
[Federal Register Volume 80, Number 162 (Friday, August 21, 2015)]
[Rules and Regulations]
[Pages 50762-50765]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-20676]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 73

[Docket No. FDA-2014-C-1552]


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 safe use of spirulina 
extract as a color additive in coating formulations applied to dietary 
supplement and drug tablets and capsules. This action is in response to 
a petition filed by Colorcon, Inc. (Colorcon).

DATES: This rule is effective September 22, 2015. See section IX for 
information on the filing of objections. Submit either electronic or 
written objections and requests for a hearing by September 21, 2015.

ADDRESSES: You may submit either electronic or written objections and 
requests for a hearing, identified by Docket No. FDA-2014-C-1552, 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-2014-C-1552 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

[[Page 50763]]

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: Molly A. Harry, Center for Food Safety 
and Applied Nutrition (HFS-265), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740-3835, 240-402-1075.

SUPPLEMENTARY INFORMATION:

I. Introduction

    In a notice published in the Federal Register of October 22, 2014 
(79 FR 63062), we announced that we had filed a color additive petition 
(CAP 4C0300), submitted by Colorcon, Inc. (petitioner), 275 Ruth Rd., 
Harleysville, PA 19438. The petition proposed to amend the color 
additive regulations in Title 21, Code of Federal Regulations (CFR) 
part 73 Listing of Color Additives Exempt From Certification to provide 
for the safe use of spirulina extract, prepared by the filtered aqueous 
extraction of the dried biomass of Arthrospira platensis (A. 
platensis), as a color additive in coating formulations applied to 
dietary supplement and drug tablets and capsules.

II. Background

    In the Federal Register of August 13, 2013 (78 FR 49117), 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 at levels 
consistent with good manufacturing practice (GMP). 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.
    In the Federal Register of April 11, 2014 (79 FR 20095), we issued 
a final rule in response to a color additive petition (CAP 2C0297) 
amending Sec.  73.530 to include the use of spirulina extract as a 
color additive 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), at levels consistent with GMP.
    The spirulina extract used for the purposes of CAP 4C0300 is a 
blue-colored powder produced by the filtered aqueous extraction of the 
spray-dried biomass of A. platensis (also known as Spirulina 
platensis), an edible blue-green cyanobacterium. The color additive 
contains phycocyanins as the principal coloring component. The maximum 
phycocyanin content of the color additive is 28 percent. Based on data 
and information provided in the petition on the identity, physical and 
chemical properties, manufacturing process, and composition of the 
color additive, we have determined that the color additive meets the 
specifications for spirulina extract in Sec.  73.530 (Ref. 1).
    Spirulina extract is intended to be used as a color additive in 
film coating formulations applied to dietary supplement and drug 
tablets and capsules in amounts consistent with GMP. The maximum GMP 
use level for spirulina extract in an individual coating will be 
determined by the desired coloring effect. Therefore, because the 
amount of the color additive used in these coatings is self-limiting, 
we have determined that there is no need for a specific upper limit on 
the percent by weight of spirulina extract in coating formulations 
applied to dietary supplement and drug tablets and capsules (Ref. 1).

III. Safety Evaluation

A. Determination 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 establish 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 exposure, or estimated daily intake (EDI), of 
the additive from all food sources to an acceptable daily 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 or drugs and on data regarding the amount consumed from all 
ingested sources of the additive. We commonly use the EDI for the 90th 
percentile consumer of a color additive as a measure of high chronic 
exposure.

B. Safety of Petitioned Use of the Color Additive

    To support the safety of the petitioned use of spirulina extract as 
a color additive in coating formulations applied to dietary supplement 
and drug tablets and capsules, Colorcon submitted an exposure estimate 
for phycocyanins (the principal coloring component). Colorcon estimated 
that the petitioned use of spirulina extract in coating formulations 
applied to dietary supplement and drug tablets and capsules will result 
in an exposure to phycocyanins of 20.9 milligrams/person/day (mg/p/d) 
for the 90th percentile consumer (Ref. 2). We agree with Colorcon's 
exposure estimate for phycocyanins and conclude that it is sufficiently 
conservative (Ref. 2).\1\
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    \1\ The petition referred to both ``drug tablets and capsules'' 
and ``pharmaceutical tablets and capsules.'' The term 
``pharmaceutical tablets and capsules'' was used regarding the 
exposure assessment (Ref. 2).
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    Regarding cumulative exposure (cumulative EDI, or CEDI) to 
phycocyanins from spirulina and spirulina-derived substances, FDA 
discussed in the final rule for use of 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 informing us of their determinations that certain uses of 
spirulina-derived substances are generally recognized as safe (GRAS) 
(78 FR 49117 at 49118). One of the GRAS notices (GRN 000424) pertains 
to the use of a spirulina-derived substance similar in chemical 
composition to the subject color additive but with a much higher 
phycocyanin content ranging from 42 to 47 percent, and included use in 
all foods (except infant formula and foods under U.S. Department of 
Agriculture's jurisdiction) at levels consistent with GMP. The upper 
bound CEDI for phycocyanins resulting from the notified uses of 
spirulina extract was estimated to be 1,140 mg/p/d in GRN 000424 based 
on conservative assumptions (Ref. 3). This exposure estimate does not 
appear to include exposure to phycocyanins from use of spirulina 
extract in dietary supplements. Colorcon estimated that the use of 
spirulina extract in coating formulations applied to dietary supplement 
and drug tablets and capsules would increase the previously estimated 
upper bound CEDI of phycocyanins by 1.8 percent. We agree that 
Colorcon's estimate is conservative, and that the petitioned use of 
spirulina

[[Page 50764]]

extract would not contribute significantly to the previously estimated 
upper bound CEDI of 1,140 mg/p/d for phycocyanins (Ref. 2).
    In support of safety of the use of spirulina extract as a color 
additive in coating formulations applied to dietary supplement and drug 
tablets and capsules in the subject petition, Colorcon referenced the 
safety determinations made by FDA for CAP 2C0293 (78 FR 49117) and CAP 
2C0297 (79 FR 20095). The petitioner also conducted a search of the 
peer-reviewed scientific literature for animal and human oral 
consumption studies that tested spirulina, spirulina-derived 
ingredients, and phycocyanins that have been published since 2011. The 
petitioner submitted the published animal and human studies that they 
had identified as being relevant to their petition. We reviewed the 
relevant studies and determined that these publications did not raise 
any safety concerns.
    In our previous evaluations of the use of spirulina extract as a 
color additive in food, we had selected as the pivotal safety study a 
21-month chronic feeding study that tested spirulina powder in rats at 
dietary concentrations of 10, 20, or 30 percent (equivalent to 5,000, 
10,000, or 15,000 milligrams per kilogram bodyweight per day (mg/kg bw/
d)). The results of this study showed that prolonged oral consumption 
of spirulina powder up to a dietary concentration of 15,000 mg/kg bw/d 
was without adverse effects. 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 kg person) based on the absence of treatment-
related adverse effects at the highest concentration tested in this 
study. We had also determined the NOEL for phycocyanins for humans to 
be between 108,000 and 184,500 mg/p/d (78 FR 49117 at 49119). Taking 
into account all the available safety information, the estimated 
exposure to phycocyanins from the petitioned use of the spirulina 
extract, and the margin of safety between the CEDI for phycocyanin 
(1,140 mg/p/d) and the NOEL for phycocyanin (108,000 to 184,500 mg/p/
d), we conclude that the petitioned use of spirulina extract as a color 
additive in coating formulations applied to dietary supplement and drug 
tablets and capsules is safe (Ref. 4).
    The potential allergenicity of spirulina phycocyanins was 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). Based on our review of 
a comparison of the known amino acid sequences of phycocyanins with the 
sequences of known protein allergens, we had determined that there is a 
low probability that phycocyanins are protein allergens. We therefore 
concluded that the spirulina phycocyanins present an insignificant 
allergy risk to consumers of the color additive. We are not aware of 
any new information that would cause us to change this conclusion.

IV. Conclusion

    Based on the data and information in the petition and other 
relevant material, we conclude that the petitioned use of spirulina 
extract in coating formulations applied to dietary supplement and drug 
tablets and capsules 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.

V. 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.

VI. Environmental Impact

    We previously considered the environmental effects of this rule, as 
stated in the October 22, 2014, notice of filing for CAP 4C0300. We 
stated that we had determined, under 21 CFR 25.32(r), 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.

VII. 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.

VIII. 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, section 301(ll) of the FD&C Act 
(21 U.S.C. 331(ll) 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 (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 containing this color additive. 
Accordingly, this final rule should not be construed to be a statement 
that a food 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.

IX. 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) of the regulation 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

[[Page 50765]]

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.

X. 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 address in this reference section, but FDA is 
not responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register).

1. Memorandum from N. Belai, Color Technology Team, OCAC, CFSAN, FDA 
to M. Harry, Division of Petition Review, OFAS, CFSAN, FDA, March 
19, 2015.
2. Memorandum from H. Lee, Division of Petition Review, OFAS, CFSAN, 
FDA to M. Harry, Division of Petition Review, OFAS, CFSAN, FDA, 
January 30, 2015.
3. Letter from D. Keefe, Office of Food Additive Safety, CFSAN, FDA 
to H. Newman, Desert Lake Technologies, LLC, Agency Response Letter 
GRAS Notice 000424, December 6, 2012, (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm335743.htm).
4. Memorandum from T. Walker, Division of Petition Review, OFAS, 
CFSAN, FDA to M. Harry, Division of Petition Review, OFAS, CFSAN, 
FDA, April 2, 2015.

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 re-
delegated 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, ready-to-eat cereals (excluding extruded 
cereals), and coating formulations applied to dietary supplement 
tablets and capsules, 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.
* * * * *


0
3. Section 73.1530 is added to subpart B to read as follows:


Sec.  73.1530  Spirulina extract.

    (a) Identity. (1) The color additive spirulina extract is prepared 
by the filtered aqueous extraction of the dried biomass of Arthrospira 
platensis. The color additive contains phycocyanins as the principal 
coloring components.
    (2) Color additive mixtures for drug use made with spirulina 
extract may contain only those diluents that are suitable and are 
listed in this subpart as safe for use in color additive mixtures for 
coloring ingested drugs.
    (b) Specifications. Spirulina extract must conform to the following 
specifications and must be free from impurities, other than those 
named, to the extent that such other impurities may be avoided by good 
manufacturing practice:
    (1) Lead, not more than 2 milligrams per kilogram (mg/kg) (2 parts 
per million (ppm));
    (2) Arsenic, not more than 2 mg/kg (2 ppm);
    (3) Mercury, not more than 1 mg/kg (1 ppm); and
    (4) Negative for microcystin toxin.
    (c) Uses and restrictions. Spirulina extract may be safely used for 
coloring coating formulations applied to drug tablets and capsules, at 
levels consistent with good manufacturing practice.
    (d) Labeling requirements. The label of the color additive and any 
mixture prepared therefrom intended solely or in part for coloring 
purposes shall conform to the requirements of Sec.  70.25 of this 
chapter.
    (e) Exemption from certification. Certification of this color 
additive is not necessary for the protection of the public health, and 
therefore batches thereof are exempt from the certification 
requirements of section 721(c) of the Federal Food, Drug, and Cosmetic 
Act.

    Dated: August 14, 2015.
Susan Bernard,
Director, Office of Regulations, Policy and Social Sciences, Center for 
Food Safety and Applied Nutrition.
[FR Doc. 2015-20676 Filed 8-20-15; 8:45 am]
 BILLING CODE 4164-01-P


