[Federal Register: March 10, 2009 (Volume 74, Number 45)]
[Proposed Rules]
[Page 10205-10207]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr10mr09-20]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-325P]
Schedules of Controlled Substances: Placement of Lacosamide into
Schedule V
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: This proposed rule is issued by the Deputy Administrator of
the Drug Enforcement Administration (DEA) to place the substance
lacosamide [(R)-2-acetoamido-N-benzyl-3-methoxy-propionamide] and all
products containing lacosamide into Schedule V of the Controlled
Substances Act (CSA). This proposed action is based on a recommendation
from the Acting Assistant Secretary for Health of the Department of
Health and Human Services (DHHS) and on an evaluation of the relevant
data by DEA. If finalized as proposed, this action will impose the
regulatory controls and criminal sanctions applicable to Schedule V
non-narcotics on those who handle lacosamide and products containing
lacosamide.
DATES: Written comments must be postmarked, and electronic comments
must be sent, on or before April 9, 2009. Commenters should be aware
that the electronic Federal Docket Management System will not accept
comments after midnight Eastern time on the last day of the comment
period.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-325'' on all written and electronic correspondence.
Written comments being sent via regular or express mail should be sent
to the Drug Enforcement Administration, Attention: DEA Federal Register
Representative/ODL, 8701 Morrissette Drive, Springfield, VA 22152.
Comments may be sent to DEA by sending an electronic message to
dea.diversion.policy@usdoj.gov. Comments may also be sent
electronically through http://www.regulations.gov using the electronic
comment form provided on that site. An electronic copy of this document
is also available at the http://www.regulations.gov Web site. DEA will
accept electronic comments containing MS Word, WordPerfect, Adobe PDF,
or Excel file formats only. DEA will not accept any file format other
than those specifically listed here.
Please note that DEA is requesting that electronic comments be
submitted before midnight Eastern time on the day the comment period
closes because http://www.regulations.gov terminates the public's
ability to submit comments at midnight Eastern time on the day the
comment period closes. Commenters in time zones other than Eastern time
may want to consider this so that their electronic comments are
received. All comments sent via regular or express mail will be
considered timely if postmarked on the day the comment period closes.
FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief,
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug
Enforcement Administration, 8701 Morrissette Drive, Springfield, VA
22152 or by phone at (202) 307-7183.
SUPPLEMENTARY INFORMATION: Posting of Public Comments: Please note that
all comments received are considered part of the public record and made
available for public inspection online at http://www.regulations.gov
and in the Drug Enforcement Administration's public docket. Such
information includes personal identifying information (such as your
name, address, etc.) voluntarily submitted by the commenter.
If you want to submit personal identifying information (such as
your name, address, etc.) as part of your comment, but do not want it
to be posted online or made available in the public docket, you must
include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the first
paragraph of your comment. You must also place all the personal
identifying information you do not want posted online or made available
in the public docket in the first paragraph of your comment and
identify what information you want redacted.
If you want to submit confidential business information as part of
your comment, but do not want it to be posted online or made available
in the public docket, you must include the phrase ``CONFIDENTIAL
BUSINESS INFORMATION'' in the first paragraph of your comment. You must
also prominently identify confidential business information to be
redacted within the comment. If a comment has so much confidential
business information that it cannot be effectively redacted, all or
part of that comment may not be posted online or made available in the
public docket.
Personal identifying information and confidential business
information identified and located as set forth above will be redacted
and the comment, in redacted form, will be posted online and placed in
the DEA's public docket file. Please note that the Freedom of
Information Act applies to all comments received. If you wish to
inspect the agency's public docket file in person by appointment,
please see the FOR FURTHER INFORMATION CONTACT paragraph.
Note Regarding This Scheduling Action
In accordance with the provisions of the CSA (21 U.S.C. 811(a)),
this action is a formal rulemaking ``on the record after opportunity
for a hearing.'' Such proceedings are conducted pursuant to the
provisions of the Administrative Procedure Act (5 U.S.C. 556 and 557).
Interested persons are invited to submit their comments, objections or
requests for a hearing with regard to this proposal. Requests for a
hearing should be made in accordance with 21 CFR 1308.44 and should
state, with particularity, the issues concerning which the person
desires to be heard. All correspondence regarding this matter should be
submitted to the DEA using the address information provided above.
Background
Lacosamide, known chemically as (R)-2-acetoamido-N-benzyl-3-
methoxy-propionamide, is a central nervous system depressant drug with
a mechanism of action different from those of other central nervous
system depressants (e.g, benzodiazepines, barbiturates etc.) that are
controlled under the CSA. Unlike other depressant drugs
(benzodiazepines, barbiturates etc.), lacosamide does not act on the
gamma amino butyric acid (GABA) system and does not have biologically
significant affinity at numerous receptors, channels and transporters
that are associated with known drugs of abuse. Although the precise
mechanism of action of lacosamide remains undetermined, in vitro
studies suggest that it causes selective enhancement of slow
inactivation of voltage-gated sodium channels and binds to the
collapsing response mediator protein 2 (CRMP-2).
On October 28, 2008, the Food and Drug Administration (FDA)
approved lacosamide [(R)-2-acetoamido-N-benzyl-3-methoxy-propionamide]
for marketing under the trade name Vimpat[supreg] for use as an
adjunctive therapy in treatment of partial-onset seizures in patients
with epilepsy aged 17 years and older.
Animal studies have demonstrated that lacosamide protects against
seizures in various anticonvulsant models and produces antinociceptive
effects in preclinical neuropathic pain models. Animal studies also
indicate that
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lacosamide has abuse potential. Lacosamide produces dose dependent
sedative-type behaviors in rats. In drug discrimination tests, Schedule
IV drugs, alprazolam and phenobarbital, partially generalizes to
lacosamide in rats trained to recognize lacosamide.
Clinical studies also indicate that lacosamide has abuse potential.
In a clinical study with recreational abusers of sedative hypnotic
drugs, lacosamide, similar to alprazolam, produced subjective responses
of ``sedation,'' ``high,'' ``euphoria,'' ``drug liking,'' and ``good
drug effects'' similar to alprazolam. These effects of lacosamide were
shorter in duration as compared to those of alprazolam. In clinical
pharmacokinetic and electrocardiographic studies, healthy subjects
reported a high rate of euphoria-type responses following lacosamide
administration, suggesting its ability to produce psychological
dependence. The data from animal and human studies indicate that
chronic administration of lacosamide does not produce physical
dependence, as there were no withdrawal symptoms upon its
discontinuation.
Adverse events from clinical studies included cognitive disorder,
disturbance in attention, mood alteration, depressed mood,
irritability, feeling drunk, memory impairment, somnolence, and
dizziness. These and other data indicate that public health risks of
lacosamide are similar, but in a lower intensity and shorter duration,
to those of other sedative hypnotics and central nervous system
depressants, such as benzodiazepines.
Lacosamide is a new molecular entity and has not been marketed in
the United States. As such, there has been no evidence of diversion,
abuse, and law enforcement encounters involving lacosamide.
On December 2, 2008, the Assistant Secretary for Health of the DHHS
sent the Administrator of the DEA a scientific and medical evaluation
and a letter recommending that lacosamide be placed into Schedule V of
the CSA. Enclosed with the December 2, 2008 letter was a document
prepared by the FDA entitled, ``Basis for the Recommendation for
Control of Lacosamide in Schedule V of the Controlled Substances Act
(CSA).'' The document contained a review of the factors which the CSA
requires the Secretary to consider (21 U.S.C. 811(b)).
The factors considered by the Acting Assistant Secretary of Health
and DEA with respect to lacosamide were:
1. Its actual or relative potential for abuse;
2. Scientific evidence of its pharmacological effects;
3. The state of current scientific knowledge regarding the drug;
4. Its history and current pattern of abuse;
5. The scope, duration, and significance of abuse;
6. What, if any, risk there is to the public health;
7. Its psychic or physiological dependence liability; and
8. Whether the substance is an immediate precursor of a substance
already controlled under this subchapter. (21 U.S.C. 811(c))
Based on the recommendation of the Acting Assistant Secretary for
Health, DHHS, received in accordance with Sec. 201(b) of the Act (21
U.S.C. 811(b)), and the independent review of the available data by the
DEA, the Deputy Administrator of the DEA, pursuant to Sec. Sec. 201(a)
and 201(b) of the Act (21 U.S.C. 811(a) and 811(b)), finds that:
1. Lacosamide has a low potential for abuse relative to the drugs
or other substances in Schedule IV;
2. Lacosamide has a currently accepted medical use in treatment in
the United States; and
3. Abuse of lacosamide may lead to limited physical dependence or
psychological dependence relative to the drugs or other substances in
Schedule IV.
Based on these findings, the Deputy Administrator of the DEA
concludes that lacosamide and all products containing lacosamide,
warrant control in Schedule V of the CSA.
Interested persons are invited to submit their comments, objections
or requests for a hearing with regard to this proposal. Requests for a
hearing should state, with particularity, the issues concerning which
the person desires to be heard. All correspondence regarding this
matter should be submitted to the DEA using the address information
provided above. In the event that comments, objections, or requests for
a hearing raise one or more issues which the Deputy Administrator finds
warrant a hearing, the Deputy Administrator shall order a public
hearing by notice in the Federal Register, summarizing the issues to be
heard and setting the time for the hearing.
Requirements for Handling Lacosamide
If this rule is finalized as proposed, lacosamide and all products
containing lacosamide would be subject to the CSA and the Controlled
Substances Import and Export Act (CSIEA) regulatory controls and
administrative, civil and criminal sanctions applicable to the
manufacture, distribution, dispensing, importing, and exporting of a
Schedule V controlled substance, including the following:
Registration. Any person who manufactures, distributes, dispenses,
imports, exports, engages in research or conducts instructional
activities with lacosamide, or who desires to manufacture, distribute,
dispense, import, export, engage in instructional activities or conduct
research with lacosamide, would need to be registered to conduct such
activities in accordance with Part 1301 of Title 21 of the Code of
Federal Regulations (CFR).
Security. Lacosamide would be subject to Schedule III-V security
requirements and must be manufactured, distributed and stored in
accordance with Sec. Sec. 1301.71, 1301.72(b), (c), and (d), 1301.73,
1301.74, 1301.75(b) and (c), 1301.76, and 1301.77 of Title 21 of the
CFR.
Labeling and Packaging. All labels and labeling for commercial
containers of lacosamide which are distributed on or after finalization
of this rule would need to comply with requirements of Sec. Sec.
1302.03-1302.07 of Title 21 of the CFR.
Inventory. Every registrant required to keep records and who
possesses any quantity of lacosamide would be required to keep an
inventory of all stocks of lacosamide on hand pursuant to Sec. Sec.
1304.03, 1304.04 and 1304.11 of Title 21 of the CFR. Every registrant
who desires registration in Schedule V for lacosamide would be required
to conduct an inventory of all stocks of the substance on hand at the
time of registration.
Records. All registrants would be required to keep records pursuant
to Sec. Sec. 1304.03, 1304.04, 1304.21, 1304.22, and 1304.23 of Title
21 of the CFR.
Prescriptions. All prescriptions for lacosamide or prescriptions
for products containing lacosamide would be required to be issued
pursuant to 21 CFR 1306.03-1306.06 and 1306.21, 1306.23-1306.27.
Importation and Exportation. All importation and exportation of
lacosamide would need to be in compliance with part 1312 of Title 21 of
the CFR.
Criminal Liability. Any activity with lacosamide not authorized by,
or in violation of, the CSA or the CSIEA occurring on or after
finalization of this proposed rule would be unlawful.
Regulatory Certifications
Executive Order 12866
In accordance with the provisions of the CSA (21 U.S.C. 811(a)),
this action is a formal rulemaking ``on the record
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after opportunity for a hearing.'' Such proceedings are conducted
pursuant to the provisions of 5 U.S.C. 556 and 557 and, as such, are
exempt from review by the Office of Management and Budget pursuant to
Executive Order 12866, Sec. 3(d)(1).
Regulatory Flexibility Act
The Deputy Administrator, in accordance with the Regulatory
Flexibility Act (5 U.S.C. 601-612), has reviewed this proposed rule and
by approving it certifies that it will not have a significant economic
impact on a substantial number of small entities. Lacosamide products
will be prescription drugs used for the treatment of partial-onset
seizures. Handlers of lacosamide often handle other controlled
substances used in the treatment of central nervous system disorders
which are already subject to the regulatory requirements of the CSA.
Executive Order 12988
This regulation meets the applicable standards set forth in
Sec. Sec. 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice
Reform.
Executive Order 13132
This rulemaking does not preempt or modify any provision of state
law; nor does it impose enforcement responsibilities on any state; nor
does it diminish the power of any state to enforce its own laws.
Accordingly, this rulemaking does not have federalism implications
warranting the application of Executive Order 13132.
Unfunded Mandates Reform Act of 1995
This rule will not result in the expenditure by state, local, and
tribal governments, in the aggregate, or by the private sector, of
$120,000,000 or more (adjusted for inflation) in any one year, and will
not significantly or uniquely affect small governments. Therefore, no
actions were deemed necessary under provisions of the Unfunded Mandates
Reform Act of 1995.
Congressional Review Act
This rule is not a major rule as defined by Sec. 804 of the Small
Business Regulatory Enforcement Fairness Act of 1996 (Congressional
Review Act). 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:
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.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Narcotics, Prescription drugs.
Under the authority vested in the Attorney General by Sec. 201(a)
of the CSA (21 U.S.C. 811(a)), and delegated to the Administrator of
DEA by Department of Justice regulations (28 CFR 0.100), and
redelegated to the Deputy Administrator pursuant to 28 CFR 0.104, the
Deputy Administrator hereby proposes that 21 CFR part 1308 be amended
as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
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.
2. Section 1308.15 is amended by revising paragraph (e)(1) adding a
new paragraph (e)(2) to read as follows:
Sec. 1308.15 Schedule V.
* * * * *
(e) * * *
(1) Lacosamide [(R)-2-acetoamido-N-benzyl-3-methoxy-propionamide]--
2746
(2) Pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid]--2782
Dated: February 26, 2009.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E9-4890 Filed 3-9-09; 8:45 am]
BILLING CODE 4410-09-P