[Federal Register Volume 78, Number 156 (Tuesday, August 13, 2013)]
[Rules and Regulations]
[Pages 49117-49120]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-19550]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 73
[Docket No. FDA-2011-C-0878]
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 made from the dried biomass of the cyanobacteria Arthrospira
platensis (A. platensis), as a color additive in candy and chewing gum.
This action is in response to a petition filed by Mars, Inc.
DATES: This rule is effective September 13, 2013. See section X for
related information on the filing of objections. Submit either
electronic or written objections and requests for a hearing by
September 12, 2013.
ADDRESSES: You may submit written or electronic objections and requests
for a hearing, identified by Docket No. FDA-2011-C-0878, 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 or CD-ROM
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-2011-C-0878 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 of this document.
Docket: For access to the docket to read background documents or
objections received, go to http://www.regulations.gov and insert the
docket number(s), 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:
[[Page 49118]]
I. Introduction
In a document published in the Federal Register of January 20, 2012
(77 FR 2935), we announced that Mars, Inc., c/o Keller and Heckman LLP,
1001 G Street NW., Suite 500 West, Washington, DC 20001, had filed a
color additive petition (CAP 2C0293). 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 blue, an extract made from the biomass of A. platensis, as
a color additive in candy and chewing gum. We are establishing
spirulina extract as the common or usual name for this color additive
instead of the proposed name spirulina blue because it more
appropriately describes the additive.
II. Identity, Manufacturing, and Specifications
The color additive that is the subject of this petition is a
concentrated aqueous extract from the dried biomass of the
cyanobacteria A. platensis, also called spirulina. Spirulina is a blue-
green filamentous cyanobacteria that occurs naturally in freshwater and
marine habitats. It has a long history as a food in many countries
(Ref. 1). Spirulina contains chlorophyll and phycobilins, which absorb
sunlight and have a role in photosynthesis. The phycobilins found in
spirulina are phycocyanins, which are blue and, together with
chlorophyll, give spirulina its characteristic blue-green color.
The petitioner describes the manufacture of spirulina extract using
the species A. platensis. Spirulina extract consists primarily of the
water soluble components of spirulina, namely phycocyanins and other
proteins, polysaccharides, lipids, and minor amounts of components such
as vitamins, minerals, and moisture. In general, spirulina extract is
manufactured as follows: (1) The spirulina biomass is obtained from
grown, harvested, rinsed, washed, and spray dried spirulina; (2) the
spirulina biomass is soaked in water to extract the water-soluble
proteins; (3) the aqueous extract is filtered and stabilized; and (4)
the stabilized filtrate is the color additive spirulina extract. The
spirulina extract manufactured by the petitioner contains not less than
10 percent phycocyanins. We have determined that because the amount of
the color additive used in food is self-limiting, there is no need for
a specific upper limit for the color additive or phycocyanin content
(Ref. 2). Therefore, we are limiting the use of spirulina extract in
candy and chewing gum to amounts consistent with good manufacturing
practice. In addition to specification limits for lead, arsenic, and
mercury, we are requiring that the color additive be negative for
microcystin toxin, which is produced by some species of cyanobacteria
that could be potentially present in the water where A. platensis is
grown and harvested.
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
We have previously considered the safety of the dried biomass of
spirulina and certain spirulina-derived substances in food as a result
of submissions from firms who have made their own determinations that
certain uses of spirulina and spirulina-derived substances in food are
generally recognized as safe (GRAS). Under section 201(s) of the FD&C
Act (21 U.S.C. 321(s)), a substance is GRAS if it is generally
recognized, among experts qualified by scientific training and
experience to evaluate its safety, as having been adequately shown
through scientific procedures (or, in the case of a substance used in
food before January 1, 1958, through either scientific procedures or
experience based on common use in food) to be safe under the conditions
of its intended use. Under section 201(s) of the FD&C Act, a substance
that is GRAS for a particular use in food is not a food additive, and
may lawfully be utilized for that use without our review and approval.
There is no GRAS exemption, however, to the definition of color
additive in section 201(t) of the FD&C Act (21 U.S.C. 321(t)).
Therefore, we must approve the use of a color additive in food before
it is marketed; otherwise the food containing the color additive is
adulterated under section 402(c) of the FD&C Act (21 U.S.C. 342(c)).
A firm may voluntarily submit information on a GRAS self-
determination to us for review through our GRAS notification program
(see 62 FR 18938 (April 17, 1997)). Through this program, we have
received four GRAS notices (GRNs) for various uses of spirulina and
spirulina-derived substances in food (GRNs 127, 394, 417, and 424).\1\
We evaluated each of these GRNs and concluded that we had no reason to
question the basis of the notifier's (a person who submits a GRAS
notice) GRAS determinations (Refs. 3 to 6). In particular, the
spirulina substance that was the subject of GRN 424 is similar in
chemical composition to the subject color additive, with phycocyanin
content ranging from 42 to 47 percent.
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\1\ GRN 127 pertains to the use of the powdered dried biomass of
A. platensis as an ingredient in specialty food bars, powdered
nutritional drink mixes, popcorn, and as a condiment in salads, at
levels ranging from 0.5 to 3.0 grams per serving. GRN 394 pertains
to the use of the powdered dried biomass of A. platensis in certain
fruit juices, low calorie fruit and vegetable juice drinks at a
level up to 0.3 percent of the food, and in medical foods at a level
up to 1.25 percent. GRN 417 pertains to the use of powdered dried
biomass of A. platensis in nonalcoholic beverages and beverage
bases, breakfast cereals, fruit juices, frozen dairy desserts and
mixes, grain products and pastas, milk products, plant protein
products, processed vegetables and vegetable juices, snack foods,
soft candy, and soups and soup mixes, at levels ranging from 0.5 to
3.0 grams per serving. Lastly, 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 (e.g.,
meat, eggs and catfish) requiring additional review by the U.S.
Department of Agriculture. FDA also is aware that spirulina-derived
substances are used as dietary ingredients in dietary supplements.
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Importantly, in our response to these GRAS notifications, we
indicated that if the substances that were the subject of these
submissions impart color to the food, they may be subject to regulation
as a color additive.
For the petitioned use of spirulina extract to color candy and
chewing gum, we focused our review primarily on the safety of the
phycocyanins because
[[Page 49119]]
these pigments are the main coloring components of the additive. As
part of our safety evaluation, we estimated the exposure to
phycocyanins from current and proposed food uses of spirulina-derived
ingredients. We estimate that the petitioned use of spirulina extract
in candy and chewing gum will result in an exposure to phycocyanins of
171 milligrams/person/day (mg/p/d) for the 90th percentile consumer 2
years of age or older. Because children typically consume more candy
and chewing gum than the general population, we estimated the exposure
to phycocyanins from the petitioned use of the subject color additive
for children 2 to 5 and 6 to 12 years of age. For these population
subgroups, we estimate the exposure at the 90th percentile to be 130
mg/p/d and 185 mg/p/d, respectively. For a cumulative exposure
estimate, we used exposure information from GRN 424. The notifier for
GRN 424 estimated a conservative exposure to phycocyanins from the
notified uses of a spirulina extract to be 1140 mg/p/d. This exposure
estimate does not include exposure to spirulina and phycocyanins from
dietary supplement use due to the 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
represents 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 (including candy and
chewing gum). We conclude that this cumulative exposure estimate of
1140 mg/p/d for phycocyanins from current and proposed uses of
spirulina-derived ingredients is sufficiently conservative (Ref. 7).
To support the safety of the petitioned use of the subject color
additive in candy and chewing gum, the petitioner provided a number of
published studies that investigated the toxicity of various spirulina
powder extracts. The results of these studies showed no toxic effects
at the doses that were tested. From these studies, we selected, as the
pivotal safety study for this color additive, 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 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 based on the highest dose
tested in this study is 15,000 mg/kg bw/d (900,000 mg/p/d for a 60
kilogram person). 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 have determined the NOEL for
phycocyanins for humans to be between 108,000 to 184,500 mg/p/d. Taking
into account the available safety information, the estimated intake of
phycocyanins from the petitioned use of the spirulina extract, and the
large margin of safety between the cumulative EDI and the NOEL, we
conclude that the proposed use of spirulina extract to color candy and
chewing gum is safe (Ref. 8).
We also evaluated the potential allergenicity of spirulina extract.
We reviewed a comparison of the known amino acid sequences of
phycocyanins with the sequences of known protein allergens and
determined that there is a low probability that the phycocyanins are
protein allergens. We conclude that spirulina phycocyanins present an
insignificant allergy risk to consumers of the color additive.
Our conclusion regarding the safety of the petitioned use of the
color additive is strengthened by the fact that the phycocyanobilin
chromophore (the part of the molecule responsible for the coloring
effect of the additive) is similar to certain bile pigments that are
excreted from the liver via the gall bladder into the intestines. Based
on a literature search and review, none of the bile pigments has been
reported to produce any toxic effect, except in diseases caused by
their presence in the blood due to inborn error of metabolism or other
cause.
V. Conclusion
Based on the data and information in the petition and other
relevant material, we conclude that the petitioned use of spirulina
extract, a color additive made from the biomass of A. platensis, in
candy and chewing gum 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. 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 have previously considered the environmental effects of this
rule as announced in the notice of filing for CAP 2C0293 (77 FR 2935).
No new information or comments have been received that would affect our
previous determination that there is no significant impact on the human
environment and that an environmental impact statement is not required.
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
[[Page 49120]]
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 of this
document; except as to any provisions that may be stayed by the filing
of proper objections. Any person who will be adversely affected by this
regulation may file with the Division of Dockets Management (see
ADDRESSES) either electronic or written objections. Each objection
shall be separately numbered, and each numbered objection shall specify
with particularity the provisions of the regulation to which objection
is made and the grounds for the objection. Each numbered objection on
which a hearing is requested shall specifically so state. Failure to
request a hearing for any particular objection shall constitute a
waiver of the right to a hearing on that objection. Each numbered
objection for which a hearing is requested shall include a detailed
description and analysis of the specific factual information intended
to be presented in support of the objection in the event that a hearing
is held. Failure to include such a description and analysis for any
particular objection shall constitute a waiver of 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. 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, but FDA is not responsible for any
subsequent changes to Web sites after this document publishes in the
Federal Register.)
1. M. A. B. Habib, M. Parvin, T. C. Huntington, and M. R. Hasan.
2008. ``A Review on Culture, Production and Use of Spirulina as Food
for Humans and Feeds for Domestic Animals and Fish.'' FAO Fisheries
and Aquaculture Circular No. 1034. Rome, FAO (ftp://ftp.fao.org/docrep/fao/011/i0424e/i0424e00.pdf).
2. Memorandum from N. Belai, Color Technology Team, OCAC, CFSAN, FDA
to F. Ellison, Division of Petition Review, OFAS, CFSAN, FDA,
December 12, 2012.
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 D. Folmer, Division of Petition Review, CFSAN,
FDA to F. Ellison, Division of Petition Review, CFSAN, FDA, May 31,
2012.
8. Memorandum from G. Erives, Division of Petition Review, CFSAN,
FDA to F. Ellison, Division of Petition Review, CFSAN, FDA, October
2, 2012.
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. Add Sec. 73.530 to subpart A to read as follows:
Sec. 73.530 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 food 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 foods.
(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 part
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 candy and chewing gum 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.
(d) Labeling requirements. The label of the color additive and of
any mixture prepared therefrom intended solely or in part for coloring
purposes must conform to 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 6, 2013.
Susan M. Bernard,
Director, Office of Regulations, Policy and Social Sciences, Center for
Food Safety and Applied Nutrition.
[FR Doc. 2013-19550 Filed 8-12-13; 8:45 am]
BILLING CODE 4160-01-P