2023-04364. 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-2 H -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: [phone].

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-2 H -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.

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).

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 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).

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 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

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.

2. In § 1308.11:

a. Redesignate paragraphs (b)(22) through (93) as paragraphs (b)(23) through (94), respectively;

b. Add new paragraph (b)(22); and

c. Remove and reserve paragraph (h)(49).

The addition reads as follows:

§ 1308.11

Schedule I.

* * * * *

(b) * * *

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

* * * * *

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.

Footnotes

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.

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.

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).