[Federal Register Volume 74, Number 97 (Thursday, May 21, 2009)]
[Rules and Regulations]
[Pages 23790-23793]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-11933]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-319F]


Schedules of Controlled Substances: Placement of Tapentadol Into 
Schedule II

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 
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

[[Page 23791]]

Controlled Substances Act (CSA). As a result of this rule, the 
regulatory controls and criminal sanctions of schedule II will be 
applicable to the manufacture, distribution, dispensing, importation, 
and exportation of tapentadol and products containing tapentadol.

DATES: Effective Date: June 22, 2009.

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

SUPPLEMENTARY INFORMATION:

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.
    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, 
Department of Health and Human Services (DHHS), sent the Deputy 
Administrator of DEA a scientific and medical evaluation and a letter 
recommending that tapentadol be placed into schedule II of the CSA. 
Enclosed with the November 13, 2008, letter was a document prepared by 
the Food and Drug Administration (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)).
    After a review of the available data, including the scientific and 
medical evaluation and the scheduling recommendation from DHHS, the 
Deputy Administrator of the DEA published a Notice of Proposed 
Rulemaking entitled ``Schedules of Controlled Substances: Placement of 
Tapentadol into Schedule II'' on February 17, 2009 (74 FR 7386), which 
proposed placement of tapentadol into schedule II of the CSA. The 
proposed rule provided an opportunity for all interested persons to 
submit their written comments on or before March 19, 2009.

Comments Received

    The DEA received three comments in response to the Notice of 
Proposed Rulemaking. One comment was from a consulting firm, one 
comment was from a concerned citizen, and the last comment was from a 
company which does research and development on pharmaceutical drugs.
    The first commenter recommended that the DEA expedite the issuance 
and effective date of the Final Rule placing tapentadol in schedule II. 
The commenter stated that tapentadol will provide a safe and effective 
substitute for other schedule II analgesics and that the conditions of 
public health necessitate and justify this request. In response, DEA 
believes that providing 30 days for this rule to become effective is 
both expeditious and sufficient to allow handlers to apply for 
registration with DEA and to comply with the regulatory requirements 
for handling schedule II controlled substances.
    A second commenter stated that since tapentadol induces effects 
similar to oxycodone and morphine, both schedule II substances, then it 
should be placed in schedule II of the Controlled Substances Act based 
on tapentadol's abuse potential. Thus, the commenter agreed with DHHS' 
recommendation and the action proposed by DEA. No response from DEA is 
necessary to this comment because it is consistent with the DEA's final 
action.
    The third commenter had four questions/comments regarding the 
implementation of this Final Rule. Each question/comment is addressed 
below.
    The commenter requested that DEA registrants be allowed enough time 
to make the changes needed to carry out handling tapentadol as a 
schedule II substance, as dictated in 21 CFR 1301.51, 1301.71, and 
1304.04. In response to this comment, the effective date of the Final 
Rule placing tapentadol in schedule II of the Controlled Substances Act 
will be thirty (30) days from the date of publication of the Final 
Rule, thus allowing ample time for those that wish to handle tapentadol 
to meet DEA regulatory requirements for handling schedule II 
substances. It has been DEA's experience that this is sufficient time 
to meet the regulatory requirements provided below.
    The commenter asked if quantities of tapentadol held by a DEA 
registrant would have to be reported once the scheduling of tapentadol 
as a schedule II substance was finalized. In response, the reporting 
and recordkeeping requirements for handling schedule II substances can 
be found in 21 CFR part 1304. Specifically, 21 CFR 1304.11(b) states 
that ``Every person required to keep records shall take an inventory of 
all stocks of controlled substances on hand on the date he/she first 
engages in the manufacture, distribution, or dispensing of controlled 
substances * * *'' In order for a manufacturer to handle a schedule II 
substance, a manufacturing or procurement quota has to be requested in 
accordance with the requirements of 21 U.S.C. 826(c) and 21 CFR part 
1303. The manufacturer's inventory of the substance is used, in part, 
to determine the manufacturer's quota.
    The commenter asked about the process for adding the CSA drug code 
for tapentadol to their registration. In response, the regulatory 
process required to obtain a DEA registration is outlined generally in 
21 CFR 1301.11 through 1301.19, and the process required to modify an 
existing DEA registration is outlined in 21 CFR 1301.51. Information 
relating to registration may be found on the Internet, http://www.DEAdiversion.usdoj.gov, or by contacting DEA's Registration Call 
Center, toll free at 1-800-882-9539.
    Finally, the commenter inquired about the process for establishing 
an NDC number for tapentadol with the Automation of Reports and 
Consolidated Orders System (ARCOS). National Drug Code (NDC) numbers 
are assigned by the Food and Drug Administration (FDA) in conjunction 
with registration and drug listing requirements of the Federal Food, 
Drug, and Cosmetic Act. Accordingly, a person manufacturing a product 
containing tapentadol must obtain an NDC number from FDA in accordance 
with 21 CFR 207.35. Once the drug code for tapentadol is added to an 
existing manufacturer's registration or a new registration is issued to 
an applicant, then that DEA-registered manufacturer must provide the 
DEA's ARCOS Unit with its established NDC number for their product 
containing tapentadol. Once that information is obtained, it can be 
used to report ARCOS reportable transactions pursuant to 21 CFR 
1304.33.

Scheduling of Tapentadol

    Based on the recommendation of the Assistant Secretary for Health, 
received

[[Page 23792]]

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, and after a review of 
the comments received in response to the Notice of Proposed Rulemaking, 
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 has a currently 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)).

Requirements for Handling Tapentadol

    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, 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 June 22, 2009 and may continue their 
activities until DEA has approved or denied that application.
    Security. Tapentadol is 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 
Code of Federal Regulations on or after June 22, 2009.
    Labeling and Packaging. All labels and labeling for commercial 
containers of tapentadol must comply with requirements of Sec. Sec.  
1302.03 through 1302.07 of Title 21 of the Code of Federal Regulations 
on or after June 22, 2009.
    Quotas. Quotas for tapentadol must be established pursuant to part 
1303 of Title 21 of the Code of Federal Regulations.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of tapentadol must 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 Code of Federal Regulations on or after 
June 22, 2009. Every registrant who desires registration in schedule II 
for tapentadol must 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 or after June 22, 2009.
    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 Code of Federal 
Regulations must do so for tapentadol.
    Orders for Tapentadol. All registrants involved in the distribution 
of tapentadol must comply with the order form requirements of part 1305 
of Title 21 of the Code of Federal Regulations on or after June 22, 
2009.
    Prescriptions. All prescriptions for tapentadol or prescriptions 
for products containing tapentadol must be issued pursuant to 
Sec. Sec.  1306.03 through 1306.06 and 1306.11 through 1306.15 of Title 
21 of the Code of Federal Regulations on and after June 22, 2009.
    Importation and Exportation. All importation and exportation of 
tapentadol must be in compliance with part 1312 of Title 21 of the Code 
of Federal Regulations on or after June 22, 2009.
    Criminal Liability. Any activity with tapentadol not authorized by, 
or in violation of, the CSA or the Controlled Substances Import and 
Export Act shall be unlawful on or after June 22, 2009.

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 final 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 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 
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 
$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 section 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.

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 Title 28, Part 0, Appendix to 
Subpart R, Section 12, the Deputy Administrator hereby amends 21 CFR 
part 1308 as follows:

[[Page 23793]]

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for part 1308 continues to read as follows:

    Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.


0
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: May 15, 2009.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E9-11933 Filed 5-20-09; 8:45 am]
BILLING CODE 4410-09-P