[Federal Register: August 29, 2006 (Volume 71, Number 167)]
[Rules and Regulations]
[Page 51115-51117]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr29au06-6]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-269F]
21 CFR Part 1308
Schedules of Controlled Substances: Placement of Embutramide Into
Schedule III
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
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SUMMARY: With the issuance of this final rule, the Deputy Administrator
of the Drug Enforcement Administration (DEA) places the substance
embutramide, including its salts, into Schedule III of the Controlled
Substances Act (CSA). As a result of this rule, the regulatory controls
and criminal sanctions of Schedule III will be applicable to the
manufacture, distribution, dispensing, importation and exportation of
embutramide and products containing embutramide.
DATES: Effective Date: September 28, 2006.
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, (202) 307-7183.
SUPPLEMENTARY INFORMATION: Embutramide has the chemical name of N-[2-
(m-methoxyphenyl)-2-ethyl-butyl]-gamma-hydroxybutyramide (CAS number
15687-14-6). On May 20, 2005, the Food and Drug Administration (FDA)
approved a New Animal Drug Application (NADA) for embutramide for
marketing under the trade name TributameTM Euthanasia
Solution (70 FR 36336). This product is a combination of embutramide,
chloroquine phosphate, and lidocaine for prescription use by
intravenous injection for euthanasia of dogs.
On January 26, 2005, the Acting Assistant Secretary for Health,
Department of Health and Human Services (DHHS), sent the Deputy
Administrator of DEA a scientific and medical evaluation and a letter
recommending that embutramide be placed into Schedule III of the CSA.
Enclosed with the January 26, 2005, letter was a document prepared by
the FDA entitled, ``Basis for the Recommendation to Control Embutramide
in Schedule III 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))
Similar to barbiturates, embutramide has a central nervous system
(CNS) depressant effect. It produces a reversible stupor-like state
(narcosis) in experimental animals. The effects of embutramide on
locomotor activity, rearing, forelimb grip strength, hind-limb splay,
and the performance of inverted screen tests on rodents were similar to
those of pentobarbital, a classical barbiturate. Embutramide mimics
discriminative stimulus effects of pentrobarbital in mice.
Methohexital-trained rhesus monkeys self-administer embutramide,
suggesting that embutramide produces positive reinforcing effects.
The pharmacological data suggest that the abuse potential of
embutramide may be similar to that of CNS depressants such as
barbiturates and their products (Schedule III through IV) that are
controlled under the CSA. Embutramide as one of the ingredients in the
veterinary euthanasia drug product T-61, was previously marketed in the
United States. T-16 was withdrawn from the market in 1991. Embutramide
is not currently marketed in the United States. During the period of
marketing of T-61, a limited number of case reports of suicides,
attempted suicides, and accidental exposures involving this and similar
embutramide containing products were published in the scientific
literature. DEA searched, but has not found, any evidence of abuse or
trafficking of either T-61 or embutramide.
After a review of the available data, including the scientific and
medical evaluation and the scheduling recommendation received from
DHHS, the Deputy Administrator of the DEA, in a July 29, 2005, Federal
Register Notice of Proposed Rulemaking (70 FR 43809), proposed
placement of embutramide into Schedule III 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 August 29, 2005.
On August 2, 2005, DEA received a request for an extension of the
period in which to comment and request a hearing. The requestor
indicated that the additional time was necessary to review the
scientific articles and other information cited by DEA in support of
its scheduling proposal. DEA granted a 30 day extension of the time to
comment and request a hearing, until September 28, 2005 (70 FR 50996).
Comments Received
DEA received two comments in response to the notice of proposed
rulemaking. One commenter supported the current proposal to control
embutramide as a Schedule III drug. Another commenter supported the
proposal to schedule embutramide, the substance, but not its finished
pharmaceutical product, TributameTM. This commenter stated
that the abuse potential of TributameTM is non-existent
because the negative characteristics such as the presence of a
cardiotoxin and the high cost of this formulation outweigh its
desirable effects.
DEA does not agree. Careful consideration of all the available data
suggests that the amounts of cardiotoxin present in the
TributameTM formulation are insufficient to eliminate the
abuse potential of this product. DEA field experience suggests that the
cost of a given product is not a consistent predictor of its actual
abuse.
DEA also received a request for a hearing on the scheduling of
embutramide and a request for an exemption of the product,
TributameTM, from scheduling; however, the requestor
subsequently withdrew these requests and asked that the scheduling of
embutramide be expedited.
Scheduling of Embutramide
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 DEA, and after a review
of the comments received in response to the notice of proposed
rulemaking, the Deputy Administrator of 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, embutramide has a potential
for abuse less than the drugs or other substances in Schedules I and
II;
(2) Embutramide has a currently accepted medical use in treatment
in the United States; and
[[Page 51116]]
(3) Abuse of embutramide may lead to moderate or low physical
dependence or high psychological dependence.
Based on these findings, the Deputy Administrator of DEA concludes
that embutramide, including its salts, warrants control in Schedule III
of the CSA. The applicable regulations are as follows:
Registration. Any person who manufactures, distributes, dispenses,
imports, exports, engages in research or conducts instructional
activities with embutramide, or who desires to manufacture, distribute,
dispense, import, export, engage in instructional activities or conduct
research with embutramide, must be registered to conduct such
activities 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 September 28, 2006 and may
continue their activities until DEA has approved or denied that
application.
Security. Embutramide is subject to Schedule III-V security
requirements and must be manufactured, distributed and stored in
accordance with Sections 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 September 28, 2006.
Labeling and Packaging. All labels and labeling for commercial
containers of embutramide shall comply with requirements of Sections
1302.03-1302.07 of Title 21 of the Code of Federal Regulations and on
and after September 28, 2006.
Inventory. Every registrant required to keep records and who
possesses any quantity of embutramide must keep an inventory of all
stocks of embutramide on hand pursuant to Sections 1304.03, 1304.04 and
1304.11 of Title 21 of the Code of Federal Regulations on and after
September 28, 2006. Every registrant who desires registration in
Schedule III for embutramide 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 Sections
1304.03, 1304.04, 1304.21, 1304.22, and 1304.23 of Title 21 of the Code
of Federal Regulations on and after September 28, 2006.
Prescriptions. All prescriptions for embutramide or prescriptions
for products containing embutramide are to be issued pursuant to 21 CFR
1306.03-1306.06 and 1306.21-1306.27. All prescriptions for embutramide
or products containing embutramide issued on and after September 28,
2006, if authorized for refiling, shall, as of that date, be limited to
five refills and shall not be refilled after six months of the date is
issuance.
Importation and Exportation. All importation and exportation of
embutramide must be in compliance with part 1312 of Title 21 of the
Code of Federal Regulations on and after September 28, 2006.
Criminal Liability. Any activity with embutramide not authorized
by, or in violation of, the Controlled Substances Act or the Controlled
Substances Import and Export Act shall be unlawful on and after
September 28, 2006.
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. 56 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. Embutramide products
will be prescription drugs used for the euthanasia of animals. Handlers
of embutramide also handle other controlled substances used to
euthanize animals which are already subject to the regulatory
requirements of the CSA.
Embutramide is a new drug in the United States; recent approval of
the product and its labeling by the FDA will allow it to be marketed
once it is placed into Schedule III of the CSA. This finalrule will
allow these entities to have 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
$118,000,000 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 section 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 Controlled Substances Act (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
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 1308.13 is amended by redesignating paragraphs (c)(5)
through (c)(13) as paragraphs (c)(6) through (c)(14), and adding a new
paragraph (c)(5) to read as follows:
Sec. 1308.13 Schedule III.
* * * * *
(c) * * *
(5) Embutramide . . . . 2020
* * * * *
[[Page 51117]]
Dated: August 22, 2006.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E6-14287 Filed 8-28-06; 8:45 am]
BILLING CODE 4410-09-P