Federal Register / Vol. 74, No. 45 / Tuesday, March 10, 2009 / Proposed Rules 10205 

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. 

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-methoxypropionamide] 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 nonnarcotics 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-methoxypropionamide, 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-benzyl3-methoxy-propionamide] for marketing 

under the trade name Vimpat® 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 

10206 Federal Register / Vol. 74, No. 45 / Tuesday, March 10, 2009 / Proposed Rules 

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 

§ 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 

§§ 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 §§ 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 

§§ 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 §§ 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 

§§ 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 

Federal Register / Vol. 74, No. 45 / Tuesday, March 10, 2009 / Proposed Rules 10207 

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, 

§ 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 §§ 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 § 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 foreignbased 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 § 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: 

§ 1308.15 Schedule V. 

* * * * * 

(e) * * * 

(1) Lacosamide [(R)-2-acetoamido-Nbenzyl-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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

45 CFR Part 88 

RIN 0991–AB49 

Rescission of the Regulation Entitled 

‘‘Ensuring That Department of Health 

and Human Services Funds Do Not 

Support Coercive or Discriminatory 

Policies or Practices in Violation of 

Federal Law’’; Proposal 

AGENCY: Office of the Secretary, HHS. 

ACTION: Proposed rule. 

SUMMARY: The Department of Health and 

Human Services proposes to rescind the 

December 19, 2008 final rule entitled 

‘‘Ensuring That Department of Health 

and Human Services Funds Do Not 

Support Coercive or Discriminatory 

Policies or Practices in Violation of 

Federal Law.’’ The Department believes 

it is important to have an opportunity to 

review this regulation to ensure its 

consistency with current 

Administration policy and to reevaluate 

the necessity for regulations 

implementing the Church Amendments, 

Section 245 of the Public Health Service 

Act, and the Weldon Amendment. 

DATES: Submit written or electronic 

comment on the regulatory changes 

proposed by this document by April 9, 

2009. 

ADDRESSES: In commenting, please refer 

to ‘‘Rescission Proposal.’’ To better 

manage the comment process, we will 

not accept comments by facsimile (FAX) 

transmission. 

You may submit comments in one of 

four ways (no duplicates, please): 

1. Electronically. You may submit 

electronic comments on this regulation 

to http://www.Regulations.gov or via email to proposedrescission@hhs.gov. To 

submit electronic comments to http:// 

www.Regulations.gov, go to the Web site 

and click on the link ‘‘Comment or 

Submission’’ and enter the keywords 

‘‘Rescission Proposal.’’ [Attachments 

should be in Microsoft Word, 

WordPerfect, or Excel; however, we 

prefer Microsoft Word.] 

2. By regular mail. You may mail 

written comments (one original and two 

copies) to the following address only: 

Office of Public Health and Science, 

Department of Health and Human 

Services, Attention: Rescission Proposal 

Comments, Hubert H. Humphrey 

Building, 200 Independence Avenue, 

SW., Room 716G, Washington, DC 

20201. 

3. By express or overnight mail. You 

may send written comments (one 

original and two copies) to the following 

address only: Office of Public Health 

and Science, Department of Health and 

Human Services, Attention: Rescission 

Proposal Comments, Hubert H. 

Humphrey Building, 200 Independence 

Avenue, SW., Room 716G, Washington, 

DC 20201. 

4. By hand or courier. If you prefer, 

you may deliver (by hand or courier) 

your written comments (one original 

and two copies) before the close of the 

comment period to the following 

address: Room 716G, Hubert H. 

Humphrey Building, 200 Independence 

Avenue, SW., Washington, DC 20201. 

(Because access to the interior of the 

Hubert H. Humphrey Building is not 

readily available to persons without 

federal government identification, 

commenters are encouraged to leave 

their comments in the mail drop slots 

located in the main lobby of the 

building. A stamp-in clock is available 

for persons wishing to retain proof of 

filing by stamping in and retaining an 

extra copy of the documents being 

filed.) 

Inspection of Public Comments: All 

comments received before the close of