
[Federal Register Volume 79, Number 70 (Friday, April 11, 2014)]
[Rules and Regulations]
[Pages 20095-20098]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2014-08099]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. FDA-2012-C-0900]


Listing of Color Additives Exempt From Certification; Spirulina 
Extract

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or we) is amending the 
color additive regulations to provide for the expanded safe use of 
spirulina extract as a color additive in food. This action is in 
response to a petition filed by GNT USA, Inc.

DATES: This rule is effective May 13, 2014. See section X for further 
information on the filing of objections. Submit either electronic or 
written objections and requests for a hearing by May 12, 2014.

ADDRESSES: You may submit either electronic or written objections and 
requests for a hearing, identified by Docket No. FDA-2012-C-0900, by 
any of the following methods:

Electronic Submissions

    Submit electronic objections in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written objections in the following ways:
     Mail/Hand Delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket No. FDA-2012-C-0900 for this rulemaking. All objections 
received will be posted without change to http://www.regulations.gov, 
including any personal information provided. For detailed instructions 
on submitting objections, see the ``Objections'' heading of the 
SUPPLEMENTARY INFORMATION section.
    Docket: For access to the docket to read background documents or 
objections received, go to http://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Felicia M. Ellison, Center for Food 
Safety and Applied Nutrition (HFS-265), Food and Drug Administration, 
5100 Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1264.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In a document published in the Federal Register of September 6, 
2012 (77 FR 54862), we announced that GNT USA, Inc., c[sol]o Hogan 
Lovells US LLP, Columbia Square, 555 Thirteenth St. NW., Washington, DC 
20004, had filed a color additive petition (CAP 2C0297). The petition 
proposed to amend the color additive regulations in part 73 Listing of 
Color Additives Exempt From Certification (21 CFR part 73) to provide 
for the safe use of spirulina concentrate, prepared from a filtered 
aqueous extract of the dried biomass of Arthrospira platensis (A. 
platensis) (an edible blue-green cyanobacterium also known as Spirulina 
platensis), as a color additive in food.
    The spirulina concentrate that is manufactured by the petitioner is 
a blue colored powder or liquid produced by extracting the water 
soluble components of A. platensis, namely phycocyanins and other 
proteins, polysaccharides, lipids, and minor amounts of components such 
as vitamins, minerals, and water, followed by evaporation and the 
addition of sugars and other food-grade carriers (and water, if liquid 
form). The principal coloring components in the concentrate are the 
phycocyanins (not more than 2 percent), with lesser amounts of 
chlorophyll and carotenoids.

II. Background

    In the Federal Register of August 13, 2013, we issued a final rule 
in response to a color additive petition (CAP 2C0293) approving the use 
of a filtered aqueous extract of the dried biomass of A. platensis as a 
color additive in candy and chewing gum (78 FR 49117). We established 
spirulina extract as the common or usual name for the color additive 
and listed it in Sec.  73.530 (21 CFR 73.530). In addition to the 
identity of the color additive, the regulation in Sec.  73.530 includes 
specifications that must be met for lead, arsenic, mercury, and 
microcystin toxin; however, the regulation does not impose a specific 
upper limit for spirulina extract in food or for the phycocyanin 
content of the color additive because FDA determined that the amount of 
the color additive used in food was self-limiting. Instead, FDA limited 
the use of spirulina extract in candy and chewing gum to amounts 
consistent with good manufacturing practice.
    The primary difference between the spirulina extract that was the 
subject of CAP 2C0293 and spirulina concentrate that is the subject of 
CAP 2C0297 is the concentration of the components. Although spirulina 
concentrate is produced with an evaporation step to concentrate the 
components, the color additive has a lower level of phycocyanins (i.e., 
not more than 2 percent) than the spirulina extract that was the 
subject of CAP 2C0293 (i.e., not

[[Page 20096]]

less than 10 percent) because of a difference in the extraction 
process. To differentiate its color additive from this other spirulina 
product, the petitioner proposed that its color additive be listed 
separately as spirulina concentrate. However, since the regulation in 
Sec.  73.530 does not have a specification or limit on the phycocyanin 
content of the color additive, we have determined that the subject 
color additive meets the specifications of identity for spirulina 
extract in Sec.  73.530. Therefore, we have concluded that the 
petitioned uses should be added to Sec.  73.530 for spirulina extract. 
The subject color additive will be referred hereinafter in this final 
rule as spirulina extract.
    For the subject petition, spirulina extract is proposed for use in 
coloring confections (including candy and chewing gum), frostings, ice 
cream and frozen desserts, dessert coatings and toppings, beverage 
mixes and powders, yogurts, custards, puddings, cottage cheese, 
gelatin, breadcrumbs, and ready-to-eat cereals (excluding extruded 
cereals). The petitioner has proposed a phycocyanin limit of 2 percent 
in the color additive. However, we have determined that because the 
amount of spirulina extract used in food is self-limiting, there is no 
need for a specific upper limit for the phycocyanin content or the 
color additive (Ref. 1). Therefore, we are limiting the use of 
spirulina extract in the proposed foods to amounts consistent with good 
manufacturing practice.

III. Evaluation of Safety

    Under section 721(b)(4) of the Federal Food, Drug, and Cosmetic Act 
(the FD&C Act) (21 U.S.C. 379e(b)(4)), a color additive may not be 
listed for a particular use unless the data and information available 
to FDA establishes that the color additive is safe for that use. Our 
color additive regulations at 21 CFR 70.3(i) define safe to mean that 
there is ``convincing evidence that establishes with reasonable 
certainty that no harm will result from the intended use of the color 
additive.'' To establish with reasonable certainty that a color 
additive intended for use in food is not harmful under its intended 
conditions of use, we consider the projected human dietary exposure to 
the additive, the additive's toxicological data, and other relevant 
information (such as published literature) available to us. We compare 
an individual's estimated daily intake (EDI) of the additive from all 
food sources to an acceptable intake level established by toxicological 
data. The EDI is determined by projections based on the amount of the 
additive proposed for use in particular foods and on data regarding the 
amount consumed from all food sources of the additive. We commonly use 
the EDI for the 90th percentile consumer of a color additive as a 
measure of high chronic dietary intake.

IV. Safety of Petitioned Use of the Additive

    As part of our safety evaluation, we considered the exposure to 
phycocyanins from both the petitioned and current uses of spirulina 
extract as a color additive. We estimated that the petitioned uses of 
spirulina extract will result in an exposure to phycocyanins of 80 
milligrams/person/day (mg/p/d) for the 90th percentile consumer 2 years 
of age or older. We also estimated the exposure to phycocyanins from 
the petitioned use of the subject color additive for various age 
groups, including children 2 to 5 and 6 to 12 years of age, and 
teenagers 13 to 18 years of age, as these age groups may consume 
greater amounts of the foods containing spirulina extract. For these 
population subgroups, we estimated the exposure to phycocyanins at the 
90th percentile to be 80 mg/p/d for children 2 to 5 years of age and 
for teenagers, and 90 mg/p/d for children 6 to 12 years of age (Ref. 
2).
    Regarding cumulative exposure to phycocyanins from spirulina and 
spirulina-derived substances, FDA discussed in the final rule for 
spirulina extract as a color additive in candy and chewing gum that 
spirulina and spirulina-derived substances have been the subject of 
four notices submitted by firms to FDA with their determinations that 
certain uses of spirulina-derived substances are generally recognized 
as safe (GRAS) (78 FR 49117 at 49118). We evaluated each of these GRAS 
notices (GRNs) and concluded that we had no reason to question the 
basis of these GRAS determinations (Refs. 3-6). One of the GRAS notices 
(GRN 424) pertains to the use of an aqueous extract of powdered A. 
platensis or A. maxima as an ingredient for use in all foods at levels 
consistent with good manufacturing practice, except for infant formula 
and those food products (e.g., meat, eggs, and catfish) requiring 
additional review by the U.S. Department of Agriculture. The spirulina 
substance that was the subject of GRN 424 is similar in chemical 
composition to the subject color additive, but with a much higher 
phycocyanin content, ranging from 42 to 47 percent. The notifier (the 
person who submits a GRAS notice) for GRN 424 estimated a conservative 
exposure to phycocyanins from the notified uses of a spirulina extract 
to be 1,140 mg/p/d. This exposure estimate does not include exposure to 
spirulina and phycocyanins from dietary supplement use due to the 
notifier's belief that their use is not widespread, and, therefore, 
would not significantly contribute to the dietary exposure of the wider 
population (Ref. 7).
    We have concluded that the exposure that was estimated for GRN 424 
continues to represent the upper bound cumulative exposure to 
phycocyanins from spirulina-based ingredients in food because of the 
high phycocyanin content of the substance that is the subject of GRN 
424 (i.e., 42 to 47 percent) and its intended use in most foods. 
Therefore, we conclude that this cumulative exposure estimate of 1,140 
mg/p/d for phycocyanins from current and proposed uses of spirulina-
derived ingredients is sufficiently conservative (Ref. 2).
    Consistent with how we evaluated the petition for the use of 
spirulina extract as a color additive in candy and chewing gum, we 
reviewed published animal feeding studies that evaluated the safety of 
spirulina powder, spirulina extract, and phycocyanins, the main 
coloring component of spirulina extract. We also evaluated the 
significance of data findings from human studies that investigated 
reported therapeutic effects of spirulina supplementation and 
considered adverse event data from case reports regarding individual 
humans that ingested spirulina for various time intervals of weeks to 
several months.
    To support the safety of the proposed use of spirulina extract, the 
petitioner conducted a search of the peer-reviewed published literature 
on spirulina and submitted the published animal and human studies that 
they identified as being relevant to their petition. The petitioner 
concluded that these publications support the petitioned use of 
spirulina extract in food. Of the publications submitted by the 
petitioner, some of the papers had been previously reviewed by FDA. Our 
review of the new information along with the information submitted in 
previously reviewed publications did not reveal any new toxicological 
issues or concerns (Ref. 8).
    In our evaluation of the petitioned use of spirulina extract to 
color candy and chewing gum, we had selected as the pivotal safety 
study a chronic feeding study that tested spirulina powder in rats for 
21 months at concentrations of 10, 20, or 30 percent of the diet (equal 
to 5,000, 10,000 or 15,000 milligrams per kilogram bodyweight per day 
(mg/kg bw/day)). We determined that the results of this study showed no

[[Page 20097]]

indications of adverse effects in rats with prolonged consumption of 
the spirulina powder at any of the doses tested. Therefore, we 
concluded that the no-observed-effect-level (NOEL) for spirulina is 
15,000 mg/kg bw/d (900,000 mg/p/d for a 60 kilogram person) based on 
the absence of any observed treatment-related effects at the highest 
dose tested in this 21-month study. The phycocyanin content in the 
spirulina powders that were tested in this study were reported to be in 
the range of 12 to 20.5 percent and, based on this range, we had 
determined the NOEL for phycocyanins for humans to be between 108,000 
to 184,500 mg/p/d (78 FR 49117 at 49119). Taking into account the 
available safety information, the estimated exposure to phycocyanins 
from the petitioned use of the spirulina extract, and the margin of 
safety between the cumulative EDI and the NOEL, we conclude that the 
petitioned uses of spirulina extract as a color additive in food is 
safe.
    The potential for spirulina phycocyanins to be allergenic was also 
discussed in the final rule for the use of spirulina extract as a color 
additive in candy and chewing gum (78 FR 49117 at 49119). We stated 
that based on our review of a comparison of the known amino acid 
sequences of phycocyanins with the sequences of known protein 
allergens, there is a low probability that the spirulina phycocyanins 
are protein allergens. Therefore, we concluded that the spirulina 
phycocyanins present an insignificant allergy risk to consumers of the 
color additive. We are not aware of any information that would cause us 
to change this conclusion.

V. Conclusion

    Based on the data and information in the petition and other 
relevant material, we conclude that the petitioned use of spirulina 
extract in confections (including candy and chewing gum), frostings, 
ice cream and frozen desserts, dessert coatings and toppings, beverage 
mixes and powders, yogurts, custards, puddings, cottage cheese, 
gelatin, breadcrumbs, and ready-to-eat cereals (excluding extruded 
cereals), is safe. We further conclude that the additive will achieve 
its intended technical effect and is suitable for the petitioned use. 
Consequently, we are amending the color additive regulations in part 73 
as set forth in this document. In addition, based upon the factors 
listed in 21 CFR 71.20(b), we conclude that certification of spirulina 
extract is not necessary for the protection of the public health.

VI. Public Disclosure

    In accordance with Sec.  71.15 (21 CFR 71.15), the petition and the 
documents that we considered and relied upon in reaching our decision 
to approve the petition will be made available for public disclosure 
(see FOR FURTHER INFORMATION CONTACT). As provided in Sec.  71.15, we 
will delete from the documents any materials that are not available for 
public disclosure.

VII. Environmental Impact

    We previously considered the environmental effects of this rule as 
stated in the September 6, 2012, notice of filing for CAP 2C0297 (77 FR 
54862). We stated that we had determined, under 21 CFR 25.32(k), that 
this action ``is of a type that does not individually or cumulatively 
have a significant effect on the human environment'' such that neither 
an environmental assessment nor an environmental impact statement is 
required. We have not received any new information or comments that 
would affect our previous determination.

VIII. Paperwork Reduction Act of 1995

    This final rule contains no collection of information. Therefore, 
clearance by the Office of Management and Budget under the Paperwork 
Reduction Act of 1995 is not required.

IX. Section 301(ll) of the FD&C Act

    Our review of this petition was limited to section 721 of the FD&C 
Act. This final rule is not a statement regarding compliance with other 
sections of the FD&C Act. For example, the Food and Drug Administration 
Amendments Act of 2007, which was signed into law on September 27, 
2007, amended the FD&C Act to, among other things, add section 301(ll) 
of the FD&C Act (21 U.S.C. 331(ll)). Section 301(ll) of the FD&C Act 
prohibits the introduction or delivery for introduction into interstate 
commerce of any food that contains a drug approved under section 505 of 
the FD&C Act (21 U.S.C. 355), a biological product licensed under 
section 351 of the Public Health Service Act (42 U.S.C. 262), or a drug 
or biological product for which substantial clinical investigations 
have been instituted and their existence has been made public, unless 
one of the exemptions in section 301(ll)(1) to (ll)(4) of the FD&C Act 
applies. In our review of this petition, we did not consider whether 
section 301(ll) of the FD&C Act or any of its exemptions apply to food 
products containing this color additive. Accordingly, this final rule 
should not be construed to be a statement that a product containing 
this color additive, if introduced or delivered for introduction into 
interstate commerce, would not violate section 301(ll) of the FD&C Act. 
Furthermore, this language is included in all color additive final 
rules that pertain to food and therefore should not be construed to be 
a statement of the likelihood that section 301(ll) of the FD&C Act 
applies.

X. Objections

    This rule is effective as shown in the DATES section, except as to 
any provisions that may be stayed by the filing of proper objections. 
If you will be adversely affected by one or more provisions of this 
regulation, you may file with the Division of Dockets Management (see 
ADDRESSES) either electronic or written objections. You must separately 
number each objection, and within each numbered objection you must 
specify with particularity the provision(s) to which you object, and 
the grounds for your objection. Within each numbered objection, you 
must specifically state whether you are requesting a hearing on the 
particular provision that you specify in that numbered objection. If 
you do not request a hearing for any particular objection, you waive 
the right to a hearing on that objection. If you request a hearing, 
your objection must include a detailed description and analysis of the 
specific factual information you intend to present in support of the 
objection in the event that a hearing is held. If you do not include 
such a description and analysis for any particular objection, you waive 
the right to a hearing on the objection.
    It is only necessary to send one set of documents. Identify 
documents with the docket number found in brackets in the heading of 
this document. Any objections received in response to the regulation 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov. We will publish notice of the objections that we 
have received or lack thereof in the Federal Register.

XI. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov. (FDA 
has verified the Web site addresses in this reference section, but FDA 
is not responsible for any subsequent changes to Web sites

[[Page 20098]]

after this document publishes in the Federal Register.)

    1. Memorandum from N. Belai, Color Technology Team, OCAC, CFSAN, 
FDA to R. Davy, Division of Petition Review, OFAS, CFSAN, FDA, 
February 6, 2013.
    2. Memorandum from H. Lee, Division of Petition Review, CFSAN, 
FDA to R. Davy, Division of Petition Review, CFSAN, FDA, May 7, 
2013.
    3. Letter from L. Tarantino, Office of Food Additive Safety, 
CFSAN, FDA to J. Dore, Cyanotech Corporation, Agency Response Letter 
GRAS Notice No. GRN 000127, October 6, 2003, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153944.htm).
    4. Letter from D. Keefe, Office of Food Additive Safety, CFSAN, 
FDA to S. Cho, Nutra Source, Agency Response Letter GRAS Notice No. 
GRN 000394, June 4, 2012, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm313046.htm).
    5. Letter from D. Keefe, Office of Food Additive Safety, CFSAN, 
FDA to J. Endres, AIBMR Life Sciences, Inc., Agency Response Letter 
GRAS Notice No. GRN 000417, August 10, 2012, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm319628.htm).
    6. Letter from D. Keefe, Office of Food Additive Safety, CFSAN, 
FDA to H. Newman, Desert Lake Technologies, LLC, Agency Response 
Letter GRAS Notice No. GRN 000424, December 6, 2012, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm335743.htm).
    7. Memorandum from H. Lee, Division of Petition Review, CFSAN, 
FDA to R. Davy, Division of Petition Review, CFSAN, FDA, January 15, 
2013.
    8. Memorandum from J. Park, Division of Petition Review, CFSAN, 
FDA to F. Ellison, Division of Petition Review, CFSAN, FDA, November 
1, 2013.

List of Subjects in 21 CFR Part 73

    Color additives, Cosmetics, Drugs, Medical devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, and 
redelegated to the Director, Center for Food Safety and Applied 
Nutrition, 21 CFR part 73 is amended as follows:

PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION

0
1. The authority citation for 21 CFR part 73 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355, 
361, 362, 371, 379e.

0
2. Section 73.530 is amended by revising paragraph (c) to read as 
follows:


Sec.  73.530  Spirulina extract.

* * * * *
    (c) Uses and restrictions. Spirulina extract may be safely used for 
coloring confections (including candy and chewing gum), frostings, ice 
cream and frozen desserts, dessert coatings and toppings, beverage 
mixes and powders, yogurts, custards, puddings, cottage cheese, 
gelatin, breadcrumbs, and ready-to-eat cereals (excluding extruded 
cereals), at levels consistent with good manufacturing practice, except 
that it may not be used to color foods for which standards of identity 
have been issued under section 401 of the Federal Food, Drug, and 
Cosmetic Act, unless the use of the added color is authorized by such 
standards.
* * * * *

    Dated: April 1, 2014.
Susan M. Bernard,
Director, Office of Regulations, Policy and Social Sciences, Center for 
Food Safety and Applied Nutrition.
[FR Doc. 2014-08099 Filed 4-10-14; 8:45 am]
BILLING CODE 4160-01-P


