[Federal Register Volume 74, Number 45 (Tuesday, March 10, 2009)]
[Proposed Rules]
[Pages 10205-10207]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-4890]



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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 
[email protected]. 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