Document ID: FDA-2018-C-4464-0019
Agency: fda
Document Type: Rule
Title: Listing of Color Additives Exempt From Certification; Soy Leghemoglobin
Posted Date: 2019-12-19T05:00Z

[Federal Register Volume 84, Number 244 (Thursday, December 19, 2019)]
[Rules and Regulations]
[Pages 69620-69626]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-27173]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. FDA-2018-C-4464]

Listing of Color Additives Exempt From Certification; Soy 
Leghemoglobin

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; response to objections and denial of public hearing 
requests; removal of administrative stay.

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SUMMARY: The Food and Drug Administration (FDA or we) is responding to 
objections that it received from the Center for Food Safety on the 
final rule entitled ``Listing of Color Additives Exempt from 
Certification; Soy Leghemoglobin,'' which published on August 1, 2019. 
The final rule amended the color additive regulations to provide for 
the safe use of soy leghemoglobin as a color additive in ground beef 
analogue products. After reviewing the objections, FDA has

[[Page 69621]]

concluded that the objections do not raise issues of material fact that 
justify a hearing or otherwise provide a basis for revoking the 
amendment to the regulations. We are also providing notice that the 
administrative stay of the effective date for this color additive 
regulation is now lifted.

DATES: The final rule that published in the Federal Register of August 
1, 2019 (84 FR 37573) with an effective date of September 4, 2019, was 
administratively stayed by the filing of objections under section 
701(e)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 
U.S.C. 371(e)(2)) as of September 3, 2019. FDA lifts the administrative 
stay as of December 19, 2019.

ADDRESSES: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number found in brackets in the heading of this final rule into 
the ``Search'' box and follow the prompts, and/or go to the Dockets 
Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Ellen Anderson, Center for Food Safety 
and Applied Nutrition, Food and Drug Administration, 5001 Campus Dr., 
College Park, MD 20740-3835, 240-402-1309.

SUPPLEMENTARY INFORMATION: 

I. Background

    In a notification published in the Federal Register of December 13, 
2018 (83 FR 64045), we announced that we filed a color additive 
petition (CAP 9C0314) submitted by Impossible Foods, Inc., c/o 
Exponent, Inc., 1150 Connecticut Avenue NW, Suite 1100, Washington, DC 
20036. The petition proposed to amend the color additive regulations in 
part 73 (21 CFR part 73), ``Listing of Color Additives Exempt from 
Certification,'' to provide for the safe use of soy leghemoglobin as a 
color additive in ground beef analogue products such that the amount of 
soy leghemoglobin protein does not exceed 0.8 percent by weight of the 
uncooked ground beef analogue product.
    Additionally, in the Federal Register of August 1, 2019 (84 FR 
37573), FDA issued a final rule entitled ``Listing of Color Additives 
Exempt from Certification; Soy Leghemoglobin,'' amending the color 
additive regulations to provide for the safe use of soy leghemoglobin 
in ground beef analogue products. Specifically, the final rule added 
Sec.  73.520 (21 CFR 73.520), entitled ``Soy leghemoglobin,'' which set 
forth the identity, specifications, uses and restrictions, labeling, 
and exemption from batch certification for the color additive. We gave 
interested persons until September 3, 2019, to file objections and 
requests for a hearing on the final rule.

II. Objections and Requests for Hearings

    Sections 701(e)(2) and 721(d) of the FD&C Act (21 U.S.C. 371(e)(2) 
and 379e(d)) collectively provide that, within 30 days after 
publication of an order relating to a color additive regulation, any 
person adversely affected by such an order may file objections, 
specifying with particularity the provisions of the order deemed 
objectionable, stating the grounds therefor, and requesting a public 
hearing upon such objections. FDA may deny a hearing request if the 
objections to the regulation do not raise genuine and substantial 
issues of fact that can be resolved at a hearing (see Sec.  12.24(b)(1) 
(21 CFR 12.24(b)(1)); see also Community Nutrition Institute v. Young, 
773 F.2d 1356, 1364 (D.C. Cir. 1985)).
    Objections and requests for a hearing are governed by part 12 (21 
CFR part 12) of FDA's regulations. Under Sec.  12.22(a) (21 CFR 
12.22(a)), each objection must meet the following conditions: (1) Must 
be submitted on or before the 30th day after the date of publication of 
the final rule; (2) must be separately numbered; (3) must specify with 
particularity the provision of the regulation or proposed order 
objected to; (4) must specifically state the provision of the 
regulation or proposed order on which a hearing is requested (failure 
to request a hearing on an objection constitutes a waiver of the right 
to a hearing on that objection); and (5) must include a detailed 
description and analysis of the factual information to be presented in 
support of the objection if a hearing is requested (failure to include 
a description and analysis for an objection constitutes a waiver of the 
right to a hearing on that objection).
    Following the publication of the final rule for the safe use of soy 
leghemoglobin as a color additive in ground beef analogue products, we 
received a submission from the Center for Food Safety providing 
objections and requesting a hearing on each objection. The objections 
are as follows:
    Objection 1: FDA should not have approved this product to be used 
in ground beef analogues that are not plant-based without additional 
safety testing and public comment.
    Objection 2: FDA should require labeling of this color additive as 
``soy leghemoglobin/P[ichia] pastoris yeast protein.'' \1\
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    \1\ Pichia pastoris (P. pastoris) is a non-pathogenic and non-
toxicogenic strain of yeast that is genetically engineered to 
express soy leghemoglobin and P. pastoris yeast proteins. Soy 
leghemoglobin protein is the principal coloring agent in the color 
additive. (See 84 FR 37573 at 37574.)
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    Objection 3: FDA should have required additional testing of the raw 
product.
    Objection 4: FDA improperly relied on Impossible Foods' Generally 
Recognized As Safe (GRAS) Notice 737 instead of independently verifying 
the safety of soy leghemoglobin for use as a color additive.
    Objection 5: FDA should have required separate testing of P. 
pastoris because it is genetically engineered.
    Objection 6: FDA violated the National Environmental Policy Act 
(NEPA) by failing to prepare an environmental assessment or 
environmental impact statement.
    See submission from Jaydee Hanson, Policy Director, and Ryan 
Talbot, Staff Attorney, Center for Food Safety, to the Dockets 
Management Staff, Food and Drug Administration, dated September 3, 
2019, at pages 1-2, 6-12 (referred to hereinafter as the 
``submission'').

III. Standards for Granting a Hearing

    Specific criteria for determining whether to grant or deny a 
request for a hearing are set out in Sec.  12.24(b). Under that 
regulation, a hearing will be granted if the material submitted by the 
requester shows, among other things, that: (1) There is a genuine and 
substantial factual issue for resolution at a hearing (a hearing will 
not be granted on issues of policy or law); (2) the factual issue can 
be resolved by available and specifically identified reliable evidence 
(a hearing will not be granted on the basis of mere allegations or 
denials or general descriptions of positions and contentions); (3) the 
data and information submitted, if established at a hearing, would be 
adequate to justify resolution of the factual issue in the way sought 
by the requester (a hearing will be denied if the data and information 
submitted are insufficient to justify the factual determination urged, 
even if accurate); (4) resolution of the factual issue in the way 
sought by the person is adequate to justify the action requested (a 
hearing will not be granted on factual issues that are not 
determinative with respect to the action requested, e.g., if the action 
would be the same even if the factual issue were resolved in the way 
sought); (5) the action requested is not inconsistent with any 
provision in the

[[Page 69622]]

FD&C Act or any regulation particularizing statutory standards (the 
proper procedure in those circumstances is for the person requesting 
the hearing to petition for an amendment or waiver of the regulation 
involved); and (6) the requirements in other applicable regulations, 
e.g., 21 CFR 10.20, 12.21, 12.22, 314.200, 514.200, and 601.7(a), and 
in the notice issuing the final regulation or the notice of opportunity 
for a hearing are met.
    A party seeking a hearing must meet a ``threshold burden of 
tendering evidence suggesting the need for a hearing'' (Costle v. 
Pacific Legal Foundation, 445 U.S. 198, 214-215 (1980), citing 
Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 620-621 
(1973)). An allegation that a hearing is necessary to ``sharpen the 
issues'' or to ``fully develop the facts'' does not meet this test 
(Georgia Pacific Corp. v. EPA, 671 F.2d 1235, 1241 (9th Cir. 1982)). If 
a hearing request fails to identify any factual evidence that would be 
the subject of a hearing, there is no point in holding one. In judicial 
proceedings, a court is authorized to issue summary judgment without an 
evidentiary hearing whenever it finds that there are no genuine issues 
of material fact in dispute, and a party is entitled to judgment as a 
matter of law (see Rule 56, Federal Rules of Civil Procedure). The same 
principle applies to administrative proceedings (see Sec.  12.28).
    A hearing request must not only contain evidence, but that evidence 
should raise a material issue of fact ``concerning which a meaningful 
hearing might be held'' (Pineapple Growers Ass'n v. FDA, 673 F.2d 1083, 
1085 (9th Cir. 1982)). Where the issues raised in the objection are, 
even if true, legally insufficient to alter the decision, an Agency 
need not grant a hearing (see Dyestuffs and Chemicals, Inc. v. 
Flemming, 271 F.2d 281, 286 (8th Cir. 1959)). A hearing is justified 
only if the objections are made in good faith and if they ``draw in 
question in a material way the underpinnings of the regulation at 
issue'' (Pactra Industries v. CPSC, 555 F.2d 677, 684 (9th Cir. 1977)). 
A hearing need not be held to resolve questions of law or policy (see 
Citizens for Allegan County., Inc. v. FPC, 414 F.2d 1125, 1128 (D.C. 
Cir. 1969); Sun Oil Co. v. FPC, 256 F.2d 233, 240 (5th Cir. 1958)).
    Even if the objections raise material issues of fact, FDA need not 
grant a hearing if those same issues were adequately raised and 
considered in an earlier proceeding. Once an issue has been so raised 
and considered, a party is estopped from raising that same issue in a 
later proceeding without new evidence. The various judicial doctrines 
dealing with finality, such as collateral estoppel, can be validly 
applied to the administrative process (see Pacific Seafarers, Inc. v. 
Pacific Far East Line, Inc., 404 F.2d 804, 809 (D.C. Cir. 1968)). In 
explaining why these principles ought to apply to an Agency proceeding, 
the U.S. Court of Appeals for the District of Columbia Circuit wrote: 
``The underlying concept is as simple as this: justice requires that a 
party have a fair chance to present his position. But overall interests 
of administration do not require or generally contemplate that he will 
be given more than a fair opportunity'' (Retail Clerks Union, Local 
1401 v. NLRB, 463 F.2d 316, 322 (D.C. Cir. 1972); see also Costle v. 
Pacific Legal Foundation, 445 U.S. at 215-17).

IV. Analysis of Objections and Response to Hearing Requests

    The submission from the Center for Food Safety contains six 
numbered objections and requests a hearing on each of them. We address 
each objection below, as well as the evidence and information filed in 
support of each, comparing each objection and the information submitted 
in support of it to the standards for granting a hearing in Sec.  
12.24(b).

A. Objection 1

    The first objection asserts that FDA should not have approved soy 
leghemoglobin as a color additive to be used in ``. . . all ground beef 
analogue products, not just in plant-based ground beef analogue 
products'' without additional safety testing and public comment.\2\ The 
objection asserts that Impossible Foods' safety testing of soy 
leghemoglobin ``was based on its use with the company's soy-based 
ground beef analogue and that is the extent to which FDA's review and 
approval should go.'' (See page 6 of the submission.) Moreover, the 
objection claims that the use of soy leghemoglobin in ``all ground beef 
analogue products requires additional testing for allergenicity.'' (See 
page 6 of the submission.) The Center for Food Safety provided no 
scientific data to support its objection.
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    \2\ We note that we specifically stated in the final rule, ``For 
the purposes of this final rule, the term ``ground beef analogue 
products'' refers to plant-based or other non-animal derived ground 
beef-like food products.'' See 84 FR 37573. Therefore, if a firm 
wanted to use soy leghemoglobin as a color additive in animal-
derived products, that use would require authorization through the 
color additive petition process.
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    We clarify that the safety testing conducted by Impossible Foods 
and described in CAP 9C0314 was not based on the use of the color 
additive with a soy-based ground beef analogue, as claimed in the 
objection. The petitioner used a weight-of-evidence approach to address 
the safety of soy leghemoglobin protein and P. pastoris proteins that 
comprise the color additive. The weight-of-evidence approach, which is 
a widely used method for assessing protein safety by experts in the 
scientific community, is based on several elements such as the known 
function of the protein and its history of exposure, whether the 
protein is from a toxigenic or allergenic source, the digestibility of 
the protein, and bioinformatic analysis of the protein to determine if 
it is structurally similar to known allergens or toxins (i.e., amino 
acid sequence homology) (Ref 1). In our review of CAP 9C0314, we 
confirmed that Impossible Foods thoroughly addressed the safety of soy 
leghemoglobin, including any potential allergenicity, using the weight-
of-evidence approach.
    Furthermore, we are not aware of any scientific evidence that 
suggests a food matrix, whether plant-based or animal-based, would 
modify the structure, function, or safety of soy leghemoglobin under 
the conditions of its intended use.
    The objection failed to include any new information or data that 
would refute our findings about the safety of soy leghemoglobin in food 
matrices other than plant-based products. The objection merely alleges 
that there is a potential for harm, without providing any scientific 
basis. A hearing will not be granted on the basis of mere allegations 
or general descriptions of positions and contentions (Sec.  
12.24(b)(2)). The objector must, at a minimum, raise a material issue 
concerning which a meaningful hearing might be held. Therefore, we are 
denying the request for a hearing on this objection.

B. Objection 2

    The second objection asserts that FDA should require labeling of 
this color additive as ``soy leghemoglobin/P. pastoris yeast protein.'' 
(See page 6 of the submission.) The Center for Food Safety alleges that 
the ``labeling approved by FDA does not provide `sufficient 
information' about Impossible Foods' product.'' (See page 6 of the 
submission.) Additionally, the objection states that both soy 
leghemoglobin and P. pastoris proteins should be identified in labeling 
for consumers who ``believe that they have allergies to either soy 
products or yeast products.'' (See page 7 of the submission.)
    FDA acknowledges that the color additive soy leghemoglobin contains 
residual amounts of P. pastoris yeast

[[Page 69623]]

protein in addition to the principal coloring component, soy 
leghemoglobin protein. The allergenicity of soy leghemoglobin protein 
and residual yeast proteins was addressed in safety studies that 
included digestibility assays in simulated gastric fluid, bioinformatic 
analyses, and animal feeding studies. The totality of evidence 
presented in the color additive petition indicated that there is a 
reasonable certainty that soy leghemoglobin protein and P. pastoris 
yeast proteins do not pose any unique allergenicity risks when 
consumed.
    Furthermore, under the Food Allergen Labeling and Consumer 
Protection Act of 2004 (FALCPA), which added section 403(w) to the FD&C 
Act (21 U.S.C. 343(w)), the label of a food that contains an ingredient 
that is or contains protein from a ``major food allergen'' must declare 
the presence of the allergen in the manner described by the law. As 
stated in the findings of FALCPA in section 202(2)(A), the major food 
allergens identified in the FD&C Act account for over 90 percent of all 
documented food allergies in the United States and represent foods that 
are likely to result in life-threatening reactions. Because soybeans 
are identified as a major food allergen, foods that contain soy 
leghemoglobin must be labeled accordingly. Yeast protein has not been 
identified as a major food allergen. The objection provided no 
scientific data on the prevalence or severity of yeast protein allergy 
to support its objection.
    The Center for Food Safety failed to provide any new information or 
data that would refute our findings about the potential for 
allergenicity to yeast proteins. The objection merely alleges that 
there is a potential for harm, without providing any evidence that we 
have not considered previously. A hearing will not be granted on the 
basis of mere allegations or general descriptions of positions and 
contentions (Sec.  12.24(b)(2)). The objection must, at a minimum, 
raise a material issue concerning which a meaningful hearing might be 
held. Therefore, we are denying the request for a hearing on this 
objection.

C. Objection 3

    The third objection asserts that FDA should have required 
additional testing of the raw color additive product. The objection 
states, ``[s]ince it is reasonably foreseeable that many consumers will 
not fully cook this analogue product, FDA should have required 
additional allergenicity testing of preparation as present in the rare 
or raw product.'' (See page 7 of the submission.) The objection failed 
to include any new information or data to support this assertion.
    We note that the safety studies submitted in support of Impossible 
Foods' color additive petition for soy leghemoglobin were conducted 
using ``raw'' soy leghemoglobin preparation. This fact is indicated in 
the color additive petition as well as in the supporting publications. 
(See pages 32, 34, and 37 of CAP 9C0314). The Center for Food Safety 
failed to include any new information or data that would refute our 
findings about the safety of the ``raw'' soy leghemoglobin preparation, 
which was considered in our evaluation. A hearing will not be granted 
on the basis of mere allegations or general descriptions of positions 
and contentions (Sec.  12.24(b)(2)). The objector must, at a minimum, 
raise a material issue concerning which a meaningful hearing might be 
held. Therefore, we are denying the request for a hearing on this 
objection.

D. Objection 4

    The fourth objection asserts that FDA's reliance on Impossible 
Foods' GRAS Notice 737 violates the definition of ``safe'' in Sec.  
70.3(i) (21 CFR. 70.3(i)). The objection claims ``that FDA relied 
heavily on Impossible Foods' GRAS Notice filed in a separate proceeding 
(and under a separate statutory provision) instead of independently 
verifying the safety of SLH [soy leghemoglobin] for use as a color 
additive.'' (See page 7 of the submission.) Furthermore, the objection 
asserts that FDA's reliance on safety studies conducted by Impossible 
Foods' employees or consultants ``undermines the integrity of the color 
additive petition process.'' (See page 8 of the submission.)
    FDA disagrees with the Center for Food Safety's assertion that our 
approval of soy leghemoglobin as a color additive in ground beef 
analogue products is in violation of Sec.  70.3(i), which defines 
``safe'' to mean there is convincing evidence that establishes with 
reasonably certainty that no harm will result from the intended use of 
the color additive. Impossible Foods submitted CAP 9C0314, a regulatory 
submission for a color additive petition distinct from GRAS notice 737, 
seeking approval for the use of soy leghemoglobin as a color additive 
in ground beef analogue products. FDA acknowledges that the subject of 
GRAS notice 737, soy leghemoglobin preparation, is the same substance 
that is the subject of CAP 9C0314. FDA also acknowledges that the 
safety studies conducted in support of GRAS notice 737 were submitted 
in support of CAP 9C0314. In addition to evaluating the safety of soy 
leghemoglobin in response to GRAS notice 737, FDA specifically 
evaluated its safety as a color additive in response to CAP 9C0314. 
Furthermore, although the regulatory programs are distinct, the 
standard of safety--a reasonable certainty of no harm from the intended 
use--is the same for food additives, color additives, and GRAS 
substances.
    As we stated in the final rule (84 FR 37573 at 37574), our safety 
evaluation for a color additive considers the additive's manufacturing; 
its stability; the projected human dietary exposure to the additive and 
any impurities resulting from the petitioned use of the additive; the 
additive's toxicological data; and other relevant information (such as 
published literature) available to us. In establishing that soy 
leghemoglobin is safe for use as a color additive, we considered the 
petitioner's weight-of-evidence approach based on: (1) The history of 
consumption of soy, soy leghemoglobin protein, and P. pastoris; (2) the 
safety of the genetically engineered P. pastoris production strain; (3) 
14-day and 28-day feeding studies of soy leghemoglobin preparation in 
rats; (4) mutagenicity and genotoxicity studies of soy leghemoglobin 
preparation; and (5) an allergenicity assessment of soy leghemoglobin 
and P. pastoris proteins present in the soy leghemoglobin preparation. 
The objection did not contain any additional information that we did 
not already consider in our evaluation of the color additive petition, 
nor did the Center for Food Safety identify any reliable evidence that 
contradicts FDA's safety determination.
    We disagree with the Center for Food Safety's assertion that we 
must conduct our own safety studies rather than rely on studies 
conducted or funded by the petitioner to adequately evaluate the safe 
use of soy leghemoglobin. Studies needed to demonstrate the safety of 
food ingredients are mostly conducted by the manufacturer or their paid 
contract laboratories. The FD&C Act and our implementing regulations in 
21 CFR parts 70 and 71 do not require us to perform safety studies 
related to color additives; rather, the burden is on petitioners to 
provide safety data as part of their petition (21 CFR 71.1). FDA's 
responsibility is to evaluate the data contained in the petition, as 
well as other information available to us, to determine if the 
petitioned use is safe. FDA provides guidance documents (Ref. 2) that 
specifically describe the type of data that we expect petitioners to 
generate or rely upon for safety decisions on food ingredients.
    We note that the objection criticized two peer-reviewed studies 
published in

[[Page 69624]]

scientific journals because they are co-authored by Impossible Foods' 
employees and/or their consultants. The utility of such publications is 
that the journal's peer review process can promote scientific rigor and 
the entire scientific community can review the studies. This 
transparency allows others to conduct further studies to test and 
verify the results and conclusions, if warranted.
    FDA disagrees with the Center for Food Safety's assertion that a 
90-day feeding study, rather than a 28-day feeding study, with soy 
leghemoglobin was appropriate because the digestibility studies in 
simulated gastric fluid showed that the soy leghemoglobin protein and 
P. pastoris proteins were mostly digested in 0.5 minutes and could not 
be detected beyond 2 minutes under the conditions of the study. These 
data indicate that both soy leghemoglobin protein and P. pastoris 
proteins are expected to be rapidly digested in the stomach, and these 
proteins would no longer be available intact following oral 
administration in either a 28-day or 90-day study. Moreover, sequence 
analysis of the soy leghemoglobin protein and P. pastoris proteins and 
their known functions suggest that the intact proteins or any fragments 
thereof are not likely to cause any adverse effects. Therefore, a 90-
day study, compared to a 28-day study, has no added utility for 
demonstrating the safety of this ingredient, as the proteins will be 
digested rapidly in the stomach just like any other consumed proteins.
    Regarding the statistical differences noted in the study and that 
the objection quotes as ``potentially adverse effects'' (see page 9 of 
the submission), observed effects that are deemed statistically 
significant are not necessarily toxicologically relevant. For an 
observed effect to be toxicologically relevant (i.e., potentially 
adverse), a clear dose-response should be seen (e.g., increasing the 
dose of a test substance causes an increase in the observed effect in 
the test subjects), and the observed effect should occur in both sexes 
of test species. If the structure and metabolism of the test substance 
is known, it may be possible to develop a hypothesis on the potential 
mechanism of adverse effects or lack thereof. The available information 
on the structure and function of soy leghemoglobin and its fate in the 
body following consumption do not lend support to the Center for Food 
Safety's claim that the statistically significant differences reported 
in the study are indicative of potentially adverse effects in humans.
    The objection cites an online report by Robinson and Antoniou 
(2019) \3\ asserting that feeding soy leghemoglobin to rats resulted in 
statistically significant changes in some clinical chemistry parameters 
compared to controls. The examples cited are changes in blood 
chemistry, blood clotting ability, and blood globulin values. The 
Center for Food Safety surmises that such statistically significant 
differences could mean potentially adverse effects and are reason for 
concern. However, differences in observed clinical chemistry 
parameters, even if statistically significant, do not necessarily mean 
that treatment-related differences exist. There are numerous accounts 
of historical control data that demonstrate the extent of inter-animal 
variability observed in rat strains commonly used in toxicological 
studies (Refs. 3 to 8). These data show that certain clinical chemistry 
parameters may have a wide range of normal values in experimental 
control animals, such that statistical differences seen between control 
animals and treatment animals due to small changes in the value of the 
parameter are not likely to be of biological or toxicological 
significance. Importantly, the changes observed for these parameters in 
Impossible Food's 28-day study were within historical ranges of control 
values, did not show a dose-response relationship, and did not occur in 
both sexes, indicating that the statistically significant differences 
were incidental and not treatment-related. The objection is based 
purely on statistical significance and not biological significance or 
toxicological relevance.
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    \3\ Available at: https://www.gmoscience.org/rat-feeding-studies-suggest-the-impossible-burger-may-not-be-safe-to-eat/.
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    The objection failed to include any new information or data that 
would refute our conclusion that the data provided in the petition was 
adequate to establish safety. A hearing will not be granted on the 
basis of general descriptions of positions and contentions (Sec.  
12.24(b)(2)). The objector must, at a minimum, raise a material issue 
concerning which a meaningful hearing might be held. Therefore, we are 
denying the request for a hearing on this objection.

E. Objection 5

    The fifth objection asserts that FDA should have required separate 
testing of P. pastoris because it is genetically engineered. The 
objection states that the use of P. pastoris should ``require separate 
testing for allergenicity as the genetically-engineered yeast proteins 
are present in the final `soy leghemoglobin/P. pastoris preparation.' 
'' (See page 9 of the submission.)
    Soy leghemoglobin was produced by genetic engineering of P. 
pastoris to express specific and targeted proteins with known 
functions. The fermentation process used to produce soy leghemoglobin 
is performed under controlled conditions and good manufacturing 
practices. Quality control tests are in place to ensure there is no 
residual P. pastoris production strain in the final product. The P. 
pastoris proteins and the soy leghemoglobin protein comprise the final 
soy leghemoglobin color additive that is the subject of this 
rulemaking. All safety studies were conducted using the soy 
leghemoglobin preparation that contained both the soy leghemoglobin 
protein and the P. pastoris proteins. Therefore, the safety of both the 
soy leghemoglobin protein and the P. pastoris proteins were considered 
in FDA's evaluation. Consequently, there is no scientific basis to 
conduct additional testing of a P. pastoris strain simply because of 
the methods used to develop the strain. In any event, as previously 
stated, the studies contained in the color additive petition 
demonstrated both types of proteins were safe. The objection provided 
no scientific evidence to support its claim that separate safety 
testing of the genetically engineered P. pastoris yeast is warranted.
    The objection failed to include any new information or data to 
support their contention that separate allergenicity testing is needed 
for P. Pastoris yeast. A hearing will not be granted on the basis of 
general descriptions of positions and contentions (Sec.  12.24(b)(2)). 
The objector must, at a minimum, raise a material issue concerning 
which a meaningful hearing might be held. Therefore, we are denying the 
request for a hearing on this objection.

F. Objection 6

    The sixth and last objection asserts that FDA violated NEPA by 
failing to prepare an environmental assessment or environmental impact 
statement. The objection states that ``FDA failed to consider whether 
there may be indirect and cumulative adverse effects to threatened and 
endangered species or their critical habitat as a result of its 
approval of Impossible Foods' petition.'' (See page 10 of the 
submission.) The objection alleges that the use of genetically 
engineered soybeans as a source of soy protein to formulate ground beef 
analogues may increase the

[[Page 69625]]

use of soybeans derived from genetically engineered soy varieties and 
compete with the livestock industry for feedstock. (See page 11 of the 
submission.) Furthermore, the Center for Food Safety suggests that the 
use of dicamba, a pesticide commonly used on certain crops engineered 
to be resistant to the pesticide, will increase due to increased 
reliance on soy protein as an ingredient in the ground beef analogue 
products. As such, the objection claims that FDA should have considered 
the potential indirect and cumulative effects of increased pesticide 
application on genetically engineered soybean crops and should have 
required an environmental assessment or an environmental impact 
statement related to CAP 9C0314.
    We do not agree that we violated NEPA by failing to prepare an 
environmental assessment or an environmental impact statement. 
Furthermore, we do not agree that we failed to consider whether there 
may be indirect or cumulative adverse effects to threatened and 
endangered species or their critical habitat resulting from the 
approval of Impossible Foods' color additive petition that would 
constitute extraordinary circumstances within the meaning of Sec.  
25.21(b) (21 CFR 25.21(b)).
    As discussed in the filing notice for the petition (83 FR 64045; 
December 13, 2018), Impossible Foods claimed that the categorical 
exclusion in Sec.  25.32(k) (21 CFR 25.32(k)) applied to the proposed 
use of soy leghemoglobin because the substance would be added directly 
to food and is intended to remain in food through ingestion by 
consumers and is not intended to replace macronutrients in food. Under 
Sec.  25.21, FDA requires at least an environmental assessment for any 
specific action that ordinarily would be excluded if extraordinary 
circumstances indicate that the specific proposed action may 
significantly affect the quality of the human environment. As discussed 
in the filing notice published in the Federal Register of December 13, 
2018, Impossible Foods stated that, to their knowledge, no 
extraordinary circumstances exist regarding the proposed use of soy 
leghemoglobin. In our analysis of the applicability of the categorical 
exclusion under Sec.  25.32(k), we focused on soy leghemoglobin 
production and potential waste products (i.e., food waste and/or 
excretion products) and identified no extraordinary circumstances 
related to production, use, or disposal of soy leghemoglobin. In the 
final rule (84 FR 37573), we stated that we did not receive any new 
information or comments regarding this claim of categorical exclusion, 
and therefore determined that the proposed action is categorically 
excluded under Sec.  25.32(k).
    No data or information was provided to support the Center for Food 
Safety's contention that the approval of soy leghemoglobin as a color 
additive would result in an increase in the cultivation of genetically 
engineered soybeans, that such cultivation would lead to an increase in 
pesticide use such as dicamba, or that such cultivation would result in 
significant adverse impacts to threatened or endangered species or 
their critical habitat, requiring the preparation of an environmental 
assessment or an environmental impact statement. Furthermore, the 
objection focuses on increased cultivation of genetically engineered 
soybeans and use of pesticides such as dicamba. The objection does not 
consider that Impossible Foods' soy leghemoglobin ingredient, the 
substance that is the subject of the color additive petition, is not 
grown or derived from genetically engineered soybean plants. Instead, 
the substance is produced by a strain of genetically engineered yeast; 
production occurs in vats rather than on a farm and does not require 
the use of pesticides such as dicamba.
    The objection cites a 2019 Forbes article \4\ as support for the 
assertion that Impossible Foods ``switch[ed] from wheat to GM soy.'' 
(See page 11 of the submission.) However, the Forbes article discusses 
the plant-based raw material that forms the burger itself, not the 
ingredient soy leghemoglobin that is the subject of FDA's action. Thus, 
the Center for Food Safety's reliance on this article for the 
proposition that FDA approval of soy leghemoglobin for use as a color 
additive will lead to an increase in genetically engineered soybean 
cultivation is misplaced. Because Impossible Foods' soy leghemoglobin 
ingredient is not derived from genetically engineered soybeans, there 
is no basis on which to conclude that FDA's approval of soy 
leghemoglobin for use as a color additive will result in increased 
cultivation of genetically engineered soybeans and/or an increased use 
of pesticides in domestic agriculture.\5\ To the extent the Center for 
Food Safety is arguing that FDA's approval of the petition may have an 
indirect effect on the production of genetically engineered soy by 
facilitating an overall increase in Impossible Foods' burger 
production, we note that this argument is speculative and the Center 
for Food Safety has not identified any evidence that FDA's approval of 
the petition will have a meaningful effect of this nature.
---------------------------------------------------------------------------

    \4\ Available at: https://www.forbes.com/sites/louisaburwoodtaylor/2019/07/31/impossible-in-full-scale-up-mode-with-new-burger-manufacturing-deal--fda-approval/.
    \5\ We note that, based on publicly available information from 
the United States Department of Agriculture, approximately 94 
percent of the soybean acres planted in 2019 in the United States 
were genetically engineered varieties (https://www.ers.usda.gov/topics/farm-practices-management/biotechnology/).
---------------------------------------------------------------------------

    The objection failed to include any new information or data that 
would change our findings with respect to the applicability of the 
categorical exclusion in Sec.  25.32(k). The request for a hearing does 
not provide any evidence to support its claims. A hearing will not be 
granted on the basis of mere allegations or general descriptions of 
positions and contentions (Sec.  12.24(b)(2)). The objections must, at 
a minimum, raise a material issue concerning which a meaningful hearing 
might be held. Therefore, we are denying the request for a hearing on 
this objection.

V. Summary and Conclusions

    Section 721 of the FD&C Act requires that a color additive be shown 
to be safe prior to marketing. Under Sec.  70.3(i), a color additive is 
safe if there is a reasonable certainty in the minds of competent 
scientists that the substance is not harmful under the intended 
conditions of use. In the final rule authorizing the use of soy 
leghemoglobin, we concluded that the data presented by the petitioner 
demonstrate that soy leghemoglobin is safe for its intended use in 
ground beef analogue products.
    The petitioner has the burden to demonstrate the safety of the 
additive to gain FDA approval. Once we make a finding of safety, the 
burden shifts to an objector, who must come forward with evidence that 
calls into question our conclusion (see section 701(e)(2) of the FD&C 
Act).
    Despite its allegations, the Center for Food Safety has not 
established that we have overlooked significant information contained 
within the record in reaching our conclusion that the use of soy 
leghemoglobin in ground beef analogue products is safe. In such 
circumstances, we have determined that the objections do not raise any 
genuine and substantial issue of fact that can be resolved by an 
evidentiary hearing (Sec.  12.24(b)). Accordingly, we are denying the 
requests for a hearing. Furthermore, after evaluating the objections, 
we have concluded that the objections do not provide any basis for us 
to reconsider our decision to issue the final rule authorizing the use 
of soy leghemoglobin in ground beef analogue products. Accordingly, we 
are not

[[Page 69626]]

making any changes in response to the objections.
    The filing of the objections served to stay automatically the 
effectiveness of Sec.  [thinsp]73.520. Section 701(e)(2) of the FD&C 
Act states that, until final action upon such objections is taken by 
the Secretary, the filing of such objections operates to stay the 
effectiveness of those provisions of the order to which the objections 
are made. Section 701(e)(3) of the FD&C Act further stipulates that, as 
soon as practicable, the Secretary shall by order act upon such 
objections and make such order public. We have completed our evaluation 
of the objections and conclude that a continuation of the stay of Sec.  
[thinsp]73.520 is not warranted.
    In the absence of any other objections and requests for a hearing, 
we conclude that this document constitutes final action on the 
objections received in response to the regulation as prescribed in 
section 701(e)(2) of the FD&C Act. Therefore, we are ending the 
administrative stay of the regulation as of December 19, 2019 for the 
Sec.  73.520 listing soy leghemoglobin as a color additive for use in 
ground beef analogue products.

VI. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (see ADDRESSES) and are available for 
viewing by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public 
display at https://www.regulations.gov because they have copyright 
restriction. Some may be available at the website address, if listed. 
References without asterisks are available for viewing only at the 
Dockets Management Staff. FDA has verified the website addresses, as of 
the date this document publishes in the Federal Register, but websites 
are subject to change over time.

1. Ladics, G.S., ``Current Codex Guidelines for Assessment of 
Potential Protein Allergenicity.'' Food and Chemical Toxicology, 46: 
S20-S23, 2008.
2. *FDA. ``Redbook 2000 Guidance for Industry and Other 
Stakeholders; Toxicological Principles for the Safety Assessment of 
Food Ingredients,'' 2007. Retrieved from https://www.fda.gov/media/79074/download.
3. Giknis, M.L.A. and C.B. Clifford, ``Clinical Laboratory 
Parameters for Crl:CD(SD) Rats,'' 2006. Retrieved from https://www.crj.co.jp/cms/pdf/info_common/50/8250933/rm_rm_r_clinical_parameters_cd_rat_06.pdf.
4. Giknis, M.L.A. and C.B. Clifford, ``Clinical Laboratory 
Parameters for Crl:WI(Han),'' 2008. Retrieved from https://www.criver.com/sites/default/files/resources/rm_rm_r_Wistar_Han_clin_lab_parameters_08.pdf.
5. Matsuzawa, T., M. Nomura, and T. Unno, ``Clinical Pathology 
Reference Ranges of Laboratory Animals. Working Group II, 
Nonclinical Safety Evaluation Subcommittee of the Japan 
Pharmaceutical Manufacturers Association.'' Journal of Veterinary 
Medical Science, 55(3): 351-362, 1993.
6. Pettersen, J.C., R.L. Morrissey, D. R. Saunders, et al., ``A 2-
Year Comparison Study of Crl:CD BR and Hsd:Sprague-Dawley SD Rats.'' 
Fundamental and Applied Toxicology, 33: 196-211, 1996.
7. Petterino, C. and A. Argentino-Storino, ``Clinical Chemistry and 
Haematology Historical Data in Control Sprague-Dawley Rats From Pre-
clinical Toxicity Studies.'' Experimental and Toxicologic Pathology, 
57: 213-219, 2006.
8. Seibel, J., K. Bodi[eacute], S. Weber, et al., ``Comparison of 
Haematology, Coagulation and Clinical Chemistry Parameters in Blood 
Samples From the Sublingual Vein and Vena Cava in Sprague-Dawley 
Rats.'' Laboratory Animals, 44: 344-351, 2010.

List of Subjects in 21 CFR Part 73

    Color additives, Cosmetics, Drugs, Foods, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 321, 341, 342, 343, 348, 351, 352, 355, 361, 362, 371, 379e) and 
under authority delegated to the Commissioner of Food and Drugs 
(section 1410.10 of the FDA Staff Manual Guide), notice is given that 
the objections and requests for hearings were filed in response to the 
August 1, 2019, final rule. Notice is also given that FDA is denying 
these objections and requests for hearings. Accordingly, the 
administrative stay on the effective date of the amendments is lifted 
as of December 19, 2019.

    Dated: December 12, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-27173 Filed 12-17-19; 11:15 am]
BILLING CODE 4164-01-P