[Federal Register Volume 88, Number 196 (Thursday, October 12, 2023)]
[Proposed Rules]
[Pages 70610-70613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-22570]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1310

[Docket No. DEA-1189]


Propionyl Chloride

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Advanced notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration finds that propionyl 
chloride 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 propionyl chloride as a list I chemical, DEA is 
soliciting information on the current uses of propionyl chloride (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 13, 2023. 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-1189'' 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 submission, you will receive a Comment 
Tracking Number for your comment. 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. They will, unless reasonable 
cause is

[[Page 70611]]

given, be made available by DEA for public inspection online at https://www.regulations.gov. Such information includes personal identifying 
information (such as your name, address, etc.) voluntarily submitted by 
the commenter. The Freedom of Information Act applies to all comments 
received. If you want to submit personal identifying information (such 
as your name, address, etc.) as part of your comment, but do not want 
it to be made publicly available, you must include the phrase 
``PERSONAL IDENTIFYING INFORMATION'' in the first paragraph of your 
comment. You must also place all of the personal identifying 
information you do not want made publicly available in the first 
paragraph of your comment and identify what information you want 
redacted.
    If you want to submit confidential business information as part of 
your comment, but do not want it to be made publicly available, you 
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the 
first paragraph of your comment. You must also prominently identify the 
confidential business information to be redacted within the comment.
    Comments containing personal identifying information or 
confidential business information identified as directed above will be 
made publicly available in redacted form. If a comment has so much 
confidential business information that it cannot be effectively 
redacted, all or part of that comment may not be made publicly 
available. Comments posted to https://www.regulations.gov may include 
any personal identifying information (such as name, address, and phone 
number) included in the text of your electronic submission that is not 
identified as directed above as confidential.
    An electronic copy of this advanced proposed rule is available at 
https://www.regulations.gov for easy reference.

Legal Authority

    The Controlled Substances Act (CSA) gives the Attorney General the 
authority to specify, by regulation, chemicals as list I chemicals.\1\ 
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.\2\ The current list of all 
listed chemicals is published at 21 CFR 1310.02. Pursuant to 28 CFR 
0.100(b), the Attorney General has delegated his authority to designate 
list I chemicals to the Administrator of DEA (Administrator). 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\ 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.\3\ 
Moreover, there are a substantial number of fentanyl analogues and 
fentanyl-related substances that are being distributed on the illicit 
drug market despite DEA's actions adding them as schedule I controlled 
substances. Illicit manufacturers attempt to utilize unregulated 
precursor chemicals to evade law enforcement detection and precursor 
chemical controls in order to manufacture fentanyl, fentanyl analogues, 
and fentanyl-related 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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    \3\ 21 U.S.C. 812(c) Schedule II(b)(6) and 21 CFR 1308.12(c).
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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 the 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.\4\
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    \4\ 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.
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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,\5\ drug-induced overdose deaths involving synthetic opioids 
(excluding methadone) in the United States increased from 36,359 in 
2019 to 56,516 in 2020 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 October 2022 is 73,570 individuals, or approximately 68 percent 
of all drug-induced overdose deaths for that time period.\6\ 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),\7\ 
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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    \5\ 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 https://wonder.cdc.gov/mcd-icd10-provisional.html on March 16, 2023.
    \6\ 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 March 15, 2023.
    \7\ The National Forensic Laboratory Information System (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 (December 12, 2011). NFLIS-Drug data 
was queried on July 31, 2023.

[[Page 70612]]



             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     61,640     89,966    108,131    125,999    164,890    165,067
Annual Reports of select fentanyl analogues and               78      2,317      7,624     21,980     16,177     20,917      7,800     26,368     29,404
 fentanyl-related substances.........................
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Role of Propionyl Chloride 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 analogues, and fentanyl-related 
substances using these methods, DEA controlled N-phenethyl-4-piperidone 
(NPP),\8\ N-(1-benzylpiperidin-4-yl)-N-phenylpropionamide 
(benzylfentanyl), N-phenylpiperidin-4-amine (4-anilinopiperidine; 
including its amides and carbamates),\9\ and 4-piperidone (piperidin-4-
one) \10\ as list I chemicals and 4-anilino-N-phenethylpiperidine 
(ANPP) \11\ and N-phenyl-N-(piperidin-4-yl)propionamide (norfentanyl) 
\12\ as schedule II immediate precursors under the CSA.
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    \8\ 72 FR 20039 (April 23, 2007).
    \9\ 85 FR 20822 (May 15, 2020).
    \10\ 88 FR 21902 (May 12, 2023).
    \11\ 75 FR 37295 (August 30, 2010).
    \12\ 85 FR 21320 (May 18, 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.\13\ 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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    \13\ https://www.dea.gov/press-releases/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals. 
Accessed March 9, 2022.
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Propionyl Chloride

    The original published synthetic pathway to fentanyl, known as the 
Janssen method, involves the list I chemical benzylfentanyl and 
schedule II immediate precursor norfentanyl. In this synthetic pathway, 
benzylfentanyl, a list I chemical under the CSA,\14\ is synthesized by 
reacting propionyl chloride with 4-anilino-1-benzylpiperidine, which is 
then converted to norfentanyl, the schedule II immediate precursor in 
this synthetic pathway.\15\ Norfentanyl is then subjected to one simple 
chemical reaction 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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    \14\ 85 FR 20822 (May 15, 2020).
    \15\ 85 FR 21320 (May 18, 2020).
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    Propionyl chloride also serves as a precursor chemical in the 
Siegfried method. In this synthetic pathway, propionyl chloride is 
reacted with ANPP,\16\ the schedule II immediate precursor in the 
Siegfried method, 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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    \16\ 75 FR 37295 (August 30, 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,\17\ 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. The resulting ANPP is reacted 
with propionyl chloride to manufacture 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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    \17\ 85 FR 20822 (May 15, 2020).
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    Propionyl chloride is attractive to illicit manufacturers because 
of the lack of regulations on this chemical, it is readily available 
from chemical suppliers, and it can be easily used in many known 
synthetic pathways used 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 propionyl chloride 
unrelated to fentanyl production (including industrial uses) in order 
to assess the potential economic impact of controlling propionyl 
chloride as a list I chemical. DEA seeks to document any unpublicized 
use(s) and other proprietary use(s) of propionyl chloride that are not 
in the public domain. Therefore, DEA is soliciting comment on the uses 
of propionyl chloride in the legitimate marketplace.
    DEA is soliciting input from all potentially affected parties 
regarding: (1) The types of legitimate industries using propionyl 
chloride; (2) the legitimate uses, legitimate needs and quantity 
produced, used, and distributed of propionyl chloride; (3) the size of 
the domestic market for propionyl chloride; (4) the number of 
manufacturers of propionyl chloride; (5) the number of distributors of 
propionyl chloride; (6) the level of import and export of propionyl 
chloride; (7) the potential burden that controlling propionyl chloride 
as a list I chemical may have on any legitimate industry and trade; (8)

[[Page 70613]]

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 propionyl chloride by industry and others. DEA invites all 
interested parties to provide any information on any legitimate uses of 
propionyl chloride 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 13, 2023. This information 
will be used to properly determine the effect that proposed regulations 
to make propionyl chloride a list 1 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'' and 
E.O. 13563, ``Improving Regulation and Regulatory Review.'' Since 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 5, 2023, 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. 2023-22570 Filed 10-11-23; 8:45 am]
BILLING CODE 4410-09-P