[Federal Register: July 22, 2005 (Volume 70, Number 140)]
[Rules and Regulations]
[Page 42271-42273]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr22jy05-8]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 73
[Docket No. 1998C-0431] (formerly 98C-0431)
Listing of Color Additives Exempt from Certification; Mica-Based
Pearlescent Pigments
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending the color
additive regulations to provide for the safe use of mica-based
pearlescent pigments as color additives in ingested drugs. This action
is in response to a petition filed by EM Industries, Inc.
DATES: This rule is effective August 23, 2005. Submit written or
electronic objections and requests for a hearing by August 22, 2005.
See section VIII of the SUPPLEMENTARY INFORMATION section of this
document for information on the filing of objections.
ADDRESSES: You may submit written or electronic objections and requests
for a hearing, identified by Docket No. 1998C-0431, by any of the
following methods:
<bullet> Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
<bullet> Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
<bullet> E-mail: fdadockets@oc.fda.gov. Include Docket No. 1998C-
0431 in the subject line of your e-mail message.
<bullet> FAX: 301-827-6870.
<bullet> Mail/Hand delivery/Courier [For paper, disk, 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 number for this rulemaking. All objections received will be
posted without change to http://www.fda.gov/ohrms/dockets/default.htm,
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
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm
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: Aydin Orstan, Center for Food
Safety and Applied Nutrition (HFS-255), Food and Drug Administration,
5100 Paint Branch Pkwy., College Park, MD 20740, 301-436-1301.
SUPPLEMENTARY INFORMATION:
I. Introduction
In a notice published in the Federal Register of June 22, 1998 (63
FR 33934), FDA announced that a color additive petition (CAP 8C0257)
had been filed by EM Industries, Inc., 7 Skyline Dr., Hawthorne, NY
10532 (now EMD Industries, Inc.). The petition proposed to amend the
color additive regulations to provide for the safe use of synthetic
iron oxide to color ingested drugs at levels higher than the current
limit and to provide for the safe use of mica to color ingested drugs.
At the time of the filing of the petition, FDA considered the pigments
that are the subjects of this petition to be color additive mixtures of
synthetic iron oxide, mica, and titanium dioxide. FDA did not include
titanium dioxide in the filing notice, because that color additive was
already listed for use in ingested drugs. During its subsequent review
of the petition, the agency determined that these pigments are
composite pigments, not color additive mixtures. Therefore, the agency
published an amended filing notice in the Federal Register of June 29,
1999 (64 FR 34816), to indicate that the petition proposed to amend the
color additive regulations to provide for the safe use of composite
pigments prepared from synthetic iron oxide, mica, and titanium dioxide
to color ingested drugs.
The petitioner is seeking approval for a maximum use level of the
resulting pigments of up to 3 percent by weight in the finished drug
product, and a maximum iron oxide content no greater than 55 percent in
those pigments containing iron oxide.
II. Manufacturing and Nomenclature
The subject color additives are manufactured by preparing a
suspension of mica platelets, adding a solution of soluble salts of
titanium, of iron, or of both, and a base to precipitate titanium
hydroxide, iron hydroxide, or both onto the mica platelets. These
particles are then heated (calcined) at temperatures up to 900 [deg]C.
During the calcination, titanium hydroxide and
[[Page 42272]]
iron hydroxide are converted into titanium dioxide, and iron oxide,
respectively. The agency has reviewed the relevant data and information
in the petition relating to the manufacturing and identity of the
subject color additives (Ref. 1), and to the proposed uses of and
estimated exposures to (Ref. 2) the subject color additives.
In a final rule published in the Federal Register of October 24,
2002 (67 FR 65311), the agency listed in Sec. 73.3128 (21 CFR 73.3128)
the color additives based on the first two combinations given above
(titanium or iron salts and mica platelets) for use in contact lenses.
In the same final rule, the agency collectively identified these color
additives as mica-based pearlescent pigments. To be consistent with
Sec. 73.3128, the agency is using the same name for the color
additives that are the subjects of the present rule.
III. Safety Evaluation
To evaluate the safety of the proposed uses of mica-based
pearlescent pigments for coloring ingested drugs, the agency reviewed
the toxicological data and information submitted in the petition as
well as other information contained in agency files (Ref. 3). In
conjunction with this review the agency notes that, based on the
chemical nature of these inorganic pigments and their individual
components, as well as the available solubility data contained in the
petition, the solubility of mica-based pearlescent pigments in media
relevant to human health (e.g., digestive fluids in the
gastrointestinal tract) is expected to be very low. As such, the
bioavailability of these pigments and/or their individual components
when ingested is also expected to be low. Considering the chemical
nature of the pigments, and their expected low solubility and
bioavailability, the agency concludes that there is no toxic potential
when ingested at levels estimated by the agency, based on their
proposed use in coloring ingested drugs. The agency also notes that it
has previously reviewed various color additive uses of iron oxide,
titanium dioxide, and mica where the additives would be ingested and
found such uses to be safe (Sec. Sec. 73.200, 73.575, 73.1200,
73.1496, 73.1575, 73.2250, 73.2496, and 73.2575).
Therefore, taking into account the available safety information,
the insoluble nature of the subject color additives, and the
conservative estimates of intake of the additives, the agency concludes
that the proposed use of mica-based pearlescent pigments to color
ingested drugs is safe (Ref. 3).
IV. Conclusion
Based on the data and information in the petition and other
relevant material, FDA concludes that the petitioned use of mica-based
pearlescent pigments prepared from synthetic iron oxide, mica, and
titanium dioxide to color ingested drugs is safe. The agency further
concludes that the additives will achieve their intended technical
effect, and are suitable for use in coloring ingested drugs. The agency
also concludes that part 73 should be amended as set forth in this
document. In addition, based upon the factors listed in Sec. 71.20(b)
(21 CFR 71.20(b)), the agency concludes that certification of mica-
based pearlescent pigments is not necessary for the protection of the
public health.
V. Inspection of Documents
In accordance with Sec. 71.15, the petition and the documents that
FDA considered and relied upon in reaching its decision to approve the
petition are available for inspection at the Center for Food Safety and
Applied Nutrition by appointment with the information contact person
(see FOR FURTHER INFORMATION CONTACT). As provided in Sec. 71.15, the
agency will delete from the documents any materials that are not
available for public disclosure before making the documents available
for inspection.
VI. Environmental Impact
The agency has previously considered the environmental effects of
this rule as announced in the notice of filing for CAP 8C0257 (63 FR
33934). No new information or comments have been received that would
affect the agency's previous determination that there is no significant
impact on the human environment and that an environmental impact
statement is not required.
VII. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.
VIII. 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) written or electronic 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. Three copies of all documents are to be
submitted and are to be identified 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. FDA will
publish notice of the objections that the agency has received or lack
thereof in the Federal Register.
IX. 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.
1. Jensen, E., Memorandum entitled ``Use of Pearlescent Pigments
as a Color Additive in Tablets and Other Pharmaceutical
Preparations,'' from the Division of Product Manufacture and Use
(HFS-246) to the Division of Petition Control (HFS-215), Center for
Food Safety and Applied Nutrition, FDA, January 21, 1999.
2. Lee, H. S., Memorandum entitled ``Update of Intake
Estimates,'' from the Division of Petition Review (HFS-265) to the
Division of Petition Review (HFS-265), Center for Food Safety and
Applied Nutrition, FDA, November 24, 2004.
3. Taras, T. L., Memorandum entitled ``Comprehensive Final
Toxicology Evaluation Memorandum: CAP 8C0257'' from the Division of
Petition Review (HFS-265) to the Division of Petition Review (HFS-
265), Center for Food Safety and Applied Nutrition, FDA, December
20, 2004.
List of Subjects in 21 CFR Part 73
Color additives, Cosmetics, Drugs, Medical devices.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
73 is amended as follows:
[[Page 42273]]
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 73.1128 is added to subpart B to read as follows:
Sec. 73.1128 Mica-based pearlescent pigments.
(a) Identity. (1) The color additive is formed by depositing
titanium and/or iron salts onto mica, followed by heating to produce
one of the following combinations: Titanium dioxide on mica; iron oxide
on mica; titanium dioxide and iron oxide on mica. Mica used to
manufacture the color additive shall conform in identity to the
requirements of Sec. 73.1496(a)(1).
(2) Color additive mixtures for drug use made with mica-based
pearlescent pigments may contain only those diluents listed in this
subpart as safe and suitable for use in color additive mixtures for
coloring ingested drugs.
(b) Specifications. Mica-based pearlescent pigments shall conform
to the following specifications and shall be free from impurities other
than those named to the extent that such other impurities may be
avoided by good manufacturing practice:
(1) Lead (as Pb), not more than 4 parts per million (ppm).
(2) Arsenic (as As), not more than 3 ppm.
(3) Mercury (as Hg), not more than 1 ppm.
(c) Uses and restrictions. Mica-based pearlescent pigments may be
safely used to color ingested drugs in amounts up to 3 percent, by
weight, of the final drug product. The maximum amount of iron oxide to
be used in producing said pigments is not to exceed 55 percent, by
weight, in the finished pigment.
(d) Labeling. The label of the color additive and of 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: July 13, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-14457 Filed 7-21-05; 8:45 am]
BILLING CODE 4160-01-S
