus among qualified experts, and
that we must exclude from eligibility for classification as GRAS any
substance whose safety has been called into question by expert
authorities or authoritative entities within the scientific community.
    (Response 20) The proponent of a GRAS conclusion for a food
substance must demonstrate that the conditions of use of the substance
satisfy the definition of ``safe'' in our regulations (i.e., that there
is reasonable certainty that the substance is not harmful under the
conditions of its intended use (see Sec.  170.3(i)). The proponent of
GRAS status also must demonstrate that there is common knowledge about
this safety throughout the knowledgeable scientific community (Sec.
170.30(a)). Although courts have established that general recognition
of safety requires a consensus of expert opinion regarding the safety
of the use of the substance, (see, e.g., United States v. Western

Serum Co., Inc., 666 F.2d 335, 338 (9th Cir. 1982) (citing Weinberger
v. Hynson, Westcott & Dunning, 412 U.S. 609, 629-32 (1973)), we
disagree that we must define the extent of agreement needed to
establish such a consensus. Courts have established that general
recognition of safety does not require unanimous agreement. See, e.g.,
United States v. Articles of Drug * * * 5,906 Boxes, 745 F.2d 105, 119
n. 22 (1st Cir. 1984); United States v. Articles of Food and Drug
(Coli-Trol 80), 518 F.2d 743, 746 (5th Cir. 1975) (``What is required
is not unanimous recognition but general recognition''). Importantly,
general recognition of safety does not exist if there is a genuine
dispute among qualified experts that the use of a substance is safe.
See, e.g., Premo Pharmaceutical Laboratories v. United States, 629 F.2d
795, 803-4 (2nd Cir. 1980) (``genuine dispute among qualified experts''
precludes finding of general recognition, and no general recognition
existed as a matter of law where there was a ``sharp difference'' of
expert opinion); United States v. Article of Food * * * Coco Rico, 752
F.2d 11, 15 n 6 (1st Cir. 1985) (substance was not GRAS as a matter of
law based on existence of ``genuine dispute among qualified experts''
regarding safety of use). For discussions of additional judicial
decisions bearing on the criteria for eligibility for classification as
GRAS, see the notice of declaratory order providing our final
determination regarding partially hydrogenated oils (80 FR 34650).
    A conclusion of GRAS status must be based on the totality of the
publicly available and corroborative evidence about the safety of the
substance under the conditions of its intended use, including both
favorable and potentially unfavorable information. Thus, reports of
expert authorities or authoritative entities within the scientific
community may indicate that there is no general recognition of safety
when the reports call into question the safety of a substance for use
in food. However, we disagree that the outcome of an evaluation of such
information can be predetermined as suggested by the comments.
Regardless of whether particular scientific data and information lead
experts to conclude that a substance is safe under the conditions of
its intended use, or raise questions about the safety of the substance
under the conditions of its intended use, the evaluation of whether a
use of a substance in food is safe, and whether safety is generally
recognized, is a case-by-case evaluation. For example, data and
information that lead expert authorities or authoritative entities
within the scientific community to raise a concern about the safety of
the substance under the conditions of its intended use in food would
have reduced significance if the concern was related to a contaminant
in the substance and scientifically valid data and information supplied
by the proponent of GRAS status provide evidence that an improved
method of manufacture eliminates that contaminant.
    See also Response 77, in which we explain that we proposed to
provide the judicial interpretation of section 201(s) of the FD&C Act
in the requirement for the comprehensive discussion of the notifier's
basis for a conclusion of GRAS status to provide more context to
notifiers than merely repeating the statutory language. However, as
discussed in Response 77, we have decided to use the statutory language
(i.e., ``generally recognized'') rather than the proposed term
``consensus'' in the submission requirements for a GRAS notice to
mirror the GRAS criteria in Sec.  170.30, which continue to use the
statutory language rather than the consensus standard applied by the
courts in applying the statutory language to specific situations.
    (Comment 21) In the proposed rule, we asked for comment on the
potential for a conclusion of GRAS status through scientific procedures
to be based in part on the ``substantial equivalence'' of the
applicable substance to a substance that is GRAS through experience
based on common use in food. One comment agrees with the view,
expressed in a 1996 JECFA Report (Ref. 30) and reported in the proposed
rule (62 FR 18938 at 18944), that ``substantial equivalence'' embodies
the concept that if a new food component is found to be substantially
equivalent to an existing food component, the food component could be
considered to be as safe as the existing food component, after taking
into account any processing that the food component may undergo as well
as the intended use and the intake by the population. Several comments
assert that the concept of substantial equivalence, although useful, is
nonetheless ambiguous. One comment asks us to clearly state our
interpretation of this concept in the final rule.
    (Response 21) We have decided not to include the term ``substantial
equivalence'' in the regulatory text of this rule, because whether, and
to what extent, similarity between two substances could support a
conclusion of GRAS status depends on too many situation-specific
variables. As discussed in section IV.N of CFSAN's 2010 experience
document, GRAS notices filed during the Interim Pilot program that
relied on the concept of ``substantial equivalence'' generally
addressed alternative sources of enzymes already used in food (Ref.
18). Most of these notices both emphasized the similarities of the new
enzyme preparations to existing enzyme preparations and explained the
differences between the new enzyme preparation and currently used
enzyme preparations. However, none of these GRAS notices relied solely
on the concept of ``substantial equivalence.'' Instead, these notices
also described other applicable data and information, such as data and
information about the biological source of the enzyme preparation; the
method of manufacture of the enzyme preparation; constituents of the
enzyme preparation that derive from the source organism or the
manufacturing process; the technical effect of the enzyme preparation;
dietary exposure to the enzyme preparation; specifications for the
enzyme preparation; and applicable safety studies.

C. Criteria for Eligibility for Classification as GRAS Through
Experience Based on Common Use in Food

    We proposed to amend the criteria for eligibility for
classification as GRAS through experience based on common use in food
(Sec.  170.30(c)(2)) to state that persons who claim that 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 claim in
accordance with the GRAS notification procedure. We received no
comments that disagreed with this proposed amendment and are finalizing
it as proposed, with conforming changes as shown in table 29.
    See section XXV.B regarding revisions to the criteria for
eligibility for classification as GRAS through experience based on
common use in food for a substance used in animal food.

D. Other Comments on the Criteria for Eligibility for Classification as
GRAS

    (Comment 22) One comment asserts that the proposed rule would add
unnecessary complexity to continued use of substances currently
presumed to be GRAS. This comment also asserts that the proposed rule
would remove the ``pre-1958 exemption'' and, as a result, would place
an unnecessary burden on food producers and processors with respect to
substances

that are the subject of previous conclusions of GRAS status.
    (Response 22) These comments are unclear. By ``pre-1958 exemption''
these comments could mean a conclusion of GRAS status through
experience based on common use in food, which requires common use in
food before January 1, 1958. Alternatively, these comments could be
referring to the statutory exception from the definition of ``food
additive'' for a substance that is the subject of a prior sanction
within the meaning of section 201(s)(4) of the FD&C Act and part 181
(21 CFR part 181). Either way, nothing in this rule would affect a
lawful use of a food substance that is GRAS based on common use in food
prior to January 1, 1958 or that is the subject of a prior sanction.
This rule does not remove GRAS status based on common use in food prior
to January 1, 1958. Likewise, the lawful use of a substance listed in
part 181 as being the subject of a prior sanction is not affected by
this rule.
    However, any person who relies on a conclusion of GRAS status
through experience based on common use in food prior to 1958 or on a
prior sanction within the meaning of section 201(s)(4) of the FD&C Act
needs to consider whether the conditions of use associated with the
applicable substance, such as the foods in which the substance would be
used and the levels of use of the substance, are within the scope of
these statutory provisions. As discussed in section I.D, in 2010 we
issued warning letters informing four companies marketing caffeinated
alcoholic beverages that caffeine, as used in the companies' products,
is an unsafe food additive, and therefore the products are adulterated
under section 402(a)(2)(C) of the FD&C Act, and the companies
subsequently ceased distribution of these products. Thus, we advise any
manufacturer or distributor to carefully consider whether there is
adequate support for concluding that a substance is GRAS under the
conditions of its intended use and to submit a GRAS notice to us if it
intends to manufacture or distribute a food product containing a
substance that has been used in food as a GRAS substance under
conditions of use different from those in the manufacturer's or
distributor's product.
    In addition, new data and information may call into question the
safety of a substance used in food as a GRAS substance, whether the
basis for a conclusion of GRAS status is through experience based on
common use in food or through scientific procedures. As discussed in
section I.A, in 1969 we deleted various cyclamate salts from the GRAS
list because they were implicated in the formation of bladder tumors in
rats; as discussed in section I.D, we recently issued a declaratory
order making a final determination that there is no longer a consensus
among qualified experts that PHOs are GRAS for any use in human food
(80 FR 34650).
    (Comment 23) One comment asks us to require minimum safety or
short-term toxicology studies for all conclusions of GRAS status,
regardless of whether the conclusion is through scientific procedures
or through experience based on common use in food before 1958. This
comment explains that such studies could corroborate safety when GRAS
status is based on common use on food, e.g., by taking into account any
impact of the manufacturing process on food safety.
    (Response 23) We decline this request. We agree that the method of
manufacture can impact safety, regardless of whether GRAS status is
through experience based on common use on food or through scientific
procedures. See, e.g., our guidance entitled ``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'' (Ref. 6). The rule requires submission of a description of
the method of manufacture in sufficient detail to evaluate the safety
of the notified substance as manufactured, regardless of whether the
basis for the conclusion of GRAS status is through scientific
procedures or through experience based on common use in food (see Sec.
170.230(b)). If the method of manufacture has changed over time, a new
evaluation of GRAS status based on scientific procedures may be
warranted. We advise any manufacturer of a substance that is used in
food based on a conclusion of GRAS status to carefully consider the
impact of its method of manufacture on the safety of the substance
before introducing the substance into commerce.
    We disagree that the rule must require minimum safety or short-term
toxicology studies for all conclusions of GRAS status because the kinds
of data and information needed to demonstrate safety (or that could be
used to corroborate safety) will vary based on the substance and its
intended use. A conclusion of GRAS status based on scientific
procedures must be based on the same quantity and quality of scientific
evidence as is required to obtain approval of a food additive (Sec.
170.30(b)). We have issued guidance on the types of data and
information in support of a food additive petition, and these types of
data and information would be useful in the evaluation of the safety of
a substance when the proponent of the substance seeks to demonstrate
that the substance is GRAS under the conditions of its intended use
(see Response 37 and Response 66).
    For a safety assessment of a chemical, the specific types of data
and information generally follow from the chemical structure and
estimated dietary exposure of the substance. For example, chemistry
data, including manufacturing information, as well as information
sufficient to estimate exposure, are necessary to consider in arriving
at a conclusion of GRAS status. Whether toxicological studies are
necessary to demonstrate safety depends on the properties of the
substance such as the presence or absence of chemical alerts, physical
properties, and physiological fate of the substance. For example, well
understood and accepted metabolism information about a substance that
is a component of commonly consumed foods (such as vegetables or
fruits) may provide sufficient safety information to arrive at a
conclusion of GRAS status at a specified level of the use of that
substance in food. As discussed in section III.A.2 of CFSAN's 2010
experience document, during the Interim Pilot program it was CFSAN's
view that toxicological studies were not necessary to evaluate the
safety of substances such as carrot fiber and dried orange pulp (Ref.
18). Likewise, for simple substances (such as minerals and their salts)
that are readily dissociated to components that have long been viewed
as GRAS (e.g., by a listing in part 182 or by a GRAS affirmation
regulation in part 184), toxicological studies would likely not be
necessary. As discussed in section III.A.2 of CFSAN's 2010 experience
document, during the Interim Pilot program it was CFSAN's view that
toxicological studies were not necessary to evaluate the safety of
substances such as potassium bisulfate and seaweed-derived calcium
(with calcium carbonate as the major component) (Ref. 18).
    For a safety assessment of a substance produced from a
microorganism, the specific types of data and information generally
follow from the identity of the microorganism and how the substance is
produced from that microorganism in addition to the substance itself.
For example, the safety of a substance produced from a microorganism
generally considers generally available microbiological data and
information about the potential toxigenicity and

pathogenicity of the microorganism. Whether toxicological studies would
be necessary to demonstrate the safety of the substance as manufactured
would depend on what the substance is and its intended use in food.

E. GRAS Status of Certain Food Substances

    We proposed to remove Sec.  170.30(f), which expresses our intent
to review the GRAS status of certain food substances. We received no
comments that disagreed with our proposal to remove Sec.  170.30(f) and
are removing it as proposed.

VII. Comments on the Substitution of a GRAS Notification Procedure for
the GRAS Affirmation

Petition Process
    Our regulations specify procedures for us to affirm the GRAS status
of the use of a food substance, whether on our own initiative (Sec.
170.35(a) and (b)) or on the petition of an interested person (Sec.
170.35(c)). We proposed to eliminate the GRAS affirmation petition
process in Sec.  170.35(c) and replace it with a GRAS notification
procedure (proposed Sec.  170.36) in which any person may notify us of
a claim that a particular use of a substance is exempt from the
statutory premarket approval requirements based on the notifier's
determination that such use is GRAS. Under the proposed notification
procedure, we would evaluate whether the submitted notice provides a
sufficient basis for a GRAS determination and whether information in
the notice or otherwise available to us raises issues that lead us to
question whether use of the substance is GRAS. We also proposed to
presumptively convert any filed GRAS affirmation petition that is
pending on the date that the petition process is replaced with a
notification procedure (``pending petition'') to a GRAS notice and
provide an opportunity for the person who had submitted a pending
petition (``affected petitioner'') to amend the petition to meet the
requirements for a GRAS notice.
    In the 2010 notice, we discussed several issues broadly applicable
to the proposed substitution of a GRAS notification procedure for the
GRAS affirmation petition process (see table 3).

  Table 3--Issues in the 2010 Notice Broadly Applicable to the Proposed
 Substitution of a GRAS Notification Procedure for the GRAS Affirmation
                            Petition Process
------------------------------------------------------------------------
              Description of
 Issue No.   our request for                   Reference
                 comment
------------------------------------------------------------------------
N/A.......  Our intent to use  75 FR 81536 at 81537.
             ``Plain
             Language'' tools
             such as pronouns
             in the final
             rule.
2.........  Our reasons for    75 FR 81536 at 81538.
             tentatively
             concluding that
             the terms
             ``conclude'' and
             ``conclusion''
             would be more
             appropriate in
             lieu of
             ``determine''
             and
             ``determination'
             '.
17........  Alternative        75 FR 81536 at 81542-81543.
             approach to
             administering
             pending GRAS
             affirmation
             petitions.
------------------------------------------------------------------------

    Several comments support the proposed replacement of the GRAS
affirmation petition process with a GRAS notification procedure. For
example, several comments support the expectation we expressed in the
proposed rule (62 FR 18938 at 18941) that the substitution of a GRAS
notification procedure for the GRAS affirmation petition process would
result in our increased awareness of the composition of the nation's
food supply and the cumulative dietary exposure to GRAS substances.
Most of these comments agree that such increased awareness could be an
advantage of the notification procedure if manufacturers view our
response to a GRAS notice as an incentive to participate in the
program. Many comments that support the proposed replacement of the
GRAS affirmation petition process with a GRAS notification procedure
nonetheless raise questions about how we would administer the pending
GRAS affirmation petitions. We discuss those comments in section XXIII.
    In the following sections, we discuss comments that disagree with
one or more aspects of our proposal to replace the GRAS affirmation
petition process with a GRAS notification procedure (see, e.g., Comment
24, Comment 25, and Comment 32); ask us to clarify how we generally
will administer the proposed GRAS notification procedure (see, e.g.,
Comment 31); or suggest one or more general changes to the proposed
GRAS notification procedure (see, e.g., Comment 27, Comment 28, Comment
30, Comment 31, and Comment 36). After considering these comments, we
are replacing the GRAS affirmation petition process with a GRAS
notification procedure, using the terms ``conclude'' and ``conclusion''
as described in the 2010 notice. As noted in the 2010 notice, the final
rule uses Plain Language tools such as pronouns.
    To improve clarity and readability we used another Plain Language
tool, i.e., the use of short regulatory sections that have limited
subparagraph designations. To do so we redesignated the single proposed
section (i.e., proposed Sec.  170.36) into several distinct, short
sections of regulatory text in a newly established subpart E (GRAS
Notice), with editorial changes associated with the new structure of
the redesignated regulations. See table 4 for the section numbers and
titles of the regulatory text in subpart E. Many provisions of the
regulatory text in subpart E use singular nouns when discussing the
intended use of the notified substance, e.g., the definition of ``GRAS
notice'' means a submission that informs us of your view that a
specified use of a substance is not subject to the premarket approval
requirements of the FD&C Act based on your conclusion that such use is
GRAS. The singular term ``use'' is employed for a simple and consistent
presentation in the regulatory text and does not mean, for example,
that you are limited to notifying us about a single use of the notified
substance.
    We also are establishing in new subpart E the process we described
in the 2010 notice for administering pending GRAS affirmation
petitions. Finally, we made editorial, clarifying, and conforming
changes as shown in table 29. Because the editorial changes associated
with the redesignation of the notification procedure in subpart E are
extensive, we do not list them in table 29.

A. Affirmation on the Initiative of the Commissioner

    We proposed to amend current Sec.  170.35(a) to clarify that the
Commissioner would affirm the GRAS status of a use of a substance,
rather than the substance itself, and to include a grammatical change
to place Sec.  170.35(a) in the singular. The single

comment that expressly addressed this proposed amendment concurred with
us on this point and we are finalizing it as proposed.
    We also proposed to amend current Sec.  170.35(a) to remove the
provision that we may review the GRAS status of a substance added to
food in response to a petition from an interested party. Under current
Sec.  170.35, such a petition would be submitted in accordance with the
provisions of the GRAS affirmation petition process established in
current Sec.  170.35(c). We are deleting this provision as proposed.
The comments we received relevant to our proposed deletion of the
petition-related provision in Sec.  170.35(a) are directed to our
proposed deletion of the GRAS affirmation petition process in current
Sec.  170.35(c), and we discuss those comments in section VII.B.

B. Deletion of the GRAS Affirmation Petition Process

    We proposed to eliminate the GRAS affirmation petition process in
current Sec.  170.35(c).
    (Comment 24) Several comments oppose our proposal to eliminate the
GRAS affirmation petition process. In general, these comments assert
that we should provide manufacturers the option of seeking GRAS
affirmation even though we would be establishing a new notification
procedure. The comments assert that such an option is essential to
support the marketing of a product in certain situations, such as when
recognition of GRAS status is needed by international standard-setting
bodies.
    (Response 24) We acknowledge that a regulation listing the use of a
substance in food could provide some support for marketing a product in
certain situations, but disagree that we should retain the GRAS
affirmation petition process. We note that CFSAN filed more than 600
GRAS notices during the time period 1998 through 2015 (Ref. 19), for an
average of approximately 34 GRAS notices per year, including 69 GRAS
notices filed during 2014 and 51 GRAS notices filed during 2015. By
contrast, during that time CFSAN finalized six GRAS affirmation
regulations. We believe that the ongoing submission of GRAS notices is
evidence that our response to a GRAS notice can support the marketing
of a food substance.
    (Comment 25) Some comments assert that the proposed GRAS
notification procedure would be less protective of food safety than the
GRAS affirmation petition process it would replace. Some comments
assert that our role in ensuring the safety of food ingredients is best
carried out by a review of the data supporting the safety of the
ingredient and that the public should also have access to these data.
These comments also assert that the GRAS affirmation petition process,
in which we conduct a review of supporting data, provides an incentive
to manufacturers to fully research each substance and that removing
this incentive would compromise safety. Other comments assert that the
GRAS notification procedure would be less thorough than the GRAS
affirmation petition process. One comment states that consumers are
concerned about the safety and wholesomeness of substances added to
food and criticizes the proposed rule as not being ``rigorous enough''
and as not creating a ``meaningful process for adequately reviewing the
safety of substances used in human and animal food.''
    (Response 25) We disagree that the notification procedure is less
protective of food safety than the affirmation petition process. In the
proposed rule, we stated that our response to a GRAS notice would not
be equivalent to an agency affirmation of GRAS status because we would
neither receive nor review the detailed data and information that
support the GRAS determination (62 FR 18938 at 18951). These comments
may have misinterpreted that statement to mean that we would not
conduct a substantive evaluation of the summary information that we
receive in a GRAS notice. This is not the case. CFSAN's 2010 experience
document (Ref. 18) demonstrates that we have conducted a substantive
evaluation of the GRAS notices that we received during the Interim
Pilot program. For example, section III.C.1 of CFSAN's 2010 experience
document describes examples of situations in which we contacted a
notifier to request clarification about data and information in the
notice. CFSAN's 2010 experience document also demonstrates that during
the period 1998-2009 CFSAN had questions about 21 percent of GRAS
notices, such that CFSAN either responded to the notifier that the
submitted GRAS notice did not provide a basis for a conclusion of GRAS
status or the notifier asked us to cease to evaluate the GRAS notice
(see section III.B of CFSAN's 2010 experience document). Furthermore,
we believe that the GRAS notification procedure provides us with
greater flexibility to respond to safety concerns that may arise about
a substance that is the subject of a GRAS notice, compared to a
substance that is the subject of a GRAS affirmation regulation, which
would require rulemaking to revoke.
    We acknowledge that the term (i.e., ``evaluate'') we use to
describe our actions when we receive a GRAS notice is different from
the term (i.e., ``review'') we use to describe our actions when we
receive a petition (whether a food or color additive petition or a GRAS
affirmation petition). We decided to use a different term because, as
already noted, the data and information we will receive in a GRAS
notice (i.e., summary data and discussions) are different from the data
and information we receive in a petition (which generally includes the
underlying data from studies described in the petition).
    As discussed in Response 120, we currently make a hyperlink to an
electronic copy of each GRAS notice accessible from our Internet site
and, thus, the public has access to each GRAS notice. We also make our
response to each GRAS notice accessible from our Internet site (see
Sec.  170.275(b), Response 115, and Response 116). We acknowledge that
supporting data and information that are provided to us in the form of
a petition can provide the public with ready access to such data and
information (e.g., through a FOIA request), but disagree that
substitution of the GRAS notification procedure for the GRAS
affirmation petition process has a fundamental impact on the public's
access to supporting data and information, because a conclusion of GRAS
status must be based on generally available data and information. Under
the notification procedure, the publicly accessible GRAS notice both
summarizes the available data and information and provides a list of
publicly available data and information (see Sec. Sec.  170.250 and
170.255). Under the GRAS affirmation petition process, we placed a copy
of each publication provided by the petitioner to support a conclusion
of GRAS status in the public docket for that petition, but our current
practice with respect to copyrighted publications is to refer the
public to the primary records (see Sec.  20.51, Referral to primary
source of records).
    We cannot say whether a petition process would provide an incentive
for a manufacturer to more fully research the safety of a substance
before sending a GRAS notice to us. However, we advise a manufacturer
who intends to submit a GRAS notice to expect a substantive evaluation
of that GRAS notice by us. Likewise, we advise a manufacturer who
reaches a conclusion that a substance is GRAS under the conditions of
its intended use, but does not submit a GRAS notice to us, that when a
substance is not GRAS under

the conditions of its intended use (or is not otherwise excepted from
the definition of ``food additive'' in section 201(s) of the FD&C Act),
that use of the substance is a food additive use subject to our
premarket review as mandated by the FD&C Act. In such circumstances, we
can take various actions, including issuing a warning letter (which we
make public on our Web site) to companies that manufacture or
distribute the food additive and/or food containing the food additive;
issuing a public alert; taking enforcement action to stop distribution
of the food substance and foods containing it on the grounds that such
foods are or contain an unlawful food additive; and issuing a
declaratory order determining that the substance is not GRAS under the
conditions of its intended use and is a food additive subject to
section 409 of the FD&C Act. For example, as already discussed in
section I.D, we recently issued a declaratory order making a final
determination that there is no longer a consensus among qualified
experts that PHOs are GRAS for any use in human food (80 FR 34650). As
another example discussed in section I.D, we have issued warning
letters informing four companies marketing caffeinated alcoholic
beverages that caffeine, as used in the companies' products, is an
unsafe food additive, and therefore the products are adulterated under
section 402(a)(2)(C) of the FD&C Act (Ref. 10 through Ref. 13), and the
companies subsequently ceased distribution of these products. Thus, we
advise any manufacturer or distributor to carefully consider whether
there is adequate support for concluding that a substance is GRAS under
the conditions of its intended use and to submit its conclusion of GRAS
status to us in the form of a GRAS notice.
    (Comment 26) A few comments express skepticism that the
substitution of a GRAS notification procedure for the GRAS affirmation
petition process would result in our increased awareness of the
composition of the nation's food supply and the cumulative dietary
exposure to GRAS substances. These comments assert that the proposed
notification procedure offered a risk (i.e., the risk of a publicly
available ``insufficient basis letter'') without the potential benefit
that was available under the petition process (i.e., a regulation
affirming GRAS status). These comments predict that, unless we modify
the proposed rule substantially, we likely would have less awareness of
GRAS substances under the notification procedure than we currently have
under the GRAS affirmation petition process.
    One comment asserts that the notification procedure would in no
manner be equivalent to the GRAS affirmation petition process, and the
substitution of a notification procedure for a petition process would
be anything but neutral. This comment asserts that the proposed
substitution of a notification process for the affirmation process
would actually reduce the incentive for producers to notify FDA,
because notification would invite regulatory scrutiny without requiring
FDA to attest to a conclusion of GRAS status.
    (Response 26) We disagree that the notification procedure we are
establishing in this rule will reduce the incentive for producers to
notify us. As already noted in Response 24, CFSAN has filed more than
600 GRAS notices between 1998 and 2015, for an average of approximately
34 GRAS notices per year. In contrast, as discussed in section IV.L of
CFSAN's 2010 experience document (Ref. 18), between 1987 and 1996 CFSAN
received a total of fewer than 100 GRAS affirmation petitions, with an
average of approximately 8 GRAS affirmation petitions per year. These
data support the expectation we expressed in the proposed rule that the
substitution of a GRAS notification procedure for the GRAS affirmation
petition process would result in our increased awareness of the
composition of the nation's food supply and the cumulative dietary
exposure to GRAS substances.
    The comments that predict that we would need to modify the final
rule substantially to achieve increased awareness of the nation's food
supply did not suggest specific modifications for this purpose.
However, this document discusses the changes we have made to the
proposed notification procedure as a result of comments, described in
this document and the 2010 notice, that raised specific issues and
concerns regarding the proposed notification procedure. For example,
the final rule defines the term ``amendment'' (Sec.  170.203) and
expressly provides that a notifier may submit a timely amendment to
address our questions (Sec.  170.260(a)). As another example, the final
rule expressly provides that a notifier may ask us to cease to evaluate
a GRAS notice (Sec.  170.260(b)). In addition, see Response 80
regarding our willingness to engage with a notifier to clarify
particular aspects of the notice and Response 96 and Response 97
regarding comments that raise concerns about a publicly available
insufficient basis letter. For a summary of the principal changes to
the notification procedure in this final rule relative to the proposed
rule, see table 2.
    (Comment 27) One comment asks us to require the submission of a
GRAS affirmation petition on a random basis for 20 percent of the GRAS
notices we receive. This comment states that such a requirement would
be essential in light of our concurrent proposal to broaden the types
of safety information that could support GRAS status in the criteria
for eligibility for classification as GRAS through scientific
procedures. The comment refers to this procedure as a ``verification
audit'' and describes a ``verification audit'' as a detailed evaluation
of the scientific data and other technical information. The comment
asks that the final rule give FDA such ``verification authority'' and
asserts that such a verification system would give consumers greater
confidence that the new notification system was not just a system of
deregulation.
    (Response 27) We decline this request. Both the GRAS notification
procedure and the GRAS affirmation petition process that it is
replacing are voluntary procedures and, thus, the comment's position
that we could require a GRAS affirmation petition--on a random or any
other basis--is incorrect. Moreover, we disagree that the revised
criteria for eligibility for GRAS status through scientific procedures
have any bearing on whether we should evaluate a conclusion of GRAS
status through a notification procedure or a petition process. The
revised criteria reflect the nature of substances being added to food,
and the fact that the quantity and quality of scientific evidence
required to demonstrate safety vary considerably depending upon the
estimated dietary exposure to the substance and the chemical, physical,
and physiological properties of the substance. See Response 23.

C. General Comments on the Proposed GRAS Notification Procedure

    (Comment 28) Some comments ask us to require that companies notify
us of a conclusion of GRAS status and assert that we have implied legal
authority to require such notification. These comments express concern
that potentially dangerous substances could enter the food supply
without our knowledge or supervision. Other comments emphasize that the
GRAS notification procedure should remain voluntary and assert that we
lack express statutory authority to require companies to submit GRAS
notices.
    (Response 28) We agree that we lack express statutory authority to
require

companies to submit GRAS notices. In creating the premarket approval
requirement for food additives in the 1958 amendment, Congress excluded
a substance that is GRAS under the conditions of its intended use from
the definition of food additive. The creation of this GRAS provision
reflected Congress' determination that many substances intentionally
added to food for a specific use do not need premarket review by FDA to
ensure their safety, either because their safety has been established
by a long history of use in food, or because their safety has been
established by information that is generally available to and accepted
by qualified experts, regarding the intended conditions of use of a
substance in food. Subsequently, in 1997, the Food and Drug
Administration Modernization Act (FDAMA) amended section 409 of the
FD&C Act to require the establishment of a mandatory food contact
notification program for human food. By contrast, Congress has not
amended section 409 of the FD&C Act to require the establishment of a
premarket GRAS notification procedure--either voluntary or mandatory.
    We did not propose to require the submission to FDA of notices
concerning all conclusions of GRAS status. We recognize that some
comments suggest that such a requirement might be within our legal
authority, even if not expressly required by the FD&C Act. We will
consider these comments and our experience under this final rule in
evaluating what, if any, further action is needed with respect to
ensuring the safety of the food supply. However, mandating submission
of GRAS notices would need to be done in a separate rulemaking to
ensure adequate notice and comment.
    (Comment 29) One comment notes that the proposed rule did not
specifically ask members of the food industry to notify us of all
conclusions of GRAS status. This comment suggests that the final rule
include such a request, explaining that such a provision would help us
to achieve our goal of increasing our awareness of substances added to
food.
    (Response 29) We view our establishment of the GRAS notification
procedure in this final rule, as well as our announcement of the
Interim Pilot program in the proposed rule, as an invitation to
industry to submit GRAS notices to us for evaluation. See also Sec.
170.205, entitled ``Opportunity to submit a GRAS notice.'' The ongoing
submission of GRAS notices during the Interim Pilot program
demonstrates that the food industry is actively submitting GRAS
notices. As already noted in Response 26, we believe that our filing of
more than 600 GRAS notices for substances used in human food is
evidence that we have increased our awareness of the composition of the
nation's food supply and the dietary exposure to GRAS substances.
    (Comment 30) Some comments ask us to require certain postmarket
submissions of exposure and safety data related to all GRAS substances,
to require submissions for conclusions of GRAS status that predate the
final rule, and to require any notifier who ``withdraws'' a GRAS notice
or receives an ``insufficient basis letter'' to notify us about any use
of that substance.
    (Response 30) We decline this request for the same reasons that we
discuss in Response 28. See also the discussions in Response 25 and
Response 35 regarding the responsibility of a manufacturer to ensure
that a substance added to food complies with the FD&C Act, and the
potential that we may disagree with a conclusion of GRAS status and
take regulatory action against use of the food substance when we do so.
    (Comment 31) Some comments ask us to clarify all the information we
expect to be submitted in a GRAS notice. One comment states its
opposition for the proposed GRAS notification procedure, but also
states that if we implement such a program we should establish the
framework and criteria for the voluntary submission of GRAS notices.
Another comment asks us to include core requirements in the final rule.
Another comment asks us to provide more explicit instructions
concerning the level of detail necessary within the required elements
of a GRAS notice.
    (Response 31) Subpart E of part 170 (subpart E) establishes a
comprehensive framework for the submission of GRAS notices, describing
in detail ``core requirements'' such as the seven distinct parts of a
GRAS notice. Subpart E also includes provisions that will govern what
we will do when we receive a GRAS notice, as well as provisions that
will govern disclosure of a GRAS notice. Section 170.30 establishes the
revised criteria for eligibility for classification of the food use of
a substance as GRAS.
    (Comment 32) One comment expresses concern that the proposed GRAS
notification procedure would be viewed as a ``fast-track'' option that
would tempt a company that should submit a food additive petition to
submit a GRAS notice instead.
    (Response 32) We recognize that there is a possibility that some
manufacturers of food ingredients may decide that they do not need to
submit a food additive petition because they have concluded that the
substance is GRAS under the conditions of its intended use; this
possibility exists regardless of how we structure the GRAS notification
procedure. However, a manufacturer's decision that a food additive
petition is not required must be based on the extent to which the
manufacturer has information both that the intended conditions of use
of a substance in food are ``safe,'' and that there is ``general
recognition'' of that safety. In this rule, we clarify the criteria
(Sec.  170.30) that govern when the intended conditions of use of a
substance in food are more properly the subject of a food additive
petition than a GRAS notice.
    The record of our actions during the Interim Pilot program
demonstrates that we will, when appropriate, issue an ``insufficient
basis letter'' or a ``cease to evaluate letter'' signaling that a
petition to obtain a regulation is more appropriate than a GRAS notice.
As described in sections III.A.4 and III.N.2 of CFSAN's 2010 experience
document (Ref. 18), in several cases during the Interim Pilot program
the outcome of CFSAN's review of a GRAS notice was the notifier's
subsequent submission of a food additive petition.
    (Comment 33) One comment expresses the opinion that a GRAS notice
could be an appropriate mechanism to inform us of a view that an
additional use of an approved food additive is GRAS.
    (Response 33) We agree, provided that the available data and
information demonstrate that the criteria for GRAS status are
satisfied. Whether an additional use of a food additive is GRAS depends
on both whether that additional use is safe and on whether the safety
of that additional use is generally recognized by qualified experts. To
support a conclusion of GRAS status for the additional use of the
substance, there must be evidence that qualified experts generally (not
solely FDA experts who conducted a premarket review of a food additive
petition) have evaluated generally available data and information about
the intended conditions of use of the substance, and reached agreement
that those generally available data and information establish the
safety of the additional use of the substance. During the Interim Pilot
program, CFSAN received several GRAS notices informing CFSAN of a
conclusion that an additional use of an approved food additive is GRAS.
As discussed in section III.A.4 of CFSAN's 2010 experience document
(Ref. 18), CFSAN's response to these GRAS notices has been a case-by-
case response

that depends on the circumstances. In several cases, CFSAN had no
questions about the notifier's conclusion of GRAS status for an
additional use of a food additive; in one case, the GRAS notice did not
support GRAS status for the additional use of the food additive, and
the notifier subsequently submitted a food additive petition for the
additional use of the substance.
    (Comment 34) One comment suggests that the GRAS notification
procedure would shift the burden of proof to FDA to demonstrate that a
use of a substance is not safe or not GRAS after the substance is
already on the market.
    (Response 34) We disagree. Under the FD&C Act, the burden of
supporting a conclusion that a substance is GRAS under the conditions
of its intended use is on the proponent of this conclusion. United
States v. An Article of Food, 752 F.2d 11, 15 (1st Cir. P.R. 1985).
This burden of proof remains after the substance is on the market
regardless of whether the proponent asks FDA to evaluate that GRAS
conclusion, and our rule does not change this. By establishing a
process for the submission of GRAS notices for FDA to review, our rule
encourages firms to seek our evaluation of their conclusions, before
they introduce the substance into the market.
    (Comment 35) A few comments note that a notifier who markets a food
substance before we issue our letter responding to the notice runs the
risk that we may disagree with the conclusion of GRAS status. One
comment expresses concern that we would take regulatory action to
remove the substance from the food supply rather than discuss our
concerns with the notifier.
    (Response 35) The comments are correct that a notifier who markets
a food substance before we issue our letter based on our evaluation of
the notice runs the risk that we may disagree with the conclusion of
GRAS status. (We note that a manufacturer who markets a food substance
without submitting a GRAS notice runs a similar risk.) However, we make
every effort to evaluate the data and information submitted on a timely
basis, and in this rule we commit to responding to a GRAS notice within
180 days after filing the notice, with the option to extend an
additional 90 days as needed. Because a substance that is GRAS under
the conditions of its intended use is not subject to premarket review
as a food additive under the FD&C Act, a notifier could decide to
introduce the substance into the market without waiting for the letter;
we could subsequently determine that the substance is an unapproved
food additive, and we may take action to remove the substance from the
food supply.
    See also the discussion in Response 80. Our experience during the
Interim Pilot program demonstrates that we are willing to contact a
notifier to clarify particular aspects of a GRAS notice. As also
discussed in Response 80, under the final rule, we intend to contact a
notifier when we identify a safety concern. However, whether the
purpose of the contact is to provide an opportunity to address that
concern (e.g., in an amendment or in a newly submitted GRAS notice), or
to alert the notifier to our concerns while we prepare an
``insufficient basis letter,'' has been, and will continue to be, a
matter committed to our discretion depending on the totality of the
circumstances.
    (Comment 36) One comment suggests that we ask notifiers who
previously received a ``no questions letter'' under the Interim Pilot
program to review their prior submissions and align them with the
requirements of the final rule.
    (Response 36) We decline this suggestion. The final rule does not
pose any substantially different data requirements than did the Interim
Pilot program in terms of data quality and quantity to support the
conclusion of GRAS status. We do not anticipate, as a general matter,
the need to ask previous notifiers who received a ``no questions
letter'' to provide any supplemental information. However, if we become
aware of data or information that questions the GRAS status of the use
of a substance that has been the subject of a ``no questions letter,''
we may send the notifier a subsequent letter advising the notifier of
those questions (see Sec.  170.265(c)). Because we would make the
subsequent letter readily accessible to the public (see Sec.
170.275(b)(2)), other stakeholders would have ready access to those
questions.
    (Comment 37) One comment states that GRAS ``determinations'' must
be evaluated based on adequate science and recommends that GRAS
``determinations'' comply with our guidance on food additive testing.
    (Response 37) We agree that safe use(s) of a substance must be
supported by adequate science. We do have extensive guidance on food
additive testing (Ref. 31 through Ref. 35), and we agree that this
guidance on food additive testing can be useful in the evaluation of
the safety of a substance when the proponent of the substance seeks to
demonstrate that the substance is GRAS under the conditions of its
intended use. As discussed in Response 128, as resources allow we
intend to re-visit these scientific guidance documents to determine
whether and how to modify them to clarify that our guidance on
evaluating the safety of a food substance generally applies regardless
of whether the substance would be used in food as a food additive or as
a GRAS substance.
    Recently, we issued a notice (79 FR 64603, October 30, 2014)
announcing a public meeting, and requesting comments, on our intent to
update our guidance entitled ``Guidance for Industry and Other
Stakeholders: Toxicological Principles for the Safety Assessment of
Food Ingredients'' (Ref. 35; commonly referred to as our ``Redbook'').
In that notice, we reiterated that general recognition of safety based
upon scientific procedures requires the same quantity and quality of
evidence as is required to approve a food additive. We also asked for
comment on how we should balance the desire for transparency and
consistency in risk assessment, as described in the Redbook, with the
goal of flexibility in applying the most appropriate analysis for
specific contexts.
    (Comment 38) One comment states that the resource-intensive
petition process would be reserved for ingredients not eligible to meet
GRAS criteria, or those which pose questions necessitating indepth
review by FDA scientists, even though the safety standard for GRAS
ingredients and food additives is the same.
    (Response 38) The comment is correct that a food additive petition
would be required for an ingredient that is not eligible for
classification as GRAS and is not otherwise excepted from the statutory
definition of a food additive. We agree that indepth review of the
safety of a substance under the conditions of its intended use in food
by FDA scientists is necessary when there is no basis for a conclusion
that the intended conditions of use have GRAS status. However, see
Response 25. Our evaluation of a GRAS notice is a substantive
evaluation even though we respond to a GRAS notice by letter rather
than by establishing a regulation.
    (Comment 39) One comment asserts that we tentatively concluded that
the proposed notification procedure would allow us to direct our
resources to the more significant questions about GRAS status, without
further explaining what these ``more significant questions'' are. This
comment further asserts that the obvious conclusion is that we will
simply reduce the Federal layer of oversight in the interests of
efficiency and in doing so ignore the history of food law, which has
repeatedly shown

that the public suffers when FDA declines to regulate.
    (Response 39) See the actions we describe in section I.D, on PHOs
and caffeinated alcoholic beverages, for examples of what we mean by
``more significant questions.'' We disagree that directing our
resources in such a manner reduces our oversight; on the contrary, such
actions demonstrate that we will take appropriate steps to address
concerns about the safety of substances marketed under the GRAS
provision of the FD&C Act. The comment provides no basis for its
assertion that the notification procedure ignores the history of food
law or that the public will suffer.
    (Comment 40) One comment points out that our response to a GRAS
notice addresses the question of whether a particular use of a notified
substance is GRAS, without limiting that question to production of that
food substance by a specific manufacturer (e.g., the notifier who
submitted the GRAS notice). This comment asks us to require that any
other food producer who uses the substance in food on the basis of a
GRAS conclusion submitted to FDA in a GRAS notice meet all requirements
and specifications in the submitted GRAS notice, including use of the
same source for the production of the food substance.
    (Response 40) The comment is correct that our response to a GRAS
notice would not limit a food producer other than the notifier from
relying on the submitted GRAS notice, and our response to that GRAS
notice, when that food producer concludes that a substance is GRAS
under the conditions of its intended use in food. The method of
manufacture (including any source specified for the production of the
notified substance) and specifications identified in a GRAS notice are
relevant to both the identity of the substance and its safety for use
in food. We advise any food producer who relies on a GRAS notice
submitted by another person to carefully consider whether its
production process, and/or the intended conditions of use of the
notified substance, fall within the parameters, such as method of
manufacture (including a specified source) and specifications,
addressed by the submitted GRAS notice. We recently issued guidance to
help food producers to do so. See our guidance entitled ``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'' (Ref. 6).

D. Comments on Certain Terms Used in the Proposed Regulatory Text

1. Replacing the Terms ``Determine'' and ``Determination'' With the
Terms ``Conclude'' and ``Conclusion''
    In the 2010 notice, we explained our reasons for tentatively
concluding that the terms ``conclude'' and ``conclusion'' would be more
appropriate in lieu of ``determine'' and ``determination'' and
requested comment on these terms (see Issue 2, 75 FR 81536 at 81538).
    (Comment 41) Many comments support replacing the terms
``determine'' and ``determination'' with the terms ``conclude'' and
``conclusion.'' One comment disagrees with changing the terms
``determine'' and ``determination.'' This comment asserts that the
terms ``determine'' and ``determination'' are more appropriate because
a determination is made based on the sum of the total assembled data
and conclusions. This comment also disagrees with changing the terms
because individuals who already are involved in the GRAS notification
procedure as a result of the Interim Pilot program are already familiar
with the terms and meanings of ``determine'' and ``determination.''
    One comment observes that the terms ``determined'' and
``determination'' are used in Sec.  170.30 of our regulations within
the context of establishing GRAS status. This comment asks us to
clarify how we would apply the terms ``determined,'' ``determination,''
``conclude,'' and ``conclusion'' and whether we would limit how some
terms apply depending on whether a substance is the subject of a GRAS
notice. This comment expresses concern that such a distinction in terms
could lead to a misperception that a substance that is the subject of a
GRAS notice has a more authoritative and/or superior legal standing
than a substance that does not.
    (Response 41) We are replacing the term ``determination'' with
``conclusion,'' and referring to a ``conclusion of GRAS status'' rather
than to a ``GRAS determination,'' throughout the regulatory text for
the GRAS notification procedure. We recognize that notifiers involved
with the GRAS notification procedure may be more familiar with the
terms ``determine'' and ``determination.'' Nevertheless, we believe
that as notifiers gain more experience with the GRAS notification
procedure set forth in this final rule, notifiers will adjust to using
``concludes'' and ``conclusion.''
    We are making conforming changes to current regulations regarding
the use of GRAS substances in food to no longer use the terms
``determine'' and ``determination'' (see the changes to Sec. Sec.
170.3(k), 170.30(c)(1), and 170.30(e) in table 29). We are making these
conforming changes to clarify that there would be no distinction
between a conclusion of GRAS status submitted to us as a GRAS notice
and a conclusion of GRAS status that remains with its proponent as an
independent conclusion (formerly referred to as a ``self-
determination'') of GRAS status.
2. The Terms ``Exempt,'' ``Exemption,'' and ``Claim''
    Several provisions in the proposed rule would use terms such as
``exempt,'' ``exemption,'' and ``claim.''
    (Comment 42) Several comments object to some terms used in the
proposed procedure for submitting a GRAS notice. Some comments object
to proposed title for the GRAS notification procedure, i.e., ``Notice
of a claim for exemption based on a GRAS determination.'' Most of these
comments also object to our characterization of one of the proposed
provisions (proposed Sec.  170.36(c)(1)) as a ``GRAS exemption claim.''
In general, these comments assert that nothing in the FD&C Act or in
the legislative history of the FD&C Act supports designation of GRAS
status as an ``exemption.'' In addition, several comments object to our
use of the term ``claim'' in various proposed provisions because our
use of this term implies that we have legal authority to deny a claim
or that GRAS status is not operative unless a claim is filed.
    (Response 42) We have made the following editorial changes
throughout the regulatory text to no longer use terms such as
``exempt,'' ``exemption,'' and ``claim.'' First, we replaced the term
``exempt'' with the phrase ``not subject to.'' Section 201(s) of the
FD&C Act provides that a substance that is GRAS under the conditions of
its intended use is not within the definition of food additive. Whether
the statutory GRAS provision in section 201(s) is an ``exemption,'' or,
is an ``exclusion,'' is not essential to this rulemaking and, thus, we
need not include any variations of the term ``exempt'' in the final
rule. Second, we replaced the term ``claim'' (when used as a noun) with
the term ``view.'' In the past, we have used the term ``view'' when
describing a statement or assertion that a use of a substance is GRAS
(see, e.g., 62 FR 36749, July 9, 1997). Finally, we simplified the
title of the regulatory text to ``Generally Recognized as Safe (GRAS)
Notice.''

E. Comments on the Use of ``Plain Language'' in the Regulatory Text

    In the 2010 notice, we noted our intent to use ``Plain Language''
tools such as pronouns in the final rule (75 FR 81536 at 81537). The
use of ``Plain Language'' tools in government writing, now called
``plain writing,'' is consistent with the government-wide initiative to
promote transparency, public participation, and collaboration
throughout the Federal Government's programs and activities as set out
in ``Improving Electronic Dockets on Regulations.gov and the Federal
Docket Management System: Best Practices for Federal Agencies'' (Ref.
22).
    (Comment 43) One comment recommends that we use Plain Language
throughout the regulatory text to foster greater understanding about
the regulatory requirements and expectations for the notification
procedure, leading to a more effective program.
    (Response 43) We have used ``Plain Language'' tools (such as short
sections and the use of pronouns) throughout the regulatory text of
subpart E, which establishes the requirements for the GRAS notification
procedure. See table 4 for the section numbers and titles of the
redesignated regulatory text in subpart E.

 Table 4--Redesignation of the GRAS Notification Procedure in Subpart E
------------------------------------------------------------------------
         Section                               Title
------------------------------------------------------------------------
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 FSIS.
170.275..................  Public disclosure of a GRAS notice.
170.280..................  Submission of a supplement.
170.285..................  Disposition of pending GRAS affirmation
                            petitions.
------------------------------------------------------------------------

VIII. Definitions Applicable to a GRAS Notice

A. Definitions We Described in the 2010 Notice

    In the 2010 notice, we requested comment on definitions for the
terms ``amendment,'' ``notified substance,'' ``notifier,'' ``qualified
expert,'' and ``supplement'' (see Issue 3, 75 FR 81536 at 81538). We
received several comments that generally support adding definitions for
these terms, and we are establishing a section in the regulatory text
of subpart E to define these and other terms (see Sec.  170.203).

B. Definition of ``GRAS Notice''

    (Comment 44) Some comments express concern about the potential for
confusion between the proposed GRAS notification procedure and another
FDA ``notification program'', i.e., the premarket notification program
for food contact substances (in part 170, subpart D) that we
established under FDAMA. These comments assert that this confusion can
lead to uncertainty about the nature of the proposed GRAS notification
procedure, such as with respect to market ``exclusivity'' for the
notified substance. One comment states that the terms ``GRAS notice''
and ``GRAS notification'' appear to be used interchangeably in the 2010
notice and asks whether it is our intention to use ``notice,''
``notification,'' or both terms with regard to the proposed procedure
for submission of a conclusion of GRAS status for a use of a food
substance.
    Another comment notes that the proposed rule to establish a GRAS
notification procedure was followed soon thereafter by the rulemaking
to establish the premarket notification program for food contact
substances as authorized by FDAMA (the FCN program; proposed rule 65 FR
43269, July 13, 2000; final rule 67 FR 35724, May 21, 2002). This
comment asserts that although the proposed GRAS notification procedure
and the established FCN program are distinct, industry reasonably
relied on the close temporal proximity of the 1997 proposed rule to
establish a GRAS ``notification'' procedure, and the rulemaking to
establish the FCN program, as contemporaneous guidance for the meaning
of the term ``notification'' under FDAMA. Because the FCN program
provides market ``exclusivity'' for the food contact substance, the
comment asserts that it is understandable why regulated industry would
think that submitting a GRAS notice likewise implies ``exclusivity''
for the substance. The comment notes that FDA is not responsible for
misinterpretations made by industry, but asks us to recognize this lack
of transparency and clarity and remedy it in a fair and equitable
manner.
    (Response 44) In the proposed rule and in this final rule, we use
the term ``notice'' as a noun to refer to the submission that you send
to us and we use the term ``notification'' as an adjective, e.g., to
modify the noun ``procedure.'' In contrast, the FCN program uses the
term ``notification'' as a noun in addition to using the term as an
adjective, consistent with FDAMA's use of the term as a noun. We
continue to use the term ``notification'' as an adjective (e.g., GRAS
notification procedure) in this preamble discussion of the requirements
for submitting a GRAS notice. However, in the regulatory text we only
use the term ``notice,'' and we have added a definition of the term
``GRAS notice'' to the regulatory text (see Sec.  170.203).
    The ``exclusivity'' within the FCN program is provided by section
409(h)(2)(C) of the FD&C Act. See also our implementing regulation at

Sec.  170.100(a), which provides that a FCN is effective for the food
contact substance manufactured or prepared by the manufacturer or
supplier identified in the FCN submission. There is no similar
provision in the FD&C Act or our regulations providing exclusivity for
a substance that is used in food based on a conclusion that the
substance is GRAS under the conditions of its intended use.
C. Other Terms We Are Defining in the Rule
    We are defining the abbreviation ``GRAS'' to mean ``generally
recognized as safe'' so that we can use that abbreviation throughout
the regulatory text without defining it in each section where it
appears. To clarify how pronouns apply in the regulatory text, we also
are specifying in the definition section that ``you'' and ``your''
refer to a notifier, and that ``we,'' ``our,'' and ``us'' refer to FDA.

IX. Opportunity To Submit a GRAS Notice

    We proposed to provide that any person may notify FDA of a claim
that a particular use of a substance is exempt from the statutory
premarket approval requirements based on the notifier's determination
that such use is generally recognized as safe (GRAS) (proposed Sec.
170.36(a)). We are establishing this statement of an opportunity to
submit a GRAS notice in Sec.  170.205, with the editorial changes
described in Response 41 and Response 42.

X. Comments on Administrative Procedures for Submission of a GRAS
Notice

    We proposed that a notice of a ``GRAS exemption claim'' be
submitted in triplicate to a specified address (proposed Sec.
170.36(b)). We also asked for comment on whether it would be
appropriate to require or recommend that the submission include an
electronic copy in addition to the three paper copies (62 FR 18938 at
18946) or, at a minimum, an electronic copy of the proposed ``GRAS
exemption claim'' (proposed Sec.  170.36(c)(1); final Sec.  170.225
(part 1 of a GRAS notice).
    In the 2010 notice, we described comments asking us to permit a
notifier to reference a previously submitted GRAS notice to support a
view that an additional use of the applicable substance is GRAS. We
also discussed a coordinated evaluation process with FSIS when the use
of a notified substance includes use in products subject to regulation
by FSIS. (Note that the discussion in the 2010 notice referred to a
``coordinated review process.'' As discussed in Response 25, we are
using the term ``evaluation'' rather than ``review'' in connection with
GRAS notices. In addition, in a Memorandum of Understanding (MOU)
between FDA and FSIS (Ref. 36), we specify that we will inform the
notifier in writing that the notice will also be ``evaluated'' by FSIS
to determine the suitability of the use of the substance in the
production of meat, poultry, or egg products. Given the discussion in
Response 25 and the terms of the MOU with FSIS, in this document, we
use the term ``coordinated evaluation'' rather than ``coordinated
review.'') We asked for comment relevant to these administrative
procedures (see table 5).

      Table 5--Issues in the 2010 Notice Relevant to Procedures for
                       Administering a GRAS Notice
------------------------------------------------------------------------
              Description of
 Issue No.   our request for                   Reference
                 comment
------------------------------------------------------------------------
4.........  Whether the final  75 FR 81536 at 81538.
             rule should
             include a
             provision to
             expressly permit
             a notifier to
             incorporate into
             a GRAS notice
             data and
             information that
             were previously
             submitted by the
             notifier, or
             public data and
             information
             submitted by
             another party,
             when such data
             and information
             remain in our
             files.
13........  Whether a          75 FR 81536 at 81541-81542.
             notifier who
             submits a GRAS
             notice for such
             a substance
             should provide
             an additional
             paper copy or an
             electronic copy
             of the GRAS
             notice that we
             could send to
             FSIS.
------------------------------------------------------------------------

    Several comments support the administrative procedures that we
proposed or described in the 2010 notice. For example, several comments
support adding a provision to allow a notifier to incorporate
information into a GRAS notice, including data and information
previously submitted by the notifier and public data and information
submitted by another party, because such a provision would be
practical, promote administrative efficiency, or reduce paper. In the
following sections, we discuss comments that disagree with one or more
aspects of the administrative procedures that we proposed or described
as potential modifications in the 2010 notice (see, e.g., Comment 45);
ask us to clarify these administrative procedures (see, e.g., Comment
48 and Comment 49); or suggest one or more changes to these
administrative procedures (see, e.g., Comment 47). After considering
these comments, we are providing that you may submit a GRAS notice
either in electronic format that is accessible for our evaluation or on
paper; for paper submissions, a single paper copy of a GRAS notice is
sufficient.
    We also are finalizing a provision to allow for incorporation into
a GRAS notice of data and information as described in the 2010 notice,
with clarification that the referenced data and information must be
specifically identified. As discussed in the 2010 notice, the provision
specifies that incorporation into a GRAS notice applies only when data
and information remain in our files. We do not retain records
indefinitely; rather, records may be retired to a Federal Records
Center and subsequently disposed of in accordance with our Records
Control Schedule.

A. How To Send a GRAS Notice to FDA

    We proposed to specify in the regulatory text the address where you
would send a GRAS notice. We are finalizing this administrative
provision with updates to reflect the current mailing address and the
editorial changes described in Response 42. See the regulatory text in
Sec.  170.210(a).
    (Comment 45) One comment asserts that a single GRAS notice to
either CFSAN or CVM should suffice to inform both Centers of a
conclusion of GRAS status.
    (Response 45) We disagree. Our regulations directed to human food
are established in subchapter B of 21 CFR (i.e., Food For Human
Consumption, parts 100-199), whereas our regulations directed to animal
food are established in subchapter E of 21 CFR (i.e., Animal Drugs,
Feeds, And Related Products, parts 500-599). We have separately
established requirements applicable to GRAS substances for use in human
food in subchapter B of 21 CFR (e.g., in parts 170, 182, 184, and 186)
and requirements applicable to GRAS substances for use in animal food
in subchapter E of 21 CFR (e.g., in parts 570, 582, and 584). We also
had separately established requirements for the GRAS affirmation
petition process

(which the GRAS notification procedure is replacing) for substances for
use in human food in subchapter B of 21 CFR (i.e., in Sec.  170.35(c))
and requirements applicable to the GRAS affirmation petition process
for substances for use in animal food in subchapter E of 21 CFR (i.e.,
in Sec.  570.35(c)). We address food substances separately for human
use and for animal use because the safety evaluation of a food
substance relates to the conditions of its intended use, and the
conditions of use of a substance in human food can raise different
safety questions than the conditions of use of that same substance in
animal food. For example, a substance containing copper can be safely
used in human food and in food for many animal species, but even small
amounts of copper can be toxic to sheep. As another example, FDA has
affirmed that several uses of propylene glycol in human food are GRAS
(Sec.  184.1666), but propylene glycol is known to be toxic to cats and
FDA has prohibited its use in cat food (see Sec.  589.1001). Therefore,
the final rule establishes separate (albeit parallel) requirements for
submission of a GRAS notice to CFSAN for the use of a substance in
human food and for submission of a GRAS notice to CVM for the use of a
substance in animal food.

B. Option for Submission of Electronic or Paper Copies of a GRAS Notice

    (Comment 46) Most of the comments that responded to our request for
comment on the submission of an electronic copy of a GRAS notice
encourage us to recommend, but not require, submission of an electronic
copy, explaining that an electronic copy would make our administration
of the notification procedure more efficient. However, one comment
notes that electronic technology may not be universally available. As
discussed in Comment 47, another comment expresses concern about
protection for confidential information in an electronic copy. One
comment suggests that if we use an electronic means to make GRAS
notices readily accessible to the public, then we should require that
the submission include an electronic copy. Comments that address Issue
13 support requiring the notifier to provide an additional paper copy
that we would send to FSIS as part of this procedure.
    (Response 46) We agree that an electronic copy will make our
administration of the GRAS notification procedure more efficient. For
example, an electronic copy generated from a word processing format
generally is searchable without the need for Optical Character
Recognition techniques, but an electronic copy generated by scanning a
paper document into ``Portable Document Format'' (``pdf'') requires
Optical Character Recognition before it can be searched electronically.
Furthermore, the Government Paperwork Elimination Act of 1998 (Pub. L.
105-277, Title XVII) requires Federal agencies to give persons who
correspond with these agencies the option of doing so electronically
when practicable as a substitute for paper, and to use electronic
authentication (electronic signature) methods to verify the identity of
the sender and the integrity of the electronic content. We acknowledge
that technology may not be available to every notifier and, thus, the
final rule does not require the submission of an electronic copy.
Instead, the final rule provides that when you submit your GRAS notice,
you may do so either in electronic format that is accessible for our
evaluation or on paper (see Sec.  170.210(b)). Because you have an
option to submit a GRAS notice either electronically or on paper, an
electronic copy will essentially replace the need for a paper copy. In
2010, CFSAN issued draft guidance for how to transmit a submission,
including a GRAS notice, in electronic format (Ref. 37).
    We used electronic means to make submitted GRAS notices accessible
to the public during the Interim Pilot program, and intend to continue
to do so under the final rule. However, we decline the request to
require that the submission include an electronic copy solely because
we are doing so. We acknowledge that an electronic copy will improve
the efficiency with which we make GRAS notices available to the public
(see the public disclosure provisions of this rule in Sec.  170.275).
However, during the Interim Pilot program we made an electronic copy of
a submitted GRAS notice available on the Internet by scanning the paper
GRAS notice to create an electronic pdf document, and we intend to
continue to do so when you submit a GRAS notice on paper under the
final rule.
    We have decided that a single copy of a GRAS notice that is
submitted on paper is acceptable (rather than the three copies that we
proposed to require) and have specified that a single paper copy is
sufficient in the regulatory text (Sec.  170.210(b)). We proposed to
require three copies of a submitted GRAS notice to make it easier to
provide a paper copy of the GRAS notice to all members of our staff who
will evaluate the GRAS notice. However, in practice during the Interim
Pilot program we developed internal procedures in which we scan a GRAS
notice submitted on paper to create an electronic pdf version of the
GRAS notice, and we make the electronic pdf document available to all
staff who will evaluate the GRAS notice. This procedure has reduced the
resources needed to distribute the GRAS notice to our staff, and we
intend to continue to use this procedure when we receive a GRAS notice
on paper. When we coordinate our evaluation of a GRAS notice with FSIS,
we send an electronic copy to FSIS and, thus, an additional paper copy
for use by FSIS is not necessary.
    (Comment 47) One comment expresses concern about the security of
confidential information in an electronic submission. This comment asks
us to allow a notifier to edit an electronic copy to remove
confidential information and present that information only in the paper
copy. Another comment asks us to provide the same protections that
would apply to confidential information in written records to
confidential information in electronic records.
    (Response 47) We decline the request to allow you to edit an
electronic copy of your GRAS notice such that the electronic copy would
differ from the paper copy. If you have concerns about the security of
confidential information in an electronic submission, you have the
option to send the GRAS notice on paper (see Response 46). The
protections applicable to confidential information are the same
regardless of whether the information is in written or electronic form
(see part 20, ``Public Information''). In particular, under Sec.
20.20(e), ``Policy on disclosure of Food and Drug Administration
records,'' the term ``record'' (as well as any other term used in Sec.
20.20 in reference to information) includes any information that would
be an agency record maintained by the Agency in any format, including
an electronic format.
    In addition, the final rule requires you to state in writing your
view as to whether any of the data and information in your GRAS notice
are exempt from disclosure under FOIA (e.g., as trade secret or as
commercial or financial information that is privileged or confidential)
(see Sec.  170.225(c)(8)). The final rule also requires that if you
view any of the data and information in your GRAS notice as exempt from
disclosure under FOIA, you must identify the specific data and
information (Sec.  170.250(d)). Together, these provisions will give us
notice as to whether we will need to evaluate specific data and
information under the FOIA and take steps to protect applicable data
and information from public disclosure.

C. Incorporation Into a GRAS Notice

    (Comment 48) One comment supports adding a provision to allow a
notifier to incorporate data and information into a GRAS notice as long
as the notifier has explicit first-hand knowledge of the referenced
files. Other comments address the limitation, discussed in the 2010
notice, that data and information that are submitted by a person other
than the notifier must be public, noting that it would be difficult to
prevent the use of public information by others or that incorporating
such data and information into a GRAS notice would be consistent with
the criteria for general recognition of safety.
    (Response 48) A notifier must have sufficient knowledge of data and
information submitted by another party to be able to identify the
specific data and information that would be incorporated into a GRAS
notice. To make this clear, the provision we are adding to the rule to
allow for incorporation of data and information into a GRAS notice
requires that such data and information be specifically identified. For
example, we expect you to provide a specific file number (e.g., for a
GRAS notice or a food additive petition) that contains the referenced
data and information, and to identify the specific data and information
in that file (rather than to broadly incorporate into a GRAS notice the
entire file without explaining which data and information to
incorporate). Although you may also incorporate into a GRAS notice a
``food master file'' (provided that you specifically identify both the
file number and the data and information in that file that you are
asking us to incorporate into a GRAS notice), the regulatory text does
not include ``food master file'' as an example of the type of file that
you may reference because we do not have a regulatory definition for
``food master file.'' See the discussion of ``food master file'' in
Response 49.
    A notifier also must have sufficient knowledge of data and
information submitted by another party to be able to discuss these data
and information in the narrative that is required in part 6 of a GRAS
notice (see Sec.  170.250). This narrative must explain the basis for
the notifier's view that the notified substance is safe under the
conditions of its intended use and that GRAS criteria--for both general
availability and general acceptance--are satisfied. In other words, a
GRAS notice must present the independent conclusions of the notifier
regarding the basis for GRAS status, even if the data and information
on which the notifier relies were submitted by another person.
    Consistent with the discussion in the 2010 notice, the provision we
are adding to allow for incorporation of data and information into a
GRAS notice specifies that data and information submitted by another
party must be ``public.'' By ``public,'' we mean data and information
that we have provided (or would provide) in response to a request under
the FOIA, or that are otherwise publicly available (e.g., in a docket).
Consistent with the views expressed in the comments, we see no reason
to preclude you from referring us to such public information when we
already have such information in our files, provided that you identify
the specific data and information and the file(s) containing these data
and information. We would not, for example, search our files to look
for the referenced data and information. However, if you intend to
incorporate into a GRAS notice data and information that were submitted
by another party, and that you believe to be public information, we
recommend that you explain the basis for your view that the data and
information are public. If we need to evaluate the status of the data
and information under the FOIA (e.g., because the data and information
have not previously been disclosed to the public), we may decline to
file the GRAS notice until we have evaluated the status of the
referenced data and information under the FOIA. Doing so would be
appropriate in light of the perspective of the comments, as discussed
in the 2010 notice, that the process of incorporation would be
administratively efficient (75 FR 81536 at 81538) and the limited time
(i.e., 180 days) that we have to respond after we file a submission as
a GRAS notice (see Sec.  170.265(b)). A notifier who intends to
incorporate data and information that we must evaluate under the FOIA
before we determine whether the data and information can be disclosed
under the FOIA may find it advantageous to request those data and
information under our public information procedures (see part 20), and
then either include the data and information we disclose in response to
that request in the submitted GRAS notice, or refer us to
administrative information identifying the completed FOIA request when
asking us to incorporate the data and information into a GRAS notice.
    (Comment 49) One comment states its presumption that a ``food
master file'' is not available for public viewing, referring to a
``long-standing center policy'' that such files are confidential. This
comment asks us to continue to provide that a ``food master file'' be a
confidential repository for proprietary data, such as utility and
manufacturing information.
    (Response 49) We establish a ``food master file'' for a variety of
reasons. For example, a person who submits a food additive petition may
need us to evaluate data and information regarding a substance that the
petitioner purchases from another party for use in the manufacture of
the food additive. The petitioner may ask the manufacturer of that
substance to provide the applicable data and information to us, and we
then place the submitted data and information in a food master file.
Although some or all of the data in such a food master file may be
exempt from public disclosure (e.g., as trade secret information or
confidential commercial information), a determination of whether
specific data and information in a food master file is exempt from
public disclosure is based on the status of the data and information
under FOIA rather than on the type of file in which we place the data
and information. We do not limit the type of data and information that
may be included in a food master file to proprietary data and
information.
    See also Sec.  170.215 and Response 48. Data and information
submitted by a party other than a notifier must be public information.
If you previously submitted a food master file to us, and you view the
data and information in your food master file as proprietary, you must
explain in part 6 of your GRAS notice how GRAS criteria are satisfied
(see Sec.  170.250(e)).

XI. General Requirements Applicable to a GRAS Notice

    The final rule specifies two general provisions applicable to a
GRAS notice (see Sec.  170.220). As discussed in Response 43, we have
redesignated the single proposed section (i.e., proposed Sec.  170.36)
into several distinct, short sections of regulatory text in a newly
established subpart E (GRAS Notice). The first general provision
specifies that a GRAS notice has seven parts, refers the user to the
regulatory text for each of these parts, and specifies that you must
submit the information specified in each of these parts on separate
pages or sets of pages (Sec.  170.220 (a)). Submitting the information
on separate pages or sets of pages is consistent both with the guidance
we developed for preparation of a GRAS notice in electronic format
(Ref. 37) and with long-standing requirements for other regulatory
submissions, such as a food additive petition (see Sec.  171.1(f)) and
a health claim petition (see Sec.  101.70(g)).

    The second general provision specifies that you must include each
of the seven parts; if a part is not included, you must include an
explanation of why that part does not apply to your GRAS notice (Sec.
170.220 (b)). We added this provision because some parts of a GRAS
notice (e.g., Part 4 (self-limiting levels of use) and Part 5
(experience based on common use in food before 1958)) would not apply
to most GRAS notices. Specifying that Parts 4 and 5 do not apply to a
particular GRAS notice will make it clear that a notifier is aware of
the requirements of those parts and has acknowledged that they do not
apply.

XII. Comments on Part 1 of a GRAS Notice: Signed Statements and
Certification

    We proposed that a GRAS notice must include a dated and signed
claim that a particular use of a substance is exempt from the premarket
approval requirements of the FD&C Act because the notifier has
determined that such use is GRAS. The proposed ``GRAS exemption claim''
would include: (1) The name and address of the notifier; (2) the common
or usual name of the notified substance; (3) the applicable conditions
of use of the notified substance, including the foods in which the
substance is to be used, levels of use in such foods, and the purposes
for which the substance is used, including, when appropriate, a
description of the population expected to consume the substance; (4)
the basis for the GRAS determination (i.e., through scientific
procedures or through experience based on common use in food); and (5)
a statement that the data and information that are the basis for the
notifier's GRAS determination are available for our review and copying
at reasonable times at a specific address set out in the notice or will
be sent to us upon request (proposed Sec.  170.36(c)(1)). In the 2010
notice, we requested comment on several issues relevant to the proposed
``GRAS exemption claim'' (see table 6).
    As discussed in Response 42, we have made editorial changes
throughout the rule to replace the term ``exempt'' with the phrase
``not subject to'' and to replace the term ``claim'' (when used as a
noun) with the term ``view.'' In light of these editorial changes, in
the remainder of this section we generally use the term ``proposed
signed statements'' (rather than ``GRAS exemption claim'') when
referring to the provisions that we had proposed to include in proposed
Sec.  170.36(c)(1)).

    Table 6--Issues in the 2010 Notice Regarding the Proposed Signed
                       Statements in a GRAS Notice
------------------------------------------------------------------------
              Description of
 Issue No.   our request for                   Reference
                 comment
------------------------------------------------------------------------
6a........  How to best        75 FR 81536 at 81539.
             ensure that the
             identity and
             authority of the
             person who is
             signing the GRAS
             notice is made
             clear.
6b........  Whether to         75 FR 81536 at 81539.
             require that a
             notifier submit
             a statement that
             to the best of
             his knowledge,
             the GRAS notice
             is a
             representative
             and balanced
             submission that
             includes
             unfavorable
             information, as
             well as
             favorable
             information,
             known to him and
             pertinent to the
             evaluation of
             the safety of
             the substance.
6b........  Whether to         75 FR 81536 at 81539.
             require a
             notifier to
             certify to the
             statement
             (described in
             Issue 6a)
             regarding the
             representative
             and balanced
             nature of the
             GRAS notice.
7.........  Whether to         75 FR 81536 at 81539.
             require that the
             GRAS notice
             include the name
             of the notified
             substance, using
             an appropriately
             descriptive
             term, instead of
             the ``common or
             usual name'' of
             the notified
             substance.
8.........  Whether to         75 FR 81536 at 81539.
             explicitly
             require that the
             information
             submitted in the
             ``GRAS exemption
             claim'' exclude
             non-public
             information.
9b *......  Whether to         75 FR 81536 at 81540.
             require that a
             notifier who
             identifies one
             or more trade
             secret(s) in the
             GRAS notice
             explain why it
             is trade secret
             information and
             how qualified
             experts could
             conclude that
             the intended use
             of the notified
             substance is
             safe without
             access to the
             trade secret(s).
9c *......  Whether to         75 FR 81536 at 81540.
             require that a
             notifier who
             identifies
             confidential
             commercial or
             financial
             information in
             the GRAS notice
             explain why it
             is confidential
             commercial or
             financial
             information and
             how qualified
             experts could
             conclude that
             the intended use
             of the notified
             substance is
             safe without
             access to such
             information.
13........  Whether to make    75 FR 81536 at 81541-81542.
             our coordinated
             evaluation
             process with
             FSIS explicit in
             the final rule.
------------------------------------------------------------------------
* In the 2010 notice, Issues 9b and 9c asked how qualified experts could
  conclude that the intended use of the notified substance is ``GRAS''
  rather than ``safe.'' However, the qualified experts evaluate safety
  rather than GRAS status; the person who is responsible for the
  conclusion of GRAS status considers the view of the qualified experts
  on safety in reaching the conclusion that GRAS criteria are satisfied.
  In the remainder of this document, we describe Issues 9b and 9c with
  respect to whether qualified experts could conclude that the intended
  use of the substance is ``safe'' rather than ``GRAS.''

    In general, comments directed to the proposed signed statements
agree that we should modify the provisions as discussed in Issues 6a,
6b, 7, 8, 9a, 9b, 9c, and 13 in the 2010 notice. In the following
sections, we discuss comments that address the issues discussed in the
2010 notice (see, e.g., Comment 50, Comment 51, Comment 57, Comment 58,
and Comment 59); address provisions of the proposed signed statements
that we did not discuss in the 2010 notice (see, e.g., Comment 53); ask
us to clarify how we will interpret the provisions of the proposed
signed statements and potential modifications (see, e.g., Comment 54
and Comment 55); or suggest one or more changes to the proposed signed
statements and potential modifications (see, e.g., Comment 52, Comment
56, and Comment 59). After considering these comments, we are
establishing requirements for Part 1 of a GRAS notice to include
certain signed statements and a certification as shown in table 7, with
editorial, clarifying, and conforming changes as shown in table 29.
(See Sec.  170.225.) Table 7 identifies changes we made relative to the
proposed rule or the description in the 2010 notice other than the
editorial, clarifying, and conforming changes shown in table 29 and the
additional editorial changes associated with the redesignation of
proposed Sec.  170.36(c)(1) as Sec.  170.225.
    We did not receive comments disagreeing with the proposed
requirement for a GRAS notice to: (1) Be dated and signed by a
responsible official of your organization, or by your attorney or
agent; (2) provide your name and address; and (3) provide the
applicable conditions of use of the notified substance. Therefore, we
are establishing those requirements in the rule (see Sec.
170.225(c)(1), (2), and (4)).

See Comment 42 for our discussion of comments on the terms used in
final Sec.  170.225(c)(6), in which you inform us of your view that the
notified substance is not subject to the premarket approval
requirements of the FD&C Act based on your conclusion that the
substance is GRAS under the conditions of its intended use; see
Response 42 for the editorial changes we made in response to those
comments.

        Table 7--Final Requirements for Signed Statements and a Certification in Part 1 of a GRAS Notice
----------------------------------------------------------------------------------------------------------------
                                                                                Revisions (other
                                                                                than editorial,
                                         Proposed        Issue No.  in  Description. Part 1    clarifying, and
    Final designation in  the       designation in the     the 2010        of your  GRAS     conforming changes)
    regulatory text  (Sec.   )       regulatory text        notice            notice:           relative to the
                                        (Sec.   )                                              proposed rule or
                                                                                the  2010 notice
----------------------------------------------------------------------------------------------------------------
170.225(a).......................  170.36(c)(1).......             N/A  Must be dated and    N/A.
                                                                         signed by a
                                                                         responsible
                                                                         official of your
                                                                         organization, or
                                                                         by your attorney
                                                                         or agent.
170.225(b).......................  N/A................               8  Must not include     Makes an exception
                                                                         any information      for Sec.
                                                                         that is trade        170.225(c)(8),
                                                                         secret or            which requires you
                                                                         confidential         to state your view
                                                                         commercial           as to whether any
                                                                         information.         of the data and
                                                                                information in
                                                                                Parts 2 through 7
                                                                                of your GRAS
                                                                                notice are exempt
                                                                                from disclosure
                                                                                under the FOIA.
170.225(c)(1)....................  N/A................             N/A  Informs us that you  N/A.
                                                                         are submitting a
                                                                         GRAS notice in
                                                                         accordance with
                                                                         subpart E.
170.225(c)(2)....................  170.36(c)(1)(i)....             N/A  Provides the name    N/A.
                                                                         and address of
                                                                         your organization.
170.225(c)(3)....................  170.36(c)(1)(ii)...               7  Provides the name    N/A.
                                                                         of the notified
                                                                         substance, using
                                                                         an appropriately
                                                                         descriptive term.
170.225(c)(4)....................  170.36(c)(1)(iii)..             N/A  Describes the        Uses the term
                                                                         intended             ``subpopulation''
                                                                         conditions of use    rather than
                                                                         of the notified      ``population''.
                                                                         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
                                                                         substance.
170.225(c)(5)....................  170.36(c)(1)(iv)...             N/A  Informs us of the     Specifies
                                                                         statutory basis      that a conclusion
                                                                         for your             of GRAS status
                                                                         conclusion of GRAS   through scientific
                                                                         status (i.e.,        procedures is in
                                                                         through scientific   accordance with
                                                                         procedures or        both Sec.
                                                                         through experience   170.30(a) and (b).
                                                                         based on common      Specifies
                                                                         use in food).        that a conclusion
                                                                                of GRAS status
                                                                                through experience
                                                                                based on common
                                                                                use in food is in
                                                                                accordance with
                                                                                both Sec.
                                                                                170.30(a) and (c).
170.225(c)(6)....................  170.36(c)(1).......               2  States your view     See Response 42.
                                                                         that the notified
                                                                         substance is not
                                                                         subject to the
                                                                         premarket approval
                                                                         requirements of
                                                                         the FD&C Act based
                                                                         on your conclusion
                                                                         that the substance
                                                                         is GRAS under the
                                                                         conditions of its
                                                                         intended use.
170.225(c)(7)....................  170.36(c)(1)(v)....             N/A  States your          You agree to a
                                                                         agreements           procedure in which
                                                                         regarding making     we can access data
                                                                         data and             and information
                                                                         information          ``during customary
                                                                         available to us      business hours''
                                                                         upon our request.    rather than ``at
                                                                                reasonable
                                                                                times''.
170.225(c)(8)....................  N/A................               9  States your view as  N/A.
                                                                         to whether any of
                                                                         the data and
                                                                         information in
                                                                         Parts 2 through 7
                                                                         of your GRAS
                                                                         notice are exempt
                                                                         from disclosure
                                                                         under the FOIA.
170.225(c)(9)....................  170.36(c)(4).......              6b  Certifies that, to   Specifies that your
                                                                         the best of your     GRAS notice is
                                                                         knowledge, your      ``complete'' in
                                                                         GRAS notice is a     addition to
                                                                         complete,            ``representative''
                                                                         representative,      and ``balanced''.
                                                                         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.
170.225(c)(10)...................  170.36(c)(1).......              6a  States both the      N/A.
                                                                         name and position
                                                                         or title of the
                                                                         person who signs
                                                                         the GRAS notice.

170.225(c)(11)...................  N/A................              13  When applicable,     We added a
                                                                         states whether       statement
                                                                         you: (1) Authorize   communicating how
                                                                         us to send any       you want us to
                                                                         trade secrets to     handle trade
                                                                         FSIS; or (2) ask     secret information
                                                                         us to exclude any    in a copy of a
                                                                         trade secrets from   GRAS notice that
                                                                         the copy of the      we send to FSIS.
                                                                         GRAS notice that
                                                                         we will send to
                                                                         FSIS.
----------------------------------------------------------------------------------------------------------------

A. Exclusion of Trade Secret and Confidential Commercial Information
From the Signed Statements

    (Comment 50) Several comments support a provision specifying that
information submitted in the signed statements exclude non-public
information. One of these comments states that the information in the
signed statements should be publicly disclosed because public
disclosure is critical to the continued success of the GRAS program,
and that for the use of a substance to be ``generally recognized as
safe'' the data and research supporting a conclusion of GRAS status
must be available for public view. Other comments disagree that non-
public information should be excluded from the signed statements and
assert that the final rule should allow for the submission of limited
amounts of non-public information at the discretion of the notifier or
when necessary to clarify the safety of the notified substance for the
purposes of our evaluation. These comments emphasize we should take
care to remove such non-public information from any public disclosure
or, or at a minimum, discuss or clear our intent to disclose non-public
information with the notifier before disclosing it.
    (Response 50) Some of these comments appear to misinterpret the
reach of our request for comment in Issue 8 in the 2010 notice. We
narrowly directed Issue 8 to the signed statements that would provide
the name and address of the notifier; the name of the notified
substance; the applicable conditions of use of the notified substance;
the statutory basis for the conclusion of GRAS status; and agreement to
make the data and information that are the basis for the notifier's
conclusion of GRAS status available for our review and copying. The
signed statements provide administrative information rather than safety
information and, as discussed in the 2010 notice, we extract notice-
specific information from the signed statements for the purpose of
informing the public about GRAS notices that we are evaluating.
However, some comments seem to be addressing the issue of whether other
sections of a GRAS notice (e.g., Part 2 of a GRAS notice (in which a
notifier describes the method of manufacture of the notified substance)
and Part 6 of a GRAS notice (in which a notifier discusses the safety
of the notified substance)) can include non-public information.
    Consistent with our request for comment in Issue 8, the final rule
specifies that a notifier must not include any information that is
trade secret or confidential commercial information in Part 1 of a GRAS
notice, except in the statement in Sec.  170.225(c)(8) (see Sec.
170.225(b) and the discussion of Sec.  170.225(c)(8) in Response 57).
This provision does not preclude a notifier from including non-public
information in other parts of a GRAS notice. However, if a notifier
views any submitted data and information as exempt from disclosure
under the FOIA then that notifier must identify the specific data and
information, and explain how there could be a basis for a conclusion of
GRAS status if qualified experts generally do not have access to those
data and information (see Sec.  170.250(d) and (e)). Section 170.250(d)
and (e) is consistent with the criteria for eligibility for
classification as GRAS, because: (1) The criteria provide that general
recognition of safety may be corroborated by unpublished information;
and (2) the notifier has a burden to explain how GRAS criteria are
satisfied given that certain data and information in the GRAS notice
are trade secret or confidential commercial information.
    See section XIII.B for a discussion of comments regarding including
non-public information in part 2 of a GRAS notice (particularly with
respect to the method of manufacture). Regarding whether we would
``clear our intent'' to disclose non-public information with the
notifier before disclosing it, see Response 70. Regarding how we treat
non-public information in a GRAS notice, see section XXI regarding the
provisions of the final rule regarding public disclosure of information
in a GRAS notice. Under Sec.  170.275(c), we will disclose information
that is not exempt from public disclosure in accordance with part 20.

B. Name of the Notified Substance, Using an Appropriately Descriptive
Term

    (Comment 51) Some comments agree that the signed statements should
identify the name of the notified substance using an ``appropriately
descriptive term'' instead of the ``common or usual name,'' and also
agree with our statement in the 2010 notice that the ``appropriately
descriptive term'' may be the same as the common or usual name of the
substance in some circumstances (75 FR 81536 at 81539). One comment
disagrees and asks us to continue to specify that the signed statements
in a GRAS notice identify the name of the notified substance using the
common or usual name of the notified substance. This comment recommends
that a notifier work with us to establish the common or usual name of
the notified substance if the common or usual name is not known or well
defined. This comment also asks us to include the common or usual name
of the notified substance in any ``no questions letter'' from us to
make the common our usual name clear to the public. A few comments
support requiring that the signed statements include both the common or
usual name of the notified substance, as well as an appropriately
descriptive term for the notified substance. One comment asks us to
continue the practice, described in the 2010 notice (75 FR 81536 at
81539), of reminding notifiers that our response to a GRAS notice
should not be considered an endorsement for any given term for the
purpose of complying with the labeling provisions of the FD&C Act.

    (Response 51) The final rule requires that you provide the name of
the notified substance, using an appropriately descriptive term, in
Part 1 of your GRAS notice (Sec.  170.225(c)(3)). The appropriately
descriptive term may be the same as the common or usual name of the
substance under our labeling regulations (see 21 CFR 102.5). We decline
the request to use resources that we are directing to the evaluation of
the safety and regulatory status of food substances under sections 201
and 409 of the FD&C Act to also address the labeling requirements of
the FD&C Act given the limited time (i.e., 180 days) that we have to
respond (see Sec.  170.265(b)). You may consult with our staff in
operating divisions that address the labeling requirements of the FD&C
Act, currently CFSAN's Office of Nutrition and Food Labeling (for human
food); however, doing so would be a separate process from the GRAS
notification procedure. (See section XXV.C for contact information for
CVM.)

C. Intended Conditions of Use of the Notified Substance

    We did not receive comments disagreeing with the proposed
requirement for the signed statements in a GRAS notice to include the
applicable conditions of use of the notified substance, including the
foods in which the substance is to be used, levels of use in such
foods, and the purposes for which the substance is used, including,
when appropriate, a description of the population expected to consume
the substance, and we are establishing this requirement in the final
rule (see Sec.  170.225(c)(4)). As noted in table 29, the final rule
refers to the ``intended conditions of use'' rather than the
``applicable conditions of use'' for consistency with other provisions
in the rule. The final rule also uses the term ``subpopulation'' rather
than ``population'' to provide more context about when it would be
appropriate to specify the expected consumers of a food. Most foods are
broadly available to all consumers; a few are more specifically
targeted to particular subpopulations, such as persons with specific
dietary needs (such as persons on liquid diets or persons with
conditions like phenylketonuria), infants consuming infant formula, and
persons seeking alternatives to commonly used food ingredients (such as
persons on a gluten-free diet).

D. Statutory Basis for the Conclusion of GRAS Status

    (Comment 52) Some comments ask us to modify the rule to provide
that the statutory basis for a conclusion of GRAS status may be through
scientific procedures, through experience based on common use in food,
or through both scientific procedures and experience based on common