Proposed Rule2024-24616
Possible Control of Phenethyl Bromide as a List I Chemical
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Published
October 28, 2024
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration (DEA) finds that phenethyl bromide is used in the illicit manufacture of the controlled substance fentanyl, as well as fentanyl analogues and fentanyl-related substances, and is important to the manufacture of these substances because it is often used in synthetic pathways to illicitly manufacture fentanyl, fentanyl analogues, and fentanyl-related substances. Prior to proposing to list phenethyl bromide as a list I chemical under the Controlled Substances Act, DEA is soliciting information on the current uses of phenethyl bromide (other than for the synthesis of fentanyl) in order to properly determine the effect such a proposed action would have on legitimate industry.
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<title>Federal Register, Volume 89 Issue 208 (Monday, October 28, 2024)</title>
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[Federal Register Volume 89, Number 208 (Monday, October 28, 2024)]
[Proposed Rules]
[Pages 85459-85462]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-24616]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1310
[Docket No. DEA-1282]
Possible Control of Phenethyl Bromide as a List I Chemical
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Advanced notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration (DEA) finds that phenethyl
bromide is used in the illicit manufacture of the controlled substance
fentanyl, as well as fentanyl analogues and fentanyl-related
substances, and is important to the manufacture of these substances
because it is often used in synthetic pathways to illicitly manufacture
fentanyl, fentanyl analogues, and fentanyl-related substances. Prior to
proposing to list phenethyl bromide as a list I chemical under the
Controlled Substances Act, DEA is soliciting information on the current
uses of phenethyl bromide (other than for the synthesis of fentanyl) in
order to properly determine the effect such a proposed action would
have on legitimate industry.
DATES: Comments must be submitted electronically or postmarked on or
before November 27, 2024. Commenters should be aware that the
electronic Federal Docket Management System will not accept any
comments after 11:59 p.m. Eastern Time on the last day of the comment
period.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-1282'' on all electronic and written correspondence,
including any attachments.
<bullet> Electronic comments: The Drug Enforcement Administration
(DEA) encourages that all comments be submitted electronically through
the Federal eRulemaking Portal, which provides the ability to type
short comments directly into the comment field on the web page or
attach a file for lengthier comments. Please go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and follow the online instructions at that site for
submitting comments. Upon completion of your comment submission, you
will receive a Comment Tracking Number. Please be aware that submitted
comments are not instantaneously available for public view on
<a href="http://Regulations.gov">Regulations.gov</a>. If you have received a Comment Tracking Number, your
comment has been successfully submitted and there is no need to
resubmit the same comment.
<bullet> 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.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
Posting of Public Comments
Please note that all comments received in response to this docket
are considered part of the public record. The Drug Enforcement
Administration (DEA) will make comments available for public inspection
online at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Such information includes
personal or business identifying information (such as name, address,
State or Federal identifiers, etc.) voluntarily submitted by the
commenter. Generally, all information voluntarily submitted by the
commenter, unless clearly marked as Confidential Information in the
method described below, will be publicly posted. Comments may be
submitted anonymously. The Freedom of Information Act applies to all
comments received.
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 PII and business
information already redacted. DEA will post only the redacted comment
on <a href="https://www.regulations.gov">https://www.regulations.gov</a> for public inspection.
For easy reference, an electronic copy of this document and a plain
language summary of this advanced notice of proposed rulemaking are
available at <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Legal Authority
The Controlled Substances Act (CSA) authorizes the Attorney General
to specify, by regulation, chemicals as list I chemicals.\1\ The
Attorney General has delegated his authority to designate list I
chemicals to the Administrator of DEA (Administrator).\2\ A ``list I
chemical'' is a chemical that is used in manufacturing a controlled
substance in violation of the CSA and is important to the manufacture
of the controlled substances.\3\ The current list of all listed
chemicals is published at 21 CFR
[[Page 85460]]
1310.02. DEA regulations set forth the process by which DEA may add a
chemical as a listed chemical. As set forth in 21 CFR 1310.02(c), the
agency may do so by publishing a final rule in the Federal Register
following a published notice of proposed rulemaking with at least 30
days for public comments.
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\1\ 21 U.S.C. 802(34).
\2\ 28 CFR 0.100(b).
\3\ Id.
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Background
The clandestine manufacture of fentanyl, fentanyl analogues, and
fentanyl-related substances remains extremely concerning as the
distribution of illicit fentanyl, fentanyl analogues, and fentanyl-
related substances continues to drive drug-related overdose deaths in
the United States. Fentanyl is a synthetic opioid and was first
synthesized in Belgium in the late 1950s. Fentanyl was introduced into
medical practice and is approved for medical practitioners in the
United States to prescribe lawfully for anesthesia and analgesia. Yet,
due to its pharmacological effects, fentanyl can be used as a
substitute for heroin, oxycodone, and other opioids in opioid dependent
individuals. Therefore, despite its accepted medical use in treatment
in the United States, DEA controls fentanyl as a schedule II controlled
substance due to its high potential for abuse and dependence.\4\
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\4\ 21 U.S.C. 812(c) Schedule II(b)(6); 21 CFR 1308.12(c).
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Moreover, there are a substantial number of fentanyl analogues \5\
and fentanyl-related substances \6\ that are being distributed on the
illicit drug market despite DEA's recent actions adding them as
scheduled controlled substances.\7\ Illicit manufacturers of fentanyl,
fentanyl analogues, and fentanyl-related substances attempt to utilize
unregulated precursor chemicals to evade law enforcement detection and
precursor chemical controls in order to keep manufacturing these
substances. This strategy allows for the synthesis of a variety of
fentanyl analogues and fentanyl-related substances by making slight
modifications to the core fentanyl structure while maintaining the same
synthetic methodology used to synthesize fentanyl, fentanyl analogues,
and fentanyl-related substances.
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\5\ Schedules of Controlled Substances: Temporary Placement of
Seven Fentanyl-Related Substances in Schedule I. 83 FR 4580 (Feb. 1,
2018).
\6\ Schedules of Controlled Substances: Temporary Placement of
Fentanyl-Related Substances in Schedule I, 83 FR 5188 (Feb. 6,
2018).
\7\ Schedules of Controlled Substances: Placement of 10 Specific
Fentanyl-Related Substances in Schedule I, 86 FR 22113 (Apr. 27,
2021).
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The unlawful trafficking of fentanyl, fentanyl analogues, and
fentanyl-related substances in the United States continues to pose an
imminent hazard to public safety. Since 2012, fentanyl has shown a
dramatic increase in the illicit drug supply as a single substance, in
mixtures with other illicit drugs (i.e., heroin, cocaine, and
methamphetamine), and in forms that mimic pharmaceutical preparations
including prescription opiates and benzodiazepines.\8\
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\8\ United Nations Office on Drugs and Crime, Global SMART
Update Volume 17, March 2017. <a href="https://www.unodc.org/documents/scientific/Global_SMART_Update_17_web.pdf">https://www.unodc.org/documents/scientific/Global_SMART_Update_17_web.pdf</a>.
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DEA has noted a significant increase in overdoses and overdose
fatalities from fentanyl, fentanyl analogues, and fentanyl-related
substances in the United States in recent years. According to the
Centers for Disease Control and Prevention (CDC), opioids, mainly
synthetic opioids (which includes fentanyl), are predominantly
responsible for drug overdose deaths in recent years. According to CDC
WONDER,\9\ drug-induced overdose deaths involving synthetic opioids
(excluding methadone) in the United States increased from 36,359 in
2019, to 56,516 in 2020, and to 70,601 in 2021. Based on provisional
data, the predicted number of drug overdose deaths involving synthetic
opioids (excluding methadone) in the United States for the 12 months
ending March 2023 is 76,472 individuals, or approximately 69.2 percent
of all drug-induced overdose deaths for that time period.\10\ The
increase in overdose fatalities involving synthetic opioids coincides
with a dramatic increase in law enforcement encounters of fentanyl,
fentanyl analogues, and fentanyl-related substances. According to the
National Forensic Laboratory Information System (NFLIS-Drug),\11\
reports from forensic laboratories of drug items containing fentanyl,
fentanyl analogues, and fentanyl-related substances increased
dramatically since 2014, as shown in Table 1.
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\9\ Centers for Disease Control and Prevention, National Center
for Health Statistics. National Vital Statistics System, Provisional
Mortality on CDC WONDER Online Database. Data are from the final
Multiple Cause of Death Files, 2018-2021, and from provisional data
for years 2022-2023, as compiled from data provided by the 57 vital
statistics jurisdictions through the Vital Statistics Cooperative
Program. Accessed at <a href="http://wonder.cdc.gov/mcd-icd10-provisional.html">http://wonder.cdc.gov/mcd-icd10-provisional.html</a> on March 16, 2023.
\10\ Ahmad FB, Cisewski JA, Rossen LM, Sutton P. Provisional
drug overdose death counts. National Center for Health Statistics.
2023. Accessed at <a href="https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm">https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm</a> on August 17, 2023.
\11\ NFLIS-Drug is a national forensic laboratory reporting
system that systematically collects results from drug chemistry
analyses conducted by Federal, State and local forensic laboratories
in the United States. While NFLIS-Drug data is not direct evidence
of abuse, it can lead to an inference that a drug has been diverted
and abused. See 76 FR 77330, 77332 (Dec. 12, 2011). NFLIS-Drug data
was queried on July 31, 2023, and August 17, 2023.
Table 1--Annual Reports of Fentanyl and Select Fentanyl Analogues and Fentanyl-Related Substances Identified in Drug Encounters
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Year 2014 2015 2016 2017 2018 2019 2020 2021 2022
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Annual Fentanyl Reports.................................... 5,554 15,461 37,154 61,642 89,967 108,133 126,0099 165,104 165,920
Annual Reports of select fentanyl analogues and fentanyl- 78 2,317 7,624 21,980 16,033 20,864 7,774 26,363 29,404
related substances........................................
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Role of Phenethyl Bromide in the Synthesis of Fentanyl
Fentanyl, fentanyl analogues, and fentanyl-related substances are
not naturally occurring substances. As such, the manufacture of these
substances requires them to be produced through synthetic organic
chemistry. Synthetic organic chemistry is the process in which a new
organic molecule is created through a series of chemical reactions,
which involve precursor chemicals. Through chemical reactions, the
chemical structures of precursor chemicals are modified in a desired
fashion. These chemical reaction sequences, also known as synthetic
pathways, are designed to create a desired substance. Several synthetic
pathways to fentanyl, fentanyl analogues, and fentanyl-related
substances have been identified in clandestine laboratory settings;
these include the original ``Janssen method,'' the ``Siegfried
method,'' and the ``Gupta method.'' In response to the illicit
manufacture of fentanyl, fentanyl
[[Page 85461]]
analogues, and fentanyl-related substances using these methods, DEA
controlled N-phenethyl-4-piperidone (NPP),\12\ N-(1-benzylpiperidin-4-
yl)-N-phenylpropionamide (benzylfentanyl), N-phenylpiperidin-4-amine
(4-anilinopiperidine; including its amides and carbamates),\13\ and 4-
piperidone (piperidin-4-one) \14\ as list I chemicals, and 4-anilino-N-
phenethylpiperidine (ANPP) \15\ and N-phenyl-N-(piperidin-4-
yl)propionamide (norfentanyl) \16\ as schedule II immediate precursors
under the CSA.
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\12\ Control of a Chemical Precursor Used in the Illicit
Manufacture of Fentanyl as a List I Chemical, 72 FR 20039 (Apr. 23,
2007).
\13\ Designation of Benzylfentanyl and 4-Anilinopiperidine,
Precursor Chemicals Used in the Illicit Manufacture of Fentanyl, as
List I Chemicals, 85 FR 20822 (Apr. 15, 2020).
\14\ Designation of 4-Piperidone as a List I Chemical, 88 FR
21902 (Apr. 12, 2023).
\15\ Control of Immediate Precursor Used in the Illicit
Manufacture of Fentanyl as a Schedule II Controlled Substance, 75 FR
37295 (June 29, 2010).
\16\ Control of the Immediate Precursor Norfentanyl Used in the
Illicit Manufacture of Fentanyl as a Schedule II Controlled
Substance, 85 FR 21320 (Apr. 17, 2020).
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In 2017, the United Nations Commission on Narcotic Drugs placed NPP
and ANPP in Table I of the Convention Against Illicit Traffic in
Narcotic Drugs and Psychotropic Substances of 1988 (1988 Convention) in
response to the international reintroduction of fentanyl on the illicit
drug market. As such, member states of the United Nations are required
to regulate these precursor chemicals at the national level.
Importantly, the People's Republic of China regulated NPP and ANPP on
February 1, 2018.\17\ Subsequently, in 2022, the United Nations
Commission on Narcotic Drugs placed norfentanyl, 1-boc-4-
anilinopiperidine, and 4-anilinopiperidine in Table I of the 1988
Convention in response to the international reintroduction of fentanyl
on the illicit drug market and the introduction of new precursors used
in the illicit manufacture of fentanyl.
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\17\ <a href="https://www.dea.gov/press-releases/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals">https://www.dea.gov/press-releases/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals</a>.
Accessed March 9, 2022.
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Phenethyl Bromide
The original published synthetic pathway to fentanyl, known as the
Janssen method, involves the list I chemical benzylfentanyl \18\ and
schedule II immediate precursor norfentanyl.\19\ In this synthetic
pathway, benzylfentanyl, a list I chemical under the CSA, is then
converted to norfentanyl, the schedule II immediate precursor in this
synthetic pathway. Norfentanyl is reacted with phenethyl bromide (also
known as 2-bromoethyl benzene) to complete the synthesis of fentanyl.
This synthetic pathway can also be easily modified to produce fentanyl
analogues and fentanyl-related substances.
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\18\ Designation of Benzylfentanyl and 4-Anilinopiperidine,
Precursor Chemicals Used in the Illicit Manufacture of Fentanyl, as
List I Chemicals, 85 FR 20822 (April 15, 2020).
\19\ Control of the Immediate Precursor Norfentanyl Used in the
Illicit Manufacture of Fentanyl as a Schedule II Controlled
Substance, 85 FR 21320 (April 17, 2020).
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Phenethyl bromide also serves as a precursor chemical in the
Siegfried method. In this synthetic pathway, phenethyl bromide is
reacted with 4-piperidone, a list I chemical under the CSA, to produce
NPP, another list I chemical, which is further converted to ANPP,\20\
the schedule II immediate precursor in the Siegfried method. One
additional step completes the synthesis of fentanyl. This synthetic
pathway can also be easily modified to produce fentanyl analogues and
fentanyl-related substances.
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\20\ Control of Immediate Precursor Used in the Illicit
Manufacture of Fentanyl as a Schedule II Controlled Substance, 75 FR
37295 (June 29, 2010).
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In addition to the Janssen and Siegfried methods, clandestine
manufacturers are using other methods to synthesize fentanyl, one of
which is known as the Gupta method. In this synthetic pathway, 4-
piperidone, a list I chemical under the CSA, is used to synthesize 4-
anilinopiperidine, another list I chemical under the CSA,\21\ which
serves as an alternative precursor chemical to NPP, a list I chemical,
in the synthesis of ANPP, a schedule II immediate precursor, albeit
through a different synthetic process. 4-Anilinopiperidine is reacted
with phenethyl bromide to produce ANPP, which is then converted to the
schedule II controlled substance, fentanyl. This synthetic pathway can
also be easily modified to produce fentanyl analogues and fentanyl-
related substances.
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\21\ Designation of Benzylfentanyl and 4-Anilinopiperidine,
Precursor Chemicals Used in the Illicit Manufacture of Fentanyl, as
List I Chemicals, 85 FR 20822 (April 15, 2020).
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Phenethyl Halides and Sulfonates
Phenethyl bromide is attractive to illicit manufacturers due to the
lack of regulations on this chemical; it is readily available from
chemical suppliers. Additionally, related phenethyl halides (i.e.,
phenethyl chloride, phenethyl iodide, etc.) and phenethyl sulfonates
(i.e., phenethyl tosylate, phenethyl mesylate, etc.) can be used as
substitutes for phenethyl bromide in many of the known synthetic
pathways. These pathways can be easily used, and modified, in the
illicit manufacture of fentanyl, fentanyl analogues, and fentanyl-
related substances.
Solicitation for Information
With this advanced notice of proposed rulemaking, DEA is soliciting
information on any possible legitimate uses of phenethyl bromide, and
related halides and sulfonates, unrelated to fentanyl production
(including industrial uses) in order to assess the potential economic
impact of controlling phenethyl bromide as a list I chemical. DEA seeks
to document any unpublicized use(s) and other proprietary use(s) of
phenethyl bromide, and related halides and sulfonates, that are not in
the public domain. Therefore, DEA is soliciting comment on the uses of
phenethyl bromide, and related halides and sulfonates, in the
legitimate marketplace.
DEA is soliciting input from all potentially affected parties
regarding: (1) the types of legitimate industries using phenethyl
bromide, and related halides and sulfonates; (2) the legitimate uses,
legitimate needs, and quantities produced, used, and distributed of
phenethyl bromide, and related halides and sulfonates; (3) the size of
the domestic market for phenethyl bromide, and related halides and
sulfonates, if any; (4) the number of manufacturers of phenethyl
bromide, and related halides and sulfonates; (5) the number of
distributors of phenethyl bromide, and related halides and sulfonates;
(6) the level of import and export of phenethyl bromide, and related
halides and sulfonates; (7) the potential burden that controlling
phenethyl bromide, and related halides and sulfonates, as a list I
chemical may have on any legitimate industry and trade; (8) the
potential number of individuals/firms that may be adversely affected by
such regulatory controls (particularly with respect to the impact on
small businesses); and (9) any other information on the manner of
manufacturing, distribution, consumption, storage, disposal, and uses
of phenethyl bromide, and related halides and sulfonates, by industry
and others. DEA invites all interested parties to provide any
information on any legitimate uses of phenethyl bromide, and related
halides and sulfonates, in industry, commerce, academia, research and
development, or other applications. DEA seeks both quantitative and
qualitative data.
Such information may be submitted electronically to the address
listed above and is requested by November 27, 2024. This information
will be used to properly determine the effect that
[[Page 85462]]
proposed regulations to make phenethyl bromide a list I chemical under
the CSA would have on industry.
Handling of Confidential or Proprietary Information
Confidential or proprietary information may be submitted as part of
a comment regarding this advanced notice of proposed rulemaking. Please
see the ``POSTING OF PUBLIC COMMENTS'' section above for a discussion
of the identification and redaction of confidential business
information and personally identifying information.
Regulatory Analyses
This ANPRM was developed in accordance with the principles of
Executive Order (E.O.) 12866, ``Regulatory Planning and Review,'' E.O.
13563, ``Improving Regulation and Regulatory Review,'' and E.O. 14094,
``Modernizing Regulatory Review.'' Because this action is an ANPRM, the
requirement of E.O. 12866 to assess the costs and benefits of this
action does not apply.
Furthermore, the requirements of the Regulatory Flexibility Act do
not apply to this action because, at this stage, it is an ANPRM and not
a ``rule'' as defined in 5 U.S.C. 601. Following review of the comments
received in response to this ANPRM, if DEA proceeds with a notice of
proposed rulemaking regarding this matter, DEA will conduct all
relevant analyses as required by statute or E.O.
Signing Authority
This document of the Drug Enforcement Administration was signed on
October 10, 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. 2024-24616 Filed 10-25-24; 8:45 am]
BILLING CODE 4410-09-P
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This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.