[Federal Register Volume 78, Number 231 (Monday, December 2, 2013)]
[Rules and Regulations]
[Pages 72013-72016]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-28778]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-374]
Schedules of Controlled Substances: Placement of Perampanel into
Schedule III
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
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SUMMARY: With the issuance of this final rule, the Deputy Administrator
of the Drug Enforcement Administration (DEA) places the substance
perampanel [2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)
benzonitrile], including its salts, isomers, and salts of isomers, into
schedule III of the Controlled Substances Act (CSA). This scheduling
action is pursuant to the CSA which requires that such actions be made
on the record after opportunity for a hearing through formal
rulemaking. This action imposes the regulatory controls and
administrative, civil, and criminal sanctions applicable to schedule
III controlled substances on persons who handle (manufacture,
distribute, dispense, import, export, engage in research, conduct
instructional activities with, or possess) or propose to handle
perampanel.
DATES: Effective Date: January 2, 2014.
FOR FURTHER INFORMATION CONTACT: Ruth A. Carter, Chief, Policy
Evaluation and Analysis Section, Office of Diversion Control, Drug
Enforcement Administration; Mailing Address: 8701 Morrissette Drive,
Springfield, Virginia 22152; Telephone: (202) 598-6812.
SUPPLEMENTARY INFORMATION:
Legal Authority
The DEA implements and enforces titles II and III of the
Comprehensive Drug Abuse Prevention and Control Act of 1970, as
amended. Titles II and III are referred to as the ``Controlled
Substances Act'' and the ``Controlled Substances Import and Export
Act,'' respectively, but they are collectively referred to as the
``Controlled Substances Act'' or the ``CSA'' for the purposes of this
action. 21 U.S.C. 801-971. The DEA publishes the implementing
regulations for these statutes in title 21 of the Code of Federal
Regulations (CFR) parts 1300 to 1321. The CSA and its implementing
regulations are designed to prevent, detect, and eliminate the
diversion of controlled substances and listed chemicals into the
illicit market while providing for the legitimate medical, scientific,
research, and industrial needs of the United States. Controlled
substances have the potential for abuse and dependence and are
controlled to protect the public health and safety.
Under the CSA, controlled substances are classified in one of five
schedules based upon their potential for abuse, their currently
accepted medical use, and the degree of dependence the substance may
cause. 21 U.S.C. 812. The initial schedules of controlled substances
established by Congress are found at 21 U.S.C. 812(c) and the current
list of scheduled substances is published at 21 CFR part 1308.
Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule,
``add to such a schedule or transfer between such schedules any drug or
other substance if he (A) finds that such drug or other substance has a
potential for abuse, and (B) makes with respect to such drug or other
substance the findings prescribed by [21 U.S.C. 812(b)] for the
schedule in which such drug is to be placed. . . .'' Pursuant to 28 CFR
0.100(b), the Attorney General has delegated this scheduling authority
to the Administrator of the DEA, who has further delegated this
authority to the Deputy Administrator of the DEA. 28 CFR 0.104.
The CSA provides that scheduling of any drug or other substance may
be initiated by the Attorney General (1) on his own motion; (2) at the
request of the Secretary of the Department of Health and Human Services
(HHS),\1\ or (3) on the petition of any interested party. 21 U.S.C.
811(a). This action is based on a recommendation from the Assistant
Secretary of the HHS and on an evaluation of all other relevant data by
the DEA. This action imposes the regulatory controls and
administrative, civil, and criminal sanctions applicable to schedule
III controlled substances on persons who handle or propose to handle
perampanel.
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\1\ As set forth in a memorandum of understanding entered into
by the HHS, the Food and Drug Administration (FDA), and the National
Institute on Drug Abuse (NIDA), the FDA acts as the lead agency
within the HHS in carrying out the Secretary's scheduling
responsibilities under the CSA, with the concurrence of NIDA. 50 FR
9518, Mar. 8, 1995. In addition, because the Secretary of the HHS
has delegated to the Assistant Secretary for Health of the HHS the
authority to make domestic drug scheduling recommendations, for
purposes of this document, all subsequent references to
``Secretary'' have been replaced with ``Assistant Secretary.''
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Background
Perampanel [2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-
yl) benzonitrile] is a new chemical entity with central nervous system
(CNS)
[[Page 72014]]
depressant and hallucinogenic properties. On October 22, 2012, the Food
and Drug Administration (FDA) approved a new drug application for
perampanel as an adjunctive therapy for the treatment of partial-onset
seizures with or without secondarily generalized seizures in patients
with epilepsy aged 12 years and older. Perampanel will be marketed in
the United States under the trade name FYCOMPA[supreg]. Perampanel is a
non-competitive AMPA ([alpha]-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid)-type glutamate receptor antagonist. Perampanel
was approved in Europe in May 2012 and has been marketed there since
July 2012.
HHS and DEA Eight-Factor Analyses
On January 22, 2013, the Assistant Secretary of the HHS provided to
the DEA a scientific and medical evaluation and scheduling
recommendation entitled ``Basis for the Recommendation for Control of
Perampanel and its Salts in Schedule III of the Controlled Substances
Act.'' Following consideration of the eight factors and findings
related to the substance's abuse potential, legitimate medical use, and
dependence liability, the Assistant Secretary of the HHS recommended
that perampanel be controlled in schedule III of the CSA under 21
U.S.C. 812(b). In response, the DEA conducted its own eight-factor
analysis of perampanel pursuant to 21 U.S.C. 811(c). Electronic copies
of these documents are available at www.regulations.gov for easy
reference.
Determination to Schedule Perampanel
After a review of the available data, including the scientific and
medical evaluation and the scheduling recommendation from the HHS, the
Deputy Administrator of the DEA published in the Federal Register a
notice of proposed rulemaking (NPRM) entitled ``Schedules of Controlled
Substances: Placement of Perampanel into Schedule III'' on October 22,
2013 (78 FR 62500), which proposed placement of perampanel in schedule
III of the CSA. The NPRM provided an opportunity for interested persons
to file a request for hearing in accordance with DEA regulations on or
before November 21, 2013. No requests for such a hearing were received
by the DEA. The NPRM also provided an opportunity for interested
persons to submit written comments on the proposed rule on or before
November 21, 2013.
Comments Received
The DEA received two comments on the proposed rule to schedule
perampanel. One commenter was in favor of controlling perampanel as a
schedule III controlled substance. Another commenter requested that the
DEA make the rule effective on the same date as the publication of the
final rule.
Support for the Proposed Rule: One commenter supported controlling
perampanel as a schedule III controlled substance, as opposed to a
schedule II controlled substance, but expressed concern about the
unknown effects and abuse potential of this new drug at higher doses.
However, the commenter indicated that the controls applicable to
schedule III controlled substances are appropriate until there is more
available data on perampanel's effects.
DEA Response: The DEA appreciates the comment in support of this
rulemaking.
Request to Change Effective Date: One commenter requested that the
DEA make this rule effective on the same date as publication to enable
physicians and their patients to have access to perampanel as soon as
possible and pointed out that the DEA has included an earlier effective
date in the final rule for other drugs including zopiclone, pregablin,
and ezogabine.
DEA Response: The DEA appreciates the commenter's request, but does
not believe an earlier effective date is warranted. As provided in 21
CFR 1308.45, final orders shall not have an effective date of ``less
than 30 days from the date of publication in the Federal Register
unless the Administrator finds that the conditions of public health or
safety necessitate an earlier effective date . . . .'' The
Administrator finds that the conditions of public health or safety do
not necessitate such an earlier effective date in this instance. There
are other anti-seizure medications currently available, specifically
lacosamide, an anti-epileptic medication that has a similar clinical
indication to perampanel. Though the mechanisms of actions of
perampanel and lacosamide are different, the indications are very
similar. Like perampanel, lacosamide is indicated as an adjunctive
therapy for the treatment of partial-onset seizures, and did not have
its 30-day implementation period waived. Furthermore, the DEA believes
that providing 30 days for this Final Rule to become effective is
expeditious and sufficient to allow handlers to obtain the appropriate
registration with the DEA and to comply with regulatory requirements
for handling schedule III controlled substances.
Scheduling Conclusion
Based on consideration of all comments, the scientific and medical
evaluation and accompanying recommendation of the HHS, and based on the
DEA's consideration of its own eight-factor analysis, the DEA finds
that these facts and all relevant data constitute substantial evidence
of potential for abuse of perampanel. As such, the DEA is scheduling
perampanel as a controlled substance under the CSA.
Determination of Appropriate Schedule
The CSA establishes five schedules of controlled substances known
as schedules I, II, III, IV, and V. The statute outlines the findings
required for placing a drug or other substance in any particular
schedule. 21 U.S.C. 812(b). After consideration of the analysis and
recommendation of the Assistant Secretary for Health of the HHS and
review of all available data, the Deputy Administrator of the DEA,
pursuant to 21 U.S.C. 812(b)(3), finds that:
1. Perampanel has a potential for abuse less than the drugs or
other substances in schedules I and II;
2. Perampanel has a currently accepted medical use in treatment in
the United States. Perampanel was approved for marketing by the FDA as
an adjunctive treatment of partial-onset seizures with or without
secondarily generalized seizures in patients with epilepsy aged 12
years and older; and
3. Abuse of perampanel may lead to moderate or low physical
dependence or high psychological dependence.
Based on these findings, the Deputy Administrator of the DEA
concludes that perampanel, including its salts, isomers, and salts of
isomers, warrants control in schedule III of the CSA. 21 U.S.C.
812(b)(3).
Requirements for Handling Perampanel
Upon the effective date of this final rule, any person who handles
perampanel is subject to the CSA's schedule III regulatory controls and
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, dispensing, importing, exporting, engagement
of research, and conduct of instructional activities, of schedule III
controlled substances including the following:
Registration. Any person who handles (manufactures, distributes,
dispenses, imports, exports, engages in research, or conducts
instructional activities with) perampanel, or who desires to handle
perampanel, must be registered with the DEA to conduct such activities,
pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21
CFR parts 1301 and 1312 as of January 2, 2014. Any person who is
currently engaged in any of the above activities and is not registered
with the DEA must
[[Page 72015]]
submit an application for registration and may not continue their
activities as of January 2, 2014 unless the DEA has approved that
application, pursuant to 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312.
Security. Perampanel is subject to schedule III-V security
requirements and must be handled and stored in accordance with 21 CFR
1301.71-1301.93, pursuant to 21 U.S.C. 823, 821, 871(b) as of January
2, 2014.
Labeling and Packaging. All labels and labeling for commercial
containers of perampanel must be in accordance with 21 CFR 1302.03-
1302.07, pursuant to 21 U.S.C. 825, 958(e) as of January 2, 2014.
Inventory. Every DEA registrant who possesses any quantity of
perampanel on the effective date of this final rule is required to take
an inventory of all stocks of perampanel on hand as of January 2, 2014,
pursuant to 21 U.S.C. 827, 958(e), and in accordance with 21 CFR
1304.03, 1304.04, and 1304.11(a) and (d). Any person who becomes
registered with the DEA after January 2, 2014 is required to take an
initial inventory of all controlled substances (including perampanel)
on hand at the time of registration, pursuant to 21 U.S.C. 827, 958(e)
and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a) and (b).
After the initial inventory, every DEA registrant is required to take a
biennial inventory of all controlled substances (including perampanel),
on hand pursuant to 21 U.S.C. 827, 958(e) and in accordance with 21 CFR
1304.03, 1304.04 and 1304.11.
Records. All DEA registrants must keep records with respect to
perampanel pursuant to 21 U.S.C. 827, 958(e) and in accordance with 21
CFR parts 1304, 1307, and 1312, as of January 2, 2014.
Prescriptions. All prescriptions for perampanel or prescriptions
for products containing perampanel must comply with 21 U.S.C. 829 and
must be issued in accordance with 21 CFR part 1306 as of January 2,
2014.
Importation and Exportation. All importation and exportation of
perampanel must be done in accordance with 21 CFR part 1312, pursuant
to 21 U.S.C. 952, 953, 957, and 958 as of January 2, 2014.
Criminal Liability. Any activity involving perampanel not
authorized by, or in violation of, the CSA, occurring as of January 2,
2014 is unlawful, and may subject the person to administrative, civil,
and/or criminal sanctions.
Regulatory Analyses
Executive Orders 12866 and 13563
In accordance with 21 U.S.C. 811(a), this scheduling action is
subject to formal rulemaking procedures performed ``on the record after
opportunity for a hearing,'' which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the procedures
and criteria for scheduling a drug or other substance. Such actions are
exempt from review by the Office of Management and Budget (OMB)
pursuant to section 3(d)(1) of Executive Order 12866 and the principles
reaffirmed in Executive Order 13563.
Executive Order 12988
This regulation meets the applicable standards set forth in
sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice Reform
to eliminate drafting errors and ambiguity, minimize litigation,
provide a clear legal standard for affected conduct, and promote
simplification and burden reduction.
Executive Order 13132
This rulemaking does not have federalism implications warranting
the application of Executive Order 13132. The rule does not have
substantial direct effects on the States, on the relationship between
the national government and the States, or the distribution of power
and responsibilities among the various levels of government.
Executive Order 13175
This rule does not have tribal implications warranting the
application of Executive Order 13175. It does not have substantial
direct effects on one or more Indian tribes, on the relationship
between the Federal Government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
Government and Indian tribes.
Regulatory Flexibility Act
The Deputy Administrator, in accordance with the Regulatory
Flexibility Act (RFA) (5 U.S.C. 601-612), has reviewed this rule and by
approving it certifies that it will not have a significant economic
impact on a substantial number of small entities. The purpose of this
rule is to place perampanel, including its salts, isomers, and salts of
isomers, into schedule III of the CSA. No less restrictive measures
(i.e., non-control or control in a lower schedule) enable the DEA to
meet its statutory obligations under the CSA. In preparing this
certification, the DEA has assessed economic impact by size category
and has considered costs with respect to the various DEA registrant
business activity classes.
Perampanel is a new molecular entity, approved by the FDA on
October 22, 2012. It was approved in Europe in May 2012, and has been
marketed in Europe since July 2012. According to publically available
information reviewed by the DEA, perampanel is currently anticipated to
enjoy patent protection for at least a decade before generic
equivalents may be manufactured and marketed. Accordingly, the number
of currently identifiable manufacturers, importers, and distributors
for perampanel is extremely small. The publically available materials
also specify the readily identifiable persons subject to direct
regulation by this final rule. Based on guidelines utilized by the
Small Business Administration (SBA), the perampanel manufacturer/
distributor/importer was determined not to be a small entity. Once
generic equivalents are developed and approved for manufacturing and
marketing, there may be additional manufacturers, importers, and
distributors of perampanel, but whether they may qualify as small
entities cannot be determined at this time.
There are approximately 1.5 million controlled substance
registrants, who represent approximately 381,000 entities. The DEA
estimates that 371,000 (97 percent) of these businesses are considered
``small entities'' in accordance with the RFA and SBA standards. 5
U.S.C. 601(6) and 15 U.S.C. 632. Due to the wide variety of
unidentifiable and unquantifiable variables that could potentially
influence the dispensing rates of new chemical entities, the DEA is
unable to determine the number of small entities that might dispense
(including administer and prescribe) perampanel (e.g., pharmacies and
prescribers).
Despite the fact that the number of small businesses potentially
impacted by this final rule could not be determined at this time, the
DEA concludes that they would not experience a significant economic
impact as a result of this rule. The DEA estimates all anticipated
perampanel handlers to be DEA registrants and currently 98 percent of
DEA registrants (most of which are small businesses) are authorized to
handle schedule III controlled substances. Even if we assume that all
of the DEA registrants were to dispense perampanel, (e.g.,
practitioners prescribe, administer, or dispense the substance, and
pharmacies dispense the prescriptions), the costs that they would incur
as a result of perampanel scheduling would be
[[Page 72016]]
minimal. Registrants that dispense (but not prescribe) would incur
nominal additional security, inventory, recordkeeping, and labeling
costs, as they have already established and implemented the required
systems and processes to handle schedule III controlled substances. For
example, pharmacies and institutional practitioners may disperse
schedule II-V controlled substances throughout their stock of non-
controlled substances in such a manner as to obstruct theft or
diversion of the controlled substances. The inclusion of one additional
substance to this system would result in little or no additional burden
to such practitioners. In addition, because DEA-registered dispensers
must label all schedule II-V controlled substances dispensed, the
requirement to label all controlled substances containing perampanel
would not impose a significant economic burden upon DEA-registered
dispensers (as the infrastructure and materials for doing so would
already be in place). Accordingly, compliance would not require
significant manpower, capital investments, or recordkeeping burdens.
Registrants who only prescribe perampanel by oral or written
prescription would not incur any additional security, inventory,
recordkeeping, or labeling costs as a result of this rule, as they
would not physically handle perampanel.
Because of these facts, this rule will not result in significant
economic impact on a substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995
(2 U.S.C. 1501 et seq.), on the basis of information contained in the
``Regulatory Flexibility Act'' section above, the DEA has determined
and certifies pursuant to UMRA that this action would not result in any
Federal mandate that may result ``in the expenditure by State, local,
and tribal governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted for inflation) in any one year . . . .''
Therefore, neither a Small Government Agency Plan nor any other action
is required under provisions of UMRA of 1995.
Paperwork Reduction Act of 1995
This action does not impose a new collection of information
requirement under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3521). This action would not impose recordkeeping or reporting
requirements on State or local governments, individuals, businesses, or
organizations. An agency may not conduct or sponsor, and a person is
not required to respond to, a collection of information unless it
displays a currently valid OMB control number.
Congressional Review Act
This rule is not a major rule as defined by section 804 of the
Small Business Regulatory Enforcement Fairness Act of 1996
(Congressional Review Act (CRA)). This rule will not result in: an
annual effect on the economy of $100,000,000 or more; a major increase
in costs or prices for consumers, individual industries, Federal,
State, or local government agencies, or geographic regions; or
significant adverse effects on competition, employment, investment,
productivity, innovation, or on the ability of United States-based
companies to compete with foreign based companies in domestic and
export markets. However, pursuant to the CRA, the DEA has submitted a
copy of this final rule to both Houses of Congress and to the
Comptroller General.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, 21 CFR part 1308 is amended as
follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for 21 CFR part 1308 continues to read as
follows:
Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.
0
2. Amend Sec. 1308.13 by redesignating paragraphs (c)(11) through
(c)(14) as paragraphs (c)(12) through (c)(15) and adding new paragraph
(c)(11) to read as follows:
Sec. 1308.13 Schedule III.
* * * * *
(c) * * *
(11) Perampanel, and its salts, isomers, and salts of isomers.. 2261
* * * * *
Dated: November 25, 2013.
Thomas M. Harrigan,
Deputy Administrator.
[FR Doc. 2013-28778 Filed 11-29-13; 8:45 am]
BILLING CODE 4410-09-P