Proposed Rule2023-22570
Propionyl Chloride
Primary source
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Published
October 12, 2023
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
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.
Full Text
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<title>Federal Register, Volume 88 Issue 196 (Thursday, October 12, 2023)</title>
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[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 [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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 <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 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
<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. They will, unless reasonable
cause is
[[Page 70611]]
given, be made available by DEA for public inspection online at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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
<a href="https://www.regulations.gov">https://www.regulations.gov</a> 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. <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,\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 <a href="https://wonder.cdc.gov/mcd-icd10-provisional.html">https://wonder.cdc.gov/mcd-icd10-provisional.html</a> 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 <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 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.
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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\ <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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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)
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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
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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.