[Federal Register Volume 78, Number 231 (Monday, December 2, 2013)]
[Rules and Regulations]
[Pages 72013-72016]
From the Federal Register Online via the Government Printing 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