[Federal Register Volume 89, Number 249 (Monday, December 30, 2024)]
[Proposed Rules]
[Pages 106384-106393]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-30798]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1457]
Schedules of Controlled Substances: Placement of Seven Specific
Fentanyl-Related Substances in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration proposes placing seven
fentanyl-related substances, as identified in this proposed rule, in
schedule I of the Controlled Substances Act. These seven substances
fall within the definition of fentanyl-related substances set forth in
the February 6, 2018 temporary scheduling order. Through the Temporary
Reauthorization and Study of Emergency Scheduling of Fentanyl Analogues
Act, which became law on February 6, 2020, Congress extended the
temporary control of fentanyl-related substances until May 6, 2021.
This temporary order was subsequently extended multiple times, most
recently on December 29, 2022, through the Consolidated Appropriations
Act, 2023, which extended the order until December 31, 2024. If
finalized, this action would make permanent the existing 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, conduct instructional
activities or chemical analysis, or possess), or propose to handle
these seven specific controlled substances.
DATES: Comments must be submitted electronically or postmarked on or
before January 29, 2025.
Interested persons may file a request for a hearing or waiver of
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.47 and/or 1316.49, as applicable. Requests for a hearing, and
waivers of an opportunity for a hearing or to participate in a hearing,
must be received on or before January 29, 2025.
ADDRESSES: Interested persons may file written comments on this
proposal in accordance with 21 CFR 1308.43(g). To ensure proper
handling of comments, please reference ``Docket No. DEA-1457'' on all
electronic and written correspondence, including any attachments.
Electronic comments: The Drug Enforcement Administration
(DEA) encourages commenters to submit all comments electronically
through the Federal eRulemaking Portal which provides the ability to
type short comments directly into the comment field on the web page or
to attach a file for lengthier comments. Please go to https://www.regulations.gov and follow the online instructions at that site for
submitting comments. Upon completion of your submission, you will
receive a Comment Tracking Number for your comment. Submitted comments
are not instantaneously available for public view on Regulations.gov.
If you have received a Comment Tracking Number, your comment has been
successfully submitted and there is no need to resubmit the same
comment. Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after 11:59 p.m. Eastern
Time on the last day of the comment period.
Paper comments: Paper comments that duplicate electronic
submissions are not necessary. Should you wish to mail a paper comment
in lieu of an electronic comment, it should be sent via regular or
express mail to: Drug Enforcement Administration, Attn: DEA Federal
Register Representative/DPW, 8701 Morrissette Drive, Springfield,
Virginia 22152.
Hearing requests: All requests for a hearing and waivers
of participation, together with a written statement of position on the
matters of fact and law asserted in the hearing, must be filed with the
DEA Administrator, who will make the determination of whether a hearing
will be needed to address such matters of fact and law in the
rulemaking. Such requests must be sent to: Drug Enforcement
Administration, Attn: Administrator, 8701 Morrissette Drive,
Springfield, Virginia 22152. For informational purposes, a courtesy
copy of requests for hearing and waivers of participation should also
be sent to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/
OALJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) Drug
Enforcement Administration, Attn: DEA Federal Register Representative/
DPW, 8701 Morrissette Drive, Springfield, Virginia 22152.
Paperwork Reduction Act Comments: All comments concerning
collections of information under the Paperwork Reduction Act must be
submitted to the Office of Information and Regulatory Affairs, OMB,
Attention: Desk Officer for DOJ, Washington, DC 20503. Please state
that your comment refers to Docket No. DEA-1457.
FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and
Chemical
[[Page 106385]]
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION: In this proposed rule, the Drug Enforcement
Administration (DEA) proposes to permanently schedule the following
seven 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:
para-chlorofentanyl (N-(4-chlorophenyl)-N-(1-
phenethylpiperidin-4-yl)propionamide),
ortho-chlorofentanyl (N-(2-chlorophenyl)-N-(1-
phenethylpiperidin-4-yl)propionamide),
meta-fluorofuranyl fentanyl (N-(3-fluorophenyl)-N-(1-
phenethylpiperidin-4-yl)furan-2-carboxamide),
ortho-methylcyclopropyl fentanyl (N-(2-methylphenyl)-N-(1-
phenethylpiperidin-4-yl)cyclopropanecarboxamide),
beta-methylacetyl fentanyl (N-phenyl-N-(1-(2-
phenylpropyl)piperidin-4-yl)acetamide),
tetrahydrothiofuranyl fentanyl (N-(1-phenethylpiperidin-4-
yl)-N-phenyltetrahydrothiophene-2-carboxamide),
para-fluoro valeryl fentanyl (N-(4-fluorophenyl)-N-(1-
phenethylpiperidin-4-yl)pentanamide).
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. DEA will make comments available for public
inspection online at https://www.regulations.gov, unless reasonable
cause is given. Such information includes personal or business
identifiers (such as name, address, state of federal identifiers, etc.)
voluntarily submitted by the commenter.
Commenters submitting comments which include personal identifying
information (PII), confidential, or proprietary business information
that the commenter does not want made publicly available should submit
two copies of the comment. One copy must be marked ``CONTAINS
CONFIDENTIAL INFORMATION'' and should clearly identify all PII or
business information the commenter does not want to be made publicly
available, including any supplemental materials. DEA will review this
copy, including the claimed PII and confidential business information,
in its consideration of comments. The second copy should be marked ``TO
BE PUBLICLY POSTED'' and must have all claimed confidential PII and
business information already redacted. DEA will post only the redacted
comment on https://www.regulations.gov for public inspection. DEA
generally will not redact additional information contained in the
comment marked ``TO BE PUBLICLY POSTED.'' The Freedom of Information
Act applies to all comments received.
For easy reference, an electronic copy of this document and
supplemental information to this proposed scheduling action are
available at https://www.regulations.gov.
Request for Hearing or Appearance; Waiver
Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking
``on the record after opportunity for a hearing.'' Such proceedings are
conducted pursuant to the provisions of the Administrative Procedure
Act (APA), 5 U.S.C. 551-559.\1\ Interested persons, as defined in 21
CFR 1300.01(b), may file requests for a hearing in conformity with the
requirements of 21 CFR 1308.44(a) and 1316.47(a), and such requests
must:
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\1\ 21 CFR 1308.41 through 1308.45; 21 CFR part 1316, subpart D.
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(1) state with particularity the interest of the person in the
proceeding;
(2) state with particularity the objections or issues concerning
which the person desires to be heard; and
(3) state briefly the position of the person with regard to the
objections or issues.
Any interested person may file a waiver of an opportunity for a
hearing or to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(c), together with a written statement of
position on the matters of fact and law involved in any hearing.\2\
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\2\ 21 CFR 1316.49.
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All requests for a hearing and waivers of participation, together
with a written statement of position on the matters of fact and law
involved in such hearing, must be sent to DEA using the address
information provided above. The decision whether a hearing will be
needed to address such matters of fact and law in the rulemaking will
be made by the Administrator. If a hearing is needed, DEA will publish
a notification of hearing on the proposed rulemaking in the Federal
Register.\3\ Further, once the Administrator determines a hearing is
needed to address such matters of fact and law in rulemaking, she will
then designate an Administrative Law Judge (ALJ) to preside over the
hearing. The ALJ's functions shall only commence upon designation, as
provided in 21 CFR 1316.52.
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\3\ 21 CFR 1308.44(b), 1316.53.
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In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl meet the statutory criteria for
placement in schedule I, as proposed in this rule.
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 an
interested party.\4\ This proposed action is initiated on the
Administrator's own motion and supported by, inter alia, 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. If finalized, this action would make
permanent the existing temporary regulatory controls and
administrative, civil, and criminal sanctions of schedule I controlled
substances on any person who handles or proposes to handle these seven
substances.
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\4\ 21 U.S.C. 811(a).
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Background
On February 6, 2018, pursuant to 21 U.S.C. 811(h)(1), DEA published
an order in the Federal Register (83 FR 5188) temporarily placing
fentanyl-related substances, as defined in that order, in schedule I of
the CSA based upon a finding that these substances pose an imminent
hazard to the public safety.\5\ As discussed below in Factor 3, the
seven substances named in this proposed rule meet the existing
definition of fentanyl-related substances as they are not otherwise
controlled in any other schedule (i.e., not included under another DEA
Controlled Substance Code Number) and are structurally related to
fentanyl by one or more of the five modifications listed under the
definition. That temporary
[[Page 106386]]
order was effective upon the date of publication. Pursuant to 21 U.S.C.
811(h)(2), the temporary control of fentanyl-related substances, a
class of substances as defined in the order, as well as the seven
specific substances already covered by that order, was set to expire on
February 6, 2020. However, on February 6, 2020, as explained in DEA's
April 10, 2020 correcting amendment),\6\ Congress extended that
expiration date until May 6, 2021, by enacting the Temporary
Reauthorization and Study of the Emergency Scheduling of Fentanyl
Analogues Act.\7\ This temporary order was subsequently extended
multiple times, most recently on December 29, 2022, through the
Consolidated Appropriations Act, 2023,\8\ which extended the order
until December 31, 2024. Consequently, the temporary control of these
seven substances will remain in effect until December 31, 2024, unless
it is extended. Accordingly, as published elsewhere in this issue of
the Federal Register, the DEA Administrator is ordering an extension of
this temporary order as it relates to these seven substances.
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\5\ Schedules of Controlled Substances: Temporary Placement of
Fentanyl-Related Substances in Schedule I, 83 FR 5188 (Feb. 6,
2018).
\6\ Schedules of Controlled Substances: Temporary Placement of
Fentanyl-Related Substances in Schedule I; Correction, 85 FR 20155
(Apr. 10, 2020).
\7\ Public Law 116-114, sec. 2, 134 Stat. 103.
\8\ Public Law 117-328, division O, title VI, sec. 601.
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The Administrator, on her own motion pursuant to 21 U.S.C. 811(a),
is initiating proceedings to permanently schedule para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl in
schedule I of the CSA. Pursuant to 21 U.S.C. 811(b), DEA gathered the
necessary data and reviewed the available information regarding the
pharmacology, chemistry, trafficking, actual abuse, pattern of abuse,
and the relative potential for abuse for these substances. On April 3,
2023, in accordance with 21 U.S.C. 811(b), the Administrator submitted
a request to the Assistant Secretary to provide DEA with a scientific
and medical evaluation of available information and a scheduling
recommendation for these seven substances.
On October 25, 2024, the Assistant Secretary submitted HHS's
scientific and medical evaluation and scheduling recommendation for
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl and
their salts to the Administrator. The Secretary recommended placing
these seven fentanyl related substances 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 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 seven substances.
Proposed Determination To Permanently Schedule Seven Specific Fentanyl-
Related Substances
As discussed in the background section, the Administrator is
initiating proceedings, pursuant to 21 U.S.C. 811(a), to permanently
add para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl to
schedule I. DEA reviewed the scientific and medical evaluation and
scheduling recommendation received from HHS, and all other relevant
data and conducted its own eight-factor analysis of the abuse potential
of these seven substances pursuant to 21 U.S.C. 811(c). Included below
is a brief summary of each factor as analyzed by HHS and DEA, and as
considered by DEA in its proposed scheduling action. Readers should
refer to the full eight-factor analyses prepared by HHS and by DEA in
support of this proposal, which are available in their entirety under
``Supporting Documents'' of the public docket for this proposed rule at
https://www.regulations.gov under Docket Number ``DEA-1457.''
1. The Drug's Actual or Relative Potential for Abuse
In addition to considering the information HHS provided in its
scientific and medical evaluation document for these seven fentanyl-
related substances, DEA also considered all other relevant data
regarding actual or relative potential for abuse of these three
substances. The term ``abuse'' is not defined in the CSA; however, the
legislative history of the CSA suggests that DEA consider the following
criteria when determining whether a particular drug or substance has a
potential for abuse: \9\
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\9\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted in 1970
U.S.C.C.A.N. 4566, 4603.
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(a) There is evidence that individuals are taking the drug or drugs
containing such a substance in amounts sufficient to create a hazard to
their health or to the safety of other individuals or to the community;
or
(b) There is significant diversion of the drug or drugs containing
such a substance from legitimate drug channels; or
(c) Individuals are taking the drug or drugs containing such a
substance on their own initiative rather than on the basis of medical
advice from a practitioner licensed by law to administer such drugs in
the course of his professional practice; or
(d) The drug or drugs containing such a substance are new drugs so
related in their action to a drug or drugs already listed as having a
potential for abuse to make it likely that the drug will have the same
potentiality for abuse as such drugs, thus making it reasonable to
assume that there may be significant diversions from legitimate
channels, significant use contrary to or without medical advice, or
that it has a substantial capability of creating hazards to the health
of the user or to the safety of the community.
Law enforcement seizure data indicate that individuals have and are
using para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl on their own initiative rather than on
the basis of medical advice from a practitioner licensed by law to
administer such drugs in the course of his professional practice,
especially since there is no currently accepted medical use for these
seven substances. According to the National Forensic Laboratory
Information System (NFLIS-Drug) \10\ database, which collects drug
identification results from drug cases submitted to and analyzed by
Federal, State, and local forensic laboratories, there have been 214
reports for para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl
between 2020 and 2024. According to HHS, para-
[[Page 106387]]
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-
fluoro valeryl fentanyl are not legally marketed as drugs in the United
States or anywhere else in the world. These substances have no approved
medical use other than their limited use in scientific research. As
such, the legal sources of the substances are limited to legitimate
chemical companies supplying them for scientific research.
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\10\ The National Forensic Laboratory Information System (NFLIS)
represents an important resource in monitoring illicit drug
trafficking, including the diversion of legally manufactured
pharmaceuticals into illegal markets. NFLIS is a comprehensive
information system that includes data from forensic laboratories
that handle more than 96% of an estimated 1.0 million distinct
annual State and local drug analysis cases. 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 (Dec. 12, 2011). NFLIS data were queried November 1, 2024.
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para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl are not approved for medical use and
are not formulated or approved for clinical use. As such, all use is on
an individual's own initiative, rather than on the basis of medical
advice from a practitioner licensed by law to administer drugs. Law
enforcement seizures and case reports demonstrate that individuals are
taking these seven fentanyl-related substances on their own initiative,
rather than on the basis of medical advice from a licensed
practitioner.
Based on available data, para-chlorofentanyl, ortho-chlorofentanyl,
meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl, are related in their effects to the actions of other
mu-opioid receptor (MOR) agonists,\11\ such as fentanyl, that are
already listed as having potential for abuse. Because high doses of MOR
agonists can produce respiratory depression leading to death, these
fentanyl-related substances at high doses have substantial capability
of creating hazards to the health of the user or to the safety of the
community. According to HHS, these seven fentanyl-related substances
exert their actions at least in part through the MOR and thus have a
high likelihood of having substantially similar potential for abuse as
other schedule I opioids. Both DEA's and HHS's eight-factor analyses
found that the abuse potential of these substances is similar to other
schedule I opioids and presents a hazard to the health and safety of
individuals and the community.
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\11\ Drug Enforcement Administration-Veterans Affairs (DEA-VA)
Interagency Agreement. Binding and Functional Activity at Delta,
Kappa and Mu Opioid Receptors. In Vitro Receptor and Transporter
Assays for Abuse Liability Testing for the DEA by the VA
(unpublished data).
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2. Scientific Evidence of the Drug's Pharmacological Effects, if Known
According to DEA and HHS, the pharmacological activity of these
substances in humans is unknown. Data obtained from preclinical studies
show that these fentanyl-related substances (para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl)
exhibit a pharmacological profile similar to that of fentanyl,
morphine, and several schedule I opioid substances that are
structurally related to fentanyl. Similar to fentanyl and other
structurally related synthetic opioids, fentanyl-related substances
namely para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl have
been shown to bind to the mu-opioid receptors with varying
affinities.\12\ Also, similar to fentanyl and other structurally
related synthetic opioids, these seven fentanyl-related substances
behave as agonists at the MOR sites in in vitro functional studies.
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\12\ in vitro Pharmacology data was collected through DEA--
Veterans Affairs interagency agreement: ``in vitro Receptor and
Transporter Assays for Abuse Liability Testing for the DEA by the
VA''.
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Studies conducted to examine the antinociceptive effect of the
seven fentanyl-related substances in a warm water tail-withdrawal assay
and their mediation by opioid receptors as determined by naltrexone
antagonism showed these seven fentanyl-related substances, similar to
fentanyl and morphine, produced antinociceptive effects as measured by
an increase in tail withdrawal latency.\13\ Pre-treatment with
naltrexone, an opioid receptor antagonist, attenuated antinociceptive
effects of the seven-fentanyl related substances. These data
demonstrate that similar to morphine and fentanyl, para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, para-fluoro valeryl fentanyl produced
dose-dependent antinociception in the warm-water tail-withdrawal assay
that can be attenuated by naltrexone pre-treatment.
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\13\ Gatch MB. (2024). Test of analgesic effects alone and in
combination with naltrexone. 15DDHQ19F00001173, ``Evaluation of
Abuse Potential of Synthetic Opioids Using in Vivo Pharmacological
Studies'' (unpublished data).
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There is a strong correlation between the discriminative stimulus
effects of a given drug in animals and its subjective effects in
humans.\14\ Data from drug discrimination studies \15\ show that the
seven-fentanyl related substances fully and dose-dependently substitute
for the discriminative stimulus effects produced by morphine in Sprague
Dawley rats trained to discriminate 3.2 mg/kg morphine from saline.\16\
These data demonstrate para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl, similar to morphine (schedule II) and fentanyl
(schedule II), are mu-opioid receptor agonists.
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\14\ Solinas M, Panlilio LV, Justinova Z, Yasar S, Goldberg SR.
(2006). Using drug-discrimination techniques to study the abuse-
related effects of psychoactive drugs in rats. Nat Protoc.1(3):1194-
206.
\15\ Drug discrimination is widely used to determine whether a
new test drug or substance is pharmacologically similar to a known
drug of abuse.
\16\ DEA-Synthetic Opioids Purchase Agreement (2022-2024).
Evaluation of synthetic opioid substances using analgesia and the
drug discrimination assay. In Vivo Testing for the DEA by Gatch
(Univ. of North Texas).
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3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl are
synthetic opioids in the 4-anilidopiperidine structural class which
includes fentanyl. As defined in the February 6, 2018 temporary
scheduling order, fentanyl-related substances include any substance not
otherwise controlled in any schedule (i.e., not included under any
other Administration Controlled Substance Code Number) that is
structurally related to fentanyl by one or more of the following
modifications:
(A) Replacement of the phenyl portion of the phenethyl group by any
monocycle, whether or not further substituted in or on the monocycle;
(B) substitution in or on the phenethyl group with alkyl, alkenyl,
alkoxyl, hydroxyl, halo, haloalkyl, amino or nitro groups;
(C) substitution in or on the piperidine ring with alkyl, alkenyl,
alkoxyl, ester, ether, hydroxyl, halo, haloalkyl, amino or nitro
groups;
(D) replacement of the aniline ring with any aromatic monocycle,
whether
[[Page 106388]]
or not further substituted in or on the aromatic monocycle; and/or
(E) replacement of the N-propionyl group by another acyl group.
[GRAPHIC] [TIFF OMITTED] TP30DE24.017
Figure 1: Regions of the Chemical Structure of Fentanyl Described in
The Definition of a Fentanyl-Related Substance
According to the February 6, 2018 temporary scheduling order, the
existence of a substance with anyone, or any combination, of above-
mentioned modifications (see figure 1) would meet the structural
requirements of the definition of fentanyl-related substances. The
present seven substances fall within the definition of fentanyl-related
substances by the following modifications:
1. para-chlorofentanyl: substitution on the aniline ring (meets
definition for modification D);
2. ortho-chlorofentanyl: substitution on the aniline ring (meets
definition for modification D);
3. meta-fluorofuranyl fentanyl: substitution on the aniline ring
and replacement of the N-propionyl group with another acyl group (meets
definition for modifications D and E);
4. ortho-methylcyclopropyl fentanyl: substitution on the aniline
ring and replacement of the N-propionyl group with another acyl group
(meets definition for modifications D and E);
5. beta-methylacetyl fentanyl: substitution on the phenethyl group
with an alkyl group and replacement of the N-propionyl group with
another acyl group (meets definition for modifications B and E);
6. tetrahydrothiofuranyl fentanyl: replacement of the N-propionyl
group with another acyl group (meets definition for modification E);
7. para-fluoro valeryl fentanyl: substitution on the aniline ring
and replacement of the N-propionyl group with another acyl group (meets
definition for modifications D and E).
4. Its History and Current Pattern of Abuse
Evidence suggests that the pattern of abuse of para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl
parallels that of prescription opioid analgesics. Currently, the United
States is in the midst of an illicit opioid abuse epidemic. There has
been a marked increase in the encounters of synthetic opioids that are
structurally related to fentanyl that parallels an increase in deaths
related to synthetic opioids. Thus, the recreational abuse of fentanyl-
like substances continues to be a significant concern. These substances
are distributed to users, often with unpredictable outcomes. para-
Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-
fluoro valeryl fentanyl have been encountered by law enforcement
officials.
Law enforcement encountered these seven substances in the United
States. According to the NFLIS \17\ database, 214 reports were
registered containing six of the substances (para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, beta-methylacetyl
fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl
fentanyl) from state or local forensic laboratories from 2020 to 2024.
ortho-Methylcyclopropyl fentanyl was not specifically listed in the
NFLIS database, although in 2018, there were three reports of
methylcyclopropyl fentanyl.
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\17\ NFLIS data were queried November 1, 2024. NFLIS data
reporting is still pending for 2023 and 2024 due to normal lag time.
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5. The Scope, Duration, and Significance of Abuse
The rapid appearance of fentanyl-related substances presents
numerous challenges for forensic and toxicology laboratories. The
identification of a new substance requires full structural elucidation,
sometimes requiring specialized instrumentation not available to all
forensic laboratories. Laboratories are required to quickly adapt
testing procedures to identify new substances. It remains likely that
the prevalence of these substances in opioid related emergency room
admissions and deaths is underreported as standard immunoassays may not
differentiate fentanyl from substances structurally related to
fentanyl.
The population likely to abuse fentanyl-related substances overlaps
with the population abusing prescription opioid analgesics, heroin,
fentanyl, and other synthetic opioid substances. Because abusers of
fentanyl-related substances are likely to obtain these substances
through unregulated sources, the identity, purity, and quantity are
uncertain and inconsistent, thus posing significant adverse health
risks to the end user. The misuse and abuse of opioids have been
demonstrated and are well characterized. According to the most recent
data from the National Survey on Drug Use and Health (NSDUH) \18\ of
the Substance Abuse and Mental Health Services Administration
(SAMHSA),\19\ in 2023, an estimated 8.9 million people aged 12 or older
misused opioids in the past year, including 8.6 million prescription
pain reliever misusers and 660,000 heroin users. In 2023, among people
aged 12 or older, 828,000 people misused fentanyl in the past year.
NSDUH data show that among people aged 12 or older in 2023, 627,000
people used illicitly manufactured fentanyl in the past year. This
population is likely to be at risk of abusing fentanyl-related
substances. Individuals who initiate (i.e., use a drug for the first
time) use of fentanyl-related substances are likely to be at risk of
developing substance use disorder, overdose, and death, similar to the
risks of other opioid analgesics (e.g., fentanyl, morphine, etc.).
---------------------------------------------------------------------------
\18\ The National Survey on Drug Use and Health, formerly known
as the National Household Survey on Drug Abuse (NHSDA), is conducted
annually by the Department of Health and Human Services Substance
Abuse and Mental Health Services Administration (SAMHSA). It is the
primary source of estimates of the prevalence and incidence of
nonmedical use of pharmaceutical drugs, illicit drugs, alcohol, and
tobacco use in the United States. The survey is based on a
nationally representative sample of the civilian, non-
institutionalized population 12 years of age and older. The survey
excludes homeless people who do not use shelters, active military
personnel, and residents of institutional group quarters such as
jails and hospitals. The NSDUH provides yearly national and state
level estimates of drug abuse, and includes prevalence estimates by
lifetime (i.e., ever used), past year and past month abuse or
dependence.
\19\ The Substance Abuse and Mental Health Services
Administration (SAMHSA) is a branch of the U.S. Department of Health
and Human Services (HHS). It is charged with improving the quality
and availability of prevention, treatment, and rehabilitative
services in order to reduce illness, death disability, and cost to
society resulting from substance abuse and mental illness.
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According to HHS, it is highly likely that the prevalence of these
fentanyl-related substances in emergency room admissions and fatalities
is under reported because standard immunoassays may not be sufficient
to distinguish between fentanyl and
[[Page 106389]]
substances that are structurally related to fentanyl. Law enforcement
reports demonstrate para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl are being illicitly distributed and abused. The use of
these seven fentanyl-related substances is likely to increase the
scope, duration, and significance of abuse based on their
pharmacological similarity to drugs that are abused in the current
opioid epidemic (e.g., fentanyl).
6. What, if Any, Risk There Is to the Public Health
The increase in opioid overdose deaths in the United States has
been exacerbated by the availability of potent synthetic opioids such
as fentanyl and numerous other structurally related substances in the
illicit drug market.\20\ These substances have a history of being
trafficked as replacements for other opioids, such as heroin and other
synthetic opioids. Fentanyl is a potent synthetic opioid that is
primarily prescribed for acute and chronic pain and is approximately
100 times more potent than morphine. As such, fentanyl has a high risk
of abuse, dependence and overdose that can lead to death. Because
fentanyl-related substances have a similar chemical structure to
fentanyl, these substances are expected to have similar biological
effects. Indeed, these seven fentanyl-related substances produced
pharmacological effects similar to fentanyl. The adverse effects of
substances structurally related to fentanyl on humans are largely
identical to those of fentanyl and other opioid analgesics. These
fentanyl-related substances pose the same qualitative public health
risks as heroin, fentanyl, and other opioid analgesic substances. The
DEA Toxicology Testing Program (DEA-Tox) \21\ identified three drug
paraphernalia where para-chlorofentanyl was detected. These cases
occurred between May 2022 and June 2024. As the data demonstrate, the
potential for overdoses exists for these substances and these
substances pose risk to public health.
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\20\ Centers for Disease Control and Prevention, (2024, April).
Understanding the opioid overdose epidemic. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdoseepidemic.html Spencer, M. R., Warner, M., Cisewski, J. A.,
Mini[ntilde]o, A., Dodds, D., Perera, J., & Ahmad, F. B., Estimates
of drug overdose deaths involving fentanyl, methamphetamine,
cocaine, heroin, and oxycodone: United States, 2021. Vital
Statistics Rapid Release (Report No. 27). National Center for Health
Statistics; Zibbell, J. E., Aldridge, A., Grabenauer, M., Heller,
D., Duhart Clarke, S., Pressley, D., & Smiley-McDonald, H. (2023).
Associations between opioid overdose deaths and drugs confiscated by
law enforcement and submitted to crime laboratories for analysis,
United States, 2014-2019: An observational study. The Lancet
Regional Health--Americas, 25.
\21\ DEA-TOX is a DEA-run program whereby unused biological
samples from victims of drug overdoses can be extensively tested for
the presence of novel psychoactive substances, in addition to other
drugs of abuse.
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According to HHS, the lack of hospitalization or fatality for these
seven fentanyl-related substances is not surprising because the enzyme
linked immunosorbent assay (ELISA) which is used to detect fentanyl
cross-reacts with fentanyl-related substances when fentanyl is present
above a threshold level.\22\ Thus, fatalities that might be associated
with the fentanyl-related substances may be underreported. As with any
opioid not approved for medical use, the health and safety risks for
users are high. Public health data suggest that para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl may be
a direct risk to public health.
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\22\ Guerrieri D, Kjellqvist F, Kronstrand R, Gr[eacute]en H.
(2019). Validation and Cross-Reactivity Data for Fentanyl Analogs
with the Immunalysis Fentanyl ELISA. J Anal Toxicol. 43(1):18-24.
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7. Its Psychic or Physiological Dependence Liability
According to HHS, the psychic or physiologic dependence of these
seven fentanyl-related substances has not been studied in clinical
studies and is therefore unknown. HHS notes that pharmacology data for
these substances as MOR agonists with known abuse potential
demonstrates their property of producing physical and psychic
dependence similar to other MOR agonists. The discontinuation of the
use of MOR agonists, such as morphine and fentanyl (Schedule II drugs),
is associated with withdrawal symptoms indicative of physical
dependence. Opioid withdrawal syndrome is characterized by central
nervous system irritability, gastrointestinal dysfunction, yawning,
diaphoresis, and fever.\23\ Thus, the pharmacological similarity and
pattern of abuse of para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl are indicative of their potential to possess a psychic
and physiological dependence liability similar to that of other mu
opioid receptor agonist substances, such as heroin and fentanyl.
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\23\ Katz R, Kelly W, Hsi A. (1994). Prospective-study on the
occurrence of withdrawal in critically ill children who receive
fentanyl by continuous-infusion. Critical Care Medicine 16:763-767.
---------------------------------------------------------------------------
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA
para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl are
not immediate precursors of any controlled substance of the CSA, as
defined by 21 U.S.C. 802(23).
Conclusion: Based on consideration of the scientific and medical
evaluation and accompanying recommendation of HHS, and on DEA's own
eight-factor analysis, DEA finds that these facts and all relevant data
constitute substantial evidence of potential for abuse of para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl. As
such, DEA proposes to permanently schedule these seven substances as
controlled substances under the CSA.
Proposed 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.\24\ 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 812(b)(1),
finds that:
---------------------------------------------------------------------------
\24\ See 21 U.S.C. 812(b).
---------------------------------------------------------------------------
(1) para-Chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl,
similar to fentanyl, are mu-opioid receptor agonists. The seven
fentanyl-related substances have analgesic effects, and these effects
are mediated by [mu]-opioid receptor agonism. These substances that
produce mu-opioid receptor agonist effects in the CNS are considered as
having a high potential for abuse (e.g. morphine and fentanyl). Data
obtained from drug discrimination studies indicate that para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl
[[Page 106390]]
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl fully substituted for the
discriminative stimulus effects of morphine. Thus, these substances
have a high potential for abuse.
(2) There is no FDA-approved drug application for para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl in the
United States. Further, there are no adequate and well-controlled
clinical studies for any of these substances, and there are no well-
defined finished dosage forms for any of these fentanyl-related
substances. There are no known therapeutic applications for these seven
fentanyl-related substances, and thus they have no currently accepted
medical use in the United States.\25\
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\25\ Pursuant to 21 U.S.C. 812(b)(1)(B), when placing a drug or
substance in schedule I of the CSA, DEA must consider whether the
substance has a currently accepted medical use in treatment in the
United States. First, DEA looks to whether the drug or substance has
FDA approval. When no FDA approval exists, DEA has traditionally
applied a five-part test to a drug or substance to determine whether
a drug or substance has a currently medical use: 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.
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 applied the traditional five-part test and concluded
the test was not satisfied. 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 providers 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). In its eight-factor assessment, HHS determined that these
seven fentanyl-related substances did not satisfy this two-part
test. Therefore, since both DEA and HHS have determined that these
seven fentanyl-related substances do not satisfy the five-part test,
and HHS has determined that these seven fentanyl-related substances
do not satisfy the additional two-part test, DEA concludes that
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl
fentanyl, ortho-methylcyclopropyl fentanyl, beta-methylacetyl
fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl
fentanyl do not have a currently accepted medical use.
---------------------------------------------------------------------------
(3) There is a lack of accepted safety for use of para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl under
medical supervision. Because these seven substances have no FDA-
approved medical use and have not been investigated as new drugs, their
safety for use under medical supervision has not been determined.
Therefore, there is a lack of accepted safety for use of these seven
substances under medical supervision.
Based on these findings, the Administrator of DEA concludes that
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl,
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.\26\
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\26\ 21 U.S.C. 812(b)(1).
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Requirements for Handling para-Chlorofentanyl, ortho-Chlorofentanyl,
meta-Fluorofuranyl fentanyl, ortho-Methylcyclopropyl fentanyl, beta-
Methylacetyl fentanyl, Tetrahydrothiofuranyl fentanyl, and para-Fluoro
valeryl fentanyl
As discussed above, these seven fentanyl-related substances are
currently subject to a temporary scheduling order, which added them to
schedule I. If this rule is finalized as proposed, para-chlorofentanyl,
ortho-chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-
methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl would
be subject, on a permanent basis, to the CSA's schedule I regulatory
controls and administrative, civil, and criminal sanctions applicable
to the manufacture, distribution, dispensing, importing, exporting,
research, and conduct of instructional activities, including the
following:
1. Registration. Any person who handles (manufactures, distributes,
dispenses, imports, exports, engages in research, or conducts
instructional activities or chemical analysis with, or possesses) para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl 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.
2. Security. para-Chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl are subject to schedule I security requirements and
must be handled and stored pursuant to 21 U.S.C. 821, 823, and in
accordance with 21 CFR 1301.71 through 1301.76. Non-practitioners
handling these seven substances also must comply with the screening
requirements of 21 CFR 1301.90 through 1301.93.
3. Labeling and Packaging. All labels and labeling for commercial
containers of para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl must comply with 21 U.S.C. 825 and 958(e) and be in
accordance with 21 CFR part 1302.
4. Quota. Only registered manufacturers are permitted to
manufacture para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl in accordance with a quota assigned pursuant to 21
U.S.C. 826 and in accordance with 21 CFR part 1303.
5. Inventory. Any person registered with DEA to handle para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl 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 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 para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl) on
hand
[[Page 106391]]
every two years pursuant to 21 U.S.C. 827 and 958(e) and in accordance
with 21 CFR 1304.03, 1304.04, and 1304.11.
6. Records and Reports. Every DEA registrant must maintain records
and submit reports with respect to para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl, 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 para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl to the
Automation of Reports and Consolidated Order System pursuant 21 U.S.C.
827, and in accordance with 21 CFR parts 1304 and 1312.
7. Order Forms. Every DEA registrant who distributes para-
chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must
comply with the order form requirements, pursuant to 21 U.S.C. 828 and
21 CFR part 1305.
8. Importation and Exportation. All importation and exportation of
para-chlorofentanyl, ortho-chlorofentanyl, meta-fluorofuranyl fentanyl,
ortho-methylcyclopropyl fentanyl, beta-methylacetyl fentanyl,
tetrahydrothiofuranyl fentanyl, and para-fluoro valeryl fentanyl must
be in compliance with 21 U.S.C. 952, 953, 957, and 958, and in
accordance with 21 CFR part 1312.
9. Liability. Any activity involving para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl 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, 13563, and 14094 (Regulatory Review)
In accordance with 21 U.S.C. 811(a), this proposed 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 proposed 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 proposed rulemaking does not have federalism implications
warranting the application of E.O. 13132. The proposed 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 proposed 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 February 6, 2018, DEA
published an order to temporarily place fentanyl-related substances, as
defined in the order, in schedule I of the CSA pursuant to the
temporary scheduling provisions of 21 U.S.C. 811(h). However, as
explained in DEA's April 10, 2020 correcting amendment,\27\ Congress
extended that expiration date until May 6, 2021, by enacting the
Temporary Reauthorization and Study of the Emergency Scheduling of
Fentanyl Analogues Act.\28\ This temporary order was subsequently
extended multiple times, most recently on December 29, 2022, through
the Consolidated Appropriations Act, 2023,\29\ which extended the order
until December 31, 2024. DEA estimates that all entities handling or
planning to handle para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl have already established and implemented systems and
processes required to handle these substances which meet the definition
of fentanyl-related substances.
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\27\ Schedules of Controlled Substances: Temporary Placement of
Fentanyl-Related Substances in Schedule I; Correction, 85 FR 20155
(Apr. 10, 2020).
\28\ Public Law 116-114, sec. 2, 134 Stat. 103.
\29\ Public Law 117-328, division O, title VI, sec. 601.
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There are currently 170 registrations authorized to specifically
handle the fentanyl-related substances as a class, which include one or
more of the following substances: para-chlorofentanyl, ortho-
chlorofentanyl, meta-fluorofuranyl fentanyl, ortho-methylcyclopropyl
fentanyl, beta-methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl,
and para-fluoro valeryl fentanyl, as well as a number of registered
analytical labs that are authorized to handle schedule I controlled
substances generally. Some of these entities are likely to be large
entities. However, since DEA does not have information of registrant
size, DEA conservatively assumes all of 170 registrants affected by
this rule are small entities.
A review of the 170 registrations indicates that all entities that
currently handle para-chlorofentanyl, ortho-chlorofentanyl, meta-
fluorofuranyl fentanyl, ortho-methylcyclopropyl fentanyl, beta-
methylacetyl fentanyl, tetrahydrothiofuranyl fentanyl, and para-fluoro
valeryl fentanyl 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 that
this proposed rule will impose minimal or no economic impact on any
affected entities; and thus, will not have a significant economic
impact on any of the 95 affected small entities. Therefore,
[[Page 106392]]
DEA has concluded that this proposed 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 (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 the UMRA
of 1995.
Paperwork Reduction Act of 1995
This proposed rule would not impose a new collection or modify an
existing collection of information under the Paperwork Reduction Act of
1995.\30\ Also, this proposed rule would not impose new or modify
existing recordkeeping or reporting requirements on state or local
governments, individuals, businesses, or organizations. However, this
proposed 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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\30\ 44 U.S.C. 3501-3521.
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Signing Authority
This document of the Drug Enforcement Administration was signed on
December 19, 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.
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 proposes to amend 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)(104) through (109) as paragraphs (b)(111)
through (116);
0
b. Redesignate paragraphs (b)(87) through (103) as paragraphs (b)(93)
through (109);
0
c. Redesignate paragraphs (b)(84) through (86) as paragraphs (b)(89)
through (91);
0
d. Redesignate paragraphs (b)(82) and (83) as paragraphs (b)(86) and
(87);
0
e. Redesignate paragraphs (b)(76) through (81) as paragraphs (b)(79)
through (84);
0
f. Redesignate paragraphs (b)(59) through (75) as paragraphs (b)(61)
through (77);
0
g. Redesignate paragraphs (b)(21) through (58) as paragraphs (b)(22)
through (59); and
0
h. Add new paragraphs (b)(21), (60), (78), (85), (88), (92), and (110).
The additions read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(b) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
* * * * * * *
(21) beta-methylacetyl fentanyl (N-phenyl-N-(1-(2- 9868
phenylpropyl)piperidin-4-yl)acetamide).................
* * * * * * *
(60) meta-fluorofuranyl fentanyl (N-(3-fluorophenyl)-N- 9871
(1-phenethylpiperidin-4-yl)furan-2-carboxamide)........
* * * * * * *
(78) ortho-chlorofentanyl (N-(2-chlorophenyl)-N-(1- 9828
phenethylpiperidin-4-yl)propionamide...................
* * * * * * *
(85) ortho-methylcyclopropyl fentanyl (N-(2- 9849
methylphenyl)-N-(1-phenethylpiperidin-4-
yl)cyclopropanecarboxamide)............................
* * * * * * *
(88) para-chlorofentanyl (N-(4-chlorophenyl)-N-(1- 9818
phenethylpiperidin-4-yl)propionamide)..................
* * * * * * *
(92) para-fluoro valeryl fentanyl (N-(4-fluorophenyl)-N- 9870
(1-phenethylpiperidin-4-yl)pentanamide)................
* * * * * * *
(110) tetrahydrothiofuranyl fentanyl (also known as: 9869
tetrahydrothiophene fentanyl) (N-(1-phenethylpiperidin-
4-yl)-N-phenyltetrahydrothiophene-2-carboxamide).......
* * * * * * *
------------------------------------------------------------------------
[[Page 106393]]
* * * * *
[FR Doc. 2024-30798 Filed 12-27-24; 8:45 am]
BILLING CODE 4410-09-P