[Federal Register Volume 74, Number 30 (Tuesday, February 17, 2009)]
[Proposed Rules]
[Pages 7386-7388]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-3150]



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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-319P]


Schedules of Controlled Substances: Placement of Tapentadol Into 
Schedule II

AGENCY: Drug Enforcement Administration, Department of Justice.

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 
tapentadol, including its isomers, esters, ethers, salts and salts of 
isomers, esters, and ethers whenever the existence of such isomers, 
esters, ethers, and salts is possible, into schedule II of the 
Controlled Substances Act (CSA). This proposed action is based on a 
recommendation from the 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 would impose the 
regulatory controls and criminal sanctions of schedule II on those who 
handle tapentadol and products containing tapentadol.

DATES: Written comments must be postmarked on or before March 19, 2009, 
and electronic comments must be sent on or before midnight Eastern time 
March 19, 2009.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-319'' on all written and electronic correspondence. 
Written comments sent via regular or express mail should be sent to the 
Drug Enforcement Administration, Attention: DEA Federal Register 
Representative/ODL, 8701 Morrissette Drive, Springfield, Virginia 
22152. Comments may be sent to DEA 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.
    Please note that DEA is requesting that electronic comments be 
submitted before midnight Eastern time on the day the comment period 
closes because http://www.regulations.gov terminates the public's 
ability to submit comments at midnight Eastern time on the day the 
comment period closes. Commenters in time zones other than Eastern time 
may want to consider this so that their electronic comments are 
received. All comments sent via regular or express mail will be 
considered timely if postmarked on the day the comment period closes.

FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief, 
Drug and Chemical Evaluation Section, Drug Enforcement Administration, 
8701 Morrissette Drive, Springfield, Virginia 22152, Telephone: (202) 
307-7183.

SUPPLEMENTARY INFORMATION:
    Posting of Public Comments: Please note that all comments received 
are considered part of the public record and made available for public 
inspection online at http://www.regulations.gov and in the Drug 
Enforcement Administration's public docket. Such information includes 
personal identifying information (such as your name, address, etc.) 
voluntarily submitted by the commenter.
    If you want to submit personal identifying information (such as 
your name, address, etc.) as part of your comment, but do not want it 
to be posted online or made available in the public docket, you must 
include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the first 
paragraph of your comment. You must also place all the personal 
identifying information you do not want posted online or made available 
in the public docket in the first paragraph of your comment and 
identify what information you want redacted.
    If you want to submit confidential business information as part of 
your comment, but do not want it to be posted online or made available 
in the public docket, you must include the phrase ``CONFIDENTIAL 
BUSINESS INFORMATION'' in the first paragraph of your comment. You must 
also prominently identify confidential business information to be 
redacted within the comment. If a comment has so much confidential 
business information that it cannot be effectively redacted, all or 
part of that comment may not be posted online or made available in the 
public docket.
    Personal identifying information and confidential business 
information identified and located as set forth above will be redacted 
and the comment, in redacted form, will be posted online and placed in 
the DEA's public docket file.
    Please note that the Freedom of Information Act applies to all 
comments received. If you wish to inspect the agency's public docket 
file in person by appointment, please see the FOR FURTHER INFORMATION 
CONTACT paragraph.

Background

    On November 20, 2008, the Food and Drug Administration (FDA) 
approved tapentadol for marketing in the United States as a 
prescription drug product for the treatment of moderate-to-severe acute 
pain. Tapentadol is a new molecular entity with centrally-acting 
analgesic properties.
    Tapentadol has dual modes of action namely, mu ([mu]) opioid 
receptor agonistic action and inhibition of reuptake of norepinephrine 
at the norepinephrine transporter. The chemical name of its 
monohydrochloride salt form is 3-[(1R,2R)-3-(dimethylamino)-1-ethyl-2-
methylpropyl]phenol hydrochloride.
    Tapentadol shares substantial pharmacological effects and abuse 
potential with other schedule II opioid analgesics, e.g., morphine, 
oxycodone, and hydromorphone. Tapentadol has rewarding and reinforcing 
effects similar to those of morphine in animal models. It generalizes 
to the discriminative stimulus effects of morphine in rats and monkeys. 
Tapentadol, similar to morphine, produced conditioned place preference 
in rats, and this effect was antagonized by naloxone (anopioid receptor 
antagonist). In a clinical study with opioid-experienced non-dependent 
subjects, the subjective scores for drug liking of a single dose of 
tapentadol (50, 100 and 200 mg) were comparable to equianalgesic doses 
of hydromorphone (4, 8, and 16 mg). In clinical studies, tapentadol 
showed an adverse event profile similar to other schedule II opioids. 
The most commonly reported adverse events are nausea, dizziness, 
vomiting, somnolence, vertigo, and headache. In a clinical study in 
which the patients received equianalgesic doses of tapentadol or 
oxycodone for 90 days, the reports of withdrawal symptoms were 
comparable for both treatment groups upon discontinuance of 
administration. The ability of tapentadol to produce psychological 
dependence is suggested by a level of drug liking comparable to that 
produced by hydromorphone.
    Since tapentadol is a new molecular entity, there has been no 
evidence of diversion, abuse, or law enforcement encounters involving 
the drug. On November 13, 2008, the Assistant Secretary for Health, 
DHHS, sent the Deputy Administrator of DEA a scientific and medical 
evaluation and a letter recommending that tapentadol be

[[Page 7387]]

placed into schedule II of the CSA. Enclosed with the November 13, 
2008, letter was a document prepared by the FDA entitled, ``Basis for 
the Recommendation for Control of Tapentadol in Schedule II of the 
Controlled Substances Act.'' 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 Assistant Secretary of Health and the 
DEA with respect to tapentadol 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 Assistant Secretary for Health, 
received in accordance with Sec.  201(b) of the Act (21 U.S.C. 811(b)), 
and the independent review of the available data by DEA, the Deputy 
Administrator of DEA, pursuant to Sec. Sec.  201(a) and 201(b) of the 
Act (21 U.S.C. 811(a) and 811(b)), finds that:
    (1) Tapentadol has a high potential for abuse;
    (2) Tapentadol currently has accepted medical use in treatment in 
the United States; and
    (3) Abuse of tapentadol may lead to severe psychological or 
physical dependence.
    Based on these findings, the Deputy Administrator of DEA concludes 
that tapentadol, including its isomers, esters, ethers, salts and salts 
of isomers, esters, and ethers whenever the existence of such isomers, 
esters, ethers, and salts is possible, warrants control in schedule II 
of the CSA. (21 U.S.C. 812 (b)(2))
    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 be heard. All correspondence regarding this 
matter should be submitted to the DEA to the address 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 Tapentadol

    If this rule is finalized as proposed, tapentadol would be subject 
to the CSA regulatory controls and administrative, civil and criminal 
sanctions applicable to the manufacture, distribution, dispensing, 
importing, and exporting of a schedule II controlled substance, 
including the following:
    Registration. Any person who manufactures, distributes, dispenses, 
imports, exports, engages in research or conducts instructional 
activities with tapentadol, or who desires to manufacture, distribute, 
dispense, import, export, engage in instructional activities or conduct 
research with tapentadol, would be required to be registered to conduct 
such activities in accordance with Part 1301 of Title 21 of the Code of 
Federal Regulations (CFR).
    Security. Tapentadol would be subject to schedule II security 
requirements and must be manufactured, distributed and stored in 
accordance with Sec. Sec.  1301.71, 1301.72(a), (c), and (d), 1301.73, 
1301.74, 1301.75(b) and (c), 1301.76 and 1301.77 of Title 21 of the 
CFR.
    Labeling and Packaging. All labels and labeling for commercial 
containers of tapentadol which are distributed after finalization of 
this rule would be required to comply with requirements of Sec. Sec.  
1302.03-1302.07 of Title 21 of the CFR.
    Quotas. Quotas for tapentadol would be established pursuant to part 
1303 of Title 21 of the CFR.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of tapentadol would be required to keep an 
inventory of all stocks of tapentadol on hand pursuant to Sec. Sec.  
1304.03, 1304.04 and 1304.11 of Title 21 of the CFR. Every registrant 
who desires registration in schedule II for tapentadol 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 CFR.
    Reports. All registrants required to submit reports to the 
Automation of Reports and Consolidated Order System (ARCOS) in 
accordance with Sec.  1304.33 of Title 21 of the CFR would be required 
to do so for tapentadol.
    Orders for tapentadol. All registrants involved in the distribution 
of tapentadol would be required to comply with the order form 
requirements of part 1305 of Title 21 of the CFR.
    Prescriptions. All prescriptions for tapentadol or prescriptions 
for products containing tapentadol would be required to be issued 
pursuant to 21 CFR Sec.  1306.03-1306.06 and 1306.11-1306.15.
    Importation and Exportation. All importation and exportation of 
tapentadol would need to be in compliance with part 1312 of Title 21 of 
the CFR.
    Criminal Liability. Any activity with tapentadol not authorized by, 
or in violation of, the CSA 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. 601-612), 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. Tapentadol products 
will be prescription drugs used for the treatment of moderate-to-severe 
acute pain. Handlers of tapentadol will also 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 
Sec. Sec.  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.

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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 
$120,000,000 or more (adjusted for inflation) 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.

Congressional Review Act

    This rule is not a major rule as defined by Sec.  804 of the Small 
Business Regulatory Enforcement Fairness Act of 1996 (Congressional 
Review Act). 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 Sec.  201(a) 
of the CSA (21 U.S.C. 811(a)), and delegated to the Administrator of 
the DEA by the 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

    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 1308.12 is amended in the table by adding a new 
paragraph (c)(28) to read as follows:


Sec.  1308.12   Schedule II.

* * * * *
    (c) * * *
    (28) Tapentadol 9780
* * * * *

    Dated: January 27, 2009.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E9-3150 Filed 2-13-09; 8:45 am]
BILLING CODE 4410-09-P