[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 [www.gpo.gov]
[FR Doc No: 2024-24616]


=======================================================================
-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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 https://www.regulations.gov 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 
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.
    <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 https://www.regulations.gov. 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 https://www.regulations.gov 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 https://www.regulations.gov.

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.
---------------------------------------------------------------------------

    \1\ 21 U.S.C. 802(34).
    \2\ 28 CFR 0.100(b).
    \3\ Id.
---------------------------------------------------------------------------

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\
---------------------------------------------------------------------------

    \4\ 21 U.S.C. 812(c) Schedule II(b)(6); 21 CFR 1308.12(c).
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \8\ United Nations Office on Drugs and Crime, Global SMART 
Update Volume 17, March 2017. https://www.unodc.org/documents/scientific/Global_SMART_Update_17_web.pdf.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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 http://wonder.cdc.gov/mcd-icd10-provisional.html 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 https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
                            Year                               2014     2015      2016      2017      2018       2019       2020       2021       2022
--------------------------------------------------------------------------------------------------------------------------------------------------------
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........................................
--------------------------------------------------------------------------------------------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \17\ https://www.dea.gov/press-releases/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals. 
Accessed March 9, 2022.
---------------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \20\ Control of Immediate Precursor Used in the Illicit 
Manufacture of Fentanyl as a Schedule II Controlled Substance, 75 FR 
37295 (June 29, 2010).
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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