[Federal Register Volume 88, Number 43 (Monday, March 6, 2023)]
[Rules and Regulations]
[Pages 13692-13694]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-04364]



[[Page 13692]]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-716]


Schedules of Controlled Substances: Placement of Brorphine in 
Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final order.

-----------------------------------------------------------------------

SUMMARY: With the issuance of this final order, the Administrator of 
the Drug Enforcement Administration is permanently placing 1-(1-(1-(4-
bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one 
(commonly known as brorphine), 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 brorphine.

DATES: Effective April 5, 2023.

FOR FURTHER INFORMATION CONTACT: Dr. 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. 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)), of the Controlled Substances 
Act (CSA), 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). 28 CFR 0.100.

Background

    On March 1, 2021, Drug Enforcement Administrator (DEA) issued a 
temporary scheduling order, placing brorphine [1-(1-(1-(4-
bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-
one] in schedule I of the Controlled Substances Act (CSA). 86 FR 11862. 
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)(49).
    In November 2021, the Director-General of the World Health 
Organization (WHO) notified the Secretary-General of the 
recommendation, from the 44th meeting of WHO's Expert Committee on Drug 
Dependence, that brorphine 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., brorphine is similar to drugs such as morphine and 
fentanyl) and has dependence and abuse potential. On May 27, 2022, the 
United States government was informed by the Secretariat of the United 
Nations, by letter, that during its 65th session in March 2022, the 
Commission voted to place brorphine in Schedule I of the Single 
Convention (CND Mar/65/1).

Brorphine

    As discussed in the background section, brorphine is temporarily 
controlled in schedule I of the CSA upon the Acting Administrator's 
finding it poses imminent hazard to the public safety. Brorphine has a 
pharmacological profile similar to fentanyl (schedule II) and other 
schedule I and II synthetic opioids that act as mu-opioid receptor 
agonists. Because of the pharmacological similarities of brorphine to 
heroin (schedule I) and fentanyl (schedule II), a potent mu-opioid 
agonist, the use of brorphine presents a high risk of abuse and has 
negatively affected users and communities. The abuse of brorphine has 
been associated with at least 21 fatalities in the United States 
between August 2019 and June 2021.1 2 The positive 
identification of this substance in many post-mortem cases is a serious 
concern to the public safety.
---------------------------------------------------------------------------

    \1\ Vohra V, King AM, Jacobs E, Aaron C. Death associated with 
brorphine, an emerging novel synthetic opioid. Clin Toxicol (Phila). 
2021, 59:851-852.
    \2\ Krotulski AJ, x Krotulski AJ, Papsun DM, Noble C, Kacinko 
SL, Nelson L, Logan BK. Public Health Alert: The Rise of Brorphine--
A Potent New Synthetic Opioid Identified in the Midwestern United 
States. CFSRE--NPS Discovery, 2020.
---------------------------------------------------------------------------

    Brorphine on 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 brorphine is being 
illicitly distributed and abused. 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 157 
reports for brorphine between April 2020 and June 2022 \4\ (query date: 
July 6, 2022).
---------------------------------------------------------------------------

    \3\ Health Canada Drug Analysis Service (2019); Analyzed Drug 
Report Canada 2019--Q3 (July to September); European Monitoring 
Centre for Drugs and Drug Addiction (EMCDDA) (2020); EU Early 
Warning System Situation Report, Situation report--June 2020.
    \4\ Reports for NFLIS-Drug are still pending for 2022.
---------------------------------------------------------------------------

    DEA is not aware of any claims or any medical or scientific 
literature suggesting that brorphine 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 October 27, 
2020, that there were no investigational new drug applications or 
approved new drug applications for brorphine in the United States. 
Because brorphine 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 
brorphine has no currently accepted medical use in treatment in the 
United States \5\ and

[[Page 13693]]

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 brorphine pursuant to 21 U.S.C. 
811(a).
---------------------------------------------------------------------------

    \5\ Although, as discussed above, there is no evidence 
suggesting that brorphine 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).
---------------------------------------------------------------------------

Conclusion

    In order to meet the United States' obligations under the Single 
Convention and because brorphine has no currently accepted medical use 
in treatment in the United States, the Administrator has determined 
that brorphine, 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

    Brorphine has been controlled as a schedule I controlled substance 
since March 1, 2021. Upon the effective date of the final order 
contained in this document, brorphine 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 brorphine 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. Brorphine 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. Brorphine is subject to schedule I security 
requirements and must be handled and stored pursuant to 21 U.S.C. 823 
and in accordance with 21 CFR 1301.71-1301.76. Non-practitioners 
handling brorphine 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 brorphine must be in compliance with 21 U.S.C. 
825 and be in accordance with 21 CFR part 1302.
    5. Quota. Only registered manufacturers are permitted to 
manufacture brorphine 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 
brorphine has been required to keep an inventory of all stocks of this 
substance on hand as of March 1, 2021, pursuant to 21 U.S.C. 827 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 brorphine pursuant to 21 U.S.C. 827 and 
in accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), 1307.11, and 
parts 1304, 1312, and 1317. Manufacturers and distributors must submit 
reports regarding brorphine 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 brorphine 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 
brorphine 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 brorphine not authorized by, 
or in violation of the CSA, is unlawful and may subject the person to 
administrative, civil, and/or criminal sanctions.

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. This action makes no 
change in the status quo, as brorphine is already listed as a schedule 
I controlled substance.

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, and ``without regard to'' 
the findings and rulemaking procedures

[[Page 13694]]

otherwise required for scheduling actions in 21 U.S.C. 811(a) and (b).
    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 opposed 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.

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.

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, pursuant to the CRA, DEA is 
submitting a copy of this final rule to both Houses of Congress and to 
the Comptroller General.

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)(22) through (93) as paragraphs (b)(23) 
through (94), respectively;
0
b. Add new paragraph (b)(22); and
0
c. Remove and reserve paragraph (h)(49).
    The addition reads as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

 (22) brorphine (1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-yl)-      9098
 1,3-dihydro-2H-benzo[d]imidazol-2-one)........................
 

* * * * *

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
February 27, 2023, by Administrator Anne Milgram. That document with 
the original signature and date is maintained by DEA. For 
administrative purposes only, and in compliance with requirements of 
the Office of the Federal Register, the undersigned DEA Federal 
Register Liaison Officer has been authorized to sign and submit the 
document in electronic format for publication, as an official document 
of DEA. This administrative process in no way alters the legal effect 
of this document upon publication in the Federal Register.

Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2023-04364 Filed 3-3-23; 8:45 am]
BILLING CODE 4410-09-P