Schedules of Controlled Substances: Placement of 2-Methyl AP-237 in Schedule I, 18793-18796 [2024-05543]

Download as PDF Federal Register / Vol. 89, No. 52 / Friday, March 15, 2024 / Rules and Regulations section 513(f)(2) of the act, is pending before the Food and Drug Administration, or (ii) There is a predetermined change control plan (PCCP) cleared under section 515C of the act, provided that the change is consistent with the PCCP. * * * * * § 807.87 [Amended] 3. Amend § 807.87 by removing the phrase ‘‘(Information collection requirements in this section were approved by the Office of Management and Budget (OMB) and assigned OMB control number 0910–0281)’’ that appears after paragraph (m). ■ PART 814—PREMARKET APPROVAL OF MEDICAL DEVICES 4. The authority citation for part 814 continues to read as follows: ■ Authority: 21 U.S.C. 351, 352, 353, 360, 360c–360j, 360bbb–8b, 371, 372, 373, 374, 375, 379, 379e, 379k–1, 381. 5. In § 814.39, revise paragraph (b) to read as follows: ■ § 814.39 PMA supplements. * * * * * (b) An applicant may make a change in a device after FDA’s approval of a PMA for the device without submitting a PMA supplement if the change does not affect the device’s safety or effectiveness and the change is reported to FDA in post approval periodic reports required as a condition to approval of the device, e.g., an editorial change in labeling which does not affect the safety or effectiveness of the device, or if the change is consistent with a predetermined change control plan (PCCP) approved under section 515C of the act. * * * * * Dated: March 11, 2024. Lauren K. Roth, Associate Commissioner for Policy. [FR Doc. 2024–05473 Filed 3–14–24; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF JUSTICE Drug Enforcement Administration khammond on DSKJM1Z7X2PROD with RULES 21 CFR Part 1308 [Docket No. DEA–1245] Schedules of Controlled Substances: Placement of 2-Methyl AP–237 in Schedule I Drug Enforcement Administration, Department of Justice. AGENCY: VerDate Sep<11>2014 16:00 Mar 14, 2024 Jkt 262001 ACTION: Final amendment; final order. With the issuance of this final order, the Administrator of the Drug Enforcement Administration is permanently placing 1-(2-methyl-4-(3phenylprop-2-en-1-yl)piperazin-1yl)butan-1-one (commonly known as 2methyl AP–237), including its optical and geometric 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 imposes 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 2-methyl AP–237. DATES: Effective April 15, 2024. FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and Chemical Evaluation Section, Diversion Control Division, Drug Enforcement Administration; Telephone: (571) 362– 3249. SUMMARY: SUPPLEMENTARY INFORMATION: Legal Authority The United States is a party to the 1961 United Nations Single Convention on Narcotic Drugs, March 30, 1961, 18 U.S.T. 1407, 570 U.N.T.S. 151 (Single Convention), 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) 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. PO 00000 Frm 00045 Fmt 4700 Sfmt 4700 18793 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 In a letter dated November 24, 2022, the Director-General of the World Health Organization recommended to the Secretary-General of the United Nations that 2-methyl AP–237 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., 2-methyl AP–237 is similar to drugs such as isotonitazene) and has dependence and abuse potential. On May 17, 2023, the United States Government was informed by the Secretariat of the United Nations, by letter, that during its 66th session in March 2023, the Commission voted to place 2-methyl AP–237 in Schedule I of the Single Convention (CND Mar/66/1). 2-Methyl AP–237 2-Methyl AP–237 has a pharmacological profile similar to other classical opioids such as fentanyl (schedule II), morphine (schedule II) and heroin (schedule I), which act as mu-opioid receptor agonists. Because of the pharmacological similarities of 2methyl AP–237 to the aforementioned opioids, 2-methyl AP–237 presents a high risk of abuse and has negatively affected users and communities. According to the DEA Toxicology Testing Program (DEA TOX) 1 and a recent publication,2 the abuse of 2methyl AP–237 has been associated with at least seven fatalities in the United States between February 2020 and July 2023. The identification of this substance in post-mortem cases is a serious concern to public safety. In June 2019, 2-methyl AP–237 emerged on the United States illicit drug market as evidenced by its identification in drug seizures.3 Law enforcement 1 The DEA Toxicology Testing Program (DEA TOX) was initiated in response to the ongoing novel synthetic drug abuse epidemic. This program provides toxicology data on synthetic drugs from biological samples that may not be routinely identified, which are generated from drug overdose victims. Data queried on 8/7/2023. 2 Fogarty, MF, Vandeputte, MM, Krotulski, AJ, Walton, SE, Stove, CP, and Logan, BK (2022). Toxicological and pharmacological characterization of novel cinnamylpiperazine synthetic opioids in humans and in vitro including 2-methyl AP–237 and AP–238. Archives of Toxicology 96:1701–1710. 3 NFLIS represents an important resource in monitoring illicit drug trafficking, including the diversion of legally manufactured pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive E:\FR\FM\15MRR1.SGM Continued 15MRR1 18794 Federal Register / Vol. 89, No. 52 / Friday, March 15, 2024 / Rules and Regulations khammond on DSKJM1Z7X2PROD with RULES reports demonstrate that 2-methyl AP– 237 is being illicitly distributed and abused. The illicit use and distribution of this substance is 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 92 reports of 2-methyl AP–237 in the United States since 2019 (data queried July 17, 2023). DEA is not aware of any claims or any medical or scientific literature suggesting that 2-methyl AP–237 has a currently accepted medical use in treatment in the United States. In addition, the Assistant Secretary for Health of the U.S. Department of Health and Human Services, by a letter to DEA dated December 22, 2022, stated that there are no investigational new drug applications or approved new drug applications for 2-methyl AP–237 in the United States; hence, there are no legitimate channels for this substance as a marketed drug product in the United States. Because 2-methyl AP–237 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 2-methyl AP–237 has no currently accepted medical use in treatment in the United States 4 and is most appropriately information system that includes data from forensic laboratories that handle the nation’s drug analysis cases. NFLIS-Drug participation rate, defined as the percentage of the national drug caseload represented by laboratories that have joined NFLIS, is currently 98.5 percent. NFLIS includes drug chemistry results from completed analyses only. While NFLIS data is not direct evidence of abuse, it can lead to an inference that a drug has been diverted and abused. See Schedules of Controlled Substances: Placement of Carisoprodol Into Schedule IV; 76 FR 77330, 77332, December 12, 2011. NFLIS data was queried on July 17, 2023. Reports to NFLIS-Drug are still pending for 2023. 4 Although, as discussed above, there is no evidence suggesting that 2-methyl AP–237 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 VerDate Sep<11>2014 16:00 Mar 14, 2024 Jkt 262001 placed in schedule I of the CSA. Because control is required under the Single Convention, DEA will not be initiating regular rulemaking proceedings to permanently schedule 2methyl AP–237 pursuant to 21 U.S.C. 811(a). Conclusion In order to meet the United States’ obligations under the Single Convention and because 2-methyl AP–237 has no currently accepted medical use in treatment in the United States, the Administrator has determined that 2methyl AP–237, including its optical and geometric 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 be placed in schedule I of the CSA. Requirements for Handling Upon the effective date of the final order contained in this document, 2methyl AP–237 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, 2methyl AP–237 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 this substance in a manner not authorized by the CSA is unlawful and those in possession of any quantity of this substance may be subject to prosecution pursuant to the CSA. 2. Disposal of stocks. 2-Methyl AP– 237 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. 2-Methyl AP–237 is subject to schedule I security proving efficacy; iv. the drug must be accepted by qualified experts; and v. the scientific evidence must be widely available. 57 FR 10499 (Mar 26,1992), pet. for rev. denied, Alliance for Cannabis Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C. Cir. 1994). PO 00000 Frm 00046 Fmt 4700 Sfmt 4700 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 2methyl AP–237 must 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 2-methyl AP–237 must comply with 21 U.S.C. 825, and be in accordance with 21 CFR part 1302. 5. Quota. Only registered manufacturers are permitted to manufacture 2-methyl AP–237 in accordance with a quota assigned pursuant to 21 U.S.C. 826, and in accordance with 21 CFR part 1303. 6. Inventory. Any person registered with DEA to handle 2-methyl AP–237 must have an initial inventory of all stocks of controlled substances (including this substance) on hand on the date the registrant first engages in the handling of controlled substances pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. After the initial inventory, every DEA registrant must take a new inventory of all stocks of controlled substances (including 2-methyl AP–237) on hand every two years 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 2-methyl AP–237 pursuant to 21 U.S.C. 827, and in accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), and 1307.11 and parts 1304, 1312, and 1317. Manufacturers and distributors must submit reports regarding 2-methyl AP– 237 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 2-methyl AP–237 must comply with the 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 2-methyl AP–237 must comply with 21 U.S.C. 952, 953, 957, and 958, and in accordance with 21 CFR part 1312. 10. Liability. Any activity involving 2methyl AP–237 not authorized by, or in violation of the CSA, is unlawful, and may subject the person to administrative, civil, and/or criminal sanctions. E:\FR\FM\15MRR1.SGM 15MRR1 18795 Federal Register / Vol. 89, No. 52 / Friday, March 15, 2024 / Rules and Regulations Regulatory Analyses Executive Orders 12866 (Regulatory Planning and Review) and 13563 (Improving Regulation and Regulatory Review) and 14094 (Modernizing 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), as amended by E.O. 14094, section 1(b), 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, and ‘‘without regard to’’ the findings and rulemaking procedures otherwise required for scheduling actions in 21 U.S.C. 811(a) and (b). 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 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. OMB may be obtained at https:// www.reginfo.gov/public/do/PRAMain. 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 reports under the CRA to both Houses of Congress and to the Comptroller General. List of Subjects in 21 CFR Part 1308 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 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: ■ This order would modify an existing collection of information requirement under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501–3521. Pursuant to section 3507(d) of the PRA of 1995 (44 U.S.C. 3507(d)), DEA is adding new reporting and recordkeeping requirements for 1117–0003. This order also involves existing collection 1117– 0004, but would not modify the existing collection of information requirement under the PRA. An agency may not conduct or sponsor, and a person is not required to respond to a collection of information, unless it displays a valid OMB control number. Copies of existing information collections approved by Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise noted. 2. In § 1308.11: a. Redesignate paragraphs (b)(59) through (b)(103) as follows: ■ ■ Old paragraph New paragraph (b)(59) through (103) (b)(60) through (104). ■ b. Add new paragraph (b)(59). The addition reads as follows: § 1308.11 * Schedule I. * * (b) * * * * * khammond on DSKJM1Z7X2PROD with RULES * * * * * * * (59) 2-Methyl AP–237 (1-(2-methyl-4-(3-phenylprop-2-en-1-yl)piperazin-1-yl)butan-1-one) ....................................................................... * * * * * * * * Signing Authority This document of the Drug Enforcement Administration was signed VerDate Sep<11>2014 16:00 Mar 14, 2024 Jkt 262001 * * on March 8, 2024, by Administrator Anne Milgram. That document with the original signature and date is maintained by DEA. For administrative purposes only, and in compliance with PO 00000 Frm 00047 Fmt 4700 Sfmt 4700 * 9664 * 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 E:\FR\FM\15MRR1.SGM 15MRR1 18796 Federal Register / Vol. 89, No. 52 / Friday, March 15, 2024 / Rules and Regulations 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. Heather Achbach, Federal Register Liaison Officer, Drug Enforcement Administration. [FR Doc. 2024–05543 Filed 3–14–24; 8:45 am] BILLING CODE 4410–09–P DEPARTMENT OF STATE 22 CFR Part 126 [Public Notice: 12306] RIN 1400–AF80 International Traffic in Arms Regulations: Addition to List of Proscribed Countries Regulatory Analysis and Notices Department of State. ACTION: Final rule. AGENCY: khammond on DSKJM1Z7X2PROD with RULES Administrative Procedure Act The Department of State is amending the International Traffic in Arms Regulations (ITAR) to add Nicaragua in the list of countries for which it is the policy of the United States to deny licenses or other approvals for exports and imports of defense services and defense articles, except as otherwise provided. DATES: The rule is effective on March 15, 2024. FOR FURTHER INFORMATION CONTACT: Ms. Maria Tatarska, Foreign Affairs Officer, Office of Defense Trade Controls Policy, U.S. Department of State, telephone (771) 205–7671; email DDTCCustomerService@state.gov ATTN: Regulatory Change, ITAR Section 126.1: Nicaragua. SUPPLEMENTARY INFORMATION: Due to growing concerns regarding Nicaragua’s continuing dismantling of democratic institutions, attacks on civil society, and increased security cooperation with Russia, to include support of Russia’s full-scale invasion of Ukraine, the Under Secretary of State for Arms Control and International Security has determined that it is in the best interests of U.S. national security and foreign policy to restrict, with certain exceptions, the export and import of defense articles and defense services destined for or originating in Nicaragua. This policy reflects the U.S. government’s opposition to the trade of arms with Nicaragua and its authoritarian government dominated by President Daniel Ortega Saavedra and his wife, Vice President Rosario Murillo Zambrana. Pursuant to this determination, the Department is adding SUMMARY: VerDate Sep<11>2014 16:00 Mar 14, 2024 Jkt 262001 Nicaragua to ITAR § 126.1 in paragraph (p). The policy of denial toward Nicaragua applies to licenses or other approvals for exports and imports of defense articles or defense services, except that a license or other approval may be issued on a case-by-case basis for non-lethal military equipment intended solely for humanitarian assistance, to include natural disaster relief. Further, in accordance with ITAR § 129.7, no broker, as described in ITAR § 129.2, may engage in or make a proposal to engage in brokering activities subject to the ITAR that involve Nicaragua without obtaining the approval of the Directorate of Defense Trade Controls. Consistent with ITAR § 129.7(d), the Department of State will apply the same policy of denial to such requests. This rulemaking is exempt from the rulemaking requirements of section 553 of the Administrative Procedure Act (APA) pursuant to 5 U.S.C. 553(a)(1) as a military or foreign affairs function of the United States. Regulatory Flexibility Act Since this rule is exempt from the notice-and-comment provisions of 5 U.S.C. 553, the rule does not require analysis under the Regulatory Flexibility Act. Unfunded Mandates Reform Act of 1995 This rulemaking does not involve a mandate that will result in the expenditure by State, local, and tribal governments, in the aggregate, or by the private sector, of $100 million or more in any year and it will not significantly or uniquely affect small governments. Therefore, no actions are deemed necessary under the provisions of the Unfunded Mandates Reform Act of 1995. Congressional Review Act The Department does not believe this rulemaking is a major rule within the definition of 5 U.S.C. 804. Executive Orders 12372 and 13132 This rulemaking does not have sufficient federalism implications to require consultations or warrant the preparation of a federalism summary impact statement. The regulations implementing Executive Order 12372 regarding intergovernmental consultation on Federal programs and activities do not apply to this rulemaking. PO 00000 Frm 00048 Fmt 4700 Sfmt 4700 Executive Orders 12866, 13563, and 14094 Executive Order 12866, as amended by Executive Orders 13563 and 14094, directs agencies to assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health and safety effects, distributed impacts, and equity). As a result of this change, certain exemptions to licensing requirements will not be available for exports, reexports, retransfers, and temporary imports destined for or originating in Nicaragua. However, a license or other approval may be issued on a case-bycase basis for non-lethal military equipment intended solely for humanitarian assistance, to include natural disaster relief. Because the scope of this rule does not impose significant additional regulatory requirements or obligations, the Department believes costs associated with this rule will be minimal. This rule has been designated a ‘‘significant regulatory action’’ by the Office and Information and Regulatory Affairs under Executive Order 12866. Executive Order 12988 The Department of State has reviewed this rulemaking in light of Executive Order 12988 to eliminate ambiguity, minimize litigation, establish clear legal standards, and reduce burden. Executive Order 13175 The Department of State determined that this rulemaking will not have Tribal implications, will not impose substantial direct compliance costs on Indian Tribal governments, and will not preempt tribal law. Accordingly, Executive Order 13175 does not apply to this rulemaking. Paperwork Reduction Act This rulemaking does not impose or revise any information collections subject to 44 U.S.C. Chapter 35. List of Subjects in 22 CFR Part 126 Arms and munitions, Exports. For the reasons set forth above, title 22, chapter I, subchapter M, part 126 is amended as follows: PART 126—GENERAL POLICIES AND PROVISIONS 1. The authority citation for part 126 continues to read as follows: ■ Authority: 22 U.S.C. 287c, 2651a, 2752, 2753, 2776, 2778, 2779, 2779a, 2780, 2791, 2797; Sec. 1225, Pub. L. 108–375, 118 Stat. 2091; Sec. 7045, Pub. L. 112–74, 125 Stat. E:\FR\FM\15MRR1.SGM 15MRR1

Agencies

[Federal Register Volume 89, Number 52 (Friday, March 15, 2024)]
[Rules and Regulations]
[Pages 18793-18796]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-05543]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-1245]


Schedules of Controlled Substances: Placement of 2-Methyl AP-237 
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 1-(2-methyl-
4-(3-phenylprop-2-en-1-yl)piperazin-1-yl)butan-1-one (commonly known as 
2-methyl AP-237), including its optical and geometric 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 imposes 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 2-methyl AP-237.

DATES: Effective April 15, 2024.

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, March 30, 1961, 18 U.S.T. 1407, 570 
U.N.T.S. 151 (Single Convention), 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) 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 of 
DEA or Administrator). 28 CFR 0.100.

Background

    In a letter dated November 24, 2022, the Director-General of the 
World Health Organization recommended to the Secretary-General of the 
United Nations that 2-methyl AP-237 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., 2-methyl AP-237 is similar to drugs such as 
isotonitazene) and has dependence and abuse potential. On May 17, 2023, 
the United States Government was informed by the Secretariat of the 
United Nations, by letter, that during its 66th session in March 2023, 
the Commission voted to place 2-methyl AP-237 in Schedule I of the 
Single Convention (CND Mar/66/1).

2-Methyl AP-237

    2-Methyl AP-237 has a pharmacological profile similar to other 
classical opioids such as fentanyl (schedule II), morphine (schedule 
II) and heroin (schedule I), which act as mu-opioid receptor agonists. 
Because of the pharmacological similarities of 2-methyl AP-237 to the 
aforementioned opioids, 2-methyl AP-237 presents a high risk of abuse 
and has negatively affected users and communities. According to the DEA 
Toxicology Testing Program (DEA TOX) \1\ and a recent publication,\2\ 
the abuse of 2-methyl AP-237 has been associated with at least seven 
fatalities in the United States between February 2020 and July 2023. 
The identification of this substance in post-mortem cases is a serious 
concern to public safety.
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    \1\ The DEA Toxicology Testing Program (DEA TOX) was initiated 
in response to the ongoing novel synthetic drug abuse epidemic. This 
program provides toxicology data on synthetic drugs from biological 
samples that may not be routinely identified, which are generated 
from drug overdose victims. Data queried on 8/7/2023.
    \2\ Fogarty, MF, Vandeputte, MM, Krotulski, AJ, Walton, SE, 
Stove, CP, and Logan, BK (2022). Toxicological and pharmacological 
characterization of novel cinnamylpiperazine synthetic opioids in 
humans and in vitro including 2-methyl AP-237 and AP-238. Archives 
of Toxicology 96:1701-1710.
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    In June 2019, 2-methyl AP-237 emerged on the United States illicit 
drug market as evidenced by its identification in drug seizures.\3\ Law 
enforcement

[[Page 18794]]

reports demonstrate that 2-methyl AP-237 is being illicitly distributed 
and abused. The illicit use and distribution of this substance is 
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 92 reports of 2-methyl 
AP-237 in the United States since 2019 (data queried July 17, 2023).
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    \3\ NFLIS represents an important resource in monitoring illicit 
drug trafficking, including the diversion of legally manufactured 
pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive 
information system that includes data from forensic laboratories 
that handle the nation's drug analysis cases. NFLIS-Drug 
participation rate, defined as the percentage of the national drug 
caseload represented by laboratories that have joined NFLIS, is 
currently 98.5 percent. NFLIS includes drug chemistry results from 
completed analyses only. While NFLIS data is not direct evidence of 
abuse, it can lead to an inference that a drug has been diverted and 
abused. See Schedules of Controlled Substances: Placement of 
Carisoprodol Into Schedule IV; 76 FR 77330, 77332, December 12, 
2011. NFLIS data was queried on July 17, 2023. Reports to NFLIS-Drug 
are still pending for 2023.
---------------------------------------------------------------------------

    DEA is not aware of any claims or any medical or scientific 
literature suggesting that 2-methyl AP-237 has a currently accepted 
medical use in treatment in the United States. In addition, the 
Assistant Secretary for Health of the U.S. Department of Health and 
Human Services, by a letter to DEA dated December 22, 2022, stated that 
there are no investigational new drug applications or approved new drug 
applications for 2-methyl AP-237 in the United States; hence, there are 
no legitimate channels for this substance as a marketed drug product in 
the United States. Because 2-methyl AP-237 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 
2-methyl AP-237 has no currently accepted medical use in treatment in 
the United States \4\ and is most appropriately placed in schedule I of 
the CSA. Because control is required under the Single Convention, DEA 
will not be initiating regular rulemaking proceedings to permanently 
schedule 2-methyl AP-237 pursuant to 21 U.S.C. 811(a).
---------------------------------------------------------------------------

    \4\ Although, as discussed above, there is no evidence 
suggesting that 2-methyl AP-237 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 (Mar 26,1992), pet. for rev. denied, Alliance for Cannabis 
Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C. 
Cir. 1994).
---------------------------------------------------------------------------

Conclusion

    In order to meet the United States' obligations under the Single 
Convention and because 2-methyl AP-237 has no currently accepted 
medical use in treatment in the United States, the Administrator has 
determined that 2-methyl AP-237, including its optical and geometric 
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 be 
placed in schedule I of the CSA.

Requirements for Handling

    Upon the effective date of the final order contained in this 
document, 2-methyl AP-237 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, 2-methyl AP-
237 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 this substance in a manner not authorized by the CSA is 
unlawful and those in possession of any quantity of this substance may 
be subject to prosecution pursuant to the CSA.
    2. Disposal of stocks. 2-Methyl AP-237 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. 2-Methyl AP-237 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 2-methyl AP-237 must 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 2-methyl AP-237 must comply with 21 U.S.C. 
825, and be in accordance with 21 CFR part 1302.
    5. Quota. Only registered manufacturers are permitted to 
manufacture 2-methyl AP-237 in accordance with a quota assigned 
pursuant to 21 U.S.C. 826, and in accordance with 21 CFR part 1303.
    6. Inventory. Any person registered with DEA to handle 2-methyl AP-
237 must have an initial inventory of all stocks of controlled 
substances (including this substance) on hand on the date the 
registrant first engages in the handling of controlled substances 
pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 1304.03, 
1304.04, and 1304.11.
    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including 2-methyl 
AP-237) on hand every two years 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 2-methyl AP-237 pursuant to 21 U.S.C. 
827, and in accordance with 21 CFR 1301.74(b) and (c), 1301.76(b), and 
1307.11 and parts 1304, 1312, and 1317. Manufacturers and distributors 
must submit reports regarding 2-methyl AP-237 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 2-methyl AP-237 
must comply with the 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 
2-methyl AP-237 must comply with 21 U.S.C. 952, 953, 957, and 958, and 
in accordance with 21 CFR part 1312.
    10. Liability. Any activity involving 2-methyl AP-237 not 
authorized by, or in violation of the CSA, is unlawful, and may subject 
the person to administrative, civil, and/or criminal sanctions.

[[Page 18795]]

Regulatory Analyses

Executive Orders 12866 (Regulatory Planning and Review) and 13563 
(Improving Regulation and Regulatory Review) and 14094 (Modernizing 
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), as amended by E.O. 14094, section 1(b), 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, and ``without regard to'' 
the findings and rulemaking procedures otherwise required for 
scheduling actions in 21 U.S.C. 811(a) and (b). 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 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.

Paperwork Reduction Act of 1995

    This order would modify an existing collection of information 
requirement under the Paperwork Reduction Act (PRA), 44 U.S.C. 3501-
3521. Pursuant to section 3507(d) of the PRA of 1995 (44 U.S.C. 
3507(d)), DEA is adding new reporting and recordkeeping requirements 
for 1117-0003. This order also involves existing collection 1117-0004, 
but would not modify the existing collection of information requirement 
under the PRA. An agency may not conduct or sponsor, and a person is 
not required to respond to a collection of information, unless it 
displays a valid OMB control number. Copies of existing information 
collections approved by OMB may be obtained at https://www.reginfo.gov/public/do/PRAMain.

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 reports 
under the CRA 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)(59) through (b)(103) as follows:

------------------------------------------------------------------------
               Old paragraph                        New paragraph
------------------------------------------------------------------------
(b)(59) through (103).....................  (b)(60) through (104).
------------------------------------------------------------------------

0
b. Add new paragraph (b)(59).
    The addition reads as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

 
                              * * * * * * *
(59) 2-Methyl AP-237 (1-(2-methyl-4-(3-phenylprop-2-en-1-           9664
 yl)piperazin-1-yl)butan-1-one)..............................
 
                              * * * * * * *
 

* * * * *

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
March 8, 2024, 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

[[Page 18796]]

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.

Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2024-05543 Filed 3-14-24; 8:45 am]
BILLING CODE 4410-09-P

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