[Federal Register Volume 89, Number 207 (Friday, October 25, 2024)]
[Rules and Regulations]
[Pages 85047-85050]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-24635]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-900N]
Schedules of Controlled Substances: Placement of Butonitazene,
Flunitazene, and Metodesnitazene Substances in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
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SUMMARY: The Drug Enforcement Administration places butonitazene,
flunitazene, and metodesnitazene including their isomers, esters,
ethers, salts and salts of isomers, esters and ethers in schedule I of
the Controlled Substances Act. The regulatory controls and
administrative, civil, and criminal sanctions applicable to schedule I
controlled substances on persons who handle (manufacture, distribute,
reverse distribute, import, export, engage in research, conduct
instructional activities or chemical analysis with, or possess), or
propose to handle these three specific controlled substances will
continue to apply as a result of this action.
DATES: Effective October 25, 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: In this final rule, the Drug Enforcement
Administration (DEA) permanently schedules the following three
controlled substances in schedule I of the Controlled Substances Act
(CSA), including their 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:
Butonitazene (2-(2-(4-butoxybenzyl)-5-nitro-1H-
benzimidazol-1-yl)-N,N-diethylethan-1-amine),
Flunitazene (N,N-diethyl-2-(2-(4-fluorobenzyl)-5-nitro-1H-
benzimidazol-1-yl)ethan-1-amine),
Metodesnitazene (N,N-diethyl-2-(2-(4-methoxybenzyl)-1H-
benzimidazol-1-yl)ethan-1-amine).
Legal Authority
The CSA provides that proceedings for the issuance, amendment, or
repeal of the scheduling of any drug or other substance may be
initiated by the Attorney General (delegated to the Administrator of
DEA pursuant to 28 CFR 0.100) on his own motion, at the request of the
Secretary of Health and Human Services (HHS), or on the petition of any
interested party.\1\ This action is supported, inter alia, by a
recommendation from the Assistant Secretary for Health of HHS
(Assistant Secretary for HHS or Assistant Secretary) and an evaluation
of all other relevant data by DEA. This action continues the imposition
of the regulatory controls and administrative, civil, and criminal
sanctions of schedule I controlled substances on any person who handles
(manufactures, distributes, imports, exports, engages in research, or
conducts instructional activities or chemical analysis with, or
possesses) or proposes to handle butonitazene, flunitazene, and
metodesnitazene.
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\1\ 21 U.S.C. 811(a).
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Background
On April 12, 2022, pursuant to 21 U.S.C. 811(h)(1), DEA published
an order in the Federal Register temporarily placing butonitazene,
flunitazene, metodesnitazene, and four additional benzimidazole-opioids
in schedule I of the Controlled Substances Act (CSA) based upon a
finding that these substances pose an imminent hazard to the public
safety.\2\ That temporary order was effective upon the date of
publication. Under 21 U.S.C. 811(h)(2), the temporary scheduling of a
substance expires at the end of two years from the date of issuance of
the scheduling order, except that DEA may extend temporary scheduling
of that substance for up to one year during the pendency of permanent
scheduling proceedings under 21 U.S.C. 811(a)(1) with respect to the
substance. Pursuant to 21 U.S.C. 811(h)(2), the temporary scheduling of
butonitazene, flunitazene, and metodesnitazene was set to expire on
April 12, 2024. However, on April 11, 2024, the DEA Administrator
extended the temporary order in a separate action.\3\ On the same day,
the Administrator, on her own motion pursuant to 21 U.S.C. 811(a),
initiated scheduling proceedings and published a notice of proposed
rulemaking (NPRM) to permanently control butonitazene, flunitazene, and
metodesnitazene in schedule I of the CSA.\4\ Specifically, DEA proposed
to add these substances to the opiates list under 21 CFR 1308.11(b).
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\2\ See Schedules of Controlled Substances: Temporary Placement
of Butonitazene, Etodesnitazene, Flunitazene, Metodesnitazene,
Metonitazene, N-Pyrrolidino etonitazene, and Protonitazene in
Schedule I, 87 FR 21556 (Apr. 12, 2022). The four additional
benzimidazole-opioids were etodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and protonitazene. DEA pursued separate
scheduling actions for metonitazene, see 88 FR 56466 (Aug. 18, 2023)
and for etodesnitazene, N-pyrrolidino etonitazene, and
protonitazene, see 89 FR 25514 (Apr. 11, 2024) to remain as schedule
I substances under the CSA in order to meet the United States'
obligations under the United Nations Single Convention on Narcotic
Drugs, Mar. 30, 1961, 18 U.S.T. 1407, 520 U.N.T.S. 151 (Single
Convention), as amended by the 1972 Protocol.
\3\ See Schedules of Controlled Substances: Extension of
Temporary Placement of Butonitazene, Flunitazene, and
Metodesnitazene in Schedule I of the Controlled Substances Act, 89
FR 25517 (Apr. 11, 2024).
\4\ See Schedules of Controlled Substances: Placement of
Butonitazene, Flunitazene, and Metodesnitazene Substances in
Schedule I, 89 FR 25544 (Apr. 11, 2024).
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DEA and HHS Eight Factor Analyses
On November 15, 2023, the Assistant Secretary submitted HHS's
scientific and medical evaluation and scheduling recommendation for
butonitazene, flunitazene, metodesnitazene, and three other
benzimidazole-opioids and their salts to the Administrator,\5\ which
recommended placing butonitazene, flunitazene, and metodesnitazene and
their salts in schedule I of the CSA. In accordance with 21 U.S.C.
811(c), upon receipt of the scientific and medical evaluation and
scheduling
[[Page 85048]]
recommendation from HHS, DEA reviewed the documents and all other
relevant data, and conducted its own eight-factor analysis of the abuse
potential of these three substances. Please note that both the DEA and
HHS eight-factor analyses are available in their entirety under the tab
``Supporting Documents'' of the public docket for this action at http://www.regulations.gov under Docket Number ``DEA-900N.''
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\5\ DEA published a final order to permanently place the three
other benzimidazole-opioids (etodesnitazene, N-pyrrolidino
etonitazene, and protonitazene) in schedule I of the CSA. See
Schedules of Controlled Substances: Placement of Etodesnitazene, N-
Pyrrolidino Etonitazene, and Protonitazene in Schedule I, 89 FR
25514 (Apr. 11, 2024).
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Determination To Permanently Schedule Butonitazene, Flunitazene, and
Metodesnitazene
After review of the available data including the scientific and
medical evaluation and the scheduling recommendation from HHS, DEA
published an NPRM in the Federal Register on April 11, 2024, which
proposed the placement of butonitazene, flunitazene, and
metodesnitazene in schedule I of the CSA.\6\ The NPRM provided an
opportunity for interested persons to file a request for a hearing in
accordance with DEA regulations on or before May 13, 2024. DEA received
no hearing requests. The NPRM also provided an opportunity for
interested persons to submit comments on the proposed rule on or before
May 13, 2024.
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\6\ See Schedules of Controlled Substances: Placement of
Butonitazene, Flunitazene, and Metodesnitazene Substances in
Schedule I, 89 FR 25544 (Apr. 11, 2024).
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Comments Received
DEA received two comments on the proposed rule to control
butonitazene, flunitazene, and metodesnitazene in schedule I of the
CSA. One commenter provided support for the rule. This commenter noted
that permanent placement of these substances would be beneficial to the
community safety. DEA appreciates the support for this rulemaking. The
second commenter commended the proposed rule but noted that a class
control action for the nitazene drug class would be more appropriate as
opposed to individually scheduling substances in the benzimidazole-
opioid drug class. DEA appreciates this comment as a potential
alternative for consideration. However, due to the current threat of
these specific substances, DEA will continue with solely scheduling
these three substances.
Scheduling Conclusion
After consideration of the relevant matters presented through
public comments, the scientific and medical evaluation and accompanying
scheduling recommendation of HHS, and DEA's own eight-factor analysis,
DEA finds that these facts and all relevant data constitute substantial
evidence of potential for abuse of butonitazene, flunitazene, and
metodesnitazene. DEA is therefore permanently scheduling these three
benzimidazole-opioids as schedule I controlled substances under the
CSA.
Determination of Appropriate Schedule
The CSA establishes five schedules of controlled substances known
as schedules I, II, III, IV, and V. The CSA also outlines the findings
required to place a drug or other substance in any particular
schedule.\7\ After consideration of the analysis and recommendation of
the Assistant Secretary for HHS and review of all other available data,
the Administrator of DEA, pursuant to 21 U.S.C. 811(a) and 21 U.S.C.
812(b)(1), finds that:
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\7\ 21 U.S.C. 812(b).
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(1) Butonitazene, flunitazene, and metodesnitazene have a high
potential for abuse. Butonitazene, flunitazene, and metodesnitazene,
similar to etonitazene and fentanyl, are mu-opioid receptor agonists.
These three benzimidazole-opioids have analgesic effects, and these
effects are mediated by mu-opioid receptor agonism. HHS states that
substances that produce mu-opioid receptor agonist effects in the
central nervous system are considered as having a high potential for
abuse (e.g. morphine and fentanyl). Data obtained from drug
discrimination studies indicate that butonitazene, flunitazene, and
metodesnitazene fully substituted for the discriminative stimulus
effects of morphine.
(2) Butonitazene, flunitazene, and metodesnitazene have no
currently accepted medical use in the United States. There are no FDA-
approved drug products for butonitazene, flunitazene, and
metodesnitazene in the United States. There are no known therapeutic
applications for these benzimidazole-opioids, and DEA is not aware of
any currently accepted medical uses for these substances in the United
States.\8\
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\8\ To place a drug or other substance in schedule I under the
CSA, DEA must consider whether the substance has a currently
accepted medical use in treatment in the United States. 21 U.S.C.
812(b)(1)(B). There is no evidence suggesting that butonitazene,
flunitazene, and metodesnitazene have a currently accepted medical
use in treatment in the United States. To determine whether a drug
or other substance has a currently accepted medical use, DEA has
traditionally applied a five-part test to a drug or substance that
has not been approved by the FDA: 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. See Marijuana
Scheduling Petition; Denial of Petition; Remand, 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). DEA
and HHS applied the traditional five-part test for currently
accepted medical use in this matter. In a recent published letter in
a different context, HHS applied an additional two-part test to
determine currently accepted medical use for substances that do not
satisfy the five-part test: (1) whether there exists widespread,
current experience with medical use of the substance by licensed
health care practitioners operating in accordance with implemented
jurisdiction-authorized programs, where medical use is recognized by
entities that regulate the practice of medicine, and, if so, (2)
whether there exists some credible scientific support for at least
one of the medical conditions for which part (1) is satisfied. On
April 11, 2024, the Department of Justice's Office of Legal Counsel
(OLC) issued an opinion, which, among other things, concluded that
HHS's two-part test would be sufficient to establish that a drug has
a currently accepted medical use. Office of Legal Counsel,
Memorandum for Merrick B. Garland Attorney General Re: Questions
Related to the Potential Rescheduling of Marijuana at 3 (April 11,
2024). For purposes of this final rule, there is no evidence that
health care providers have widespread experience with medical use of
butonitazene, flunitazene, and metodesnitazene, or that the use of
butonitazene, flunitazene, and metodesnitazene are recognized by
entities that regulate the practice of medicine under either the
traditional five-part test or the two-part test.
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(3) There is a lack of accepted safety for use of butonitazene,
flunitazene, and metodesnitazene under medical supervision. Because
these substances have no FDA-approved medical use and have not been
investigated as new drugs, their safety for use under medical
supervision is not determined.
Based on these findings, the Administrator of DEA concludes that
butonitazene, flunitazene, and metodesnitazene, including their
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, warrant
continued control in schedule I of the CSA.\9\
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\9\ 21 U.S.C. 812(b)(1).
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Requirements for Handling Butonitazene, Flunitazene, and
Metodesnitazene
As discussed above, these three substances are currently subject to
a temporary scheduling order, which added them to schedule I.
Butonitazene, flunitazene, and metodesnitazene will continue to be
subject to the CSA's schedule I regulatory controls and administrative,
civil, and criminal sanctions applicable to the manufacture,
distribution, reverse distribution, dispensing, importation,
exportation, engagement in research, and conduct of instructional
activities or chemical analysis with, and possession of schedule I
substances, including the following:
[[Page 85049]]
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, dispenses, imports, exports, engages in research,
or conducts instructional activities or chemical analysis with, or
possesses) or who desires to handle butonitazene, flunitazene, and
metodesnitazene 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. Butonitazene, flunitazene, and
metodesnitazene 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. Butonitazene, flunitazene, and metodesnitazene are
subject to schedule I security requirements and must be handled and
stored pursuant to 21 U.S.C. 821, 823, and 871(b), and in accordance
with 21 CFR 1301.71-1301.76. Non-practitioners handling these three
substances also must comply with the screening requirements of 21 CFR
1301.90-1301.93.
4. Labeling and Packaging. All labels and labeling for commercial
containers of butonitazene, flunitazene, and metodesnitazene 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 butonitazene, flunitazene, and metodesnitazene 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
butonitazene, flunitazene, and metodesnitazene must have an initial
inventory of all stocks of controlled substances (including these
substances) on hand on the date the registrant first engages in the
handling of controlled substances pursuant to 21 U.S.C. 827 and 958,
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
butonitazene, flunitazene, and metodesnitazene) on hand every two years
pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR
1304.03, 1304.04, and 1304.11.
7. Records and Reports. Every DEA registrant must maintain records
and submit reports with respect to butonitazene, flunitazene, and
metodesnitazene, pursuant to 21 U.S.C. 827, 832(a), and 958(e), and in
accordance with 21 CFR 1301.74(b) and (c) and 1301.76(b) and parts
1304, 1312, and 1317. Manufacturers and distributors would be required
to submit reports regarding butonitazene, flunitazene, and
metodesnitazene 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. Every DEA registrant who distributes butonitazene,
flunitazene, and metodesnitazene must comply with the order form
requirements, pursuant to 21 U.S.C. 828 and 21 CFR part 1305.
9. Importation and Exportation. All importation and exportation of
butonitazene, flunitazene, and metodesnitazene must comply with 21
U.S.C. 952, 953, 957, and 958, and be in accordance with 21 CFR part
1312.
10. Liability. Any activity involving butonitazene, flunitazene,
and metodesnitazene not authorized by, or in violation of, the CSA or
its implementing regulations is unlawful, and may subject the person to
administrative, civil, and/or criminal sanctions.
Regulatory Analyses
Executive Orders 12866 (Regulatory Planning and Review), 13563
(Improving Regulation and Regulatory Review), and 14094 (Modernizing
Regulatory Review)
In accordance with 21 U.S.C. 811(a), this final scheduling action
is subject to formal rulemaking procedures done ``on the record after
opportunity for a hearing,'' which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for
scheduling a drug or other substance. Such actions are exempt from
review by the Office of Management and Budget (OMB) pursuant to section
3(d)(1) of Executive Order (E.O.) 12866 and the principles reaffirmed
in E.O. 13563. E.O. 14094 modernizes the regulatory review process to
advance policies that promote the public interest and address national
priorities.
Executive Order 12988, Civil Justice Reform
This regulation 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 rulemaking does not have federalism implications warranting
the application of E.O. 13132. The rule does not have substantial
direct effects on the states, on the relationship between the national
government and the States, or the distribution of power and
responsibilities among the various levels of government.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This rule does not have tribal implications warranting the
application of E.O. 13175. It 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.
Regulatory Flexibility Act
The Administrator, in accordance with the Regulatory Flexibility
Act, 5 U.S.C. 601-612, has reviewed this rule and, by approving it,
certifies that it will not have a significant economic impact on a
substantial number of small entities.
On April 12, 2022, DEA published an order to temporarily place
seven benzimidazole-opioids in schedule I of the CSA pursuant to the
temporary scheduling provisions of 21 U.S.C. 811(h). DEA estimates that
all entities handling or planning to handle butonitazene, flunitazene,
and metodesnitazene have already established and implemented systems
and processes required to handle these substances.
There are currently 45 registrations authorized to specifically
handle butonitazene, flunitazene, or metodesnitazene, as well as 1,239
registered analytical labs and 861 researchers that are authorized to
handle schedule I controlled substances generally. These 45
registrations represent 31 entities. A review of the 45 registrations
indicates that all entities that currently handle butonitazene,
flunitazene, and metodesnitazene also handle other schedule I
controlled substances and have established and implemented (or
maintained) systems and processes required to handle these substances.
Therefore, DEA anticipates this final rule will impose minimal or no
economic impact on any affected entities; and thus, will not have a
significant economic impact on any affected small entity. Therefore,
DEA
[[Page 85050]]
has concluded that this rule will not have a significant economic
impact on a substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act of 1995 (UMRA),
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 the UMRA.
Paperwork Reduction Act of 1995
This rule would not impose a new collection or modify an existing
collection of information under the Paperwork Reduction Act of
1995.\10\ Also, this rule would not impose new or modify existing
recordkeeping or reporting requirements on state or local governments,
individuals, businesses, or organizations. However, this rule would
require compliance with the following existing OMB collections: 1117-
0003, 1117-0004, 1117-0006, 1117-0008, 1117-0009, 1117-0010, 1117-0012,
1117-0014, 1117-0021, 1117-0023, 1117-0029, and 1117-0056. 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.
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\10\ 44 U.S.C. 3501-3521.
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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 21 CFR 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)(62) through (106) as (b)(65) through
(109)
0
b. Redesignate paragraphs (b)(44) through (61) as (b)(46) through (63);
0
c. Redesignate paragraphs (b)(24) through (43) as (b)(25) through (44);
0
d. Add new paragraphs (b)(24), (b)(45), and (b)(64); and
0
e. Remove and reserve paragraphs (h)(50), (52), and (53).
The additions to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(b) * * *
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* * * * * * *
(24) Butonitazene (2-(2-(4-butoxybenzyl)-5-nitro-1H- 9751
benzimidazol-1-yl)-N,N-diethylethan-1-amine)...........
* * * * * * *
(45) Flunitazene (N,N-diethyl-2-(2-(4-fluorobenzyl)-5- 9756
nitro-1H-benzimidazol-1-yl)ethan-1-amine)..............
* * * * * * *
(64) Metodesnitazene (N,N-diethyl-2-(2-(4-methoxybenzyl)- 9764
1H-benzimidazol-1-yl)ethan-1-amine)....................
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* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
October 15, 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 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. 2024-24635 Filed 10-24-24; 8:45 am]
BILLING CODE 4410-09-P