[Federal Register Volume 81, Number 249 (Wednesday, December 28, 2016)]
[Rules and Regulations]
[Pages 95475-95477]
[FR Doc No: 2016-31227]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 52

[EPA-R05-OAR-2016-0502; FRL-9955-89-Region 5]

Air Plan Approval; Illinois; Volatile Organic Compounds
Definition

AGENCY: Environmental Protection Agency (EPA).

ACTION: Direct final rule.

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SUMMARY: Under the Clean Air Act (CAA), the Environmental Protection
Agency (EPA) is approving a state submission as a revision to the
Illinois State Implementation Plan (SIP). The revision amends the
Illinois Administrative Code (IAC) by updating the definition of
volatile organic material (VOM), otherwise known as volatile organic
compounds (VOC), to exclude 2-amino-2-methyl-1-propanol (AMP). This
revision is in response to an EPA rulemaking in 2014 which exempted
this compound from the Federal definition of VOC on the basis that the
compound makes a negligible contribution to tropospheric ozone
formation.

DATES: This direct final rule will be effective February 27, 2017,
unless EPA receives adverse comments by January 27, 2017. If adverse
comments are received, EPA will publish a timely withdrawal of the
direct final rule in the Federal Register informing the public that the
rule will not take effect.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-R05-
OAR-2016-0502 at http://www.regulations.gov or via email to
<EMAIL_ADDRESS>For comments submitted at Regulations.gov,
follow the online instructions for submitting comments. Once submitted,
comments cannot be edited or removed from Regulations.gov. For either
manner of submission, EPA may publish any comment received to its
public docket. Do not submit electronically any information you
consider to be Confidential Business Information (CBI) or other
information whose disclosure is restricted by statute. Multimedia
submissions (audio, video, etc.) must be accompanied by a written
comment. The written comment is considered the official comment and
should include discussion of all points you wish to make. EPA will
generally not consider comments or comment contents located outside of
the primary submission (i.e. on the web, cloud, or other file sharing
system). For additional submission methods, please contact the person
identified in the FOR FURTHER INFORMATION CONTACT section. For the full
EPA public comment policy, information about CBI or multimedia
submissions, and general guidance on making effective comments, please
visit http://www2.epa.gov/dockets/commenting-epa-dockets.

FOR FURTHER INFORMATION CONTACT: Michelle Becker, Life Scientist,
Attainment Planning and Maintenance Section, Air Programs Branch (AR-
18J), Environmental Protection Agency, Region 5, 77 West Jackson
Boulevard, Chicago, Illinois 60604,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Throughout this document whenever ``we,''
``us,'' or ``our'' is used, we mean EPA. This supplementary information
section is arranged as follows:

I. What is the background for this action?
II. What is EPA's analysis of the SIP Revision?
III. What action is EPA taking?
IV. Incorporation by Reference
V. Statutory and Executive Order Reviews

I. What is the background for this action?

    The Illinois Environmental Protection Agency (IEPA) submitted a
revision to the Illinois SIP to EPA for approval on August 9, 2016. The
SIP revision excludes the chemical compound 2-amino-2-methyl-1-propanol
(AMP) from the definition of VOM or VOC at 35 IAC Part 211, Subpart B,
Section 211.7150(a).
    The Illinois Pollution Control Board (IPCB) held a public hearing
on the proposed SIP revision on January 8, 2015. There were no public
comments received at the public hearing. IPCB received one comment from
the American Coatings Association in a letter dated December 16, 2014,
supporting the exemption of AMP from

the Illinois regulated VOCs. IPCB adopted the amendment to 35 IAC
211.7150(a) on March 5, 2015. IPCB also adopted minor administrative
changes such as alphabetizing compound names, adding a subpart heading
previously omitted, and replacing the word ``above'' with ``of this
Section'' in 35 IAC 211.7150(d) for ease of cross-referencing within a
section of the regulations.

II. What is EPA's analysis of the SIP Revision?

    In 2012, EPA received a petition requesting that AMP be exempted
from VOC control based on its low reactivity to ethane. On March 27,
2014 (79 FR 17037), EPA responded to the petition by amending 40 CFR
51.100(s)(1) to exclude this chemical compound from the definition of
VOC for purposes of preparing SIPs to attain the national ambient air
quality standard for ozone under title I of the CAA (78 FR 9823). Based
on the mass maximum incremental reactivity value for the compound being
equal to or less than that of ethane, EPA concluded that this compound
makes negligible contributions to tropospheric ozone formation. (79 FR
17037). Additionally, EPA considered risks not related to tropospheric
ozone associated with currently allowed uses of the chemical to be
acceptable. EPA's action became effective on June 25, 2014. IEPA's SIP
revision is consistent with EPA's action amending the definition of VOC
at 40 CFR 51.100(s).

III. What action is EPA taking?

    EPA is approving into the Illinois SIP revisions to 35 IAC 211
contained in the August 9, 2016, submittal. We are publishing this
action without prior proposal because we view this as a
noncontroversial amendment and anticipate no adverse comments. However,
in the proposed rules section of this Federal Register publication, we
are publishing a separate document that will serve as the proposal to
approve the state plan if relevant adverse written comments are filed.
This rule will be effective February 27, 2017 without further notice
unless we receive relevant adverse written comments by January 27,
2017. If we receive such comments, we will withdraw this action before
the effective date by publishing a subsequent document that will
withdraw the final action. All public comments received will then be
addressed in a subsequent final rule based on the proposed action. EPA
will not institute a second comment period. Any parties interested in
commenting on this action should do so at this time. Please note that
if EPA receives adverse comment on an amendment, paragraph, or section
of this rule and if that provision may be severed from the remainder of
the rule, EPA may adopt as final those provisions of the rule that are
not the subject of an adverse comment. If we do not receive any
comments, this action will be effective February 27, 2017.

IV. Incorporation by Reference

    In this rule, EPA is finalizing regulatory text that includes
incorporation by reference. In accordance with requirements of 1 CFR
51.5, EPA is finalizing the incorporation by reference of the Illinois
Regulations described in the amendments to 40 CFR part 52 set forth
below. EPA has made, and will continue to make, these documents
generally available through www.regulations.gov, and/or at the National
Archives and Records Administration (NARA), and/or at the EPA Region 5
Office (please contact the person identified in the FOR FURTHER
INFORMATION CONTACT section of this preamble for more information). For
information on the availability of this material at NARA, go to:
www.archives.gov/federal-register/cfr/ibr-locations.html.

V. Statutory and Executive Order Reviews

    Under the CAA, the Administrator is required to approve a SIP
submission that complies with the provisions of the CAA and applicable
Federal regulations. 42 U.S.C. 7410(k); 40 CFR 52.02(a). Thus, in
reviewing SIP submissions, EPA's role is to approve state choices,
provided that they meet the criteria of the CAA. Accordingly, this
action merely approves state law as meeting Federal requirements and
does not impose additional requirements beyond those imposed by state
law. For that reason, this action:
     Is not a significant regulatory action subject to review
by the Office of Management and Budget under Executive Orders 12866 (58
FR 51735, October 4, 1993) and 13563 (76 FR 3821, January 21, 2011);
     Does not impose an information collection burden under the
provisions of the Paperwork Reduction Act (44 U.S.C. 3501 et seq.);
     Is certified as not having a significant economic impact
on a substantial number of small entities under the Regulatory
Flexibility Act (5 U.S.C. 601 et seq.);
     Does not contain any unfunded mandate or significantly or
uniquely affect small governments, as described in the Unfunded
Mandates Reform Act of 1995 (Public Law 104-4);
     Does not have Federalism implications as specified in
Executive Order 13132 (64 FR 43255, August 10, 1999);
     Is not an economically significant regulatory action based
on health or safety risks subject to Executive Order 13045 (62 FR
19885, April 23, 1997);
     Is not a significant regulatory action subject to
Executive Order 13211 (66 FR 28355, May 22, 2001);
     Is not subject to requirements of Section 12(d) of the
National Technology Transfer and Advancement Act of 1995 (15 U.S.C. 272
note) because application of those requirements would be inconsistent
with the Clean Air Act; and
     Does not provide EPA with the discretionary authority to
address, as appropriate, disproportionate human health or environmental
effects, using practicable and legally permissible methods, under
Executive Order 12898 (59 FR 7629, February 16, 1994).
    In addition, the SIP is not approved to apply on any Indian
reservation land or in any other area where EPA or an Indian tribe has
demonstrated that a tribe has jurisdiction. In those areas of Indian
country, the rule does not have tribal implications and will not impose
substantial direct costs on tribal governments or preempt tribal law as
specified by Executive Order 13175 (65 FR 67249, November 9, 2000).
    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the
Small Business Regulatory Enforcement Fairness Act of 1996, generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report, which includes a copy of the rule,
to each House of the Congress and to the Comptroller General of the
United States. EPA will submit a report containing this action and
other required information to the U.S. Senate, the U.S. House of
Representatives, and the Comptroller General of the United States prior
to publication of the rule in the Federal Register. A major rule cannot
take effect until 60 days after it is published in the Federal
Register. This action is not a ``major rule'' as defined by 5 U.S.C.
804(2).
    Under section 307(b)(1) of the CAA, petitions for judicial review
of this action must be filed in the United States Court of Appeals for
the appropriate circuit by February 27, 2017. Filing a petition for
reconsideration by the Administrator of this final rule does not affect
the finality of this action for the purposes of judicial review nor
does it extend the time within which a petition for judicial review may
be filed, and

shall not postpone the effectiveness of such rule or action. Parties
with objections to this direct final rule are encouraged to file a
comment in response to the parallel notice of proposed rulemaking for
this action published in the proposed rules section of today's Federal
Register, rather than file an immediate petition for judicial review of
this direct final rule, so that EPA can withdraw this direct final rule
and address the comment in the proposed rulemaking. This action may not
be challenged later in proceedings to enforce its requirements. (See
section 307(b)(2).)

List of Subjects in 40 CFR Part 52

    Environmental protection, Air pollution control, Incorporation by
reference, Intergovernmental relations, Ozone, Reporting and
recordkeeping requirements, Volatile organic compounds.

    Dated: November 18, 2016.
Robert A. Kaplan,
Acting Regional Administrator, Region 5.
    40 CFR Part 52 is amended as follows:

PART 52--APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS

0
1. The authority citation for part 52 continues to read as follows:

    Authority: 42 U.S.C. 7401 et seq.

0
2. Section 52.720 is amended by adding paragraph (c)(209) to read as
follows:

Sec.  52.720  Identification of plan.

* * * * *
    (c) * * *
    (209) On August 9, 2016, the state submitted a proposed revision to
the Illinois SIP updating the definition of Volatile Organic Material
(VOM) or Volatile Organic Compound (VOC) to exclude the chemical
compound 2-amino-2-methyl-1-propanol (AMP), along with minor
administrative revisions.
    (i) Incorporation by reference. Illinois Administrative Code, Title
35: Environmental Protection, Subtitle B: Air Pollution, Chapter I:
Pollution Control Board, Subchapter c: Emissions Standards and
Limitations for Station Sources, Part 211: Definitions and General
Provisions, Subpart B: Definitions, Section 211.7150 Volatile Organic
Material (VOM) or Volatile Organic Compounds (VOC), effective March 24,
2015.

[FR Doc. 2016-31227 Filed 12-27-16; 8:45 am]
 BILLING CODE 6560-50-P


[Federal Register Volume 76, Number 25 (Monday, February 7, 2011)]
[Proposed Rules]
[Pages 6575-6578]
[FR Doc No: 2011-2610]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2010-0673; Directorate Identifier 2009-NM-208-AD]
RIN 2120-AA64

Airworthiness Directives; BAE Systems (Operations) Limited Model
BAe 146 and Avro 146-RJ Airplanes

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Supplemental notice of proposed rulemaking (NPRM); reopening of
comment period.

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SUMMARY: We are revising an earlier NPRM for the products listed above.
This action revises the earlier NPRM by expanding the scope. This
proposed AD results from mandatory continuing airworthiness information
(MCAI) originated by an aviation authority of another country to
identify and correct an unsafe condition on an aviation product. The
MCAI describes the unsafe condition as:

    In June 2000, prompted by a crack found at the top of the Nose
Landing Gear (NLG) oleo, BAE Systems (Operations) Ltd (BAE

Systems) issued Inspection Service Bulletin (ISB) ISB.32-158. * * *
    Later, as part of an accident investigation, the examination of
a fractured NLG main fitting showed that M-D (Messier-Dowty) SB.146-
32-150 was not accomplished * * * BAE Systems determined that more
NLG units could be similarly affected. * * *
    Subsequently, investigation and analysis by M-D identified the
need for a reduction of the inspection threshold and the repetitive
inspection interval for the affected NLG units. * * *
* * * * *
    * * * [I]nvestigation by M-D showed that if any undetected crack
was present at the time of the embodiment of M-D SB 146-32-150, Part
B or Part C, it could continue to grow while the NLG is in service
and could lead to the failure of the main fitting and possible
collapse of the NLG. * * * [B]AE Systems have received additional
reports of cracked NLG main fittings. One operator reported a crack
in a premodification main fitting. * * *
* * * * *
    Undetected cracks could lead to failure of the NLG Main Fitting
and collapse of the NLG.
* * * * *
    The unsafe condition is cracking of the NLG, which could adversely
affect the airplane's safe landing. The proposed AD would require
actions that are intended to address the unsafe condition described in
the MCAI.

DATES: We must receive comments on this proposed AD by March 24, 2011.

ADDRESSES: You may send comments by any of the following methods:
     Federal eRulemaking Portal: Go to http://www.regulations.gov. Follow the instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590.
     Hand Delivery: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-40, 1200 New
Jersey Avenue, SE., Washington, DC, between 9 a.m. and 5 p.m., Monday
through Friday, except Federal holidays.
    For service information identified in this proposed AD, contact BAE
Systems (Operations) Limited, Customer Information Department,
Prestwick International Airport, Ayrshire, KA9 2RW, Scotland, United
Kingdom; telephone +44 1292 675207; fax +44 1292 675704; e-mail
<EMAIL_ADDRESS>Internet http://www.baesystems.com/Businesses/RegionalAircraft/index.htm. You may review copies of the
referenced service information at the FAA, Transport Airplane
Directorate, 1601 Lind Avenue, SW., Renton, Washington. For information
on the availability of this material at the FAA, call<PHONE_NUMBER>.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://www.regulations.gov; or in person at the Docket Operations office
between 9 a.m. and 5 p.m., Monday through Friday, except Federal
holidays. The AD docket contains this proposed AD, the regulatory
evaluation, any comments received, and other information. The street
address for the Docket Operations office (telephone<PHONE_NUMBER>) is
in the ADDRESSES section. Comments will be available in the AD docket
shortly after receipt.

FOR FURTHER INFORMATION CONTACT: Todd Thompson, Aerospace Engineer,
International Branch, ANM-116, Transport Airplane Directorate, FAA,
1601 Lind Avenue, SW., Renton, Washington 98057-3356; telephone (425)
227-1175; fax<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Comments Invited

    We invite you to send any written relevant data, views, or
arguments about this proposed AD. Send your comments to an address
listed under the ADDRESSES section. Include ``Docket No. FAA-2010-0673;
Directorate Identifier 2009-NM-208-AD'' at the beginning of your
comments. We specifically invite comments on the overall regulatory,
economic, environmental, and energy aspects of this proposed AD. We
will consider all comments received by the closing date and may amend
this proposed AD based on those comments.
    We will post all comments we receive, without change, to http://www.regulations.gov, including any personal information you provide. We
will also post a report summarizing each substantive verbal contact we
receive about this proposed AD.

Discussion

    We proposed to amend 14 CFR part 39 with an earlier NPRM for the
specified products, which was published in the Federal Register on July
7, 2010 (75 FR 38953). That earlier NPRM proposed to supersede AD 2002-
03-10, Amendment 39-12651 (67 FR 6855, February 14, 2002), to require
actions intended to address the unsafe condition for the products
listed above.
    Since that NPRM was issued, we have determined that the actions
specified in the earlier NPRM apply to all airplanes; therefore, we
have removed from this supplemental NPRM the inspection to determine
whether an affected nose landing gear (NLG) unit is installed. Also, we
have determined that the compliance time for the special detailed
inspection for cracking needs to be reduced. We have also determined
that replacing the NLG is not a terminating action for the repetitive
inspections.
    The European Aviation Safety Agency (EASA), which is the Technical
Agent for the Member States of the European Community, has issued EASA
Airworthiness Directive 2010-0202R1, dated October 14, 2010 (referred
to after this as ``the MCAI''), to correct an unsafe condition for the
specified products. The MCAI states:

    In June 2000, prompted by a crack found at the top of the Nose
Landing Gear (NLG) oleo, BAE Systems (Operations) Ltd (BAE Systems)
issued Inspection Service Bulletin (ISB) ISB.32-158. This ISB was
classified mandatory by the United Kingdom Civil Aviation Authority
under AD number 002-06-2000, requiring repetitive Non-Destructive
Testing (NDT) crack inspections on the upper end of the NLG oleo.
The AD also provided an optional terminating action for the
repetitive inspections, by embodiment of Messier-Dowty (M-D) Service
Bulletin (SB) SB.146-32-150.
    Later, as part of an accident investigation, the examination of
a fractured NLG main fitting showed that M-D SB.146-32-150 was not
accomplished, although the records indicated that it had been. BAE
Systems determined that more NLG units could be similarly affected.
These NLG units were overhauled at Messier Services in Sterling,
Virginia, in the United States. To address this situation, EASA
issued Emergency AD 2009-0043-E to require repetitive NDT
inspections of each affected NLG unit and, if cracks are found,
replacement with a serviceable unit, in accordance with the
instructions of BAE Systems Alert ISB.A32-180 and M-D SB.146-32-149.
    Subsequently, investigation and analysis by M-D identified the
need for a reduction of the inspection threshold and the repetitive
inspection interval for the affected NLG units and replaced M-D SB
146-32-149 with M-D SB.146-32-174. Consequently, BAE Systems SB 32-
158 was withdrawn and superseded by BAE Systems Alert ISB.A32-180
Revision 1, which was mandated by EASA Emergency AD 2009-0197-E.
    As further information became available, BAE Systems saw a need
to clarify the compliance instructions in the ISB and issued
Revision 2 of Alert Service Bulletin ISB.A32-180. The layout of
Revision 2 was no longer compatible with the instructions of EASA
Emergency AD 2009-0197-E, so EASA issued AD 2010-0001-E which
superseded EASA AD 2009-0197-E and which reduced the threshold and
interval of the repetitive NDT inspections and required repetitive
NDT inspections of each affected NLG unit and, if cracks were found,
the replacement of the NLG with a serviceable unit.
    The optional closing action of EASA AD 2010-0001-E is embodiment
of M-D B 146-32-150 (polishing and shot peening of the NLG main
fitting) or confirmation that it has

already been accomplished, as applicable. Further investigation by
M-D showed that if any undetected crack was present at the time of
the embodiment of M-D SB 146-32-150, Part B or Part C, it could
continue to grow while the NLG is in service and could lead to the
failure of the main fitting and possible collapse of the NLG. For
this reason, EASA issued AD 2010-0072 (and its revision 1) which
required the introduction of repetitive NDT inspections (defined in
BAE Systems ISB 32-181) on NLG main fittings following embodiment of
M-D SB 146-32-150. Despite the aforementioned measures, BAE Systems
have received additional reports of cracked NLG main fittings. One
operator reported a crack in a pre-modification main fitting. Shot
peening was not present, as this was a pre-modification gear, but
the surface finish was better than that required for a post-
modification fitting. This implies that the surface finish achieved
by the modification may not be effective in preventing cracking. In
addition, a positive inspection return from BAE Systems ISB 32-181
also questions whether the combination of improved surface finish
and shot peening are effective, as a crack may have initiated from a
surface which is compliant with the modification standard.
    It has been concluded that the polishing and the shot peening of
the NLG main fitting embodied through M-D SB 146-32-150 are
potentially ineffective in preventing cracks and that all NLG main
fittings should be subject to the same 300 Flight Cycles (FC)
repetitive inspection to ensure pre-critical crack detection.
    Undetected cracks could lead to failure of the NLG Main Fitting
and collapse of the NLG.
    With that view, BAE Systems issued ISB.32-182 to implement this
repetitive 300 FC inspection on all NLG main fittings regardless of
their modification standard. ISB.32-182 supersedes existing ISBs
A32-180 and 32-181, initially with no closing action.
    For the reasons described above, this AD supersedes EASA
Emergency AD 2010-0001-E and EASA AD 2010-0072 Revision 1 and
requires repetitive NDT inspections of all NLG main fittings and, if
cracks are found, replacement of the NLG with a serviceable unit.
    This AD is revised to require corrective actions on the NLG main
fittings and not on the whole NLGs. NLGs and NLG main fittings may
have accumulated different flight cycle amounts.

    The unsafe condition is cracking of the NLG, which could adversely
affect the airplane's safe landing. You may obtain further information
by examining the MCAI in the AD docket.

Relevant Service Information

    Messier-Dowty has issued Service Bulletin 146-32-174, Revision 2,
including Appendix A, dated August 16, 2010. The actions described in
this service information are intended to correct the unsafe condition
identified in the MCAI.

Comments

    We gave the public the opportunity to participate in developing
this AD. We received no comments on the NPRM or on the determination of
the cost to the public.

FAA's Determination and Requirements of This Proposed AD

    This product has been approved by the aviation authority of another
country, and is approved for operation in the United States. Pursuant
to our bilateral agreement with the State of Design Authority, we have
been notified of the unsafe condition described in the MCAI and service
information referenced above. We are proposing this AD because we
evaluated all pertinent information and determined an unsafe condition
exists and is likely to exist or develop on other products of the same
type design.
    Certain changes described above expand the scope of the earlier
NPRM. As a result, we have determined that it is necessary to reopen
the comment period to provide additional opportunity for the public to
comment on this proposed AD.

Differences Between This AD and the MCAI or Service Information

    We have reviewed the MCAI and related service information and, in
general, agree with their substance. But we might have found it
necessary to use different words from those in the MCAI to ensure the
AD is clear for U.S. operators and is enforceable. In making these
changes, we do not intend to differ substantively from the information
provided in the MCAI and related service information.
    We might also have proposed different actions in this AD from those
in the MCAI in order to follow FAA policies. Any such differences are
highlighted in a Note within the proposed AD.

Costs of Compliance

    Based on the service information, we estimate that this proposed AD
would affect 1 product of U.S. registry.
    There are no retained actions in this supplemental NPRM that are
required by AD 2002-03-10.
    We estimate that it would take about 1 work-hour per product to
comply with the new basic requirements of this proposed AD. The average
labor rate is $85 per work-hour. Based on these figures, we estimate
the cost of the proposed AD on U.S. operators to be $85.
    We have received no definitive data that would enable us to provide
a cost estimate for the on-condition actions specified in this AD.

Authority for This Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. ``Subtitle VII: Aviation
Programs,'' describes in more detail the scope of the Agency's
authority.
    We are issuing this rulemaking under the authority described in
``Subtitle VII, Part A, Subpart III, Section 44701: General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.

Regulatory Findings

    We determined that this proposed AD would not have federalism
implications under Executive Order 13132. This proposed AD would not
have a substantial direct effect on the States, on the relationship
between the national Government and the States, or on the distribution
of power and responsibilities among the various levels of government.
    For the reasons discussed above, I certify this proposed
regulation:
    1. Is not a ``significant regulatory action'' under Executive Order
12866;
    2. Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979); and
    3. Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.
    We prepared a regulatory evaluation of the estimated costs to
comply with this proposed AD and placed it in the AD docket.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Incorporation by
reference, Safety.

The Proposed Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

    1. The authority citation for part 39 continues to read as follows:

    Authority: 49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13  [Amended]

    2. The FAA amends Sec.  39.13 by removing Amendment 39-12651 (67 FR
6855, February 14, 2002) and adding the following new AD:

BAE Systems (Operations) Limited: Docket No. FAA-2010-0673;
Directorate Identifier 2009-NM-208-AD.

Comments Due Date

    (a) We must receive comments by March 24, 2011.

Affected ADs

    (b) The AD supersedes AD 2002-03-10, Amendment 39-12651.

Applicability

    (c) This AD applies to BAE Systems (Operations) Limited Model
BAe 146-100A, -200A, and -300A airplanes and Model Avro 146-RJ70A,
146-RJ85A, and 146-RJ100A airplanes; certificated in any category;
all serial numbers.

Subject

    (d) Air Transport Association (ATA) of America Code 32: Landing
Gear.

Reason

    (e) The mandatory continuing airworthiness information (MCAI)
states:
    In June 2000, prompted by a crack found at the top of the Nose
Landing Gear (NLG) oleo, BAE Systems (Operations) Ltd (BAE Systems)
issued Inspection Service Bulletin (ISB) ISB.32-158. * * *
    Later, as part of an accident investigation, the examination of
a fractured NLG main fitting showed that M-D (Messier-Dowty) SB.146-
32-150 was not accomplished * * * BAE Systems determined that more
NLG units could be similarly affected. * * *
    Subsequently, investigation and analysis by M-D identified the
need for a reduction of the inspection threshold and the repetitive
inspection interval for the affected NLG units. * * *
* * * * *
    * * * [I]nvestigation by M-D showed that if any undetected crack
was present at the time of the embodiment of M-D SB 146-32-150, Part
B or Part C, it could continue to grow while the NLG is in service
and could lead to the failure of the main fitting and possible
collapse of the NLG. * * * [B]AE Systems have received additional
reports of cracked NLG main fittings. One operator reported a crack
in a premodification main fitting. * * *
* * * * *
    Undetected cracks could lead to failure of the NLG Main Fitting
and collapse of the NLG.
* * * * *
    The unsafe condition is cracking of the NLG, which could
adversely affect the airplane's safe landing.

Compliance

    (f) You are responsible for having the actions required by this
AD performed within the compliance times specified, unless the
actions have already been done.

Inspection

    (g) Before the accumulation of 5,000 total flight cycles on the
NLG main fitting, or within 300 flight cycles after the effective
date of this AD, whichever occurs later, do an ultrasonic inspection
on the upper part of the NLG main fitting for any crack, in
accordance with the Accomplishment Instructions of Messier-Dowty
Service Bulletin 146-32-174, Revision 2, including Appendix A, dated
August 16, 2010. Thereafter, repeat the inspection at intervals not
to exceed 300 flight cycles.
    (h) An inspection that has been done in accordance with the
Accomplishment Instructions of Messier-Dowty Service Bulletin 146-
32-174, Revision 1, dated September 2, 2009, or in accordance with
the Accomplishment Instructions of Messier-Dowty Service Bulletin
146-32-175, Revision 2, dated March 5, 2010, before the effective
date of this AD but not more than 300 flight cycles before the
effective date of this AD, is considered acceptable for compliance
with the initial inspection required by paragraph (g) of this AD.

Replacement

    (i) If any crack is found from the inspections required by
paragraph (g) of this AD, before further flight, replace the NLG
main fitting with a serviceable NLG main fitting, using a method
approved by the Manager, International Branch, ANM-116, Transport
Airplane Directorate, FAA; or the European Aviation Safety Agency
(EASA) (or its delegated agent).

    Note 1: Guidance on replacing the NLG main fitting with a
serviceable NLG main fitting can be found in Subsection 32-20-11 of
BAE Systems (Operations) Limited BAe 146 Series/Avro 146-RJ Series
Aircraft Maintenance Manual 146.153, Revision 101, dated July 15,
2010.

    (j) Replacing the NLG main fitting with a serviceable NLG main
fitting is not a terminating action for the repetitive inspections
required by paragraph (g) of this AD.

Parts Installation

    (k) As of the effective date of this AD, no person may install
an affected NLG main fitting on any airplane, unless that NLG main
fitting has been inspected in accordance with paragraph (g) of this
AD and no cracking is found.

FAA AD Differences

    Note 2: This AD differs from the MCAI and/or service information
as follows: No differences.

Other FAA AD Provisions

    (l) The following provisions also apply to this AD:
    (1) Alternative Methods of Compliance (AMOCs): The Manager,
International Branch, ANM-116, Transport Airplane Directorate, FAA,
has the authority to approve AMOCs for this AD, if requested using
the procedures found in 14 CFR 39.19. Send information to Attn: Todd
Thompson, Aerospace Engineer, International Branch, ANM-116,
Transport Airplane Directorate, FAA, 1601 Lind Avenue, SW., Renton,
Washington 98057-3356; telephone<PHONE_NUMBER>; fax<PHONE_NUMBER>.
Before using any approved AMOC, notify your appropriate principal
inspector, or lacking a principal inspector, the manager of the
local flight standards district office/certificate holding district
office. The AMOC approval letter must specifically reference this
AD.
    (2) Airworthy Product: For any requirement in this AD to obtain
corrective actions from a manufacturer or other source, use these
actions if they are FAA-approved. Corrective actions are considered
FAA-approved if they are approved by the State of Design Authority
(or their delegated agent). You are required to assure the product
is airworthy before it is returned to service.

Related Information

    (m) Refer to MCAI EASA Airworthiness Directive 2010-0202R1,
dated October 14, 2010; Messier-Dowty Service Bulletin 146-32-174,
Revision 2, including Appendix A, dated August 16, 2010; for related
information.

    Issued in Renton, Washington, on January 28, 2011.
Ali Bahrami,
Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. 2011-2610 Filed 2-4-11; 8:45 am]
BILLING CODE 4910-13-P


[Federal Register Volume 85, Number 125 (Monday, June 29, 2020)]
[Notices]
[Pages 38901-38905]
[FR Doc No: 2020-13974]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1046]

Use of Codeine-Containing Analgesics in Children Under 12 Years
of Age Subsequent to CYP2D6 Genetic Testing; Establishment of a Public
Docket; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of a public docket; request for comments.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or the Agency) is
announcing the establishment of a docket to solicit public comment on

specific questions pertaining to the use of codeine for analgesia in
children under 12 years of age, and the use of cytochrome P450 2D6
(CYP2D6) testing in children under 12 years of age prior to treatment
with codeine-containing analgesics. These questions are posed in
section II.

DATES: Submit either electronic or written comments by August 28, 2020.

ADDRESSES: You may submit comments as follows:
    Please note that late, untimely filed comments will not be
considered. Electronic comments must be submitted on or before August
28, 2020. The https://www.regulations.gov electronic filing system will
accept comments until 11:59 p.m. Eastern Time at the end of August 28,
2020. Comments received by mail/hand delivery/courier (for written/
paper submissions) will be considered timely if they are postmarked or
the delivery service acceptance receipt is on or before that date.

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 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): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, 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-2020-N-1046 for ``Use of Codeine-Containing Analgesics in Children
Under 12 Years of Age Subsequent to CYP2D6 Genetic Testing.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff 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 Dockets Management Staff. 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.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: LCDR Jessica Voqui, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 3121,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    Codeine-containing prescription analgesic products approved by FDA
are currently contraindicated in children under 12 years of age.\1\ The
Agency is considering a request for regulatory action to amend this
contraindication to provide for use in children under 12 years of age
who are shown to be cytochrome P450 isoenzyme 2D6 (CYP2D6) normal
metabolizers (also known as ``extensive metabolizers'') or CYP2D6
intermediate metabolizers based on pharmacogenetic testing that
includes CYP2D6 copy number or gene duplication detection. As discussed
in section I.C., below, concerns have been raised in a citizen petition
that children under 12 years of age in acute pain may not be able to
access appropriate opioid analgesic drugs, and FDA is interested in
understanding the scope and impact of any potential access issues. To
properly assess the appropriateness and potential impact of making this
amendment to the contraindication, the Agency seeks input from the
healthcare community and the public on the following issues: (1) Pain
management in children under 12 years of age; (2) availability and
clinical utility of CYP2D6 genotyping tests; and (3) e-prescribing
availability as a potential mitigation approach for opioid analgesic
access in urgent situations.
---------------------------------------------------------------------------

    \1\ See April 20, 2017, Drug Safety Communication at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-restricts-use-prescription-codeine-pain-and-cough-medicines-and. Codeine remains available through the over-the-
counter (OTC) Drug Monograph for Cold, Cough, Allergy,
Bronchodilator, and Antiasthmatic Drug Products (21 CFR 341.14, 21
CFR 341.74, 21 CFR 341.90) in combination with other medications for
cough and cold symptoms.
---------------------------------------------------------------------------

    Analgesic products with codeine as an active ingredient are opioids
that are generally indicated for the relief of mild to moderate pain
where the use of an opioid analgesic is appropriate and for which
alternative treatments are inadequate. Codeine-containing products
indicated for analgesia are marketed either as single ingredient
codeine (a Controlled Substances Act (CSA) Schedule II drug) or in
combination with other non-narcotic active ingredients, such as
acetaminophen (the combination being a CSA Schedule III drug); most of
the use is with the combination products.

There are also codeine-containing products indicated for the relief of
cough, that contain a combination of codeine with other active
ingredients in prescription products for cough and symptoms associated
with upper respiratory allergies or common cold; however, the pediatric
cough/cold indications were removed from prescription codeine cough/
cold products in January 2018.\2\ Codeine is partially metabolized to
morphine, its most potent analgesic metabolite, through the CYP2D6
pathway. CYP2D6 is a polymorphic enzyme, leading to a high degree of
variability for metabolism of codeine because of underlying genetic
differences in CYP2D6 activity. Because of this variability, depending
on CYP2D6 activity, patients may be at risk for therapeutic failure
(``poor metabolizers'') or at risk for opioid-related toxicity
(``ultra-rapid metabolizers'').
---------------------------------------------------------------------------

    \2\ See January 11, 2018, Drug Safety Communication at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-requires-labeling-changes-prescription-opioid-cough-and-cold. But see fn. 1, supra.
---------------------------------------------------------------------------

A. Regulatory History: 2007-2013

    Given the variability in the metabolism of codeine, the safety of
codeine use in children has been a concern, particularly the risk of
life-threatening or fatal respiratory depression. Over the past several
years, FDA has updated the labeling for codeine-containing prescription
products regarding the risk of respiratory depression. In 2007,
prescription codeine product labeling was updated with information
regarding polymorphic metabolism and the risk of respiratory
depression, specifically in breastfed infants of mothers who used
codeine. In August 2012, FDA issued a Drug Safety Communication (DSC)
about reports of death and respiratory depression in pediatric
patients, primarily with use of codeine following tonsillectomy and/or
adenoidectomy. In February 2013, after completing a review of the
available safety data for codeine in the FDA Adverse Event Reporting
System (FAERS) and the medical literature, FDA required a Boxed Warning
and Contraindication regarding the use of codeine-containing
prescription analgesics following tonsillectomy and/or adenoidectomy,
highlighting the risk to those children who are ultra-rapid
metabolizers of codeine due to CYP2D6 polymorphism. These children may
be particularly sensitive to the respiratory depressant effects of
codeine because ultra-rapid metabolizers metabolize standard doses of
codeine in the liver to high circulating levels of morphine (codeine's
active metabolite). As part of the review of this issue, in addition to
codeine, FDA evaluated the FDA Adverse Event Reporting System (FAERS)
and the medical literature for cases of death or overdose in children
related to the therapeutic use of immediate-release morphine,
oxycodone, or hydrocodone. This search did not reveal clear cases of
unexplainable or unconfounded death or opioid toxicity.
    In June 2013, following a review of the relevant data, the European
Medicines Agency (EMA) made the determination that ``codeine-containing
products indicated in the management of pain should only be indicated
in children above 12 years of age and contraindicated in paediatric
patients below 18 years of age undergoing tonsillectomy and/or
adenoidectomy for obstructive sleep apnoea syndrome as well as in women
during breast-feeding and in patients known to be CYP2D6 ultra-rapid
metabolisers'' (https://www.ema.europa.eu/en/medicines/human/referrals/codeine-containing-medicines).

B. Regulatory History: 2015-2017

    In April 2015, the EMA completed a review of the use of codeine for
cough and cold indications. The EMA contraindicated the use of codeine-
containing products in children under 12 years of age for cough and
cold and recommended that codeine-containing cough and cold products
not be used in children and adolescents ages 12 to 18 years of age who
have breathing problems (see ``Codeine-containing medicinal products
for the treatment of cough or cold in paediatric patients: Codeine not
to be used in children below 12 years for cough and cold,'' available
at https://www.ema.europa.eu/en/medicines/human/referrals/codeine-containing-medicinal-products-treatment-cough-cold-paediatric-patients).
    Subsequent to the release of the EMA recommendations about use of
codeine-containing products in children for cough and cold indications,
FDA initiated a safety review of available data regarding respiratory
depression and death with codeine-containing product use for cough in
children. In addition, FDA also re-evaluated available safety data
regarding codeine use for analgesia in children. Because of the
potential for shifting use to other opioids if the scope of the
February 2013 contraindication for codeine use in children was expanded
(i.e., beyond pain management following tonsillectomy and/or
adenoidectomy), FDA also evaluated the safety of other opioid-
containing potential treatments, including hydrocodone-containing cough
and cold products, and tramadol products.
    The Office of Surveillance and Epidemiology (OSE) within FDA's
Center for Drug Evaluation and Research (CDER) completed a Pediatric
Postmarketing Epidemiological, Pharmacovigilance, and Drug Utilization
Review on November 13, 2015. The review identified 64 cases in the
FAERS database from 1965 to May 2015 of serious respiratory depression,
including 24 deaths, in children 18 years of age and below receiving
codeine-containing products. Most of the cases (50 out of 64),
including fatal cases (21 out of 24), involved children under 12 years
of age. Among the 48 cases that reported the reason for use, 34
reported pain management (17 were post-adenotonsillectomy), and 14
reported cough and cold management; 12 of 21 deaths in children under
12 years of age occurred when a codeine-containing product was used
unrelated to pain post-adenotonsillectomy (cough and cold, n=7; general
pain, n=2; other postoperative pain, n=2; sore/strep throat pain, n=1).
Ten of 64 cases mentioned CYP2D6 genotype (7 were ultra-rapid
metabolizers and 3 were normal metabolizers); the remaining 54 cases
did not report CYP2D6 genotyping. Of the three cases that occurred in
normal metabolizers, two involved 3-year-old twin brothers who received
inadvertent overdoses of codeine for treatment of a cold (one resulted
in death) and one involved a 3-year-old female who underwent
tonsillectomy for obstructive sleep apnea. Other risk factors for
codeine toxicity were noted in several cases such as obesity,
obstructive sleep apnea, and overdose. OSE concluded that there is case
report evidence of respiratory depression following codeine use for
both pain and cough and cold treatment, particularly in pediatric
patients under 12 years of age.
    FDA held a joint meeting of the Pulmonary and Allergy Drugs and the
Drug Safety and Risk Management Advisory Committees (PADAC/DSaRM AC) on
December 10, 2015 (80 FR 65770, October 27, 2015; minutes available at
https://www.fda.gov/media/95855/download), to discuss the safety of
codeine in pediatric patients. The issue of whether to add a
recommendation to the labeling for prescription codeine drug products
to genotype children prior to prescribing codeine was not raised as a
specific topic of discussion for the AC. However,

FDA did explain why a recommendation for routine genotyping prior to
receiving codeine was not added to product labeling at the time of the
2013 labeling change. First, normal metabolizers, in some cases,
convert codeine to morphine at levels similar to ultra-rapid
metabolizers. Second, the positive predictive value of the genotyping
tests is low; thus, the number needed to be screened in order to
prevent one adverse event is very high. Third, genotyping may be
logistically difficult to implement because preoperative lab tests are
not routinely obtained before adenotonsillectomy.
    There was some discussion at the AC meeting about patient access
issues. The patient representative, a mother of a child with sickle
cell disease (SCD), expressed concerns focused on her daughter being
able to get any opioid for use at home, rather than codeine/
acetaminophen specifically. The overall theme of her comments was the
difficulty with accessing opioid medications for control of SCD-related
intermittent painful crises if a patient has to go to the emergency
department for care and see physicians who are not familiar with the
patient or the patient's family.
    Another issue raised at the 2015 PADAC/DSaRM AC meeting was that
the pediatric pain specialists on the committee contended that codeine/
acetaminophen was not an appropriate drug for the treatment of painful
sickle cell crises because the acetaminophen limits the dose of codeine
that can be administered.
    Two-thirds of the AC panel (20 out of 29) recommended that FDA
contraindicate use of codeine-containing drug products for analgesia in
children under 18, and the same number (20 out of 29) recommended that
FDA contraindicate use of codeine-containing drug products for cough in
children under 18.
    Subsequent to internal discussions about the AC's recommendations,
in April 2017, the Division of Anesthesia, Analgesia, and Addiction
Products (DAAAP) and the Division of Pulmonary, Allergy, and
Rheumatology Products (DPARP), both within CDER's Office of New Drugs,
issued a Safety Labeling Change (SLC) notification letter related to
the risk of life-threatening respiratory depression in children
associated with the use of codeine-containing products and the risk of
life-threatening respiratory depression in breastfed infants whose
mothers were treated with codeine-containing products. Although the AC
panel recommended contraindicating codeine-containing drug products for
children under 18, FDA chose to limit the contraindication to children
under 12 years of age. The Agency also included in the SLC notification
letter a requirement to add warning language regarding use of codeine-
containing products in children ages 12 to 18 years of age who may have
risk factors (e.g., obstructive sleep apnea, obesity, respiratory
conditions) making them more susceptible to life-threatening or fatal
respiratory depression with codeine.
    These labeling changes were based upon the following
considerations:
     Available data suggest that younger children (under 12
years of age) may be at highest risk of life-threatening or fatal
respiratory depression.
     In addition to the risk factor of CYP2D6 ultra-rapid
metabolizer status, some case reports suggested that other risk
factors/conditions (e.g., obesity, obstructive sleep apnea,
oropharyngeal swelling (post-tonsillectomy)) may make patients more
susceptible to respiratory depression with codeine.
     There was some sentiment from the AC that prescribing of
codeine-acetaminophen combination drug products, which are CSA Schedule
III drugs, for pain in children resulted in opioids with lower abuse or
diversion potential being in the household compared to Schedule II
opioids being prescribed.
     Contraindication of codeine-containing drug products in
children under 12 years of age would support continued availability of
codeine-containing drug products for use in children ages 12 to 18
years of age who rely on codeine for pain management.
     A contraindication of codeine-containing drug products in
children under 12 years of age is consistent with decisions made by
other regulatory authorities, such as EMA and Health Canada (see
https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/33915a-eng.php).
    On August 29, 2017, the supplements submitted in response to the
SLC notification letter were approved with updated labeling that
included new language in the sections outlined above.

C. Citizen Petition Submission--December 2017

    A citizen petition (Petition) dated December 14, 2017 (Docket no.
FDA-2017-P-6918), was submitted to FDA by Kelly Caudle, MD, Director,
Clinical Pharmacogenetics Implementation Consortium, St. Jude
Children's Research Hospital, Memphis, TN, along with other clinical
pharmacologists (Petitioners) from around the country. The Petitioners
requested that, with the exception of the post-adenotonsillectomy
setting, the contraindication of codeine-containing analgesics be
amended to provide for use of these products in children under 12 years
of age who are known to be CYP2D6 normal metabolizers or intermediate
metabolizers based on adequate pharmacogenetic testing (i.e., capable
of measuring copy number or detect gene duplications). The Petitioners
suggest that the current contraindication may cause children under 12
years of age with recurrent acute pain to have decreased access to
opioid analgesics, which may result in more emergency department and
urgent care visits. According to the Petition, such decreased access
could occur because codeine/acetaminophen combination drug products are
CSA Schedule III (able to be prescribed by telephone) whereas other
opioid analgesics that would be suitable to treat a patient's pain are
Schedule II and cannot be prescribed by telephone.
    In FDA's view, if Petitioners' proposed labeling were adopted, a
CYP2D6 genotype/phenotype determination would be essential for the safe
and effective use of codeine drug products. Thus, under the Agency's
authorities governing prescription drug labeling, the approved labeling
of codeine-containing analgesics would also need to specify that, with
respect to use in children under 12 years of age, the products are
intended for use only subsequent to the necessary genotype/phenotype
determination using an appropriate, FDA-authorized companion diagnostic
device.\3\
---------------------------------------------------------------------------

    \3\ For more information about relevant law and policy regarding
companion diagnostics and the corresponding therapeutic products,
see FDA's guidance titled, In Vitro Companion Diagnostic Devices
(available at https://www.fda.gov/media/81309/download).
---------------------------------------------------------------------------

    FDA is aware of several available CYP2D6 genotype tests, each of
which assess different alleles of CYP2D6 and which may not uniformly
assess gene copy number. FDA is also aware that these tests have been
shown to vary in performance with respect to identifying the range of
genotype combinations. For example, most CYP2D6 tests, the wild type
(referred to as ``*1'') is typically a default result, i.e., no variant
is detected and therefore the allele is assigned as the wild type (*1).
FDA is concerned that, if a test does not have the ability to detect
rare genotype variants, then patients who have these rare variants
would be called wild type, and the wrong genotype result (potentially

normal metabolizer) could be given for those patients.
    Based on prescription dispensing data obtained from a proprietary
drug utilization database available to FDA, the Agency understands that
the number of patients ages 0 to 11 who were dispensed codeine-
containing analgesic products decreased from an estimated 735,000
patients in 2013 to 230,000 patients in 2017. Following the addition of
the contraindication of codeine-containing drug products in children
under 12 years of age to the codeine product labeling in August 2017,
FDA has seen the prescription use of codeine decline further to 84,000
patients ages 0 to less than 12 years of age in 2018.\4\
---------------------------------------------------------------------------

    \4\ Source: IQVIA Total Patient TrackerTM, 2013-2018.
Data extracted May 2018 and June 2019.
---------------------------------------------------------------------------

II. Additional Issues for Consideration and Request for Information

    FDA is soliciting information and comment from stakeholders
regarding the issues described in this document. In addition to any
other aspects of these issues that stakeholders may care to comment
upon, FDA is interested in answers to the following questions in
particular:

Topic 1: Pain Management in Children Under 12 Years of Age (for
Prescribers and Other Stakeholders, as Appropriate)

    1. What factors do you consider in choosing to prescribe an opioid
analgesic for children under 12 years of age who require treatment for
recurrent episodes of acute pain (e.g., severity of pain, lack of
response to other analgesics, or the specific disease, such as children
with sickle cell disease-related pain crises)?
    2. Which pediatric populations, other than children with sickle
cell disease, typically use an opioid analgesic for recurrent episodes
of acute pain?
    3. What role, if any, do you see for codeine/acetaminophen
combination drug products in the treatment of children under 12 years
of age with recurrent episodes of acute pain?
    4. What is your institution/department/clinical practice's
recommended approach (or specific formulary options) for selecting an
opioid analgesic for a child under 12 years of age? Was your
institution/department/clinical practice's current approach modified
following FDA's August 2017 codeine labeling revision that
contraindicated codeine-containing drug products in children under 12
years of age? If there is not a recommended approach, what opioid
analgesics are typically prescribed in your practice to patients under
12 years of age?
    5. In your view/experience, is the contraindication for use of
codeine/acetaminophen combination drug products in children under 12
years of age hampering optimal patient care?
    6. What are the issues you have faced regarding urgent access to
opioid analgesics (e.g., after hours, on weekends, and holidays) for a
child under 12 years of age with recurrent episodes of acute pain
requiring an opioid analgesic?
    a. For clinicians: If you have had to face these issues, how do
they impact prescribing decisions? For example, would you consider
giving a hard copy prescription for a small amount of opioid analgesic
to be used in urgent or after-hours situations so the patient can avoid
making a visit for urgent/emergency care?
    b. For caregivers/patient advocates: How have you handled these
issues?

Topic 2: CYP2D6 Genotyping Tests (for Prescribers and Technical
Experts)

    1. Would amending the contraindication to provide for CYP2D6
genotyping for children under 12 years of age prior to prescription of
codeine-containing drug products change your clinical practice?
    2. Have you utilized a CYP2D6 genotyping test when determining
which opioid analgesic to select for a child under 12 years of age who
has recurrent acute pain severe enough to warrant treatment with an
opioid analgesic? Describe why or why not.
    3. Describe your experience with interpreting CYP2D6 genotyping
test results and using those results to make drug prescribing
decisions.
    4. For a CYP2D6 genotyping test to appropriately identify patients
who can safely receive a codeine-containing drug product, what is the
minimum genotyping accuracy and minimum acceptable coverage of the
currently known genotypes that typically result in a poor metabolizer
or ultra-rapid metabolizer phenotype?
    5. Regarding detection of ultra-rapid metabolizers, what is the
type of test output that would be needed for copy number? Is a result
of ``duplication present'' (i.e., more than one copy) sufficient, or is
specific quantitation of the number of copies needed?

Topic 3: E-Prescribing Availability (for Prescribers)

    1. Is e-prescribing available in your institution/department/
clinical practice?
    2. What is your practice regarding e-prescribing of Schedule II
opioids? Are there any limitations in your institution/department/
clinical practice for e-prescribing of Schedule II opioids?
    3. Would you e-prescribe a Schedule II opioid based on a telephone
discussion with a child's caregiver? Would you e-prescribe any opioid
(including those in Schedule III and Schedule IV) based on a telephone
discussion with a child's caregiver? Describe why or why not.
    4. If you do not have e-prescribing available, how does that impact
your ability to prescribe Schedule II opioids for children under 12
years of age, particularly with recurrent acute pain episodes?

    Dated: June 24, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-13974 Filed 6-26-20; 8:45 am]
BILLING CODE 4164-01-P