[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]
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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.
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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]
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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