[Federal Register Volume 70, Number 92 (Friday, May 13, 2005)]
[Proposed Rules]
[Pages 25502-25505]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-9634]


-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-267P]


Schedules of Controlled Substances: Placement of Pregabalin into 
Schedule V

AGENCY: Drug Enforcement Administration, Department of Justice.

[[Page 25503]]


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 
pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid], including its 
salts, and all products containing pregabalin 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, this action will impose the 
regulatory controls and criminal sanctions applicable to Schedule V 
non-narcotics on those who handle pregabalin and products containing 
pregabalin.

DATES: Written comments must be postmarked, and electronic comments 
must be sent, on or before June 13, 2005.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-267P'' on all written and electronic correspondence. 
Written comments being sent via regular mail should be sent to the 
Deputy Administrator, Drug Enforcement Administration, Washington, DC 
20537, Attention: DEA Federal Register Representative/ODL. Written 
comments sent via express mail should be sent to the Deputy 
Administrator, Drug Enforcement Administration, Attention: DEA Federal 
Register Representative/ODL, 2401 Jefferson-Davis Highway, Alexandria, 
VA 22301. Comments may be directly sent to DEA electronically 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.

FOR FURTHER INFORMATION CONTACT: Christine Sannerud, Ph.D., Chief, Drug 
and Chemical Evaluation Section, Drug Enforcement Administration, 
Washington, DC 20537, (202) 307-7183.

SUPPLEMENTARY INFORMATION:

Note Regarding This Scheduling Action

    In accordance with the provisions of the Controlled Substances Act 
(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 Drug Enforcement Administration using 
the address information provided above.

Background

    On December 31, 2004, the Food and Drug Administration (FDA) 
approved pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] for 
marketing under the trade name LyricaTM. LyricaTM 
will be marketed in the United States as a prescription drug product 
for the management of neuropathic pain associated with diabetic 
peripheral neuropathy (DPN) and postherpetic neuralgia (PHN). 
Pregabalin has recently been placed on the market in some European 
countries for the treatment of epilepsy and neuropathic pain.
    Unlike morphine-type analgesics, pregabalin does not produce 
analgesia through binding at opioid receptors. While pregabalin is an 
analog of gamma-aminobutyric acid (GABA), a major inhibitory 
neurotransmitter in the brain, it does not bind at GABA or 
benzodiazepine receptors nor alter GABA concentrations in the brain. 
Pregabalin does bind with high affinity to the alpha 2-delta receptor 
site (a subunit of voltage-gated calcium channels) in the central 
nervous system. The binding of pregabalin at this site is thought to be 
responsible for its therapeutic effect on neuropathic pain.
    Pregabalin has been shown to produce effects that are similar to 
other controlled substances. In a study with recreational users of 
sedative/hypnotic drugs, a 450 mg dose of pregabalin resulted in 
subjective ratings of ``good drug effect,'' ``high,'' and ``liking'' 
similar to 30 mg of diazepam. In clinical studies, pregabalin showed an 
adverse event profile similar to other central nervous system 
depressants. Some of these effects included dizziness, somnolence, 
ataxia, and confusion. Following abrupt or rapid discontinuation of 
pregabalin, some patients reported symptoms suggestive of physical 
dependence. The FDA determined that the dependence profile of 
pregabalin, as measured by a patient physical withdrawal checklist, was 
quantitatively less than benzodiazepines in schedule IV of the CSA.
    On April 4, 2005, the Acting Assistant Secretary for Health of the 
DHHS sent the Administrator of the DEA a scientific and medical 
evaluation and a letter recommending that pregabalin be placed into 
Schedule V of the CSA. Enclosed with the April 4, 2005, letter was a 
document prepared by the FDA entitled, ``Basis for the Recommendation 
for Control of Pregabalin 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 pregabalin 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, received in accordance with section 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 sections 201(a) 
and 201(b) of the Act (21 U.S.C. 811(a) and 811(b)), finds that:
    (1) Based on information now available, pregabalin has a low 
potential for abuse relative to the drugs or other substances in 
Schedule IV;
    (2) Pregabalin has a currently accepted medical use in treatment in 
the United States; and
    (3) Abuse of pregabalin may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
Schedule IV. (21 U.S.C. 812(b)(5))
    Based on these findings, the Deputy Administrator of the DEA 
concludes that pregabalin, including its salts, and all products 
containing pregabalin, 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

[[Page 25504]]

be heard. All correspondence regarding this matter should be submitted 
to the Drug Enforcement Administration 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 Pregabalin

    If this rule is finalized as proposed, pregabalin and all products 
containing pregabalin would be subject to the Controlled Substances Act 
and the Controlled Substances Import and Export Act 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 pregabalin, or who desires to manufacture, distribute, 
dispense, import, export, engage in instructional activities or conduct 
research with pregabalin, would need to be registered to conduct such 
activities in accordance with Part 1301 of Title 21 of the Code of 
Federal Regulations.
    Security. Pregabalin 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 
Code of Federal Regulations.
    Labeling and Packaging. All labels and labeling for commercial 
containers of pregabalin 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 Code of Federal Regulations.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of pregabalin would be required to keep an 
inventory of all stocks of pregabalin on hand pursuant to Sec. Sec.  
1304.03, 1304.04 and 1304.11 of Title 21 of the Code of Federal 
Regulations. Every registrant who desires registration in Schedule V 
for pregabalin 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 Code of Federal Regulations.
    Prescriptions. All prescriptions for pregabalin or prescriptions 
for products containing pregabalin 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 
pregabalin would need to be in compliance with part 1312 of Title 21 of 
the Code of Federal Regulations.
    Criminal Liability. Any activity with pregabalin not authorized by, 
or in violation of, the Controlled Substances Act or the Controlled 
Substances Import and Export Act 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 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, section 3(d)(1).

Regulatory Flexibility Act

    The Deputy Administrator, in accordance with the Regulatory 
Flexibility Act (5 U.S.C. 605(b)), 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. Pregabalin products 
will be prescription drugs used for the treatment of neuropathic pain. 
Handlers of pregabalin often handle other controlled substances used to 
treat pain which are already subject to the regulatory requirements of 
the CSA.

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.

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 
$115,000,000 or more 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.

Small Business Regulatory Enforcement Fairness Act of 1996

    This rule is not a major rule as defined by Sec.  804 of the Small 
Business Regulatory Enforcement Fairness Act of 1996. 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 section 
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 [AMENDED]

    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 proposed to be amended by adding a new 
paragraph (e) to read as follows:


Sec.  1308.15  Schedule V.

* * * * *
    (e) Depressants. Unless specifically exempted or excluded or unless 
listed in another schedule, any material, compound, mixture, or 
preparation which contains any quantity of the following substances 
having a depressant effect on the central nervous system, including its 
salts:
    (1) Pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid]--2782
    (2) [Reserved]


[[Page 25505]]


    Dated: May 6, 2005.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. 05-9634 Filed 5-12-05; 8:45 am]
BILLING CODE 4410-09-P