Listing of Color Additives Exempt From Certification; Titanium Dioxide and Listing of Color Additives Subject to Certification; [Phthalocyaninato (2-)] Copper, 75689-75692 [2016-26310]
Download as PDF
<![CDATA[
Federal Register / Vol. 81, No. 211 / Tuesday, November 1, 2016 / Rules and Regulations
§ 39.13
(2) Reserved.
[Amended]
2. The FAA amends § 39.13 by adding
the following new airworthiness
directive (AD):
■
2016–22–10 Turbomeca S.A.: Amendment
39–186990; Docket No. FAA–2016–6990;
Directorate Identifier 2016–NE–14–AD.
(a) Effective Date
This AD becomes effective December 6,
2016.
(b) Affected ADs
None.
(c) Applicability
This AD applies to certain Arriel 1, 1A,
1A1, 1A2, 1B, 1B2, 1C, 1C1, 1C2, 1D, 1D1,
1E, 1E2, 1K1, 1S, and 1S1 turboshaft engines,
with modification TU376 installed.
(d) Reason
This AD was prompted by an anomaly that
occurred during the grinding operation
required by modification TU376, which
increases the clearance between the rear
curvic coupling of the centrifugal impeller
and the fuel injection manifold. We are
issuing this AD to prevent failure of the
centrifugal impeller, uncontained centrifugal
impeller release, damage to the engine, and
damage to the helicopter.
(e) Actions and Compliance
Comply with this AD within the
compliance times specified, unless already
done.
(1) Remove from service, any centrifugal
impeller listed in Table 1 to paragraph (e) of
this AD, before exceeding the applicable
cycles since new (CSN) and replace with a
centrifugal impeller not listed in Table 1 to
paragraph (e) of this AD.
jstallworth on DSK7TPTVN1PROD with RULES
Part No.
0292254040
0292254040
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
0292254050
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
729225293A
VerDate Sep<11>2014
Serial No.
..........
..........
..........
..........
..........
..........
..........
..........
..........
..........
..........
..........
..........
..........
.........
.........
.........
.........
.........
.........
.........
.........
.........
.........
.........
44
1762FT
1676CAR
5333OTT
5017OTT
1136CAR
3655OTT
1757CAR
1738CAR
1149CAR
2677OTT
3109OTT
3496OTT
2074CAR
290CAR
1227FT
504FB
2517OTT
2165OTT
2194FT
1331OTT
1301FT
1567FT
783FB
98OTT
15:21 Oct 31, 2016
Electronic Submissions
(f) Alternative Methods of Compliance
(AMOCs)
The Manager, Engine Certification Office,
FAA, may approve AMOCs for this AD. Use
the procedures found in 14 CFR 39.19 to
make your request. You may email your
request to: ANE-AD-AMOC@faa.gov.
(g) Related Information
(1) For more information about this AD,
contact Philip Haberlen, Aerospace Engineer,
Engine Certification Office, FAA, Engine &
Propeller Directorate, 1200 District Avenue,
Burlington, MA 01803; phone: 781–238–
7770; fax: 781–238–7199; email:
philip.haberlen@faa.gov.
(2) Refer to MCAI, European Aviation
Safety Agency AD 2016–0090, dated May 10,
2016, for more information. You may
examine the MCAI in the AD docket on the
Internet at https://www.regulations.gov by
searching for and locating it in Docket No.
FAA–2016–6990.
(h) Material Incorporated by Reference
None.
Issued in Burlington, Massachusetts, on
October 24, 2016.
Colleen M. D’Alessandro,
Manager, Engine & Propeller Directorate,
Aircraft Certification Service.
[FR Doc. 2016–26184 Filed 10–31–16; 8:45 am]
BILLING CODE 4910–13–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 73 and 74
Listing of Color Additives Exempt
From Certification; Titanium Dioxide
and Listing of Color Additives Subject
5,129 to Certification; [Phthalocyaninato (2-)]
11,476 Copper
CSN
6,281
5,495
5,491
8,734
4,600
7,913
10,640
12,273
11,145
10,662
5,562
7,423
6,326
8,139
4,600
9,732
6,163
11,461
12,513
7,262
6,305
8,307
9,492
Jkt 241001
Submit electronic objections in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting comments.
Objections submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
objection will be made public, you are
solely responsible for ensuring that your
objection does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
objection, that information will be
posted on https://www.regulations.gov.
• If you want to submit an objection
with confidential information that you
do not wish to be made available to the
public, submit the objection as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
[Docket No. FDA–2016–F–0821]
TABLE 1 TO PARAGRAPH (e)—
CENTRIFUGAL IMPELLER CSNS
75689
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Final rule.
The Food and Drug
Administration (FDA or we) is
amending the color additive regulations
to provide for the safe use of titanium
dioxide and [phthalocyaninato (2-)]
copper to color orientation marks for
intraocular lenses. This action is in
response to a petition filed by Milton W.
Chu, M.D.
DATES: This rule is effective December 2,
2016. See section IX for further
information on the filing of objections.
Submit either electronic or written
objections and requests for a hearing by
December 1, 2016.
ADDRESSES: You may submit objections
and requests for a hearing as follows:
SUMMARY:
PO 00000
Frm 00019
Fmt 4700
Sfmt 4700
Submit written/paper submissions as
follows:
• Mail/Hand delivery/Courier (for
written/paper submissions): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper objections
submitted to the Division of Dockets
Management, FDA will post your
objection, as well as any attachments,
except for information submitted,
marked and identified, as confidential,
if submitted as detailed in
‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2016–F–0821 for ‘‘Listing of Color
Additives Exempt From Certification;
Titanium Dioxide and Listing of Color
Additives Subject to Certification;
[Phthalocyaninato (2-)] Copper.’’
Received objections will be placed in
the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
• Confidential Submissions—To
submit an objection with confidential
information that you do not wish to be
made publicly available, submit your
objections only as a written/paper
E:\FR\FM\01NOR1.SGM
01NOR1
75690
Federal Register / Vol. 81, No. 211 / Tuesday, November 1, 2016 / Rules and Regulations
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on https://
www.regulations.gov. Submit both
copies to the Division of Dockets
Management. If you do not wish your
name and contact information to be
made publicly available, you can
provide this information on the cover
sheet and not in the body of your
comments and you must identify this
information as ‘‘confidential.’’ Any
information marked as ‘‘confidential’’
will not be disclosed except in
accordance with 21 CFR 10.20 and other
applicable disclosure law. For more
information about FDA’s posting of
comments to public dockets, see 80 FR
56469, September 18, 2015, or access
the information at: https://www.fda.gov/
regulatoryinformation/dockets/
default.htm.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
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:
Laura A. Dye, Center for Food Safety
and Applied Nutrition (HFS–265), Food
and Drug Administration, 5001 Campus
Dr., College Park, MD 20740–3835, 240–
402–1275.
SUPPLEMENTARY INFORMATION:
jstallworth on DSK7TPTVN1PROD with RULES
I. Introduction
In a document published in the
Federal Register of March 22, 2016 (81
FR 15173), we announced that we had
filed a color additive petition (CAP
6C0305), submitted by Milton W. Chu,
M.D. (petitioner), 5800 Santa Rosa Rd.,
Suite 111, Camarillo, CA 93012. The
petition proposed to amend the color
additive regulations in § 73.3126 (21
CFR 73.3126) and § 74.3045 (21 CFR
74.3045) to provide for the safe use of
titanium dioxide and [phthalocyaninato
(2-)] copper to color orientation marks
for intraocular lenses (IOLs). IOLs are
devices made of materials such as glass
or plastic and are intended to be
VerDate Sep<11>2014
15:21 Oct 31, 2016
Jkt 241001
implanted to replace the natural lens of
an eye (21 CFR 886.3600). The
orientation marks are intended to aid
the surgeon in visualization and
placement of IOLs during lens
implantation surgery. Because IOLs are
permanently implanted, titanium
dioxide and [phthalocyaninato (2-)]
copper, in the colored orientation
marks, will come into direct contact
with a patient’s eye for a significant
amount of time. These color additives
are, therefore, subject to section 721 of
the Federal Food, Drug, and Cosmetic
Act (the FD&C Act) (21 U.S.C. 379e).
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
these color additives intended to color
IOL orientation marks are not harmful
under their intended conditions of use,
we considered exposure to the additives
and their impurities, each additive’s
toxicological data, and other relevant
information (such as published
literature) available to us.
II. Background
B. Safety of Petitioned Use of the Color
Additives
Regarding the petitioned use, titanium
dioxide and [phthalocyaninato (2-)]
copper are intended to color orientation
marks for IOL materials (polymers) to
create white and translucent or opaque
blue marks that are typically 100–250
microns (mm) in diameter and 80–150
mm in depth. Titanium dioxide will be
used in amounts not to exceed the
minimum reasonably required to
accomplish the intended coloring effect
of the orientation marks.
[Phthalocyaninato (2-)] copper will be
used at levels not to exceed 0.5 percent
by weight of the orientation marks.
To assess safety, we compared an
individual’s estimated exposure to these
two color additives for the petitioned
use to color IOL orientation marks to the
approved uses of these color additives,
including in IOL haptics and opaque
contact lenses, because these uses are
similar. As part of our previous
approval for titanium dioxide used to
color contact lenses, we estimated
exposure to titanium dioxide from this
use to be 270 nanograms per person per
day (ng/p/d) over the lens lifetime (51
FR 24815), which does not significantly
contribute to the cumulative exposure
when compared to the exposure to
titanium dioxide from the approved
uses of mica-based pearlescent pigments
(of which titanium dioxide is a
component) in food and
pharmaceuticals (Ref. 1). Similarly, we
previously estimated exposure to
[phthalocyaninato (2-)] copper from the
use of surgical sutures, contact lenses,
and specific monofilaments used as
supporting haptics for IOLs to be 310
ng/p/d, 280 ng/p/d, and 0.3 ng/p/d,
respectively (64 FR 23185, April 30,
1999; 51 FR 39370, October 28, 1986;
and 52 FR 15944, May 1, 1987). With
respect to the petitioned use, we
estimated that the worst-case lifetime
exposure to titanium dioxide and
[phthalocyaninato (2-)] copper used to
color orientation marks would be no
greater than 0.06 ng/p/d and 0.004 ng/
Titanium dioxide is already approved
as a color additive for foods (§ 73.575),
drugs (§ 73.1575), cosmetics (§ 73.2575),
and medical devices (§ 73.3126).
Regarding its use in medical devices,
titanium dioxide (CAS Reg. No. 13463–
67–7, Color Index No. 77891) is
currently approved under
§ 73.3126(b)(1) for use as a color
additive in contact lenses in amounts
not to exceed the minimum reasonably
required to accomplish the intended
coloring effect and must meet the
identity and specification requirements
in § 73.575(a)(1) and (b). Titanium
dioxide is exempt from certification
under section 721(c) of the FD&C Act
because we previously determined that
certification was not necessary for the
protection of public health (51 FR
24815, July 9, 1986).
[Phthalocyaninato (2-)] copper (CAS
Reg. No. 147–14–8, Color Index No.
74160) is currently approved as a color
additive under § 74.3045(c)(1) for use in
coloring certain non-absorbable sutures
for general and ophthalmic surgery, and
for use in coloring specific
monofilaments used as supporting side
struts (haptics) that hold the IOLs in
place in the eye, at a level up to 0.5
percent by weight of the suture or haptic
material. In addition, it is currently
approved as a color additive under
§ 74.3045(c)(2) for use in coloring
contact lenses in amounts not to exceed
the minimum amount reasonably
required to accomplish the intended
coloring effect. We previously
determined that batch certification was
necessary to ensure the safety of
[phthalocyaninato (2-)] copper (34 FR
6777, April 23, 1969).
III. Safety Evaluation
A. Determination of Safety
Under section 721(b)(4) of the FD&C
Act, 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
PO 00000
Frm 00020
Fmt 4700
Sfmt 4700
E:\FR\FM\01NOR1.SGM
01NOR1
jstallworth on DSK7TPTVN1PROD with RULES
Federal Register / Vol. 81, No. 211 / Tuesday, November 1, 2016 / Rules and Regulations
p/d, respectively, over a 70-year lifetime
(Ref. 2). This exposure estimate is
conservative as it assumes 100 percent
migration of the color additives from the
IOLs into the ocular fluid of the eye over
a lifespan of 70 years following lens
implantation. However, we expect that
the color additives in the orientation
marks will most likely be either
chemically bound or otherwise
integrated into the lens material, which
would limit migration of the color
additives into the ocular fluid of the
eye. This means that the actual
exposures to titanium dioxide and
[phthalocyaninato (2-)] copper to color
IOL orientation marks are expected to be
far less than the worst-case exposure
estimates for these color additives and
insignificant in comparison to the
cumulative exposures from the other
approved uses of these color additives
that we have already established to be
safe (Ref. 2).
In assessing biocompatibility and
toxicity of IOLs, we consider the
International Standard for intraocular
lens testing for biocompatibility (ISO
11979–5) as an appropriate standard. In
general, ISO 11979–5 recommends
investigations on the following
biological endpoints: Cytotoxicity,
genotoxicity, local effects after
implantation, and sensitization
potential, in the context of
physicochemical properties.
The petitioner conducted a
cytotoxicity study in which cultured
cells were exposed to a mixture of
titanium dioxide and [phthalocyaninato
(2-)] copper in direct contact for at least
24 hours. Both color additives were
found to be noncytotoxic in this study.
Cytotoxicity studies of
[phthalocyaninato (2-)] copper in
previous petitions also indicated no
cytotoxicity (Ref. 3). Additionally, the
toxicology data for [phthalocyaninato
(2-)] copper from previous petitions, as
well as relevant data found in the
Organization for Economic Cooperation
and Development’s Screening
Information Dataset (OECD’s SIDS)
database, all indicated negative results
for genotoxicity, carcinogenicity,
implantation safety, and sensitization
potential (Ref. 3). Similarly, data on
titanium dioxide in OECD’s SIDS
database reported negative results for
genotoxicity and sensitization potential.
We conclude that the available
toxicology data are sufficient to support
the safety of the proposed expanded
uses of titanium dioxide and
[phthalocyaninato (2-)] copper.
IV. Conclusion
Based on the data and information in
the petition and other relevant material,
VerDate Sep<11>2014
15:21 Oct 31, 2016
Jkt 241001
we conclude that the petitioned use of
titanium dioxide and [phthalocyaninato
(2-)] copper to color orientation marks
for IOLs is safe. We further conclude
that these additives will achieve their
intended technical effect and are
suitable for the petitioned use.
Consequently, we are amending the
color additive regulations in parts 73
and 74 as set forth in this document. In
addition, based upon the factors listed
in 21 CFR 71.20(b), we conclude that
certification of titanium dioxide remains
unnecessary for the protection of the
public health. We also conclude that
batch certification of [phthalocyaninato
(2-)] copper continues to be necessary to
protect the public health.
V. Public Disclosure and
Confidentiality of Data and Information
in a Color Additive Rule
In accordance with § 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
§ 71.15, we will delete from the
documents any materials that are not
available for public disclosure.
VI. Analysis of Environmental Impact
We previously considered the
environmental effects of this rule, as
stated in the March 22, 2016, notice of
petition for CAP 6C0305 (81 FR 15173).
We stated that we had determined,
under 21 CFR 25.32(l), 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. 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
PO 00000
Frm 00021
Fmt 4700
Sfmt 4700
75691
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.
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 https://
www.regulations.gov. We will publish
notice of the objections that we have
received or lack thereof in the Federal
Register.
IX. References
The following references are on
display in the Division of Dockets
Management (see ADDRESSES) and are
available for viewing by interested
persons between 9 a.m. and 4 p.m.,
Monday through Friday; they are also
available electronically at https://
www.regulations.gov.
1. Memorandum from H. Lee, Division of
Petition Review, Chemistry Review
Team, to P. DeLeo, Division of Petition
Review, Regulatory Group I, FDA, March
1, 2005.
2. Memorandum from H. Lee, Division of
Petition Review, Chemistry Review
Team, to L. Dye, Division of Petition
Review, Regulatory Group I, FDA, April
20, 2016.
3. Memorandum from Y. Zang, Division of
Petition Review, Toxicology Review
Team, to L. Dye, Division of Petition
Review, Regulatory Group I, FDA, June
30, 2016.
List of Subjects
21 CFR Part 73
Color additives, Cosmetics, Drugs,
Medical devices.
21 CFR Part 74
Color additives, Cosmetics, Drugs.
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
E:\FR\FM\01NOR1.SGM
01NOR1
75692
Federal Register / Vol. 81, No. 211 / Tuesday, November 1, 2016 / Rules and Regulations
Applied Nutrition, 21 CFR parts 73 and
74 are amended as follows:
PART 73—LISTING OF COLOR
ADDITIVES EXEMPT FROM
CERTIFICATION
Dated: October 25, 2016.
Susan Bernard,
Director, Office of Regulations, Policy and
Social Science, Center for Food Safety and
Applied Nutrition.
[FR Doc. 2016–26310 Filed 10–31–16; 8:45 am]
BILLING CODE 4164–01–P
1. The authority citation for part 73
continues to read as follows:
■
Authority: 21 U.S.C. 321, 341, 342, 343,
348, 351, 352, 355, 361, 362, 371, 379e.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
2. In § 73.3126, revise paragraph (b)(1)
to read as follows:
Food and Drug Administration
■
§ 73.3126
21 CFR Part 117
Titanium dioxide.
*
*
*
*
(b) * * * (1) The substance listed in
paragraph (a) of this section may be
used as a color additive in contact
lenses and intraocular lens orientation
marks in amounts not to exceed the
minimum reasonably required to
accomplish the intended coloring effect.
*
*
*
*
*
[Docket No. FDA–2011–N–0920]
PART 74—LISTING OF COLOR
ADDITIVES SUBJECT TO
CERTIFICATION
HHS.
*
Authority: 21 U.S.C. 321, 341, 342, 343,
348, 351, 352, 355, 361, 362, 371, 379e.
4. In § 74.3045, revise paragraphs
(c)(1) introductory text and (c)(1)(i) to
read as follows:
■
[Phthalocyaninato (2-)] copper.
jstallworth on DSK7TPTVN1PROD with RULES
*
*
*
*
(c) * * * (1) The color additive
[phthalocyaninato(2-)] copper may be
safely used to color polypropylene
sutures, polybutester (the generic
designation for the suture fabricated
from 1,4-benzenedicarboxylic acid,
polymer with 1,4-butanediol and alphahydro-omega-hydroxypoly(oxy-1,4butanediyl), CAS Reg. No. 37282–12–5)
nonabsorbable sutures for use in general
and ophthalmic surgery, polybutylene
terephthalate nonabsorbable
monofilament sutures for general and
ophthalmic surgery, nonabsorbable
sutures made from poly(vinylidene
fluoride) and poly(vinylidene fluorideco-hexafluoropropylene) for general and
ophthalmic surgery,
polymethylmethacrylate monofilament
used as supporting haptics for
intraocular lenses, and polymers used in
orientation marks for intraocular lenses,
subject to the following restrictions:
(i) The quantity of the color additive
does not exceed 0.5 percent by weight
of the suture, haptic material, or
orientation mark.
*
*
*
*
*
VerDate Sep<11>2014
15:21 Oct 31, 2016
Jkt 241001
Food and Drug Administration,
Notification of availability.
The Food and Drug
Administration (FDA, the Agency, or
we) is announcing the availability of a
guidance for industry entitled ‘‘What
You Need To Know About the FDA
Regulation: Current Good
Manufacturing Practice, Hazard
Analysis, and Risk-Based Preventive
Controls for Human Food’’—Small
Entity Compliance Guide. The small
entity compliance guide (SECG) is
intended to help small entities comply
with the final rule titled ‘‘Current Good
Manufacturing Practice, Hazard
Analysis, and Risk-Based Preventive
Controls for Human Food.’’
DATES: Submit either electronic or
written comments on FDA guidances at
any time.
ADDRESSES: You may submit comments
as follows:
SUMMARY:
3. The authority citation for part 74
continues to read as follows:
*
AGENCY:
ACTION:
■
§ 74.3045
What You Need To Know About the
Food and Drug Administration
Regulation: Current Good
Manufacturing Practice, Hazard
Analysis, and Risk-Based Preventive
Controls for Human Food; Small Entity
Compliance Guide; Availability
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
PO 00000
Frm 00022
Fmt 4700
Sfmt 4700
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
• Mail/Hand delivery/Courier (for
written/paper submissions): Division of
Dockets Management (HFA–305), Food
and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Division of Dockets
Management, FDA will post your
comment, as well as any attachments,
except for information submitted,
marked and identified, as confidential,
if submitted as detailed in
‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2011–N–0920 for ‘‘What You Need To
Know About the FDA Regulation:
Current Good Manufacturing Practice,
Hazard Analysis, and Risk-Based
Preventive Controls for Human Food (21
CFR part 117).’’ Received comments
will be placed in the docket and, except
for those submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on https://
www.regulations.gov. Submit both
copies to the Division of Dockets
Management. If you do not wish your
name and contact information to be
made publicly available, you can
provide this information on the cover
E:\FR\FM\01NOR1.SGM
01NOR1
]]>Agencies
[Federal Register Volume 81, Number 211 (Tuesday, November 1, 2016)]
[Rules and Regulations]
[Pages 75689-75692]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-26310]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 73 and 74
[Docket No. FDA-2016-F-0821]
Listing of Color Additives Exempt From Certification; Titanium
Dioxide and Listing of Color Additives Subject to Certification;
[Phthalocyaninato (2-)] Copper
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or we) is amending the
color additive regulations to provide for the safe use of titanium
dioxide and [phthalocyaninato (2-)] copper to color orientation marks
for intraocular lenses. This action is in response to a petition filed
by Milton W. Chu, M.D.
DATES: This rule is effective December 2, 2016. See section IX for
further information on the filing of objections. Submit either
electronic or written objections and requests for a hearing by December
1, 2016.
ADDRESSES: You may submit objections and requests for a hearing as
follows:
Electronic Submissions
Submit electronic objections in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Objections submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your objection will be
made public, you are solely responsible for ensuring that your
objection does not include any confidential information that you or a
third party may not wish to be posted, such as medical information,
your or anyone else's Social Security number, or confidential business
information, such as a manufacturing process. Please note that if you
include your name, contact information, or other information that
identifies you in the body of your objection, that information will be
posted on https://www.regulations.gov.
If you want to submit an objection with confidential
information that you do not wish to be made available to the public,
submit the objection as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper objections submitted to the Division of
Dockets Management, FDA will post your objection, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2016-F-0821 for ``Listing of Color Additives Exempt From
Certification; Titanium Dioxide and Listing of Color Additives Subject
to Certification; [Phthalocyaninato (2-)] Copper.'' Received objections
will be placed in the docket and, except for those submitted as
``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
Confidential Submissions--To submit an objection with
confidential information that you do not wish to be made publicly
available, submit your objections only as a written/paper
[[Page 75690]]
submission. You should submit two copies total. One copy will include
the information you claim to be confidential with a heading or cover
note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.''
The Agency will review this copy, including the claimed confidential
information, in its consideration of comments. The second copy, which
will have the claimed confidential information redacted/blacked out,
will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Division of Dockets
Management. If you do not wish your name and contact information to be
made publicly available, you can provide this information on the cover
sheet and not in the body of your comments and you must identify this
information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: https://www.fda.gov/regulatoryinformation/dockets/default.htm.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://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: Laura A. Dye, Center for Food Safety
and Applied Nutrition (HFS-265), Food and Drug Administration, 5001
Campus Dr., College Park, MD 20740-3835, 240-402-1275.
SUPPLEMENTARY INFORMATION:
I. Introduction
In a document published in the Federal Register of March 22, 2016
(81 FR 15173), we announced that we had filed a color additive petition
(CAP 6C0305), submitted by Milton W. Chu, M.D. (petitioner), 5800 Santa
Rosa Rd., Suite 111, Camarillo, CA 93012. The petition proposed to
amend the color additive regulations in Sec. 73.3126 (21 CFR 73.3126)
and Sec. 74.3045 (21 CFR 74.3045) to provide for the safe use of
titanium dioxide and [phthalocyaninato (2-)] copper to color
orientation marks for intraocular lenses (IOLs). IOLs are devices made
of materials such as glass or plastic and are intended to be implanted
to replace the natural lens of an eye (21 CFR 886.3600). The
orientation marks are intended to aid the surgeon in visualization and
placement of IOLs during lens implantation surgery. Because IOLs are
permanently implanted, titanium dioxide and [phthalocyaninato (2-)]
copper, in the colored orientation marks, will come into direct contact
with a patient's eye for a significant amount of time. These color
additives are, therefore, subject to section 721 of the Federal Food,
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 379e).
II. Background
Titanium dioxide is already approved as a color additive for foods
(Sec. 73.575), drugs (Sec. 73.1575), cosmetics (Sec. 73.2575), and
medical devices (Sec. 73.3126). Regarding its use in medical devices,
titanium dioxide (CAS Reg. No. 13463-67-7, Color Index No. 77891) is
currently approved under Sec. 73.3126(b)(1) for use as a color
additive in contact lenses in amounts not to exceed the minimum
reasonably required to accomplish the intended coloring effect and must
meet the identity and specification requirements in Sec. 73.575(a)(1)
and (b). Titanium dioxide is exempt from certification under section
721(c) of the FD&C Act because we previously determined that
certification was not necessary for the protection of public health (51
FR 24815, July 9, 1986).
[Phthalocyaninato (2-)] copper (CAS Reg. No. 147-14-8, Color Index
No. 74160) is currently approved as a color additive under Sec.
74.3045(c)(1) for use in coloring certain non-absorbable sutures for
general and ophthalmic surgery, and for use in coloring specific
monofilaments used as supporting side struts (haptics) that hold the
IOLs in place in the eye, at a level up to 0.5 percent by weight of the
suture or haptic material. In addition, it is currently approved as a
color additive under Sec. 74.3045(c)(2) for use in coloring contact
lenses in amounts not to exceed the minimum amount reasonably required
to accomplish the intended coloring effect. We previously determined
that batch certification was necessary to ensure the safety of
[phthalocyaninato (2-)] copper (34 FR 6777, April 23, 1969).
III. Safety Evaluation
A. Determination of Safety
Under section 721(b)(4) of the FD&C Act, 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 these
color additives intended to color IOL orientation marks are not harmful
under their intended conditions of use, we considered exposure to the
additives and their impurities, each additive's toxicological data, and
other relevant information (such as published literature) available to
us.
B. Safety of Petitioned Use of the Color Additives
Regarding the petitioned use, titanium dioxide and
[phthalocyaninato (2-)] copper are intended to color orientation marks
for IOL materials (polymers) to create white and translucent or opaque
blue marks that are typically 100-250 microns ([mu]m) in diameter and
80-150 [mu]m in depth. Titanium dioxide will be used in amounts not to
exceed the minimum reasonably required to accomplish the intended
coloring effect of the orientation marks. [Phthalocyaninato (2-)]
copper will be used at levels not to exceed 0.5 percent by weight of
the orientation marks.
To assess safety, we compared an individual's estimated exposure to
these two color additives for the petitioned use to color IOL
orientation marks to the approved uses of these color additives,
including in IOL haptics and opaque contact lenses, because these uses
are similar. As part of our previous approval for titanium dioxide used
to color contact lenses, we estimated exposure to titanium dioxide from
this use to be 270 nanograms per person per day (ng/p/d) over the lens
lifetime (51 FR 24815), which does not significantly contribute to the
cumulative exposure when compared to the exposure to titanium dioxide
from the approved uses of mica-based pearlescent pigments (of which
titanium dioxide is a component) in food and pharmaceuticals (Ref. 1).
Similarly, we previously estimated exposure to [phthalocyaninato (2-)]
copper from the use of surgical sutures, contact lenses, and specific
monofilaments used as supporting haptics for IOLs to be 310 ng/p/d, 280
ng/p/d, and 0.3 ng/p/d, respectively (64 FR 23185, April 30, 1999; 51
FR 39370, October 28, 1986; and 52 FR 15944, May 1, 1987). With respect
to the petitioned use, we estimated that the worst-case lifetime
exposure to titanium dioxide and [phthalocyaninato (2-)] copper used to
color orientation marks would be no greater than 0.06 ng/p/d and 0.004
ng/
[[Page 75691]]
p/d, respectively, over a 70-year lifetime (Ref. 2). This exposure
estimate is conservative as it assumes 100 percent migration of the
color additives from the IOLs into the ocular fluid of the eye over a
lifespan of 70 years following lens implantation. However, we expect
that the color additives in the orientation marks will most likely be
either chemically bound or otherwise integrated into the lens material,
which would limit migration of the color additives into the ocular
fluid of the eye. This means that the actual exposures to titanium
dioxide and [phthalocyaninato (2-)] copper to color IOL orientation
marks are expected to be far less than the worst-case exposure
estimates for these color additives and insignificant in comparison to
the cumulative exposures from the other approved uses of these color
additives that we have already established to be safe (Ref. 2).
In assessing biocompatibility and toxicity of IOLs, we consider the
International Standard for intraocular lens testing for
biocompatibility (ISO 11979-5) as an appropriate standard. In general,
ISO 11979-5 recommends investigations on the following biological
endpoints: Cytotoxicity, genotoxicity, local effects after
implantation, and sensitization potential, in the context of
physicochemical properties.
The petitioner conducted a cytotoxicity study in which cultured
cells were exposed to a mixture of titanium dioxide and
[phthalocyaninato (2-)] copper in direct contact for at least 24 hours.
Both color additives were found to be noncytotoxic in this study.
Cytotoxicity studies of [phthalocyaninato (2-)] copper in previous
petitions also indicated no cytotoxicity (Ref. 3). Additionally, the
toxicology data for [phthalocyaninato (2-)] copper from previous
petitions, as well as relevant data found in the Organization for
Economic Cooperation and Development's Screening Information Dataset
(OECD's SIDS) database, all indicated negative results for
genotoxicity, carcinogenicity, implantation safety, and sensitization
potential (Ref. 3). Similarly, data on titanium dioxide in OECD's SIDS
database reported negative results for genotoxicity and sensitization
potential. We conclude that the available toxicology data are
sufficient to support the safety of the proposed expanded uses of
titanium dioxide and [phthalocyaninato (2-)] copper.
IV. Conclusion
Based on the data and information in the petition and other
relevant material, we conclude that the petitioned use of titanium
dioxide and [phthalocyaninato (2-)] copper to color orientation marks
for IOLs is safe. We further conclude that these additives will achieve
their intended technical effect and are suitable for the petitioned
use. Consequently, we are amending the color additive regulations in
parts 73 and 74 as set forth in this document. In addition, based upon
the factors listed in 21 CFR 71.20(b), we conclude that certification
of titanium dioxide remains unnecessary for the protection of the
public health. We also conclude that batch certification of
[phthalocyaninato (2-)] copper continues to be necessary to protect the
public health.
V. Public Disclosure and Confidentiality of Data and Information in a
Color Additive Rule
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. Analysis of Environmental Impact
We previously considered the environmental effects of this rule, as
stated in the March 22, 2016, notice of petition for CAP 6C0305 (81 FR
15173). We stated that we had determined, under 21 CFR 25.32(l), 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. 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.
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 https://www.regulations.gov. We will publish notice of the objections that we
have received or lack thereof in the Federal Register.
IX. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES) and are available for viewing by interested
persons between 9 a.m. and 4 p.m., Monday through Friday; they are also
available electronically at https://www.regulations.gov.
1. Memorandum from H. Lee, Division of Petition Review, Chemistry
Review Team, to P. DeLeo, Division of Petition Review, Regulatory
Group I, FDA, March 1, 2005.
2. Memorandum from H. Lee, Division of Petition Review, Chemistry
Review Team, to L. Dye, Division of Petition Review, Regulatory
Group I, FDA, April 20, 2016.
3. Memorandum from Y. Zang, Division of Petition Review, Toxicology
Review Team, to L. Dye, Division of Petition Review, Regulatory
Group I, FDA, June 30, 2016.
List of Subjects
21 CFR Part 73
Color additives, Cosmetics, Drugs, Medical devices.
21 CFR Part 74
Color additives, Cosmetics, Drugs.
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
[[Page 75692]]
Applied Nutrition, 21 CFR parts 73 and 74 are amended as follows:
PART 73--LISTING OF COLOR ADDITIVES EXEMPT FROM CERTIFICATION
0
1. The authority citation for 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. In Sec. 73.3126, revise paragraph (b)(1) to read as follows:
Sec. 73.3126 Titanium dioxide.
* * * * *
(b) * * * (1) The substance listed in paragraph (a) of this section
may be used as a color additive in contact lenses and intraocular lens
orientation marks in amounts not to exceed the minimum reasonably
required to accomplish the intended coloring effect.
* * * * *
PART 74--LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION
0
3. The authority citation for part 74 continues to read as follows:
Authority: 21 U.S.C. 321, 341, 342, 343, 348, 351, 352, 355,
361, 362, 371, 379e.
0
4. In Sec. 74.3045, revise paragraphs (c)(1) introductory text and
(c)(1)(i) to read as follows:
Sec. 74.3045 [Phthalocyaninato (2-)] copper.
* * * * *
(c) * * * (1) The color additive [phthalocyaninato(2-)] copper may
be safely used to color polypropylene sutures, polybutester (the
generic designation for the suture fabricated from 1,4-
benzenedicarboxylic acid, polymer with 1,4-butanediol and alpha-hydro-
omega-hydroxypoly(oxy-1,4-butanediyl), CAS Reg. No. 37282-12-5)
nonabsorbable sutures for use in general and ophthalmic surgery,
polybutylene terephthalate nonabsorbable monofilament sutures for
general and ophthalmic surgery, nonabsorbable sutures made from
poly(vinylidene fluoride) and poly(vinylidene fluoride-co-
hexafluoropropylene) for general and ophthalmic surgery,
polymethylmethacrylate monofilament used as supporting haptics for
intraocular lenses, and polymers used in orientation marks for
intraocular lenses, subject to the following restrictions:
(i) The quantity of the color additive does not exceed 0.5 percent
by weight of the suture, haptic material, or orientation mark.
* * * * *
Dated: October 25, 2016.
Susan Bernard,
Director, Office of Regulations, Policy and Social Science, Center for
Food Safety and Applied Nutrition.
[FR Doc. 2016-26310 Filed 10-31-16; 8:45 am]
BILLING CODE 4164-01-P
