[Federal Register Volume 71, Number 167 (Tuesday, August 29, 2006)]
[Rules and Regulations]
[Pages 51115-51117]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-14287]


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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