certification statements will be required in a GRAS notice, we intend
to modify the form that we make available for the submission of a GRAS
notice (i.e., Form FDA 3667 (Ref. 38)) to likewise remind any person
who submits a GRAS notice of the applicability of criminal penalties
for a materially false, fictitious, or fraudulent statement to the U.S.
Government.
    See also Response 78. We also expect you to describe unpublished
data and information that you consider to be corroborative of safety
(e.g., if you consider that the unpublished data and information
warrant sharing with any ``GRAS panel'' that you convene).
    (Comment 77) One comment asserts that the proposed requirement for
a GRAS notice to include the basis for concluding that there is
consensus among qualified experts about the safety of the substance
misstates the statutory standard for general recognition in section
201(s) of the FD&C Act. This comment asserts that the term
``consensus'' denotes complete or near unanimity, whereas the standard
of general recognition requires that qualified experts predominantly,
but not unanimously, accept the safety of the substance. Although the
comment acknowledges that the proposed rule stated that the term
``consensus'' does not imply unanimity (62 FR 18938 at 18941), the
comment argues that the example used in our explanation, about whether
a single published report questioning the safety of use of a substance
in food would preclude general recognition, wrongly implied that
general recognition requires near unanimity (62 FR 18938 at 18941). The
comment asks us to revise the rule by replacing the term ``consensus,''
which does not appear in the statute, with the phrase ``general
recognition,'' which derives from the statute itself.
    (Response 77) As discussed in the proposed rule (62 FR 18938 at
18939), our interpretation that general recognition requires consensus
is consistent with the case law on the general recognition standard.
See United States v. Western Serum Co., Inc., 666 F.2d 335, 338 (9th
Cir. 1982); United States v. Articles of Drug...Promise Toothpaste, 624
F.Supp. 776, 778 (N.D. Ill. 1985), aff'd 826 F.2d 564 (7th Cir. 1987);
United States v. Articles of Drug...Hormonin, 498 F.Supp.2d 424, 435
(D.N.J. 1980). See also the discussion of the consensus standard in
Response 20.
    We proposed to provide our interpretation of section 201(s) of the
FD&C Act in the requirement for Part 6 of a GRAS notice to provide more
context to notifiers than merely repeating the statutory language. We
disagree with the comment's assertion that the example we described in
the proposed rule requires ``near unanimity''; CFSAN's experience
during the Interim Pilot program demonstrates that CFSAN's
``insufficient basis letters'' did not apply a standard of ``near
unanimity'' when evaluating the notifier's basis for a conclusion of
GRAS status (see section III.A.3 of CFSAN's 2010 experience document
(Ref. 18)).
    However, we have decided to use the statutory language (i.e.,
``generally recognized'') rather than the proposed term ``consensus''
because the revised GRAS criteria that we are establishing in Sec.
170.30 continue to use the statutory language rather than the consensus
standard applied by the courts in applying the statutory language to
specific situations. Using the statutory language in both the GRAS
criteria and the requirement for the submission of a narrative in a
GRAS notice will emphasize your burden to explain how the data and
information in the notice regarding the safety of the notified
substance under the conditions of its intended use satisfy the GRAS
criteria.
    See also Response 128, in which we respond to comments recommending
that we clarify that the same standards apply to a conclusion of GRAS
status regardless of whether the conclusion is submitted to us as a
GRAS notice or is not submitted to us. As noted in Response 128, we
believe that the provisions of the GRAS notification procedure will be
a useful resource to any person who intends to use a substance in food
based on a conclusion of GRAS status, regardless of whether the
conclusion of GRAS status is submitted to us in a GRAS notice. In
developing any recommendations (e.g., in guidance) that would broadly
apply to any conclusion of GRAS status, it is simpler to consistently
use the same regulatory text in both the GRAS criteria and the
submission requirements for a GRAS notice.
    (Comment 78) One comment notes that industry has various options
for handling confidential information. For example, confidential
agreements are commonly used instruments to help maintain the
confidentiality of proprietary trade secret information, and therefore
qualified experts on GRAS panels can have access to such information if
it is necessary for a conclusion of GRAS status. The comment asks us to
require that notifiers indicate whether qualified experts (such as on
the notifier's GRAS panel) had access to trade secrets when they
concluded that the substance is safe under the conditions of its
intended use.
    (Response 78) The rule establishes no requirements specific to a
GRAS panel. However, we agree that it is appropriate for a notifier to
indicate whether qualified experts (such as on the notifier's GRAS
panel) who reviewed the data and information supporting safety had
access to safety-related trade secrets in reaching a conclusion that
the notified substance is safe under the conditions of its intended
use. Therefore, we are requiring that a notifier explain how there
could be a basis for a conclusion of GRAS status if

qualified experts generally do not have access to non-public safety-
related data and information (see Sec.  170.250(e)). This requirement
applies to all non-public safety-related data and information, not just
trade secret information, and is not limited to non-public safety-
related data and information that are included in the notice. As
requested by the comment, this requirement would apply if the notifier
provided non-public safety-related information to outside experts (such
as on a GRAS panel). As already discussed, if a GRAS panel considers
non-public safety-related information that a notifier does not include
in a GRAS notice, we also expect the notifier to inform us that the
GRAS panel had access to such information, consistent with the
notifier's signed statement that the GRAS notice is a complete,
representative, and balanced submission (see Sec.  170.225(c)(9)) (see
Response 58 and Response 69).
    See also table 11 and table 15. The rule also requires that a
notifier state his view as to whether any of the data and information
in Parts 2 through 7 of a GRAS notice are exempt from disclosure under
the FOIA (see Sec.  170.225(c)(8)) and identify what specific data and
information in the notice are generally available, and what specific
data and information in the notice are not generally available (see
Sec.  170.250(a)(2) and (d)). Collectively, the requirements in
Sec. Sec.  170.225(c)(8) and (9) and 170.250(a)(2), (d), and (e)
address the underlying issue in the comment's request, i.e., that there
must be a basis for a conclusion of GRAS status if some safety-related
data and information that a notifier assesses in his deliberations are
non-public (e.g., trade secret information or otherwise are
confidential information), regardless of whether the notifier shares
such information with a GRAS panel. If a GRAS notice does not provide a
basis for a conclusion that the notified substance is safe under the
conditions of its intended use without access to such information, we
would respond to the notice with an ``insufficient basis letter.'' If
we respond with a ``no questions letter,'' and later determine that the
GRAS notice was not ``complete'' (e.g., because it did not describe
unpublished reports of investigations that are, or may appear to be,
inconsistent with the conclusion of GRAS status), we may send the
notifier a subsequent letter regarding the omission; such a letter
would be readily accessible to the public (Sec. Sec.  170.265(c) and
170.275(b)(2)).
    (Comment 79) One comment suggests that if the qualified experts are
FDA reviewers, an option might be for the notifier to submit a
``sanitized'' version of the GRAS notice, excluding non-public
information, together with a separate appendix to the GRAS notice where
the notifier would include relevant trade secrets or confidential
information needed to support the conclusion of GRAS status.
Alternatively, we could require that a notifier submit two versions of
the submission: (1) A sanitized version that excludes non-public
information; and (2) a more detailed version including the confidential
information. The comment states that these options would both allow our
reviewers access to the information and facilitate the process of
promptly making GRAS notices available for public disclosure.
    (Response 79) In enacting the GRAS provision, Congress clearly
contemplated a process of concluding that a food substance is GRAS
under the conditions of its intended use as an alternative to
submission of a food additive petition to FDA and establishment of a
regulation prescribing the conditions under which the substance may be
safely used. It follows 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'' (such as our scientific staff who evaluate GRAS notices). The
suggestion of this comment that a notifier could rely exclusively on
evaluation by FDA experts to support his view that there is a basis for
concluding that there is consensus among ``qualified experts'' is
inconsistent with the GRAS provision in section 201(s) of the FD&C Act,
which requires general recognition among qualified experts. See also
the discussion in Response 70, in which we explain our reasons for why
we may decide to decline to file a GRAS notice that is accompanied by a
separate file containing data and information that you view as non-
public.

XVIII. Comments on Steps a Notifier May Take Before We Respond to a
GRAS Notice

    In the 2010 notice, we described comments regarding steps you may
take before we respond to your GRAS notice (see table 17). As noted in
section VIII.A, we are establishing a definition for ``amendment'' in
the rule (see Sec.  170.203). In the following paragraphs, we discuss
additional comments regarding the issues in table 17. Some of these
comments agree that the rule should have such a provision. Other
comments ask us to clarify how such a provision would operate in
practice (see, e.g., Comment 82) or suggest one or more changes to the
provision as we described it in the 2010 notice (see, e.g., Comment 80,
Comment 81, and Comment 83). After considering these comments, we are
establishing two provisions regarding steps you may take before we
complete our evaluation of a GRAS notice. The first provision specifies
that you may submit a timely amendment to your filed GRAS notice, to
update your GRAS notice or in response to a question from us, before we
respond to your notice by letter (see the regulatory text of Sec.
170.260(a)). The second provision specifies that you may ask us to
cease to evaluate your GRAS notice as described in the 2010 notice,
with clarifications as a result of comments (see the regulatory text of
Sec.  170.260(b)). One clarification is that such a request does not
preclude you from submitting a future GRAS notice with respect to the
notified substance. A second clarification is that we will send you a
letter informing you of our decision regarding your request (see the
regulatory text of Sec.  170.265(b)(3)).

 Table 17--Issues in the 2010 Notice Regarding Steps You May Take Before
                     We Respond to Your GRAS Notice
------------------------------------------------------------------------
              Description of
 Issue No.   our request for                   Reference
                 comment
------------------------------------------------------------------------
3a........  Whether to define  75 FR 81536 at 81538.
             ``amendment'' to
             mean any data or
             other
             information that
             you submit
             regarding a
             filed GRAS
             notice before we
             respond to the
             notice.
5.........  Whether the final  75 FR 81536 at 81538-81539.
             rule should
             explicitly
             provide that you
             may request in
             writing that we
             cease to
             evaluate your
             GRAS notice at
             any time during
             our evaluation
             of that GRAS
             notice.
------------------------------------------------------------------------

    See section XXV.I for a discussion of comments regarding steps you
may take before we respond to your GRAS notice for a substance used in
animal food, and for our response to those comments.

A. Communicating With a Notifier Before We Respond to a GRAS Notice

    (Comment 80) Several comments note that the proposed rule did not
say that we would contact a notifier, before we issue our publicly
available response, to provide preliminary feedback regarding our
evaluation of a GRAS notice. One of these comments asks us to include a
provision specifying that we may communicate with the notifier about
any aspect of a notice while the notice is pending. Some comments
express concern that a letter listing answerable and nonsubstantive
questions about a GRAS notice could cause confusion and
misunderstanding in the marketplace, particularly if additional
information, clarification, or amendment would address our concerns.
    (Response 80) We decline the request to include a provision
specifying that we may communicate with you about any aspect of a
notice while your notice is pending. As discussed in section III.C.1 of
CFSAN's 2010 experience document (Ref. 18), during the Interim Pilot
program CFSAN contacted several notifiers to request clarification
about data and information in the notice under the framework of
existing regulations governing meetings and correspondence (Sec.
10.65(g)). It is not necessary to duplicate the existing procedures in
Sec.  10.65(g) in the requirements for the GRAS notification procedure.
    We infer that this comment is specifically asking us to require
that we contact you to provide preliminary feedback before we respond
to your GRAS notice with an ``insufficient basis letter.'' As discussed
in section III.C.1 of CFSAN's 2010 experience document (Ref. 18), our
experience during the Interim Pilot program demonstrates that we are
willing to engage in a dialog with a notifier to clarify particular
aspects of a GRAS notice. As discussed in section IV.H.4 of CFSAN's
2010 experience document (Ref. 18), our experience during the Interim
Pilot program also demonstrates that we do not issue an ``insufficient
basis letter'' with ``nonsubstantive questions.'' Although we have
issued ``insufficient basis letters'' due to an overall poor quality of
a submission, to conserve resources our practices have evolved so that
we generally do not file such submissions as GRAS notices (see section
XIX.A regarding filing decisions and section III.K of CFSAN's 2010
experience document (Ref. 18)). Although we expect to contact you when
we have questions, whether we intend to provide you with an opportunity
to submit an amendment to a GRAS notice before responding to the notice
has been, and will continue to be, a matter committed to our
discretion.
    In the following paragraphs, we discuss some key factors we intend
to consider regarding the purpose of our contact with you regarding
your GRAS notice, particularly with respect to whether we intend to
provide you with an opportunity to submit an amendment to a GRAS
notice. These factors are: (1) Whether our questions can be addressed
by a timely, clarifying amendment; (2) whether our evaluation
identifies a safety concern; and (3) whether we question whether GRAS
criteria are satisfied, even if our evaluation does not identify a
safety concern. See also the discussion in Response 85 regarding
factors that could lead us to decline to file a submission as a GRAS
notice, rather than to file it for our evaluation of your view that the
notified substance is GRAS under the conditions of its intended use and
issue an ``insufficient basis letter.''
    We agree that an ``insufficient basis letter'' listing answerable
questions about a GRAS notice could cause confusion and
misunderstanding in the marketplace, particularly if additional
information, clarification, or amendment would address our concerns.
Section III.C.1 of CFSAN's 2010 experience document provides examples
of circumstances where CFSAN contacted a notifier and expected that the
information exchanged between CFSAN and the notifier would clarify,
rather than substantively amend, the original notice. We intend to
continue contacting notifiers in such circumstances. By ``clarify,
rather than substantively amend,'' we mean that the amendment would add
or modify specific sections in the notice, not that the clarifying
information would necessarily be nonsubstantive in nature. For example,
as discussed in Response 96 during the Interim Pilot program we
contacted notifiers when the notice contained insufficient information
about dietary exposure and when the notice contained insufficient
information to adequately identify the substance. We did so because it
is efficient, for us as well as the notifier, to bring a GRAS notice to
closure with a ``no questions letter'' when it is likely that a timely,
clarifying amendment would resolve our questions. For example, it is
more efficient for us to bring a GRAS notice to closure while our
reviewers are already immersed in the substantive evaluation of the
notice, rather than to issue an ``insufficient basis letter'' and begin
the evaluation process anew when the notifier addresses the questions
in a new GRAS notice. See section XVIII.B for a discussion of what we
mean by a ``timely'' amendment.
    If we file your submission as a GRAS notice and our evaluation of
the available data and information identifies a safety concern, the
purpose of our contact with you would depend on whether the safety
concern could be addressed by a timely, clarifying amendment. For
example, in some cases the available data and information may support
safety only under modified conditions of use relative to the conditions
of use described in your GRAS notice, and our contact with you would
focus on your opportunity to address the safety concern through a
timely amendment specifying modified conditions of use. However, if we
believe that the safety concern could not be addressed through a
timely, clarifying amendment or by re-submission of a new GRAS notice
(e.g., after studies are conducted to address the safety concern), we
likely would contact you to make you aware of our concerns and then
issue an ``insufficient basis letter'' that clearly and fully
articulates our reasons for that safety concern, including the full
context of the risk to human or animal health.
    If we file your submission as a GRAS notice and find that your
narrative does not support a conclusion of GRAS status, even if the
available data and information support your view that the notified
substance is safe under the conditions of its intended use (e.g.,
because data and information that are necessary to establish safety are
not generally available), the purpose of our contact with you would
focus on your opportunity to address the regulatory status of the
notified substance. For example, it may be possible for you to submit a
new GRAS notice after publishing applicable data and information and
allowing sufficient time to allow the expert scientific community to
access the published information. Alternatively, it may be more
appropriate for you to consider the notified substance as a food
additive under the conditions of its intended use, and to make a
premarket submission such as a food additive petition. For examples of
circumstances leading to the options for addressing questions about the
regulatory status of the substance when we have not identified a safety
concern, see section III.A.4 of CFSAN's 2010 experience document (Ref.
18). Any letter we issue would

include our view of the regulatory status of the substance at the time
that we issued the letter, based on the generally available data and
information at that time.

B. Submitting an Amendment

    Comments support adding a provision to clarify that you may submit
an amendment to your GRAS notice and, thus, we are establishing a
provision specifying that you may submit a timely amendment to your
filed GRAS notice (Sec.  170.260(a)). In some cases, you would submit
such an amendment after we contact you to discuss our questions about
your GRAS notice. (See the discussion in Response 80 regarding
contacting a notifier.) In other cases, you may conclude that it is
appropriate to submit an amendment to update your GRAS notice on your
own initiative, e.g., if new data and information about the notified
substance under the conditions of its intended use become available
after we file your submission as a GRAS notice. Depending on the
circumstances, you could then decide to explain your view that the new
data and information do not alter the basis for your conclusion of GRAS
status; alternatively, you could decide to ask us to cease to evaluate
your GRAS notice while you evaluate the impact of the new data and
information on the GRAS status of the notified substance under the
conditions of its intended use (see Sec.  170.260(b)).
    By timely, we mean that you submit your amendment in a timeframe
that provides us with sufficient time to evaluate it before we respond
to your GRAS notice. Given that the rule requires us to end our
evaluation and respond to your GRAS notice within 180 days, with an
extension of up to an additional 90 days on an as needed basis Sec.
170.265(b)(1)), we reserve the right to not consider your amendment if
you submit it so late in our evaluation that it would impact our
ability to respond within our established timeframes. Therefore, as a
companion provision, the rule also provides that we will consider any
timely amendment that you submit to a filed GRAS notice, to update your
GRAS notice or in response to a question from us, before we respond to
you by letter based on our evaluation of your notice if we deem that
doing so is feasible within the established timeframes (see Sec.
170.265(a)(4)). If we deem that considering your amendment is not
feasible within the established timeframes, we will inform you that we
are not considering your amendment.
    See also the discussion in Response 101, which emphasizes that the
role of an amendment is to clarify questions that we have about your
conclusion of GRAS status rather than to substantively amend the GRAS
notice.

C. Notifier's Request That We Cease To Evaluate a GRAS Notice

    (Comment 81) Some comments ask us to make public the reason for a
notifier's request that we cease to evaluate a notice. One comment asks
that any new information, or questions about the scientific consensus
about whether a substance is safe, be made clear to the public as well
as FDA. Another comment expresses concern that companies ask FDA to
cease evaluations of their GRAS notices with ``alarming frequency.''
    (Response 81) We are establishing a provision specifying that a
notifier may ask us to cease to evaluate his GRAS notice (see Sec.
170.260(b)). As a companion provision, we are specifying that if a
notifier asks us to cease to evaluate a GRAS notice, we will send the
notifier a letter informing the notifier of our decision regarding that
request (see Sec.  170.265(b)(3)). As discussed in section III.E of
CFSAN's 2010 experience document (Ref. 18), during the Interim Pilot
program CFSAN's ``cease to evaluate letters'' generally repeated any
reason specified in a request letter, but may not have otherwise
described the reasons underlying the request. If a notified substance
is marketed even though we issue a ``cease to evaluate letter,'' there
could be confusion about the GRAS status of the notified substance even
when the conditions of use in the marketplace differ from the notified
use that was the subject of the ``cease to evaluate letter.'' For
example, a notifier could ask us to cease to evaluate a GRAS notice
because we identified a safety concern about the specified use level of
the notified substance in food products, and then decide to market the
substance at a lower use level than the level specified in the GRAS
notice, where we would no longer have that concern. In addition, as
discussed in the proposed rule we proposed to make all response letters
readily accessible to the public because such a system will properly
underscore a notifier's acceptance of responsibility for the conclusion
of GRAS status, and a GRAS notice that is submitted to us is a public
notice (62 FR 18938 at 18953). A ``cease to evaluate letter'' signals
that a submitted GRAS notice does not provide an adequate basis for a
conclusion that the notified substance is GRAS under the conditions of
its intended use, even though we do not issue an ``insufficient basis
letter.'' Given the public nature of a GRAS notice, it is appropriate
for the reasons leading to a ``cease to evaluate letter'' to also be
public. Therefore, as of October 17, 2016, we intend to change this
practice and increase transparency by describing the reasons leading to
any ``cease to evaluate letter.''
    Table 1 in CFSAN's 2010 experience document (Ref. 18) shows that
approximately 16 percent of GRAS notices that CFSAN responded to during
the 12-year period spanning 1998 through 2009 came to closure when the
notifier asked us to cease to evaluate a GRAS notice. Table 1 in
CFSAN's 2010 experience document also shows that CFSAN issued equal
numbers of ``cease to evaluate letters'' and ``insufficient basis
letters'' during the years 1998 through 2002 (i.e., 16 ``cease to
evaluate letters'' and 16 ``insufficient basis letters''). However,
during the years 2003 through 2009 CFSAN issued 31 ``cease to evaluate
letters,'' but no ``insufficient basis letters.'' In addition, table 1
in CFSAN's 2016 experience document (Ref. 19) shows that during the
years 2010 through 2015 CFSAN issued 48 ``cease to evaluate letters''
but only one ``insufficient basis letter.'' We acknowledge that there
has been a distinct shift between the ratio of the number of ``cease to
evaluate letters'' compared to the number of ``insufficient basis
letters'' issued during the years 1998 through 2002 and the
corresponding ratio for letters issued during the years 2003 through
2015. We consider that the data in the experience document demonstrate
an evolving practice in which CFSAN has declined to file some
submissions as GRAS notices when the notice lacks much of the required
data and information necessary for us to evaluate a notifier's view
that the notified substance is GRAS under the conditions of its
intended use (see Response 85). In addition, such a frequency
demonstrates that CFSAN has been willing to contact notifiers with
questions about a conclusion that the notified substance is GRAS under
the conditions of its intended use. As discussed in Response 80, when
our questions cannot be addressed by a timely amendment, contacting the
notifier provides the notifier an opportunity to re-submit a new GRAS
notice or other regulatory submission (such as a food additive
petition) that addresses our questions.
    As discussed in section III.E of CFSAN's 2010 experience document
(Ref. 18), in many cases a notifier who received a ``cease to evaluate
letter'' resubmitted a new GRAS notice, and CFSAN responded with a ``no
questions letter.'' For many GRAS notices, the

questions we raised and discussed with the notifier clearly addressed
issues other than a fundamental safety concern. For example, some of
the letters that CFSAN lists in section III.E of its 2010 experience
document provide reasons such as preparing a new notice that will not
contain any confidential business information and that will clarify
that the statutory basis for the conclusion of GRAS status is through
scientific procedures; needing to revise an estimate of dietary
exposure; and clarifying and providing additional information for a new
notice. However, CFSAN only made these reasons transparent to the
public because the notifier chose to provide these reasons in his
request that we cease to evaluate the GRAS notice. In other
circumstances, the public had no way to know what the issue was until
we responded to the resubmitted notice. We intend to continue to
contact a notifier to discuss our questions, and provide an opportunity
for the notifier to ask us to cease to evaluate the GRAS notice (e.g.,
so that the notifier can submit a new GRAS notice that addresses the
issues). However, we also intend to briefly describe these issues in a
``cease to evaluate letter'' that follows that contact. As CFSAN did
during the Interim Pilot program, we intend to consider any reasons a
notifier provides for the request, and to include those reasons in our
``cease to evaluate letter.'' If, however, we conclude that a
notifier's explanation does not adequately describe the reasons leading
to a ``cease to evaluate'' request, we intend to explain the reasons
for ceasing to evaluate the notice from our point of view. Doing so
will both ensure clear communication about the reasons and make the
reasons transparent to the public.
    As discussed in Response 80, if we identify a safety concern and
believe that the safety concern could not be addressed through a
timely, clarifying amendment, by re-submitting a new GRAS notice, or by
submitting another premarket submission (such as a food additive
petition), we likely would issue an ``insufficient basis letter'' even
though we would have contacted the notifier to discuss our concerns.
    Asking us to cease to evaluate a GRAS notice does not guarantee
that we will honor that request. Depending on the circumstances, we may
decide to decline the request and instead respond with an
``insufficient basis letter''; depending on the time remaining between
when we receive the request and the timeframes by which we must respond
to the GRAS notice, we may either send the notifier a separate letter
declining the request, or note in the ``insufficient basis letter''
that we had declined the request. See the discussion in section III.C.1
of CFSAN's 2010 experience document (Ref. 18) for an example of a
situation in which CFSAN responded with an ``insufficient basis
letter'' after a notifier asked CFSAN to cease to evaluate its GRAS
notice, submitted a new GRAS notice, and asked CFSAN to cease to
evaluate the second submitted GRAS notice.
    (Comment 82) One comment asks us to clarify that a notifier's
request that we cease to evaluate a GRAS notice would be without
prejudice for future submissions.
    (Response 82) The final provision specifies that your request that
we cease to evaluate a GRAS notice does not preclude you from
submitting a future GRAS notice with respect to the notified substance.
    (Comment 83) One comment asks us to specify that, if feasible, the
files could be returned to the notifier at the notifier's expense.
    (Response 83) We decline this request. As discussed in the 2010
notice (75 FR 81536 at 81538-81539), our current regulations regarding
public information stipulate that no person may withdraw records
submitted to FDA (see Sec.  20.29), and those regulations will apply to
any GRAS notice that we receive. To make this clear, the provision we
are establishing in the final rule provides an opportunity for you to
ask us to ``cease to evaluate'' a GRAS notice rather than ``withdraw''
a GRAS notice.
    (Comment 84) Some comments ask us to specify that if a notifier
requests that we cease to evaluate a submitted GRAS notice, such
notices will remain in our files and will be available for public
disclosure.
    (Response 84) See Sec.  20.29 and the discussion of Issue 5 in the
2010 notice (75 FR 81536 at 81538-81539). If a notifier asks us to
cease to evaluate a submitted GRAS notice, the notice will remain in
our files and will be available for public disclosure in accordance
with part 20. It is not necessary to repeat the provisions of Sec.
20.29 in the GRAS notification procedure.

XIX. Comments on What We Will Do With a GRAS Notice

    We proposed that: (1) We would acknowledge receipt of a notice,
within 30 days of receipt, by informing the notifier in writing of the
date on which the notice was received (proposed Sec.  170.36(d)); (2)
we would respond to the notifier in writing within 90 days of receipt
of the notice (proposed Sec.  170.36(e)); and (3) a copy of any
subsequent letter that we issued regarding a GRAS notice would be
readily accessible for public review and copying (proposed Sec.
170.36(f)(2)(iii)). In the 2010 notice, we asked for comment on issues
relating to what we will do with a GRAS notice as shown in table 18.

  Table 18--Issues in the 2010 Notice Regarding What We Will Do With a
                               GRAS Notice
------------------------------------------------------------------------
              Description of
 Issue No.   our request for                   Reference
                 comment
------------------------------------------------------------------------
12........  Whether we should  75 FR 81536 at 81541.
             make explicit
             the process by
             which we make a
             filing decision,
             including the
             factors we would
             use to determine
             whether to file
             a submission as
             a GRAS notice.
14........  Whether we should  75 FR 81536 at 81542.
             retain a set
             timeframe for us
             to respond to a
             GRAS notice,
             and, if so,
             whether it
             should be 90
             days or another
             timeframe.
------------------------------------------------------------------------

    In the following sections, we discuss comments on what we will do
when we receive a GRAS notice. After considering these comments, we are
establishing requirements in Sec.  170.265 for what we will do when we
receive a GRAS notice as shown in table 19, with editorial, clarifying,
and conforming changes as shown in table 29. Table 19 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(d), (e), and
(f)(2)(iii) as Sec.  170.265. See section XXV.I for a discussion of
comments specific to a filing decision for a substance used in animal
food.

                      Table 19--Final Requirements for What FDA Will Do With a GRAS Notice
----------------------------------------------------------------------------------------------------------------
                                                                                Revisions (other
                                                                                than editorial,
                                         Proposed        Issue No. in                          clarifying, and
    Final designation in  the       designation in the     the  2010        Description      conforming changes)
    regulatory text  (Sec.   )       regulatory text        notice                              relative to the
                                        (Sec.   )                                              proposed rule or
                                                                                the  2010 notice
----------------------------------------------------------------------------------------------------------------
170.265(a)(1)....................  N/A................              12  We will conduct an   N/A.
                                                                         initial evaluation
                                                                         of your submission
                                                                         to determine
                                                                         whether to file it
                                                                         as a GRAS notice
                                                                         for evaluation of
                                                                         your view that the
                                                                         notified substance
                                                                         is GRAS under the
                                                                         conditions of its
                                                                         intended use.
170.265(a)(2)....................  170.36(d)..........              12  If we file your      N/A.
                                                                         submission as a
                                                                         GRAS notice, we
                                                                         will send you a
                                                                         letter that
                                                                         informs you of the
                                                                         date of filing.
170.265(a)(3)....................  N/A................              12  If we do not file    Clarifies that we
                                                                         your submission as   would inform you
                                                                         a GRAS notice, we    by letter if we do
                                                                         will send you a      not file your
                                                                         letter that          submission as a
                                                                         informs you of       GRAS notice.
                                                                         that fact and
                                                                         provides our
                                                                         reasons.
170.265(a)(4)....................  N/A................              3a  We will consider     Clarifies that we
                                                                         any timely           will only consider
                                                                         amendment that you   an amendment if we
                                                                         submit to a filed    deem that doing so
                                                                         GRAS notice, to      is feasible within
                                                                         update your GRAS     the established
                                                                         notice or in         timeframes.
                                                                         response to a
                                                                         question from us,
                                                                         before we respond
                                                                         to you by letter
                                                                         based on our
                                                                         evaluation of your
                                                                         notice if we deem
                                                                         that doing so is
                                                                         feasible within
                                                                         the established
                                                                         timeframes. If we
                                                                         deem that
                                                                         considering your
                                                                         amendment is not
                                                                         feasible within
                                                                         the established
                                                                         timeframes, or if
                                                                         we have granted
                                                                         your request to
                                                                         cease to evaluate
                                                                         your notice, we
                                                                         will inform you
                                                                         that we are not
                                                                         considering your
                                                                         amendment.
170.265(b)(1)....................  170.36(e)..........              14  Within 180 days of    Specifies
                                                                         filing, we will      that the timeframe
                                                                         respond to you by    for our response
                                                                         letter based on      is 180 days,
                                                                         our evaluation of    rather than 90
                                                                         your notice. We      days.
                                                                         may extend the 180   Provides
                                                                         day timeframe by     for an extension
                                                                         90 days on an as     of our evaluation
                                                                         needed basis.        by 90 days on an
                                                                                as needed basis.
170.265(b)(2)....................  N/A................              14  If we extend the     Provides that we
                                                                         timeframe, we will   will inform you if
                                                                         inform you of the    we extend the
                                                                         change in writing    timeframe for our
                                                                         as soon as           response.
                                                                         practicable but no
                                                                         later than within
                                                                         180 days of filing.
170.265(b)(3)....................  N/A................               5  If you ask us to     Companion change in
                                                                         cease to evaluate    light of new
                                                                         your GRAS notice,    regulatory text
                                                                         we will send you a   (in Sec.
                                                                         letter informing     170.260(b))
                                                                         you of our           expressly
                                                                         decision regarding   providing that you
                                                                         your request.        may ask us to
                                                                                cease to evaluate
                                                                                your GRAS notice.
170.265(c).......................  170.36(f)(2)(iii)..             N/A  If circumstances     Clarifies that we
                                                                         warrant, we will     may send a
                                                                         send you a           subsequent letter,
                                                                         subsequent letter    in addition to
                                                                         about the notice.    specifying under
                                                                                the public
                                                                                disclosure
                                                                                provisions of the
                                                                                rule that such a
                                                                                letter would be
                                                                                readily available
                                                                                to the public (see
                                                                                Sec.
                                                                                170.275(b)(2)).
----------------------------------------------------------------------------------------------------------------

A. Filing Decision

    (Comment 85) One comment asks for greater refinement, clarity, and
transparency when we decline to file a GRAS notice. Some comments ask
us to communicate any questions or concerns that could be quickly
addressed upon submission of a GRAS notice. Another comment asks us to
use specific criteria for a ``decline to file'' determination when
format and general categories are adequate. Another comment states that
an explicit process for how we will make a filing decision need not be
detailed ``in the public domain'' even though it would be beneficial to
the notifier.
    Another comment asks us to specify the criteria that we use to
decide to provide verbal feedback to a notifier (e.g., by telephone)
rather than send the notifier a letter informing the notifier that we
have declined to file a submission as a GRAS notice. This comment
expresses concern that our refusal to explain the problem in a letter
could be interpreted to mean that we have safety concerns. This comment
asserts that a process in which we neither provide specific guidance,
nor provide written feedback, when we decline to file a submission as a
GRAS notice would both discourage voluntary submissions of GRAS
conclusions from industry and conflict with GAO's recommendations (in
their 2010 report) that we should take steps to increase our awareness
of independent conclusions of GRAS status.
    (Response 85) These comments raise a number of issues regarding the
importance of a written communication from us to a notifier when we
decline to file a submission as a GRAS notice, including transparency
and the potential that lack of a written explanation for why we
declined to file

a submission as a GRAS notice could lead to suppositions, such as
whether we have safety concerns. To address these issues, the final
rule provides that if we do not file a submission as a GRAS notice, we
will send the notifier a letter that informs the notifier of that fact
and provides our reasons for not filing the submission as a GRAS notice
(see Sec.  170.265(a)(3)). We would not place that letter ``in the
public domain'' by including it in our publicly available Inventory of
GRAS Notices, because the submission had not been filed as a GRAS
notice and, thus, there would be no entry where we would place the
letter. However, whether the letter would be releasable in response to
a FOIA request would be a case-by-case determination based on the
contents of the letter and the provisions of part 20.
    We are not specifying in the regulatory text the factors that could
lead us to decline to file a submission as a GRAS notice, because the
factors that apply to a particular GRAS notice may be very specific to
that notice. Importantly, a GRAS notice presents an opportunity for a
notifier to inform us about a conclusion of GRAS status rather than an
opportunity for a notifier to test a hypothesis that there is a
sufficient basis to reach a conclusion of GRAS status. If our initial
evaluation of a submission demonstrates that it lacks much of the
required data and information necessary for us to evaluate the
notifier's view that the notified substance is GRAS under the
conditions of its intended use, our current practice is to decline to
file it as a GRAS notice (see Sec.  170.265(a)(3)). By declining to
file a submission as a GRAS notice, we would both conserve our own
resources and provide the notifier an opportunity to submit a new GRAS
notice, that contains appropriate data and information and an adequate
narrative, rather than move forward knowing that an amendment necessary
for us to evaluate the notifier's view that the notified substance is
GRAS under the conditions of its intended use would be so substantive
as to make the original submission largely irrelevant. For additional
examples of factors we have considered in determining whether to file a
submission as a GRAS notice, see the examples we provided in the 2010
notice (75 FR 81536 at 81541), the discussion of filing decisions in
section III.K of CFSAN's 2010 experience document (Ref. 18), Response
48, and Response 70. As discussed in Response 152, CVM intends to
consider the same factors that CFSAN considers regarding whether to
file a submission as a GRAS notice.
    (Comment 86) In the 2010 notice, we explained that we may decide to
respond to a submission as general correspondence, rather than file it
as a GRAS notice, if the subject of the submission is: (1) Already
authorized for use under our regulations; or (2) a mixture of
substances that are already authorized for use under our regulations.
One comment asks us to clarify how we would determine that the use of a
substance is authorized for use under our regulations, with respect to
the similarity of factors such as: (1) The substance; (2) the intended
conditions of use of the substance, including food categories and use
levels; and (3) the manufacturing process.
    (Response 86) We decline this request because it is overly broad.
We do not have a ``formula'' that would apply in all circumstances.
Just as the factors that apply to a particular GRAS notice may be very
specific to that notice, the factors that would apply in determining
whether the intended conditions of use of a notified substance are
already authorized by our regulations may be very specific to that
substance. However, with regard to similarities in the manufacturing
process, we likely would apply the same factors that we have advised
industry to apply when assessing the effects of significant
manufacturing process changes on the safety and regulatory status of
food ingredients (Ref. 6).
    We note that we also may decide to respond to a submission as
general correspondence, after communicating with the submitter as
appropriate, rather than file it for evaluation as a GRAS notice, if
the subject of the submission is: (1) Already the subject of a GRAS
notice, and we have responded to that GRAS notice with a ``no questions
letter''; or (2) a mixture of substances that already are the subject
of GRAS notices, and we have responded to those GRAS notices with ``no
questions letters.'' In contrast to the statutory provisions for the
FCN program (section 409(h) of the FD&C Act), there is no provision in
the FD&C Act providing exclusivity for a notifier for the use of a
substance on the basis that it is GRAS under the conditions of its
intended use.
    (Comment 87) One comment asks us to conduct a preliminary
evaluation of a GRAS notice to determine whether the notice appears to
be inadequate because the intended conditions of use of the notified
substance raise ``general policy'' issues.
    (Response 87) It is not clear what the comment means by ``general
policy'' issues. However, we note that we would not file a submission
as a GRAS notice if the intended conditions of use of the notified
substance are not eligible for classification as GRAS because, for
example, the intended conditions of use are excepted from the
definition of ``food additive'' in section 201(s) of the FD&C Act (and
thus, from the GRAS provision included in that definition of ``food
additive''). See, for example, the exception for a color additive in
section 201(s)(3) of the FD&C Act, for a dietary ingredient intended
for use in a dietary supplement in section 201(s)(6) of the FD&C Act,
and for a new animal drug in section 201(s)(5) of the FD&C Act.
    (Comment 88) Some comments ask us to contact the notifier when our
initial evaluation of a GRAS notice raises questions, and provide the
notifier with an opportunity to withdraw the notice without prejudice
before we begin a substantive evaluation of the notice.
    (Response 88) We agree that our decision to not file a submission
as a GRAS notice would be without prejudice to a future submission of a
GRAS notice for the notified substance. However, see Response 70,
Response 112, and the discussion in the 2010 notice at 75 FR 81536 at
81539. Just as a filed GRAS notice is available for public disclosure
subject to the procedures established in part 20, a submission that you
send to us is a record that is available for public disclosure subject
to the procedures established in part 20, regardless of whether we file
that submission as a GRAS notice. Thus, you cannot ``withdraw'' a
submission from our files after you send it to us.
    (Comment 89) One comment asks whether ``substantial equivalence''
considerations are linked to ``decline to file'' decisions or play a
dominant role in ``decline to file'' decisions. This comment also asks
us to issue a letter to the notifier explaining the basis for a
``decline to file'' decision if ``substantial equivalence'' is the
reason.
    (Response 89) As discussed in section IV.N of CFSAN's 2010
experience document (Ref. 18), several GRAS notices filed during the
Interim Pilot program relied, in part, on the concept of ``substantial
equivalence''; in each of the listed examples CFSAN had no questions
about the notifier's conclusion of GRAS status. As discussed in
Response 21, whether, and to what extent, similarity between two
substances could support a conclusion of GRAS status depends on many
situation-specific variables. Thus, it would be the complete evaluation
process, rather than the initial evaluation that we conduct as part of
a filing decision, that would determine whether a GRAS notice that
relies on the concept of ``substantial equivalence''

provides a basis for a conclusion of GRAS status. As discussed in
Response 85, the final rule provides that if we do not file a
submission as a GRAS notice, we will send the notifier a letter that
informs the notifier of that fact and provide our reasons for not
filing the submission as a GRAS notice (see Sec.  170.265(a)(3)); if
problems with a notifier's use of the concept of ``substantial
equivalence'' play a role in our decision to not file a submission as a
GRAS notice, we intend to say so.

B. Our Response to a GRAS Notice

1. Administrative Content of Our Response to a GRAS Notice
    (Comment 90) Several comments address the administrative content of
a letter that responds to a GRAS notice. In general, these comments ask
us to include the following items in the response letter: (1) Name and
address of the notifier; (2) the date of our receipt of the notice; (3)
the common or usual name of the notified substance; and (4) the
applicable conditions of use of the notified substance. One comment
states that use of a standard format and language in our letters would
be administratively efficient.
    (Response 90) We agree that a standard format and language in our
letters would be administratively efficient and that the administrative
features suggested by these comments are appropriate to include in our
response letter. During the Interim Pilot program, we both developed a
standard format and language for our response letters and included the
administrative features suggested by these comments (see section
III.H.1 of CFSAN's 2010 experience document (Ref. 18)). We intend to
continue incorporating these features in letters issued under the final
rule. However, as discussed in Response 51, the final rule requires
that you provide the name of the notified substance, using an
appropriately descriptive term, rather than the ``common or usual
name'' of the notified substance (see Sec.  170.225(c)(3)). Therefore,
CFSAN's response letters will include an appropriately descriptive term
for the notified substance provided in a GRAS notice submitted to
CFSAN. See section XXV.C regarding the name of the notified substance
provided in a GRAS notice submitted to CVM.
2. Substantive Content of Our Response to a GRAS Notice
    (Comment 91) Several comments note that the proposed rule did not
specify what we would say in a letter responding to a GRAS notice and
ask us to include in the final rule the specific language for the
response letter, particularly when we do not raise any questions about
the notifier's conclusion of GRAS status. Some comments assert that a
notifier who invests resources in a GRAS notice deserves a response
that is standardized and predictable and will not change as personnel
changes occur.
    (Response 91) See table 1. During the Interim Pilot program we
developed three categories of response letter: (1) ``No questions
letter''; (2) ``insufficient basis letter''; and (3) ``cease to
evaluate letter.'' As discussed in sections IV.H.1 through IV.H.7 of
CFSAN's 2010 experience document (Ref. 18), these letters include some
standard information that is consistent across those letters, such as
opening and closing paragraphs using a standard format, and
administrative information (e.g., the date of our receipt of the GRAS
notice). They also include unique features that depend upon the
circumstances, such as labeling issues and whether the use of the
substance could require a color additive listing. The content of the
three categories of response letter has evolved over time, and may
continue to evolve. In addition, it is possible that in the future a
response to a GRAS notice may not fit squarely within one of the
current categories of response letter. Therefore, the final rule
continues to specify that we will respond to a GRAS notice but does not
specify any detail about the nature of the response.
    (Comment 92) Several comments address the content of a ``no
questions letter.'' These comments ask that a ``no questions letter''
be clear and definitive, provide clear assurance that we recognize the
GRAS status of the substance under the conditions of its intended use,
have some regulatory significance, and be as affirmative as possible.
Some of these comments note that our statements in the proposed rule
(62 FR 18938 at 18950) indicated that we would evaluate a GRAS notice
to determine whether there is a sufficient basis for the notifier's
conclusion of GRAS status and suggest that our response to a GRAS
notice could reflect those statements. Comments also suggest the
following specific statements that could be included in a ``no
questions letter'':
     ``FDA at this time does not question your determination
that the notified use(s) of this substance is (are) Generally
Recognized as Safe.''
     ``The Agency finds that there is substantial evidence
supporting both the safety of the intended uses of the substance and
the fact that this safety is generally known and accepted by qualified
experts.''
     ``The notice provides a sufficient basis for the
notifier's determination that the substance is GRAS for its intended
use.''
    (Response 92) See table 1 for the typical text of a ``no questions
letter'' that we issued during the Interim Pilot program. At this time,
we intend to continue including such text in our ``no questions
letters.'' We agree that the regulatory significance of a ``no
questions letter'' should be clear. As shown in table 1, during the
Interim Pilot program a typical ``no questions letter'' made clear
that: (1) It is the information that is provided by the notifier that
forms the basis for our response, and that the notifier (rather than
FDA) is responsible for the conclusion of GRAS status; and (2) our
response must be considered in context based on the knowledge and
information available to us at a point in time, because scientific
knowledge and information about a particular ingredient can evolve and
sometimes change over time.
    The typical text of a ``no questions letter'' issued during the
Interim Pilot program is similar to the specific suggestion of one
comment (i.e., FDA at this time does not question your determination
that the notified use of this substance is GRAS), except that under the
final rule we will use the term ``conclusion'' rather than
``determination.'' We disagree that a ``no questions letter'' should
state that we ``find'' that there is substantial evidence supporting
both the safety of the intended conditions of use of the notified
substance and the fact that this safety is generally known and accepted
by qualified experts; a GRAS notice reflects the conclusion of the
notifier, not a finding by FDA. Likewise, we disagree that a ``no
questions letter'' should state that a notice ``provides a sufficient
basis'' for the notifier's conclusion that the notified substance is
GRAS under the conditions of its intended use; the phrase ``providing a
sufficient basis'' would imply that we are taking responsibility for
the notifier's conclusion of GRAS status.
    As discussed in 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 intend to
modify the typical text of our response letters to refer to the
``notifier's conclusion'' (rather than the ``notifier's
determination'') in letters issued under the final rule (see table 20).
We also

intend to specify that we have not affirmed the GRAS status of the
notified substance under the conditions of its intended use, rather
than to specify that we have not made our own determination. However,
as noted in section II.B, we intend to adapt our practices, consistent
with the provisions of this rule, as circumstances warrant and as
necessary to administer the GRAS notification program consistent with
appropriate public health policy, current scientific information, our
available resources, and the scientific and regulatory issues raised by
specific GRAS notices. Thus, the text shown in table 20 is for
illustrative purposes only and could evolve over time.

  Table 20--Categories of Letters Responding to a GRAS Notice Under the
                               Final Rule
------------------------------------------------------------------------
                                      Typical text of for a response as
    Category of response letter      modified to incorporate terms used
                                                 in the rule
------------------------------------------------------------------------
``No questions letter''...........  Based on the information provided by
                                     the notifier, as well as other
                                     information available to FDA, the
                                     Agency has no questions at this
                                     time regarding the notifier's
                                     conclusion that the notified
                                     substance is GRAS under the
                                     conditions of its intended use. By
                                     this letter, however, the Agency
                                     has not affirmed the GRAS status of
                                     the notified substance under the
                                     conditions of its intended use in
                                     accordance with 21 CFR 170.35. As
                                     always, it is the continuing
                                     responsibility of the notifier to
                                     ensure that food ingredients that
                                     the firm markets are safe, and are
                                     otherwise in compliance with all
                                     applicable legal and regulatory
                                     requirements.
``Insufficient basis letter''.....  FDA has evaluated the data and
                                     information in the GRAS notice as
                                     well as other available
                                     information. The notice does not
                                     provide a sufficient basis for a
                                     conclusion that the notified
                                     substance is GRAS under the
                                     conditions of its intended use.
``Cease to evaluate letter''......  In correspondence dated [month, day,
                                     year], you asked that we cease to
                                     evaluate your GRAS notice. We
                                     ceased to evaluate your GRAS
                                     notice, effective the date we
                                     received your correspondence.
------------------------------------------------------------------------

    (Comment 93) One comment suggests that a written response need not
assess the quality of the submission but rather could acknowledge
whether the notice was complete in addressing all key issues.
    (Response 93) We disagree that we could acknowledge whether a
notice is ``complete'' without assessing the quality of the submission.
Providing a basis for whether the data and information regarding the
safety of a substance under the conditions of its intended use satisfy
GRAS criteria is not a matter of whether there is ``something behind
each tab.'' It would not be appropriate, for example, for us to
acknowledge that a GRAS notice is ``complete'' because it included the
narrative required by Part 6 of a GRAS notice without assessing the
adequacy of the narrative. Whether a notice is ``complete'' in
addressing all key issues depends on the nature and quality of the
submitted data and information.
    (Comment 94) Some comments ask that a ``no questions letter''
qualify that we have not affirmed that the intended conditions of use
of the notified substance are GRAS. Other comments ask that a ``no
questions letter'' qualify that we have not conducted a substantive
review.
    (Response 94) We agree that a ``no questions letter'' should be
clear that we have not affirmed that the substance is GRAS under the
conditions of its intended use. See table 20.
    However, we disagree that a ``no questions letter'' should state
that we did not conduct a substantive review of the GRAS notice. See
Response 25. Our evaluation of a GRAS notice is a substantive
evaluation of the notifier's basis for concluding that the intended
conditions of use of the notified substance are safe and the criteria
for GRAS status are satisfied. In addition, as circumstances warrant,
we evaluate information that is not included in the notice but is
otherwise available to us (see section IV.G of CFSAN's 2010 experience
document (Ref. 18)).
    (Comment 95) Some comments ask that a ``no questions letter''
include a positive statement that we have not identified a problem with
the notice because finished food producers have been reluctant to use a
substance without such documentation. These comments both assert that
the only alternative available to manufacturers whose customers require
such a positive statement would be to seek food additive approval for
an ingredient and maintain that such approval is unnecessary from a
legal perspective.
    (Response 95) Consistent with the request of these comments, we
intend to continue including a statement that we ``have no questions at
this time'' (see table 1 and table 20). Whether a manufacturer's
customer requires a regulation prescribing the conditions under which a
substance may be safely used in food, when there is a basis for
concluding that the substance is GRAS under the conditions of its
intended use, is a business matter between the manufacturer and the
customer. If the manufacturer submits a food additive petition and we
find, based on the data and information submitted in the petition, that
the intended conditions of use of the substance are safe, we would
issue a regulation prescribing the conditions under which the food
additive may be safely used.
    (Comment 96) Several comments address the specific content of an
``insufficient basis letter'' and ask us to be specific about any
deficiencies that we identify in the notice. Some comments assert that
an ``insufficient basis letter'' must clearly distinguish between
deficiencies that relate to safety and those that relate to a technical
matter, such as the level of the substance that is needed to accomplish
the intended technical effect. One comment asks us to include in the
final rule guidelines that articulate clear standards for issues that
are of sufficient magnitude to result in an ``insufficient basis
letter.''
    (Response 96) We agree that we should be specific about identified
problems and distinguish between circumstances that lead to an
insufficient basis letter. Our experience during the Interim Pilot
program demonstrates that we have done so, and we intend to continue
this practice under the final rule. For example, as discussed in
sections IV.H.4 and IV.H.7 of CFSAN's 2010 experience document (Ref.
18), we have issued an insufficient basis letter in cases where health
effects seen in toxicological or clinical studies were not adequately
explained or because the notice did not describe adequate toxicological
studies; when the notice contained insufficient information about
dietary exposure; when the notice contained insufficient information to
adequately identify the substance; when the notice contained
insufficient information to satisfy the standard for demonstration of
GRAS status through experience based on common use in food; and as a
result of the regulatory framework associated with the substance. To
date, we have not issued an insufficient basis letter solely as a
result of insufficient

evidence regarding the level of the substance that is needed to
accomplish the intended technical effect. However, CVM's experience
document demonstrates that CVM has included lack of information
regarding the intended technical effect as one of several reasons
leading to an insufficient basis letter (Ref. 20). Some ``no questions
letters'' issued by CFSAN have discussed the level of the substance
that is needed to accomplish the intended technical effect, e.g., when
CFSAN informed a notifier who received a ``no questions letter'' that
FSIS needed information regarding the lowest level necessary for the
substance to achieve its intended effect in meat, meat food product, or
poultry product (see section III.L of CFSAN's 2010 experience document
(Ref. 18)).
    Our experience during the Interim Pilot program demonstrates that
whether a notice provides a sufficient basis for a conclusion of GRAS
status is a case-by-case evaluation and that the circumstances vary.
Therefore, we decline the request to specify standards for issues that
are of sufficient magnitude to result in an ``insufficient basis
letter.'' See sections IV.H.4 and IV.H.7 of CFSAN's 2010 experience
document (Ref. 18) for information on specific GRAS notices that
received an ``insufficient basis letter'' from CFSAN, and table 1 in
CVM's experience document (Ref. 20) for information on GRAS notices
that received an ``insufficient basis letter'' from CVM. Our letters
responding to each of these GRAS notices describe the problems in more
detail and are available on CFSAN's Web site (Ref. 46) and CVM's Web
site (Ref. 47).
    (Comment 97) Some comments ask that an ``insufficient basis
letter'' include a qualifying statement that we have not conducted a
substantive review and have not concluded that the intended conditions
of use of the notified substance are not GRAS. These comments assert
that a response that does not include such a statement could have the
practical effect of challenging the use of a substance in the absence
of a threshold determination that the notified use is not GRAS.
    (Response 97) We disagree that an ``insufficient basis letter''
should state that we did not conduct a substantive review of the GRAS
notice. See Response 25 and Response 94. Our evaluation of a GRAS
notice is a substantive evaluation.
    The typical text of an ``insufficient basis letter'' specified that
``the notice does not provide a sufficient basis'' for a determination
that the notified substance is GRAS under the conditions of its
intended use (see table 1), and we intend to continue including such
text in letters issued under the final rule, modified to refer to a
``conclusion'' of GRAS status rather than a ``determination'' of GRAS
status (see table 20). This typical text addresses the adequacy of the
notice rather than the regulatory status of the substance; consistent
with the request of these comments, this text does not specify that we
have concluded that the intended conditions of use of the notified
substance are ``not GRAS.'' In several cases during the Interim Pilot
program, a notifier who received an ``insufficient basis letter''
submitted a second GRAS notice and received a ``no questions letter''
in response to the second GRAS notice (see sections III.D and IV.K of
the experience document (Ref. 18)). In these examples, CFSAN's response
to the notifier's first GRAS notice made clear that the submitted
notice did not provide a basis for a conclusion of GRAS status, but
CFSAN had no questions about the basis for GRAS status provided by the
second notice.
3. Our Consideration of a Timely Amendment
    As discussed in section XVIII.B, the rule provides that you may
submit a timely amendment to your filed GRAS notice to update your GRAS
notice or in response to a question from us (Sec.  170.260(a)). As a
companion provision, the rule also provides that we will consider any
timely amendment that you submit to a filed GRAS notice, to update your
GRAS notice or in response to a question from us, before we respond to
your notice based on our evaluation of your notice if we deem that
doing so is feasible within the established timeframes (see Sec.
170.265(a)(4)). If we deem that considering your amendment is not
feasible within the established timeframes, we will inform you that we
are not considering your amendment (see Sec.  170.265(a)(4)). We also
will inform you that we are not considering your amendment if we have
granted your request to cease to evaluate your notice (i.e., if we send
you a ``cease to evaluate letter''). See Sec.  170.265(b)) and Response
98 for the timeframe established in this rule for our response to your
GRAS notice.
4. Timeframe for Our Response to a GRAS Notice
    (Comment 98) Several comments support retaining the proposed 90-day
timeframe. According to these comments, a 90-day timeframe would
provide an incentive for a manufacturer to submit a GRAS notice. One
comment asserts that we should be held accountable to the proposed 90-
day timeframe, whereas another comment suggests that the proposed 90-
day timeframe provide a benchmark at which we should make the notifier
aware of the current status of our evaluation of the notice even if we
have not had sufficient time to completely review the safety of the
notified substance.
    One comment that asks us to retain the proposed 90-day timeframe
stresses that we should have flexibility to take additional time as
needed. Another comment agrees that it would be appropriate for us to
extend the evaluation period, provided we do so only in limited
instances.
    One comment asserts that the requirements of the GRAS notification
procedure are similar to the requirements of the GRAS affirmation
petition process and questions whether we could respond to a GRAS
notice within 90 days because we did not respond to a GRAS petition in
such a short timeframe. One comment that stresses the importance of
retaining a set evaluation timeframe suggests that the timeframe be 90-
180 days based on CFSAN's experience during the Interim Pilot program,
and opposes a timeframe greater than 180 days. Other comments support a
180-day timeframe because it would be realistic and reasonable, would
be sufficient to resolve all of the issues raised by a GRAS notice with
procedural fairness, and could be consistent and fair across both CFSAN
and CVM.
    (Response 98) We are establishing a timeframe of 180 days from the
date of filing for our response to a GRAS notice. We also are providing
that we may extend the 180-day response timeframe by 90 days on an as
needed basis; if we do so, we will inform you of the extension in
writing as soon as practicable but no later than within 180 days of
filing. (See the regulatory text of Sec.  170.265(b)(1) and (2)). We
agree that the 180-day timeframe is realistic and reasonable, would be
sufficient to resolve all of the issues raised by a GRAS notice with
procedural fairness in most cases, and could be consistent and fair
across both CFSAN and CVM.
    We disagree that we should establish a 90-day timeframe merely
because we had proposed this timeframe before we gained experience with
evaluating GRAS notices. As shown in section III.M of CFSAN's 2010
experience document, less than 12 percent of the response letters CFSAN
issued as of December 31, 2009, were sent within the proposed 90-day
timeframe (Ref.

18). Importantly, section III.M of CFSAN's 2010 experience document
also shows that in many cases a dialog between FDA and a notifier about
scientific issues associated with a GRAS notice, with an ensuing
amendment from the notifier, played a role in the timeframe for CFSAN's
response to a GRAS notice. As discussed in the 2010 notice, several
comments ask us to allow a notifier to address questions we have about
a GRAS notice by submitting an amendment to the notice (see Issue 3a,
75 FR 81536 at 81538), and the final rule expressly provides that you
may submit an amendment to a filed GRAS notice before we respond to the
notice (see Sec.  170.260(a)). Although we are including flexibility to
take additional time as needed, our goal is to do so in only limited
instances, such as when the intended conditions of use of the notified
substance raise complex scientific issues.
    We have no basis to judge whether a 90-day timeframe, but not a
180-day timeframe, would provide an incentive to a manufacturer to
submit a GRAS notice. However, as noted in Response 24 CFSAN filed more
than 600 GRAS notices during the time period 1998 through 2015,
including 69 GRAS notices filed during 2014 and 51 GRAS notices filed
during 2015, even though CFSAN rarely responded to a GRAS notice within
90 days. We believe that the ongoing submission of GRAS notices is
evidence that the 180-day timeframe that is consistent with our
experience during the Interim Pilot program is not a disincentive to a
manufacturer.
    We note that the procedural requirements of the GRAS notification
procedure are very different from the procedural requirements of the
GRAS affirmation petition process in that we respond to a GRAS notice
by letter whereas we respond to a GRAS affirmation petition through
rulemaking. As previously discussed (62 FR 18938 at 18941), the
resource-intensive rulemaking process includes: (1) Publishing a filing
notice in the Federal Register; (2) requesting comment on the
petitioned request; (3) conducting a comprehensive review of the
petition's data and information and comments received to the filing
notice to determine whether the evidence establishes that the
petitioned use of the substance is GRAS; (4) drafting a detailed
explanation of why the use is GRAS (as opposed to simply being safe);
and (5) publishing that explanation in the Federal Register. Therefore,
we disagree with the perspective of one comment that our experience in
responding to a GRAS affirmation petition should have any bearing on
the determination of an appropriate timeframe for our response to a
GRAS notice.
    (Comment 99) One comment expresses concern that a 90-day timeframe
would be unrealistic unless we allocate additional resources to the
program. This comment asks us to consider a process similar to the
process for the FCN program, where there is a fixed review period
during which we can ``object to'' a submitted notification. If we do
not object within the review period or do not request an extension to
the review period, a notification submitted to the FCN program is
considered effective.
    (Response 99) We decline this request. We disagree that the GRAS
notification procedure should be modeled after the FCN program. Unlike
the GRAS notification procedure, the FCN program is a mandatory process
for food contact substances under section 409(h) of the FD&C Act.
Furthermore, the statute provides that the FCN program shall not
operate unless it has certain appropriated funds. See section
409(h)(5)(A)(i) of the FD&C Act and Sec.  170.104(c)(3). There are no
similar statutory requirements applicable to our evaluation of the
basis for a conclusion of GRAS status.
    (Comment 100) One comment asserts that we should respond to a GRAS
notice within 90 days unless we identify a problem that warrants dialog
with the notifier and an ensuing amendment.
    (Response 100) We disagree. The suggestion of this comment could
lead to the unintended consequence of seeking unnecessary amendments
merely to stay within an established timeframe. We believe it is more
appropriate to establish a single timeframe that would broadly apply to
all GRAS notices, with the potential to extend the timeframe on an as
needed basis.
    (Comment 101) One comment asks us to stop the ``review clock'' when
we inform a notifier that we have questions about a notice and then
restart the ``review clock'' upon receipt of an amendment that answers
our questions.
    (Response 101) We decline this request. We acknowledge that there
could be an advantage to such a process, because stopping the review
clock would reduce the time pressures on our staff. However, the role
of an amendment is to clarify questions that we have about your
conclusion of GRAS status rather than to substantively amend the GRAS
notice. A process in which we stop and start a review clock implies
that the timeframe for you to submit an amendment could be so long as
to significantly impact our ability to respond within an established
timeframe. Rather than a process in which we stop and start a review
clock on a particular GRAS notice, we have provided that you may ask us
to cease to evaluate a GRAS notice when your preparation of an
amendment would impact our ability to respond within 180 days.
5. Responding to a GRAS Notice in All Circumstances
    In the proposed rule, we noted that the GRAS notification procedure
could be structured so that we respond only when we question the GRAS
status of the intended use of the substance and requested comment on
whether we should, in all cases, provide a notifier with a letter at
the conclusion of our evaluation of a notice (62 FR 18938 at 18951).
    (Comment 102) Several comments agree with our discussion in the
proposed rule that a written response from us would give manufacturers
an incentive to notify us of their conclusions of GRAS status; these
comments recommend that we respond in writing in all circumstances.
Other comments suggest that we limit our response to circumstances in
which we identify a problem with a notice because such a limitation
would make it easier for us to respond within the proposed 90-day
timeframe. One comment expresses concern that a written response could
create a misperception that we had undertaken an independent review of
the data described in the GRAS notice; to prevent this misperception,
this comment suggests that we respond in writing only if we find a
problem with the notice.
    (Response 102) We acknowledge that limiting our response to
circumstances in which we identify a problem with a notice would reduce
the number of letters that we write. However, we believe that it is
important to publicly document our evaluation of the GRAS notice in
light of all the comments submitted to this rulemaking. (See, e.g.,
Comment 25 and the comments we discuss in section VII.C). In addition,
in our experience it is the process of evaluating a submission and
reaching a decision about whether the notice provides a basis for a
conclusion of GRAS status, rather than the process of drafting and
issuing a letter, that requires the most time.
    We acknowledge the potential that a ``no questions letter'' could
be misinterpreted, e.g., to mean that FDA, rather than the notifier,
had reached a conclusion of GRAS status. To mitigate the potential for
such misinterpretation, the typical text of our response letters

issued during the Interim Pilot program referred to the notifier's
determination and stated that we have not made our own determination
regarding the GRAS status of the subject use of the notified substance
(see table 1). We intend to continue including such typical text in
letters issued under the final rule, modified as shown in table 20.
    (Comment 103) One comment suggests that we respond in writing only
at the notifier's request.
    (Response 103) We decline this suggestion, which is contrary to
emphasis that the rule places on the notifier's acceptance of
responsibility for a conclusion of GRAS status (see the discussion at
62 FR 18938 at 18953).
    (Comment 104) One comment asserts that a letter acknowledging
receipt of a GRAS notice would constitute a form of response. Another
comment suggests that a letter acknowledging receipt of a GRAS notice
state whether the notice meets the listed requirements for a GRAS
notice, eliminating the need for a second letter responding to the
notice when we complete our evaluation. This comment asserts that a
second letter would be unnecessary for two reasons. First, the notifier
has accepted full responsibility for the conclusion of GRAS status and
does not require premarket approval from us. Second, under the terms of
the rule a notifier must agree to make all data and information
available to us.
    (Response 104) The final rule provides that we will inform you of
the date on which we filed your notice rather than the date on which we
received it, as we had proposed. We disagree that a letter informing
you of the date of filing in any way responds to a GRAS notice or
should state whether the notice meets the listed requirements for a
GRAS notice. As discussed in Response 93, we cannot acknowledge whether
a notice ``meets the listed requirements'' without assessing the
quality of the submission, which we do during the evaluation that
follows filing the submission as a GRAS notice.
    We acknowledge that submitting a GRAS notice means that a notifier
has accepted full responsibility for the conclusion of GRAS status. We
also acknowledge that the use of a GRAS substance is not subject to our
premarket review. However, we disagree that a relevant factor in
determining whether we should respond to a notifier is the notifier's
agreement to make all data and information available to us if we
question whether the notice provides an adequate basis for a conclusion
of GRAS status. A GRAS notice presents an opportunity for you to inform
us about your conclusion of GRAS status rather than an opportunity for
you to test a hypothesis that there is a sufficient basis to reach a
conclusion of GRAS status.
    (Comment 105) One comment suggests that we issue a written response
only when we have reached a conclusion regarding safety.
    (Response 105) This comment may have misunderstood the proposed
notification procedure. Under the notification procedure, you analyze
the available data and information and reach a conclusion about whether
the notified substance is safe under the conditions of its intended use
and whether there is a basis to conclude that the criteria for GRAS
status are satisfied. We evaluate your conclusions regarding the
available data and information. During the Interim Pilot program, the
typical text of a ``no questions letter'' stated that we had not
reached our own determination regarding the GRAS status of the notified
substance under the conditions of its intended use (see table 1).
    To the extent that the comment is suggesting that we issue an
``insufficient basis letter'' when the problem with the notice relates
to safety, but not to general recognition, we disagree. It would be
inconsistent with the legal basis of the GRAS standard for us to only
focus on safety, and we did not do so during the Interim Pilot program.
(See section III.A.3 of CFSAN's 2010 experience document (Ref. 18),
where CFSAN identifies ``insufficient basis letters'' in which CFSAN
had questions about whether there was general recognition of safety.)

C. Additional Correspondence as Circumstances Warrant

    (Comment 106) One comment expresses the view that a ``no questions
letter'' should not affect our ability to change our position if
additional information indicates that the use of the substance raises
any safety concerns.
    (Response 106) We agree, and the final rule expressly provides that
we will send the notifier a subsequent letter about the notice if
circumstances warrant (see Sec.  170.265(c)). The circumstances may not
relate to safety. As discussed in section IV.J of CFSAN's 2010
experience document (Ref. 18), as of December 31, 2009, none of the
subsequent letters CFSAN issued during the Interim Pilot program
reflected a change in CFSAN's position and several addressed issues
other than the safety of the use of the substance. For example, CFSAN
issued subsequent letters that: (1) Clarified the intended conditions
of use; (2) clarified that the term CFSAN used to refer to the notified
substance for the purpose of the letter should not be considered an
endorsement of that term for the purpose of declaring the substance in
the ingredient statement of food products; (3) clarified FSIS' position
regarding the use of the notified substance in meat, meat food product
or poultry product; and (4) corrected a mistake in the original
response. CFSAN also sent a subsequent letter as an administratively
efficient mechanism of responding to a notifier who provided CFSAN with
information supporting a conclusion that an additional use of the
notified substance satisfied GRAS criteria.
    In addition, CFSAN has issued a subsequent letter when CFSAN's
first letter was an ``insufficient basis letter'' rather than a ``no
questions letter.'' For example, CFSAN did so when a notifier who
received an ``insufficient basis letter'' submitted a new GRAS notice
that did not address the questions CFSAN raised in the ``insufficient
basis letter.'' CFSAN also did so when a notifier who received an
``insufficient basis letter'' submitted a supplement to its original
GRAS notice rather than submit a new GRAS notice. See section IV.J of
CFSAN's 2010 experience document (Ref. 18).

D. Procedures if a Notifier Disagrees With Our Response

    In the proposed rule, we explained that there are existing
processes that we considered would be appropriate for a notifier to use
to engage us if the notifier disagreed with our response (see 62 FR
18938 at 18952 and table 21). We also noted that any person with
concerns about our response to a GRAS notice may contact our Office of
the Chief Mediator and Ombudsman; that office works on resolving issues
and conflicts that arise in any FDA component.

  Table 21--Existing Procedures in Our Regulations That Can Apply if a
          Notifier Disagrees With Our Response to a GRAS Notice
------------------------------------------------------------------------
   Regulatory section  (Sec.   )                 Description
------------------------------------------------------------------------
10.25.............................  Initiation of administrative
                                     proceedings.
10.33.............................  Administrative reconsideration of
                                     action.
10.65.............................  Meetings and correspondence.
10.75.............................  Internal agency review of decisions.
------------------------------------------------------------------------

    (Comment 107) Several comments express concern that the processes
discussed in the proposed rule would be

available only after we sent, and made readily accessible to the
public, an ``insufficient basis letter.'' Other comments express
concern about the practical effect of an ``insufficient basis letter''
on the notifier's ability to market a notified substance while the
notifier is seeking review of our evaluation. Some comments ask that
our letter be ``stayed'' until any problems that we identified in our
response to the notice are resolved under such a process.
    (Response 107) We acknowledge the concerns expressed in these
comments but are making no changes to the rule to address these
concerns. One of the underpinnings of the GRAS notification procedure
is that making our response readily accessible to the public will
properly underscore your responsibility for the conclusion of GRAS
status (62 FR 18938 at 18953). As discussed in Response 104, a GRAS
notice presents an opportunity for you to inform us about your
conclusion of GRAS status rather than for you to test a hypothesis that
there is a sufficient basis to reach a conclusion of GRAS status. If we
send you an ``insufficient basis letter,'' we advise you to carefully
consider whether marketing the notified substance would be lawful.
``Staying'' an ``insufficient basis letter'' informing you that there
may not be a legal basis to market the notified substance, e.g., so
that you could market the substance while you are working to resolve
the issues that led us to send you an ``insufficient basis letter'',
would not change the legal status of the notified substance.
    (Comment 108) Several comments assert that the processes we had
identified in the proposed rule are cumbersome and do not provide
manufacturers with a clear framework or timeline for responding to our
questions or concerns. In general, these comments ask us to include in
the final rule a prompt, fair, and effective process that would be
specific to the GRAS notification procedure. A few comments suggest
that such an appeal mechanism also apply to subsequent correspondence
from us about a GRAS notice.
    Some comments provide specific suggestions for how an appeals
mechanism specific to the GRAS notification procedure could work, e.g.,
by specifying that a notifier may submit additional data and
information for our evaluation, or by providing for an independent
advisory committee or an FDA-certified third-party review organization
to review the matter and issue an opinion. Some comments suggest that
an appeals mechanism specify appeal steps and stressed the importance
of timeframes for decisions by our officials.
    (Response 108) We decline the request to include in the final rule
an appeals process that would be specific to the GRAS notification
procedure. We agree that the process to contact us about a response to
a GRAS notice should be clear. However, we disagree that the existing
procedures are unclear, because our regulations fully describe these
procedures (Sec. Sec.  10.25, 10.33, 10.65, and 10.75). We acknowledge
that the listed procedures do not provide a clear timeline and that
some of the listed procedures (e.g., Sec. Sec.  10.25 and 10.33) are
more cumbersome than others (such as requesting a meeting under Sec.
10.65 or requesting internal Agency review of a decision under Sec.
10.75). In practice during the Interim Pilot program, several notifiers
who received an ``insufficient basis letter'' took steps to resolve our
questions and subsequently submitted a new GRAS notice or a food
additive petition (see the discussion in section III.K of CFSAN's 2010
experience document (Ref. 18)). Given the variety of circumstances that
could lead to an ``insufficient basis letter,'' we believe that taking
steps to resolve our questions, and submitting a new GRAS notice or a
food additive petition, can be an efficient mechanism for you to use in
lieu of the procedures we discussed in the proposed rule. Doing so
would be consistent with the suggestion of some comments that an
appeals mechanism specific to the GRAS notification procedure could
include submission of additional data and information for our
evaluation, except that the data and information would be submitted in
a new GRAS notice rather than be an ``appeal'' to the GRAS notice that
received an ``insufficient basis letter.''
    We do not have an FDA-certified third-party review organization
that could review the matter and issue an opinion. We disagree that
convening an independent advisory committee would be appropriate as an
additional, routine mechanism to appeal an ``insufficient basis
letter.'' Under our regulations in part 14 governing advisory
committees, it would be FDA--not a notifier--who decided to convene a
meeting of our Food Advisory Committee about the use of a substance in
food. We would have little basis to convene a meeting of our Food
Advisory Committee as part of an appeal to an ``insufficient basis
letter'' unless the notifier had first used one or more of the
procedures listed in table 21.

XX. Coordinating Our Evaluation of a GRAS Notice With FSIS

    In the 2010 notice, we described some of the terms of a MOU,
between FDA and USDA's FSIS, that provides for a coordinated evaluation
process with FSIS when the intended conditions of use of a notified
substance include use in a product or products subject to regulation by
USDA under statutes that it administers (75 FR 81536 at 81541-81542).
We also asked for comment on whether to make our coordinated evaluation
process with FSIS explicit in the final rule (see Issue 13, 75 FR 81536
at 81541-81542). In 2015, we amended that MOU to include more details
about the procedures FDA and FSIS will follow to do so (Ref. 36).
    (Comment 109) Comments support coordinating our evaluation of GRAS
notices with FSIS and including the procedure for this coordination in
the final rule. Comments also support requiring the notifier to provide
an additional paper copy that we would send to FSIS as part of this
procedure.
    (Response 109) The final rule includes procedures for coordinating
our evaluation of a GRAS notice with FSIS when the use of the notified
substance includes use in a product or products subject to regulation
by FSIS under statutes that it administers. (See Sec.  170.270). If you
send your GRAS notice on paper, a single paper copy is sufficient; we
would send FSIS an electronic copy. (See Sec.  170.210(b) and Response
46). Under Sec.  170.270(d), we will inform you of the advice we
receive from FSIS in the letter we send you in accordance with Sec.
170.265(b)(1), as appropriate. By ``as appropriate,'' we mean that in
most circumstances we do not intend to provide advice from FSIS about
the use of the notified substance when we respond with an
``insufficient basis letter,'' because doing so has the potential to
create confusion about the regulatory status of a use of the notified
substance in products subject to regulation by FSIS. Likewise, we do
not intend to provide advice from FSIS about the use of the notified
substance when we respond with a ``cease to evaluate letter'' and,
thus, the procedure described in Sec.  170.270(d) does not specify that
we will inform you of the advice we receive from FSIS in a letter we
send you in accordance with Sec.  170.265(b)(3).
    As we noted in section XII.I, this rule does not specify the data
and information that FSIS will need to evaluate whether the intended
use of the notified substance complies with applicable statutes and
regulations, or, if not, whether the use of the substance

would be permitted in products under FSIS jurisdiction under specified
conditions or restrictions. We recommend that you contact the
appropriate staff at FSIS regarding the data and information that FSIS
will need you to provide. FSIS provides contact information for its
programs on its Web site (Ref. 41).
    (Comment 110) One comment agrees that the evaluation of a GRAS
notice should be coordinated between FDA and FSIS when ``animal
products'' are involved. This comment notes that FSIS does not
currently review the use of a substance intended for use in animal food
and recommends that CVM be involved in the safety review process of the
notice if the notice involves a substance to be used in animal food.
    (Response 110) This comment appears to have misunderstood the
purpose of the coordinated evaluation process that we discussed in the
2010 notice. That process applies to the use of a substance in human
food products, such as meat and poultry products, that are subject to
regulation by USDA and would be evaluated by CFSAN; it does not apply
to the use of a substance in animal food. FSIS, under the statutes it
administers, does not evaluate a substance intended for use in animal
food and, thus, the process would not apply to a GRAS notice received
by CVM. See also Response 45.

XXI. Comments on Public Disclosure of a GRAS Notice

    We proposed that a ``GRAS exemption claim'' would be immediately
available for public disclosure on the date the notice is received. All
remaining data and information in the notice would be available for
public disclosure, in accordance with part 20, on the date the notice
is received (proposed Sec.  170.36(f)(1)). We also proposed that the
following information would be readily accessible for public review and
copying: (1) A copy of the ``GRAS exemption claim'' (proposed Sec.
170.36(f)(2)(i)); (2) a copy of our response letter (proposed Sec.
170.36(f)(2)(ii)); and (3) a copy of any subsequent letter we issued
regarding the notice (proposed Sec.  170.36(f)(2)(iii)). In the 2010
notice, we noted that although the decision to submit a GRAS notice
would be voluntary, the provisions governing the GRAS notification
procedure, including the information to be submitted, would be
mandatory (75 FR 81536 at 81540).
    In the final rule, you include the signed statements that we
proposed be in a ``GRAS exemption claim'' in Part 1 of your GRAS
notice, and we no longer use the term ``GRAS exemption claim'' (see
Response 42). As discussed in Response 50, the final rule stipulates
that you must not include any information that is trade secret or
confidential commercial information in Part 1 of your GRAS notice (see
Sec.  170.225(b)).
    In the following sections, we discuss comments on the proposed
requirements for public disclosure of a GRAS notice. After considering
these comments, we are establishing requirements applicable to the
public disclosure of a GRAS notice as shown in table 22, with
editorial, clarifying, and conforming changes as shown in table 29.
(See Sec.  170.275.) Table 22 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(f) as Sec.  170.275.

                  Table 22--Final Requirements Applicable to Public Disclosure of a GRAS Notice
----------------------------------------------------------------------------------------------------------------
                                                                                Revisions (other
                                                                                than editorial,
                                         Proposed        Issue No. in                          clarifying, and
    Final designation in  the       designation in the     the 2010         Description      conforming changes)
    regulatory text  (Sec.   )       regulatory text        notice                              relative to the
                                        (Sec.   )                                              proposed rule or
                                                                                the  2010 notice
----------------------------------------------------------------------------------------------------------------
170.275(a)(1)....................  N/A................             N/A  The data and         Clarify that a
                                                                         information in a     notice is
                                                                         GRAS notice          considered a
                                                                         (including data      mandatory, rather
                                                                         and information      than voluntary,
                                                                         submitted in any     submission for
                                                                         amendment or         purposes of their
                                                                         supplement to your   status under the
                                                                         GRAS notice or       FOIA and part 20.
                                                                         incorporated into
                                                                         your GRAS notice)
                                                                         are considered a
                                                                         mandatory, rather
                                                                         than voluntary,
                                                                         submission for
                                                                         purposes of its
                                                                         status under the
                                                                         FOIA and part 20.
170.275(a)(2)....................  170.36(f)(1).......             N/A  The data and         Clarify that part
                                                                         information in a     20 applies to
                                                                         GRAS notice          amendments and
                                                                         (including data      supplements as
                                                                         and information      well as to the
                                                                         submitted in any     GRAS notice as
                                                                         amendment or         originally
                                                                         supplement to your   submitted.
                                                                         GRAS notice or
                                                                         incorporated into
                                                                         your GRAS notice)
                                                                         are available for
                                                                         public disclosure
                                                                         in accordance with
                                                                         part 20 as of the
                                                                         date that we
                                                                         receive your GRAS
                                                                         notice.
170.275(b)(1)....................  170.36(f)(2)(i)....             N/A  We will make         Clarifies that the
                                                                         readily accessible   list of
                                                                         to the public a      submissions that
                                                                         list of filed GRAS   we make publicly
                                                                         notices, including   available are
                                                                         the information      those that we have
                                                                         described in the     ``filed'' as GRAS
                                                                         signed statements    notices.
                                                                         you include in
                                                                         Sec.
                                                                         170.225(c)(2)
                                                                         through (c)(5).
170.275(b)(2)....................  170.36(f)(2)(ii)...             N/A  We will make         N/A.
                                                                         readily accessible
                                                                         to the public the
                                                                         text of any letter
                                                                         that we issue
                                                                         under Sec.
                                                                         170.265(b)(1) or
                                                                         (3) (e.g., a ``no
                                                                         questions letter''
                                                                         or an
                                                                         ``insufficient
                                                                         basis letter'');
                                                                         or under Sec.
                                                                         170.265(c) (a
                                                                         ``subsequent
                                                                         letter'').
170.275(b)(3)....................  170.36(f)(2)(ii)...             N/A  We will make         Clarify that the
                                                                         readily accessible   provisions in
                                                                         to the public the    which we make
                                                                         text of any letter   certain letters
                                                                         that we issue        readily accessible
                                                                         under Sec.           to the public
                                                                         170.265(b)(3)        apply to a ``cease
                                                                         (e.g., a ``cease     to evaluate
                                                                         to evaluate          letter''.
                                                                         letter'').

170.275(c).......................  170.36(f)(2)(iii)..             N/A  We will disclose     N/A.
                                                                         public information
                                                                         in accordance with
                                                                         part 20.
----------------------------------------------------------------------------------------------------------------

A. Data and Information in a GRAS Notice Are Available for Public
Disclosure on the Date That We Receive It

    (Comment 111) One comment asserts that the releasability of the
contents of a GRAS notice should be governed by Sec.  20.111 (data and
information submitted voluntarily to us) because the FD&C Act does not
require submission of a GRAS notice. The comment asserts that Sec.
20.111 would affect the releasability of the content of a GRAS notice
in three ways. First, while a GRAS notice is pending, Sec.  20.111
would protect from disclosure safety data or information about an
ingredient under development. Second, Sec.  20.111 would permanently
protect from disclosure any data or information relating to
manufacturing, production or sales, or formulas. Third, Sec.  20.111
would establish that a notifier has the right to request that we
evaluate the notifier's position that specific data or information in a
GRAS notice are protected from disclosure because these data or
information fall within the exemption in Sec.  20.61 for trade secrets
and commercial or financial information, which is privileged or
confidential.
    (Response 111) We disagree that the provisions of Sec.  20.111
apply to a GRAS notice. Although your decision to submit a GRAS notice
is voluntary, the information included in your GRAS notice is required.
To make that clear, the final rule stipulates that the data and
information in a GRAS notice (including data and information submitted
in any amendment or supplement to your GRAS notice or incorporated into
your GRAS notice) are considered a mandatory, rather than voluntary,
submission for purposes of its status under the FOIA and part 20 (see
Sec.  170.275(a)(1)).
    We agree that a notifier has a right to request that we evaluate
the notifier's position that specific data or information in a GRAS
notice are protected from disclosure because these data or information
fall within the exemption in Sec.  20.61 for trade secrets and
confidential commercial information. See Sec.  170.225(c)(8), which
requires that you state your view as to whether any of the data and
information in Parts 2 through 7 of your GRAS notice are exempt from
disclosure under the FOIA.
    (Comment 112) Several comments assert that a GRAS notice should not
be publicly available until after we have completed our evaluation.
These comments also assert that a delay in disclosure, coupled with an
opportunity for a notifier to amend the notice, would: (1) Avoid the
release of information that we deemed to be inadequate or incomplete;
and (2) avoid release of a notice that was withdrawn if coupled with an
opportunity for a notifier to withdraw a notice.
    (Response 112) We disagree that we should refrain from disclosing
the existence of a GRAS notice, or the contents of a GRAS notice, until
after we have completed our evaluation. As previously discussed,
immediate disclosure of a GRAS notice underscores a notifier's
responsibility for a conclusion of GRAS status (62 FR 18938 at 18953).
As discussed in Response 2, immediate disclosure of a GRAS notice also
provides an opportunity for outside parties to make us aware of
dissenting views about whether the available data and information
support a conclusion that the notified substance is safe under the
conditions of its intended use, and we did receive information from
outside parties during the Interim Pilot program. Continuing to provide
an opportunity for public participation is consistent with our
substitution of the GRAS notification procedure for the former GRAS
affirmation petition process, in which there was a public comment
period.
    As discussed in Response 83, our current regulations regarding
public information stipulate that no person may withdraw records
submitted to FDA (see Sec.  20.29), and those regulations will apply to
a GRAS notice that you to ask us to ``cease to evaluate.''
    (Comment 113) One comment asks us to make a GRAS notice available
for public disclosure only after we accept the submission for review.
Some comments contrast our proposal for immediate disclosure of a GRAS
notice with the provisions of: (1) The GRAS affirmation petition
process, in which a GRAS affirmation petition is disclosed only after
the petition has been accepted for filing (former Sec.  170.35(c)(2));
and (2) the health claim petition process, in which a health claim
petition becomes available for public disclosure only after it is filed
and a health claim petition that is denied without filing is not
available for disclosure (21 CFR 101.70(j)).
    (Response 113) The final rule continues to specify that the data
and information in a GRAS notice are available for public disclosure as
of the date of receipt (see Sec.  170.275(a)(2)). The former GRAS
affirmation petition process did not specify when a submitted GRAS
affirmation petition would be available for public disclosure. Instead,
the former GRAS affirmation petition process merely specified that we
would place the petition on public file in the office of the Division
of Dockets Management and publish a notice of filing in the Federal
Register within 30 days after the date of filing. In addition, we
disagree that the public disclosure provisions in Sec.  101.70(j)
applicable to the health claim petition process should apply to the
GRAS notification procedure. Those provisions derive directly from the
statutory provisions that direct the health claim program (section
403(r)(4)(A)(i) of the FD&C Act (21 U.S.C. 343(r)(4)(A)(i))).
    Under Sec.  20.103, with few exceptions all correspondence from
members of the public, organization or company officials, or other
persons, is available for public disclosure at the time that we receive
it unless a different time for such disclosure is specified in other
rules established or cross-referenced in part 20. As noted in Comment
86 and Response 86, we may decide to file and respond to a submission
as general correspondence, rather than as a GRAS notice, in certain
circumstances; if we do so, the data and information in the submission
would be available as of the date of receipt. Retaining date of receipt
as the timeframe for when a submission you transmit as a GRAS notice is
available for public disclosure is both consistent with Sec.  20.103
and a practical approach to a situation in which we receive a FOIA
request for a GRAS

submission before we have determined whether to file the submission as
a GRAS notice. As a practical matter, we believe that such situations
will be rare, and that in most cases a GRAS submission will be
disclosed after we have determined whether to file it and evaluate it
as a GRAS notice, or to file it and respond to it as general
correspondence.
    (Comment 114) Some comments disagree with the assumption we stated
in the proposed rule (62 FR 18938 at 18952) that submission of a GRAS
notice would not reflect the notifier's plans about the timing or the
use of the substance in a marketed product, because a GRAS substance
may be marketed without prior approval.
    (Response 114) We acknowledge that immediate disclosure of a GRAS
notice could, in certain circumstances, provide information about the
timing of market entry. However, when the data and information
regarding the safety of the substance under the conditions of its
intended use satisfy GRAS criteria, neither the law nor this rulemaking
would prevent you from marketing a substance before submitting a GRAS
notice or during our evaluation of that notice.

B. We Will Make a List of Filed GRAS Notices and Our Responses to GRAS
Notices Readily Accessible

    (Comment 115) Several comments address our stated intention to
maintain an inventory of GRAS notices that we receive, our response,
and any subsequent relevant correspondence. (See the discussion at 68
FR 18938 at 18953.) Some of these comments agree with the discussion in
the proposed rule that an inventory of GRAS notices should be an
adjunct to the proposed rule rather than be included in the regulatory
text. Other comments disagree and ask us to include the creation and
availability of the inventory in the regulatory text. These comments
assert that a provision that merely states that the inventory exists
and is available for public review would address the concern that we
identified in the proposed rule about the need to maintain flexibility
regarding our administration of the inventory.
    (Response 115) The final rule specifies that we will make the
following readily accessible to the public: (1) A list of filed GRAS
notices, including the information described in certain of the signed
statements that are included in Part 1 of a GRAS notice (i.e., Sec.
170.225(c)(2) through (c)(5)); and (2) The text of any letter that we
issue under Sec.  170.265(b)(1) (our response to a GRAS notice based on
our evaluation of the notice), Sec.  170.265(b)(3) (a letter if we
grant a request that we cease to evaluate a GRAS notice), or Sec.
170.265(c) (a subsequent letter that we send about a GRAS notice). (See
Sec.  170.275(b).) We are not specifying that the mechanism for us to
do so is through an ``Inventory'' because the procedure we used to make
this information readily accessible to the public evolved over time
during the Interim Pilot program, and may continue to evolve (see
section III.I.1 in CFSAN's 2010 experience document (Ref. 18)).
    (Comment 116) In the proposed rule, we stated our intention to
initially maintain a paper version of an inventory at our Dockets
Management Branch (now Division of Dockets Management) and asked for
comment on making an inventory available through electronic means such
as the Internet (62 FR 18938 at 18953). Comments support maintaining an
inventory in paper format, electronic format, or both formats so that
all members of the public could have ready access to such information
regarding GRAS notices. Some comments point out that electronic access
would be particularly important to the international food industry.
Some comments support the Division of Dockets Management as the best
location for an inventory maintained in paper format.
    (Response 116) As discussed in section III.I.1 in CFSAN's 2010
experience document (Ref. 18), the procedure we used to make this
information readily accessible to the public evolved over time during
the Interim Pilot program. It began as a paper file (first maintained
at the Division of Dockets Management, and then maintained in the
public reading room of our Freedom of Information Staff), and evolved
into its current electronic format on our Internet site (Ref. 46). We
intend to continue using the Internet as the principal means to make
the inventory readily accessible because doing so is an efficient and
effective mechanism to disseminate information to anyone who has access
to the Internet. The inventory on the Internet can be accessed and
printed from computers in the public reading room at Division of
Dockets Management, as well as from computers located at businesses, at
homes, and at public locations such as libraries and Internet cafes. If
a person either does not have access to the Internet or chooses not to
access the inventory through the Internet, that person can request each
GRAS notice, and each letter listed in Sec.  170.265(b)(1) or (3) or
(c), under the FOIA. It is no longer practical for us to maintain a
paper file at the Division of Dockets Management, because all new
information sent to the Division of Dockets Management is maintained
electronically; paper submissions are scanned to electronic form.
    (Comment 117) One comment that addresses the discussion in the 2010
notice about the reasons that may lead us to decline to file a
submission as a GRAS notice, such as when the use is covered by an
existing regulation, asks us to include those submissions in the GRAS
inventory so there will be no confusion as to the status of the
ingredient.
    (Response 117) We decline this request. The purpose of the
inventory of GRAS notices is to provide a list of all the GRAS notices
that we have filed and evaluated, not to interpret the uses listed in
our regulations or, as discussed in Response 86, covered by an existing
GRAS notice.
    (Comment 118) A few comments suggest that a publicly available