[Federal Register Volume 86, Number 211 (Thursday, November 4, 2021)]
[Rules and Regulations]
[Pages 60761-60763]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-23848]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-631]


Schedules of Controlled Substances: Placement of Isotonitazene in 
Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final amendment; final order.

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SUMMARY: With the issuance of this final order, the Administrator of 
the Drug Enforcement Administration is permanently placing N,N-diethyl-
2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine 
(commonly known as
    isotonitazene), 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 within the specific 
chemical designation, in schedule I of the Controlled Substances Act. 
This scheduling action discharges the United States' obligations under 
the Single Convention on Narcotic Drugs (1961). This action continues 
to impose the regulatory controls and administrative, civil, and 
criminal sanctions applicable to schedule I controlled substances on 
persons who handle (manufacture, distribute, import, export, engage in 
research or conduct instructional activities with, or possess), or 
propose to handle isotonitazene.

DATES: Effective December 6, 2021.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical 
Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION:

Legal Authority

    The United States is a party to the 1961 United Nations Single 
Convention on Narcotic Drugs (Single Convention), March 30, 1961, 18 
U.S.T. 1407, 570 U.N.T.S. 151, as amended by the 1972 Protocol. Article 
3, paragraph 7 of the Single Convention requires that if the Commission 
on Narcotic Drugs (Commission) adds a substance to one of the schedules 
of such Convention, and the United States receives notification of such 
scheduling decision from the Secretary-General of the United Nations 
(Secretary-General), the United States, as a signatory Member State, is 
obligated to control the substance under its national drug control 
legislation. Under 21 U.S.C. 811(d)(1)), if control of a substance is 
required ``by United States obligations under international treaties, 
conventions, or protocols in effect on October 27, 1970,'' the Attorney 
General must issue an order controlling such drug under the schedule he 
deems most appropriate to carry out such obligations, without regard to 
the findings required by 21 U.S.C. 811(a) or 812(b), and without regard 
to the procedures prescribed by 21 U.S.C. 811(a) and (b). The Attorney 
General has delegated scheduling authority under 21 U.S.C. 811 to the 
Administrator of the Drug Enforcement Administration (Administrator of 
DEA or Administrator). 28 CFR 0.100.

Background

    On August 20, 2020, DEA issued a temporary scheduling order, 
placing isotonitazene (N,N-diethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-
1H-benzimidazol-1-yl)ethan-1-amine), in schedule I of the Controlled 
Substances Act (CSA). 85 FR 51342. That order was based on findings by 
the Acting Administrator of DEA (Acting Administrator) that the 
temporary scheduling of this substance was necessary to avoid an 
imminent hazard to the public safety; the order was codified at 21 CFR 
1308.11(h)(48).
    In November 2020, the Director-General of the World Health 
Organization recommended to the Secretary-General that isotonitazene be 
placed in Schedule I of the Single Convention, as this substance has an 
opioid mechanism of action and similarity to drugs that are controlled 
in Schedule I of the Single Convention (i.e., isotonitazene is similar 
to drugs such as morphine and fentanyl), and has dependence and abuse 
potential. On June 10, 2021, the Secretary-General advised the 
Secretary of State of the United States, by letter, that during its 
64th session in April 2021, the Commission voted to place isotonitazene 
in Schedule I of the Single Convention (CND Apr/64/1).

Isotonitazene

    As discussed in the background section, isotonitazene is 
temporarily controlled in schedule I of the CSA upon the Acting 
Administrator's finding it poses imminent hazard to the public safety. 
Isotonitazene has a pharmacological profile similar to etonitazene 
(schedule I), fentanyl (schedule II), and other schedule I and II 
synthetic opioids that act as mu-opioid receptor agonists. Because of 
the pharmacological similarities of isotonitazene to etonitazene (a 
potent mu-opioid agonist), the use of isotonitazene presents a high 
risk of abuse and has negatively affected users and communities. The 
abuse of isotonitazene has been associated with

[[Page 60762]]

at least 48 1 2 fatalities in the United States between 
August 2019 and July 2020. The positive identification of this 
substance in post-mortem cases is a serious concern to the public 
safety.
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    \1\ Shover CL, Falasinnu TO, Freedman RB, Humphreys K. Emerging 
Characteristics of Isotonitazene-Involved Overdose Deaths: A Case-
Control Study. J Addict Med. 2020 Nov 23:10.1097/
ADM.0000000000000775.
    \2\ Krotulski AJ, Papsun DM, Kacinko SL, Logan BK. Isotonitazene 
Quantitation and Metabolite Discovery in Authentic Forensic 
Casework. J Anal Toxicol. 2020 Jul 31;44(6):521-530.
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    Isotonitazene in the illicit drug market has been reported in 
Canada, Estonia, Germany, Latvia, Sweden, and the United States since 
April 2019.\3\ Law enforcement reports demonstrate that isotonitazene 
is being illicitly distributed and abused. The illicit use and 
distribution of this substance are similar to that of heroin (schedule 
I) and prescription opioid analgesics. According to the National 
Forensic Laboratory Information System (NFLIS-Drug) database, which 
collects drug identification results from drug cases submitted to and 
analyzed by Federal, State and local forensic laboratories, there have 
been 181 reports for isotonitazene between January 2019 and December 
2020 \4\ (query date: May 28, 2021).
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    \3\ European Monitoring Centre for Drugs and Drug Addiction and 
Europol. (2020). EMCDDA initial report on the new psychoactive 
substance N,N-diethyl-2-[[4-(1 methylethoxy)phenyl]methyl]-5-nitro-
1H-benzimidazole-1-ethanamine (isotonitazene). In accordance with 
Article 5b of Regulation (EC) No 1920/2006 (as amended), 
Publications Office of the European Union, Luxembourg.
    \4\ Reports to NFLIS-Drug are still pending for 2020.
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    DEA is not aware of any claims or any medical or scientific 
literature suggesting that isotonitazene has a currently accepted 
medical use in treatment in the United States. In addition, the 
Department of Health and Human Services advised DEA, by letter dated 
March 31, 2020, that there were no investigational new drug 
applications or approved new drug applications for isotonitazene in the 
United States. Because isotonitazene is not formulated or available for 
clinical use as an approved medicinal product, all current use of this 
substance by individuals is based on their own initiative, rather than 
on the basis of medical advice from a practitioner licensed by law to 
administer such a drug.
    Therefore, consistent with 21 U.S.C. 811(d)(1), DEA concludes that 
isotonitazene has no currently accepted medical use in treatment in the 
United States \5\ and is most appropriately placed in schedule I of the 
CSA, the same schedule in which it currently resides. Because control 
is required under the Single Convention, DEA will not be initiating 
regular rulemaking proceedings to schedule isotonitazene pursuant to 21 
U.S.C. 811(a).
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    \5\ Although, as discussed above, there is no evidence 
suggesting that isotonitazene has a currently accepted medical use 
in treatment in the United States, it bears noting that a drug 
cannot be found to have such medical use unless DEA concludes that 
it satisfies a five-part test. Specifically, with respect to a drug 
that has not been approved by the Food and Drug Administration, to 
have a currently accepted medical use in treatment in the United 
States, all of the following must be demonstrated: i. The drug's 
chemistry must be known and reproducible; ii. there must be adequate 
safety studies; iii. there must be adequate and well-controlled 
studies proving efficacy; iv. the drug must be accepted by qualified 
experts; and v. the scientific evidence must be widely available. 57 
FR 10499 (1992), pet. for rev. denied, Alliance for Cannabis 
Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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Conclusion

    In order to meet the United States' obligations under the Single 
Convention and because isotonitazene has no currently accepted medical 
use in treatment in the United States, the Administrator has determined 
that isotonitazene, 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 within the specific 
chemical designation, should remain in schedule I of the CSA.

Requirements for Handling

    Isotonitazene has been controlled as a schedule I controlled 
substance since August 20, 2020. Upon the effective date of the final 
order contained in this document, isotonitazene will be permanently 
subject to the CSA's schedule I regulatory controls and administrative, 
civil, and criminal sanctions applicable to the manufacture of, 
distribution of, importation of, exportation of, engagement in research 
or conduct of instructional activities with, and possession of, 
schedule I controlled substances, including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
imports, exports, engages in research or conducts instructional 
activities with, or possesses), or who desires to handle, isotonitazene 
must be registered with DEA to conduct such activities pursuant to 21 
U.S.C. 822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 
and 1312. Retail sales of schedule I controlled substances to the 
general public are not allowed under the CSA. Possession of any 
quantity of these substances in a manner not authorized by the CSA is 
unlawful and those in possession of any quantity of these substances 
may be subject to prosecution pursuant to the CSA.
    2. Disposal of stocks. Isotonitazene must be disposed of in 
accordance with 21 CFR part 1317, in addition to all other applicable 
federal, state, local, and tribal laws.
    3. Security. Isotonitazene is subject to schedule I security 
requirements and must be handled and stored pursuant to 21 U.S.C. 821 
and 823, and in accordance with 21 CFR 1301.71-1301.76. Non-
practitioners handling isotonitazene must also comply with the employee 
screening requirements of 21 CFR 1301.90-1301.93.
    4. Labeling and packaging. All labels, labeling, and packaging for 
commercial containers of isotonitazene must be in compliance with 21 
U.S.C. 825 and 958(e), and be in accordance with 21 CFR part 1302.
    5. Quota. Only registered manufacturers are permitted to 
manufacture isotonitazene in accordance with a quota assigned pursuant 
to 21 U.S.C. 826 and in accordance with 21 CFR part 1303.
    6. Inventory. Every DEA registrant who possesses any quantity of 
isotonitazene has been required to keep an inventory of all stocks of 
this substance on hand as of August 20, 2020, pursuant to 21 U.S.C. 827 
and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 
1304.11.
    7. Records and Reports. DEA registrants must maintain records and 
submit reports with respect to isotonitazene pursuant to 21 U.S.C. 827 
and 958(e), and in accordance with 21 CFR parts 1304, 1312, and 1317, 
and Sec.  1307.11. Manufacturers and distributors must submit reports 
regarding isotonitazene to the Automation of Reports and Consolidated 
Order System pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 
parts 1304 and 1312.
    8. Order Forms. All DEA registrants who distribute isotonitazene 
must continue to comply with order form requirements pursuant to 21 
U.S.C. 828 and in accordance with 21 CFR part 1305.
    9. Importation and Exportation. All importation and exportation of 
isotonitazene must continue to be in compliance with 21 U.S.C. 952, 
953, 957, and 958, and in accordance with 21 CFR parts 1304, 1312, and 
1317.
    10. Liability. Any activity involving isotonitazene not authorized 
by, or in violation of the CSA, is unlawful, and may subject the person 
to administrative, civil, and/or criminal sanctions.

[[Page 60763]]

Regulatory Analyses

Executive Orders 12866 (Regulatory Planning and Review) and 13563 
(Improving Regulation and Regulatory Review)

    This action is not a significant regulatory action as defined by 
Executive Order (E.O.) 12866 (Regulatory Planning and Review), section 
3(f), and the principles reaffirmed in E.O. 13563 (Improving Regulation 
and Regulatory Review); and, accordingly, this action has not been 
reviewed by the Office of Management and Budget (OMB).

Executive Order 12988, Civil Justice Reform

    This action meets the applicable standards set forth in sections 
3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors and 
ambiguity, minimize litigation, provide a clear legal standard for 
affected conduct, and promote simplification and burden reduction.

Executive Order 13132, Federalism

    This action does not have federalism implications warranting the 
application of E.O. 13132. This action does not have substantial direct 
effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This action does not have tribal implications warranting the 
application of E.O. 13175. The action does not have substantial direct 
effects on one or more Indian tribes, on the relationship between the 
Federal Government and Indian tribes, or on the distribution of power 
and responsibilities between the Federal Government and Indian tribes.

Administrative Procedure Act

    The CSA provides for an expedited scheduling action where control 
is required by the United States' obligations under international 
treaties, conventions, or protocols. 21 U.S.C. 811(d)(1). If control is 
required pursuant to such international treaty, convention, or 
protocol, the Attorney General, as delegated to the Administrator, must 
issue an order controlling such drug under the schedule he deems most 
appropriate to carry out such obligations, without regard to the 
findings or procedures otherwise required for scheduling actions. Id.
    In accordance with 21 U.S.C. 811(d)(1), scheduling actions for 
drugs that are required to be controlled by the United States' 
obligations under international treaties, conventions, or protocols in 
effect on October 27, 1970, shall be issued by order (as compared to 
scheduling by rule pursuant to 21 U.S.C. 811(a)). Therefore, DEA 
believes that the notice and comment requirements of section 553 of the 
Administrative Procedure Act (APA), 5 U.S.C. 553, do not apply to this 
scheduling action. In the alternative, even if this action does 
constitute ``rule making'' under 5 U.S.C. 551(5), this action is exempt 
from the notice and comment requirements of 5 U.S.C. 553 pursuant to 5 
U.S.C. 553(a)(1) as an action involving a foreign affairs function of 
the United States because it is being done pursuant to 21 U.S.C. 
811(d)(1), which requires that the United States comply with its 
obligations under the specified international agreements.

Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to 
rules that are subject to notice and comment under section 553(b) of 
the APA or any other law. As explained above, the CSA exempts this 
final order from notice and comment. Consequently, the RFA does not 
apply to this action.

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information 
requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. An agency may not conduct or sponsor, and a person is not 
required to respond to, a collection of information unless it displays 
a currently valid OMB control number.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
2 U.S.C. 1501 et seq., DEA has determined and certifies that this 
action would not result in any Federal mandate that may result ``in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100,000,000 or more (adjusted annually 
for inflation) in any 1 year * * *.'' Therefore, neither a Small 
Government Agency Plan nor any other action is required under UMRA of 
1995.

Congressional Review Act

    This order is not a major rule as defined by the Congressional 
Review Act (CRA), 5 U.S.C. 804. However, DEA is submitting the required 
reports to the Government Accountability Office, the House, and the 
Senate under the CRA.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, DEA amends 21 CFR part 1308 as 
follows:

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), 956(b), unless otherwise 
noted.


0
2. In Sec.  1308.11:
0
a. Redesignate paragraphs (b)(46) through (90) as paragraphs (b)(47) 
through (91);
0
b. Add new paragraph (b)(46); and
0
c. Remove and reserve paragraph (h)(48).
    The addition reads as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *


(46) Isotonitazene (N,N-diethyl-2-(2-(4-isopropoxybenzyl)-5-        9614
 nitro-1H-benzimidazol-1-yl)ethan-1-amine)......................
 

* * * * *

Anne Milgram,
Administrator.
[FR Doc. 2021-23848 Filed 11-3-21; 8:45 am]
BILLING CODE 4410-09-P