[Federal Register Volume 70, Number 144 (Thursday, July 28, 2005)]
[Rules and Regulations]
[Pages 43633-43635]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-15036]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-267F]
21 CFR Part 1308
Schedules of Controlled Substances: Placement of Pregabalin Into
Schedule V
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
-----------------------------------------------------------------------
[[Page 43634]]
SUMMARY: This final 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). As a result of this rule, the regulatory controls
and criminal sanctions of Schedule V will be applicable to the
manufacture, distribution, dispensing, importation and exportation of
pregabalin and products containing pregabalin.
DATES: This rule is effective July 28, 2005.
FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief,
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug
Enforcement Administration, Washington, DC 20537, telephone (202) 307-
7183.
SUPPLEMENTARY INFORMATION:
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.
On April 4, 2005, the Acting Assistant Secretary for Health of the
Department of Health and Human Services (DHHS), sent the Administrator
of the DEA a letter recommending that pregabalin, and its salts, 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)).
Based on the recommendation of the Acting Assistant Secretary for
Health and an independent review of the available data by the DEA, the
Deputy Administrator of the DEA, in a May 13, 2005, Federal Register
Notice of Proposed Rulemaking (70 FR 25502), proposed placement of
pregabalin into Schedule V of the CSA. The proposed rule provided an
opportunity for all interested persons to submit their comments,
objections or requests for hearing to be received by the DEA on or
before June 13, 2005.
Comments Received
The DEA received two comments in response to the Notice of Proposed
Rulemaking. One commenter stated that the DEA should not minimize the
similarity in effects produced by pregabalin and diazepam and should
place pregabalin in Schedule IV of the CSA.
The DEA does not agree. Careful consideration of all the available
data suggests that pregabalin has less abuse potential than Schedule IV
substances. Pregabalin does not substitute for benzodiazepines in
benzodiazepine-dependent animals. Data from clinical trials suggest
that some of pregabalin's positive psychic effects are limited and do
not continue with time or continued drug use. The data are consistent
with a substance that could be abused intermittently for reward, but
not for reinforcement. In addition, withdrawal effects of pregabalin
are less severe than with other substances currently controlled in
Schedule IV.
Another commenter stated that, in their experience with pregabalin
in clinical trials, pregabalin does not demonstrate any risk that would
merit being considered a scheduled drug.
The DEA does not agree. Preclinical studies indicated that
pregabalin is transiently and sporadically self-administered at rates
greater than vehicle but substantially lower than active comparators
pentobarbital (CII) and methohexital (CIV). In clinical trials,
pregabalin produces some pharmacological effects characteristic of
diazepam and alprazolam and is likely to be abused for its positive
psychic effects. The percentage of individuals that experienced acute
euphoric effects was unusually high for pregabalin in clinical trials.
Pregabalin also produced dizziness, somnolence, dry mouth, edema,
blurred vision, weight gain and attentional problems more frequently
than placebo. These data suggest that pregabalin does have sufficient
abuse potential to warrant control under the CSA. The DHHS recommended
control in Schedule V of the CSA and the DEA concurs.
Scheduling of Pregabalin
Relying on the scientific and medical evaluation and 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, and after a
review of the comments received in response to the Notice of Proposed
Rulemaking, 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) 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.
In order to make pregabalin pharmaceutical products available for
medical use as soon as possible, the Schedule V controls for pregabalin
will be effective July 28, 2005. In the event that the regulations
impose special hardships on the registrants, the DEA will entertain any
justified request for an extension of time to comply with the Schedule
V regulations regarding pregabalin. The applicable regulations are as
follows:
Registration. Any person who manufactures, distributes, dispenses,
imports, exports, conducts research or instructional activities or
chemical analysis or proposes to engage in such activities with
pregabalin, must submit an application for Schedule V registration in
accordance with part 1301 of Title 21 of the Code of Federal
Regulations. Any person who is currently engaged in any of the above
activities and is not registered with DEA must submit an application
for registration on or before August 29, 2005, and may continue their
activities until the DEA has approved or denied that application.
Security. Pregabalin is 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 on and after July 28, 2005.
Labeling and Packaging. All labels and labeling for commercial
containers of pregabalin shall 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 must keep an inventory of all
stocks of pregabalin on
[[Page 43635]]
hand pursuant to Sec. Sec. 1304.03, 1304.04 and 1304.11 of Title 21 of
the Code of Federal Regulations on and after July 28, 2005. Every
registrant who desires registration in Schedule V for pregabalin is
required to conduct an inventory of all stocks of the substance on hand
at the time of registration.
Records. All registrants must 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 on and after July 28, 2005.
Prescriptions. All prescriptions for pregabalin or prescriptions
for products containing pregabalin must 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 must be in compliance with part 1312 of Title 21 of the Code
of Federal Regulations on and after July 28, 2005.
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 and after July 28, 2005,
shall be unlawful.
Regulatory Certifications
Administrative Procedure Act
The Administrative Procedure Act permits an agency to make a rule
effective upon the date of publication when the agency finds good cause
exists and publishes its findings with the rule (5 U.S.C. 553(d)(3)).
As noted previously, on December 31, 2004, the FDA approved pregabalin
[(S)-3-(aminomethyl)-5-methylhexanoic acid] for marketing under the
trade name Lyrica. 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 scheduling recommendation that pregabalin, and
its salts, be placed in Schedule V of the CSA. Since this is a new drug
not previously available in the United States and the first drug
product specifically approved for the treatment of neuropathic pain
associated with diabetic peripheral neuropathy (DPN) and postherpetic
neuralgia (PHN), in order to prevent harm to the public health and
safety by delaying the availability of this new drug, the DEA finds
good cause to make this Final Rule effective immediately upon
publication.
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 final 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.
Pregabalin is a new drug in the United States; recent approval of
LyricaTM by the FDA will allow it to be marketed once it is
placed into Schedule V of the CSA. This final rule will allow medical
access to a new pharmaceutical product.
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.
0
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 amends 21 CFR part 1308 as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES [AMENDED]
0
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.
0
2. Section 1308.15 is 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]
Dated: July 22, 2005.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. 05-15036 Filed 7-27-05; 8:45 am]
BILLING CODE 4410-09-P