Proposed Rule2022-19974
Designation of 4-Piperidone as a List I Chemical
Primary source
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Published
September 22, 2022
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration is proposing the control of 4-piperidone, its acetals, its amides, its carbamates, its salts, and salts of its acetals, its amides, and its carbamates, whenever the existence of such is possible, as a list I chemical under the Controlled Substances Act. The Drug Enforcement Administration finds that 4-piperidone is used in the illicit manufacture of the controlled substance fentanyl, and is important to the manufacture of the controlled substance fentanyl because it cannot be replaced by other chemicals in its respective synthetic pathways which are used in the illicit manufacture of fentanyl. If finalized, this action would subject handlers of 4-piperidone to the chemical regulatory provisions of the Controlled Substances Act and its implementing regulations. This rulemaking does not establish a threshold for domestic and international transactions of 4-piperidone. As such, all transactions of chemical mixtures containing 4-piperidone will be regulated at any concentration and will be subject to control under the Controlled Substances Act.
Full Text
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<title>Federal Register, Volume 87 Issue 183 (Thursday, September 22, 2022)</title>
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[Federal Register Volume 87, Number 183 (Thursday, September 22, 2022)]
[Proposed Rules]
[Pages 57852-57859]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-19974]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1310
[Docket No. DEA-951]
Designation of 4-Piperidone as a List I Chemical
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration is proposing the control
of 4-piperidone, its acetals, its amides, its carbamates, its salts,
and salts of its acetals, its amides, and its carbamates, whenever the
existence of such is possible, as a list I chemical under the
Controlled Substances Act. The Drug Enforcement Administration finds
that 4-piperidone is used in the illicit manufacture of the controlled
substance fentanyl, and is important to the manufacture of the
controlled substance fentanyl because it cannot be replaced by other
chemicals in its respective synthetic pathways which are used in the
illicit manufacture of fentanyl. If finalized, this action would
subject handlers of 4-piperidone to the chemical regulatory provisions
of the Controlled Substances Act and its implementing regulations. This
rulemaking does not establish a threshold for domestic and
international transactions of 4-piperidone. As such, all transactions
of chemical mixtures containing 4-piperidone will be regulated at any
concentration and will be subject to control under the Controlled
Substances Act.
DATES: Comments must be submitted electronically or postmarked on or
before October 24, 2022. 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-951'' on all electronic and written correspondence,
including any attachments.
[[Page 57853]]
<bullet> Electronic comments: The Drug Enforcement Administration
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 given, be made available by the Drug Enforcement
Administration (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 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.\1\ 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).
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Background
The clandestine manufacture of fentanyl remains extremely
concerning as the distribution of illicit fentanyl 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, the DEA
controls fentanyl as a schedule II controlled substance due to its high
potential for abuse and dependence.\2\
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\2\ 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 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), or in forms that mimic pharmaceutical
preparations including prescription opiates and benzodiazepines.\3\
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\3\ 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 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 data, 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 57,802 in 2021 (provisional).\4\ Of
the drug overdose death data (106,854) predicted for the 12 month-
ending November 2021, synthetic opioids were involved in about 65.9
percent of all drug-induced overdose deaths.\5\ The increase in
overdose fatalities involving synthetic opioids coincides with a
dramatic increase in law enforcement encounters of fentanyl. According
to the National Forensic Laboratory Information System (NFLIS-Drug),\6\
reports from forensic
[[Page 57854]]
laboratories of drug items containing fentanyl increased dramatically
since 2014, as shown in Table 1.
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\4\ 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, 2018-2020, and from provisional data
for years 2021-2022, 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 May 5, 2022.
\5\ Ahmad FB, Rossen LM, Sutton P. Provisional drug overdose
death counts. National Center for Health Statistics. 2021. 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 May
5, 2022.
\6\ 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 January 13, 2022.
Table 1--Annual Reports of Fentanyl Identified in Drug Encounters
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Year 2014 2015 2016 2017 2018 2019 2020
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Reports..................... 5,535 15,456 37,142 61,604 89,764 107,080 115,762
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Role of 4-Piperidone in the Synthesis of Fentanyl
Fentanyl is not a naturally occurring substance. As such, the
manufacture of fentanyl requires it 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 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 using these methods, DEA controlled N-
phenethyl-4-piperidone (NPP),\7\ N-(1-benzylpiperidin-4-yl)-N-
phenylpropionamide (benzylfentanyl) and N-phenylpiperidin-4-amine (4-
anilinopiperidine) \8\ as list I chemicals, and 4-anilino-N-
phenethylpiperidine (ANPP) \9\ and N-phenyl-N-(piperidin-4-
yl)propionamide (norfentanyl) \10\ as schedule II immediate precursors
under the CSA.
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\7\ 72 FR 20039 (April 23, 2007).
\8\ 85 FR 20822 (May 15, 2020).
\9\ 75 FR 37295 (August 30, 2010).
\10\ 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 were 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.\11\
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\11\ <a href="https://www.dea.gov/press-release/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals">https://www.dea.gov/press-release/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals</a>.
Accessed March 9, 2022.
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To circumvent these regulations, illicit fentanyl manufacturers
continue to employ unregulated precursor chemicals in the illicit
synthesis of fentanyl. Recent law enforcement information indicates
that illicit fentanyl manufacturers may be utilizing precursor
chemicals that serve as precursors to those precursor chemicals already
controlled, sometimes referred to as ``pre-precursors.'' 4-Piperidone
(also, known as, piperidin-4-one) serves as a precursor chemical for
the previously controlled list I chemicals involved in many synthetic
routes to fentanyl; it is used to make NPP, benzylfentanyl, and 4-
anilinopiperidine, all of which are list I chemicals under the CSA.\12\
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\12\ 72 FR 20039 (April 23, 2007) and 85 FR 20822 (April 15,
2020).
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In addition to the continuous exploration of viable precursors to
manufacture fentanyl, illicit manufacturers also employ protecting
group strategies on known fentanyl precursors. These protecting group
strategies modify the chemical structure of a known precursor and are
specifically designed to disguise the known precursor to evade law
enforcement detection or to enhance the manufacturing process of the
controlled substance the known precursor is used to make. These
modified precursors are sometimes referred to as ``masked precursors.''
For example, 1-boc-4-anilinopiperidine (tert-butyl 4-
(phenylamino)piperidine-1-carboxylate, 1-boc-4-AP), a carbamate of 4-
anilinopiperidine and a list I chemical, was identified as a ``masked''
precursor chemical used in the illicit manufacture of fentanyl.
Likewise, 1-boc-4-piperidone (tert-butyl 4-oxopiperidine-1-
carboxylate), a carbamate of 4-piperidone, and 4,4-piperidinediol
(piperidine-4,4-diol) have also been identified as ``masked''
precursors. As a carbamate of 4-piperidone, 1-boc-4-piperidone would be
controlled as a list I chemical upon completion of this rulemaking, as
proposed. Similarly, 4,4-piperidinediol (Chemical Abstract Service
Registry Number (CAS RN) 73390-11-1 for the free base and CAS RN 40064-
34-4 for the hydrochloride salt) is 4-piperidone with the inclusion of
one water molecule of hydration and is known as a hydrate of 4-
piperidone. As a hydrate of 4-piperidone, 4,4-piperidinediol would also
be subject to control under the listing of 4-piperidone upon completion
of this rulemaking, as proposed. These masked precursors serve both a
role in attempts to evade law enforcement detection as well as a
strategic synthesis advantage compared to their unprotected
counterparts, namely 4-anilinopiperidine and 4-piperidone.
4-Piperidone
The original published synthetic pathway to fentanyl, known as the
Janssen method, does not involve NPP or ANPP as precursor chemicals.
This synthetic pathway involves the important precursors,
benzylfentanyl and norfentanyl. 4-Piperidone serves as a precursor
chemical to benzylfentanyl, a list I chemical under the CSA,\8\ which
is converted to norfentanyl, the schedule II immediate precursor in
this synthetic pathway. Norfentanyl is then subjected to one simple
chemical reaction to complete the synthesis of fentanyl. Norfentanyl is
controlled in schedule II of the CSA.\10\
Like the Janssen method, 4-piperidone serves as an early-stage
precursor chemical in the Siegfried method. 4-Piperidone is a precursor
to NPP, a known fentanyl precursor and list I chemical, in the
Siegfried method. NPP, a list I chemical under the CSA,\7\ is then
converted to ANPP, the schedule II immediate precursor in this
synthetic pathway. ANPP is then subjected to a simple one step chemical
reaction to complete the synthesis of fentanyl. ANPP is controlled as a
schedule II immediate precursor under the CSA.\9\
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. 4-
[[Page 57855]]
Piperidone can be used to synthesize 4-anilinopiperidine, a list I
chemical under the CSA \8\ and key precursor in the Gupta method. 4-
Anilinopiperidine serves as an alternative precursor chemical to NPP in
the synthesis of ANPP, albeit through a different synthetic process.
The resulting ANPP is then used as the immediate precursor chemical in
the illicit manufacture of the schedule II controlled substance,
fentanyl.
DEA has determined that 4-piperidone is commercially available from
both domestic and foreign suppliers. DEA is aware of at least 38
domestic suppliers and 19 foreign suppliers. 4-Piperidone is attractive
to illicit manufacturers due to the lack of regulations on this
chemical, it is readily available from chemical suppliers, and it can
be easily converted to known fentanyl precursors, including NPP,
benzylfentanyl, and 4-anilinopiperidine.
4-Piperidone and 1-boc-4-piperidone have been imported and
identified in law enforcement encounters in the United States.
According to law enforcement information, between March 2016 and
October 2021, there have been three seizures of 4-piperidone (2) and 1-
boc-4-piperidone (1) totaling 357 kilograms (kg) at ports of entry in
the United States. In addition to these encounters, a query of DEA's
Laboratory Information Management System (LIMS) resulted in three
domestic reports of 4-piperidone (1) and 1-boc-4-piperidone (2) from
analyses conducted on submitted drug evidence by DEA forensic
laboratories. 4-Piperidone was also identified at clandestine
laboratories located in Arizona and Pennsylvania, which were involved
in the illicit manufacture of fentanyl.
As of May 2019, in addition to domestic encounters, the
International Narcotics Control Board of the United Nations reported
eight international transactions of 4-piperidone (6) and 1-boc-4-
piperidone (2) through the Precursors Incident Communication System
(PICS) \13\ reporting system. These incidents reported to PICS totaled
approximately 1,900 kg and had destinations located in North America
and Europe. Along with the incidents reported to PICS, DEA is aware of
ten additional seizures of 4-piperidone (9) and 1-boc-4-piperidone (1)
at international ports of entry since May 2019, totaling approximately
1,335 kg.
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\13\ PICS is a platform that allows Governments to exchange
operational and investigative intelligence and to generate strategic
intelligence on precursors trafficking. PICS reports were collected
up to December 16, 2021.
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These recent law enforcement encounters of 4-piperidone coincide
with the placement of NPP and ANPP in Table I of the 1988 Convention,
the People's Republic of China regulating NPP and ANPP as of February
1, 2018, and the regulation of benzylfentanyl and 4-anilinopiperidine
as list I chemicals and the designation of norfentanyl as a schedule II
immediate precursor to fentanyl in the United States. The domestic and
international encounters of 4-piperidone at ports of entry and the
identification of 4-piperidone at domestic fentanyl clandestine
laboratories indicate a change in illicit fentanyl manufacturing
methods in efforts to evade international controls on NPP and ANPP and
additional controls on benzylfentanyl, 4-anilinopiperidine, and
norfentanyl in the United States.
Regulation of 4-Piperidone, Including Its Acetals, Its Amides, Its
Carbamates, Its Salts, and Salts of Its Acetals, Its Amides, and Its
Carbamates, Whenever the Existence of Such Is Possible, as a List I
Chemical
The CSA, specifically 21 U.S.C. 802(34), and its implementing
regulations at 21 CFR 1310.02(c), provide the Attorney General with the
authority to specify, by regulation, additional precursor or essential
chemicals as listed chemicals if they are used in the manufacture of
controlled substances in violation of the CSA. Recent law enforcement
encounters indicate 4-piperidone is being used in the illicit
manufacture of the schedule II controlled substance fentanyl. This
proposed rule would regulate 4-piperidone as a list I chemical because
DEA finds that 4-piperidone is used in the illicit manufacture of the
controlled substance fentanyl, and is important to the manufacture of
the controlled substance fentanyl because it cannot be replaced by
other chemicals in its respective synthetic pathways which are used in
the illicit manufacture of fentanyl.
Chemical Mixtures of 4-Piperidone
This proposed rulemaking, if finalized, would specify that chemical
mixtures containing 4-piperidone would not be exempt from regulatory
requirements at any concentration, unless an application for exemption
of a chemical mixture is submitted by a 4-piperidone manufacturer and
the application is reviewed and accepted by DEA under 21 CFR 1310.13
(Exemption by Application Process). The control of chemical mixtures
containing any amount of 4-piperidone is necessary to prevent the
extraction, isolation, and use of 4-piperidone in the illicit
manufacture fentanyl. This proposed rule would modify the Table of
Concentration Limits in 21 CFR 1310.12(c) to reflect the fact that
chemical mixtures containing any amount of 4-piperidone are subject to
the CSA chemical control provisions.
Exemption by Application Process
DEA has implemented an application process to exempt mixtures from
the requirements of the CSA and its implementing regulations.\14\ Under
the application process, manufacturers may submit an application for
exemption for those mixtures that do not qualify for automatic
exemption. Exemption status can be granted if DEA determines that the
mixture is formulated in such a way that it cannot be easily used in
the illicit production of a controlled substance and that the listed
chemical cannot be readily recovered.\15\
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\14\ 21 CFR 1310.13.
\15\ 21 CFR U.S.C. 802(39)(A)(vi).
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Requirements for Handling List I Chemicals
If this rule is finalized as proposed, 4-piperidone will be subject
to all of the regulatory controls and administrative, civil, and
criminal sanctions applicable to the manufacture, distribution,
importing, and exporting of list I chemicals. Upon publication of a
final rule, persons potentially handling 4-piperidone, including
regulated chemical mixtures containing 4-piperidone, will be required
to comply with list I chemical regulations, including the following:
1. Registration. Any person who manufactures, distributes, imports,
or exports 4-piperidone, including chemical mixtures containing 4-
piperidone, or proposes to engage in the manufacture, distribution,
importation, or exportation of 4-piperidone, including chemical
mixtures containing 4-piperidone, must obtain a registration pursuant
to 21 U.S.C. 822, 823, 957, and 958. Regulations describing
registration for list I chemical handlers are set forth in 21 CFR part
1309. DEA regulations require separate registrations for manufacturing,
distributing, importing, and exporting of list I chemicals. 21 CFR
1309.21. Further, a separate registration is required for each
principal place of business at one general physical location where list
I chemicals are manufactured, distributed, imported, or exported by a
person. 21 U.S.C. 822(e)(1) and 21 CFR 1309.23(a).
DEA notes that under the CSA, ``warehousemen'' are not required to
register and may lawfully possess list I chemicals, if the possession
of those
[[Page 57856]]
chemicals is in the usual course of business or employment. Under DEA
implementing regulations, the warehouse in question must receive the
list I chemical from a DEA registrant and shall only distribute the
list I chemical back to the DEA registrant and registered location from
which it was received. A warehouse that distributes list I chemicals to
persons other than the registrant and registered location from which
they were obtained is conducting distribution activities and is
required to register as such.
Upon publication of a final rule, any person manufacturing,
distributing, importing, or exporting 4-piperidone or a chemical
mixture containing 4-piperidone would become subject to the
registration requirement under the CSA. DEA recognizes, however, that
it is not possible for persons who are subject to the registration
requirements to immediately complete and submit an application for
registration, and for DEA to immediately issue registrations for those
activities. Therefore, to allow any continued legitimate commerce in 4-
piperidone or a chemical mixture containing 4-piperidone, DEA is
proposing to establish in 21 CFR 1310.09, a temporary exemption from
the registration requirement for persons desiring to engage in
activities with 4-piperidone or a chemical mixture containing 4-
piperidone, provided that DEA receives a properly completed application
for registration or application for exemption of a chemical mixture
under 21 CFR 1310.13 on or before 30 days after publication of a final
rule implementing regulations regarding 4-piperidone. The temporary
exemption for such persons will remain in effect until DEA takes final
action on their application for registration or application for
exemption of a chemical mixture.
The temporary exemption applies solely to the registration
requirement; all other chemical control requirements, including
recordkeeping and reporting, would become effective on the effective
date of the final rule. This is necessary because a delay in regulating
these transactions could result in increased diversion of chemicals
desirable to drug traffickers.
Additionally, the temporary exemption for registration does not
suspend applicable Federal criminal laws relating to 4-piperidone, nor
does it supersede State or local laws or regulations. All handlers of
4-piperidone must comply with applicable State and local requirements
in addition to the CSA regulatory controls.
2. Records and Reports. Every DEA registrant would be required to
maintain records and submit reports with respect to 4-piperidone
pursuant to 21 U.S.C. 830 and in accordance with 21 CFR part 1310.04
and 1310.05. Pursuant to 21 CFR 1310.04, a record must be kept for two
years after the date of a transaction involving a listed chemical,
provided the transaction is a regulated transaction.
Each regulated bulk manufacturer of a listed chemical will be
required to submit manufacturing, inventory, and use data on an annual
basis. 21 CFR 1310.05(d). Existing standard industry reports containing
the required information are acceptable, provided the information is
separate or readily retrievable from the report.
The CSA and its implementing regulations require that each
regulated person must report to DEA any regulated transaction involving
an extraordinary quantity of a listed chemical, an uncommon method of
payment or delivery, or any other circumstance that the regulated
person believes may indicate that the listed chemical will be used in
violation of subchapter I of the CSA. In addition, regulated persons
must report any proposed regulated transaction with a person whose
description or other identifying characteristics DEA has previously
furnished to the regulated person, any unusual or excessive loss or
disappearance of a listed chemical under the control of the regulated
person, and any in-transit loss in which the regulated person is the
supplier. 21 U.S.C. 830(b) and 21 CFR 1310.05(a) and (b). Importation
and Exportation. All importation and exportation of 4-piperidone or a
chemical mixture containing 4-piperidone would need to be done in
compliance with 21 U.S.C. 957, 958, and 971 and in accordance with 21
CFR part 1313.
3. Security. All applicants and registrants would be required to
provide effective controls against theft and diversion of list I
chemicals in accordance with 21 CFR 1309.71-1309.73.
4. Administrative Inspection. Places, including factories,
warehouses, or other establishments and conveyances, where registrants
or other regulated persons may lawfully hold, manufacture, distribute,
or otherwise dispose of a list I chemical or where records relating to
those activities are maintained, are controlled premises as defined in
21 U.S.C. 880(a) and 21 CFR 1316.02(c). The CSA allows for
administrative inspections of these controlled premises as provided in
21 CFR part 1316, subpart A. 21 U.S.C. 880.
5. Liability. Any activity involving 4-piperidone not authorized
by, or in violation of, the CSA, would be unlawful, and would subject
the person to administrative, civil, and/or criminal action.
Solicitation for Information
As part of this proposed rulemaking, DEA is soliciting information
on any possible legitimate uses of 4-piperidone unrelated to fentanyl
production (including industrial uses) in order to assess the potential
economic impact of controlling 4-piperidone. DEA has searched
information in the public domain for legitimate uses of this chemical,
and has not documented a legitimate commercial or industrial use for 4-
piperidone other than as an intermediary chemical in the production of
fentanyl. DEA seeks, however, to document any unpublicized use(s) and
other proprietary use(s) of 4-piperidone that are not in the public
domain. Therefore, DEA is soliciting comment on the uses of 4-
piperidone in the legitimate marketplace.
DEA is soliciting input from all potentially affected parties
regarding: (1) The types of legitimate industries using 4-piperidone;
(2) the legitimate uses of 4-piperidone, if any; (3) the size of the
domestic market for 4-piperidone; (4) the number of manufacturers of 4-
piperidone; (5) the number of distributors of 4-piperidone; (6) the
level of import and export of 4-piperidone; (7) the potential burden
these proposed regulatory controls of 4-piperidone may have on any
legitimate trade; (8) the potential number of individuals/firms that
may be adversely affected by these proposed 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 4-piperidone by industry
and others. DEA invites all interested parties to provide any
information on any legitimate uses of 4-piperidone in industry,
commerce, academia, research and development, or other applications.
DEA seeks both quantitative and qualitative data.
Handling of Confidential or Proprietary Information
Confidential or proprietary information may be submitted as part of
a comment regarding this 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.
[[Page 57857]]
Regulatory Analyses
Executive Orders 12866 and 13563, Regulatory Planning and Review,
Improving and Regulation and Regulatory Review
This proposed rule was developed in accordance with the principles
of Executive Orders (E.O.) 12866 and 13563. E.O. 12866 directs agencies
to assess all costs and benefits of available regulatory alternatives
and, if regulation is necessary, to select regulatory approaches that
maximize net benefits (including potential economic, environmental,
public health, and safety effects; distributive impacts; and equity).
E.O. 13563 is supplemental to and reaffirms the principles, structures,
and definitions governing regulatory review as established in E.O.
12866. E.O. 12866 classifies a ``significant regulatory action,''
requiring review by the Office of Management and Budget (OMB), as any
regulatory action that is likely to result in a rule that may: (1) have
an annual effect on the economy of $100 million or more or adversely
affect in a material way the economy, a sector of the economy,
productivity, competition, jobs, the environment, public health or
safety, or State, local, or tribal Governments or communities; (2)
create a serious inconsistency or otherwise interfere with an action
taken or planned by another agency; (3) materially alter the budgetary
impact of entitlements, grants, user fees, or loan programs or the
rights and obligations of recipients thereof; or (4) raise novel legal
or policy issues arising out of legal mandates, the President's
priorities, or the principles set forth in the E.O.
A review of the 38 domestic suppliers of 4-piperidone indicates
that 37 entities are not registered with DEA to handle list I
chemicals. DEA anticipates that this proposed rule will impose minimal
or no economic impact on affected entities; and thus, will not have a
significant economic impact on any of the 37 affected small entities.
Therefore, DEA has concluded that this proposed rule will not have a
significant effect on a substantial number of small entities. If
finalized as proposed, 4-piperidone will be subject to all of the
regulatory controls and administrative, civil, and criminal sanctions
applicable to the manufacture, distribution, importing, and exporting
of list I chemicals. 4-Piperidone is a precursor chemical used in, and
is important to, the illicit manufacture of the schedule II controlled
substance fentanyl. The distribution of illicitly manufactured fentanyl
has caused an unprecedented outbreak of thousands of fentanyl-related
overdoses in the United States in recent years.
DEA has searched information in the public domain for any
legitimate uses of 4-piperidone, and has not documented a use for 4-
piperidone other than as an intermediary chemical in the production of
fentanyl. Based on the review of import and quota information for NPP,
ANPP, and fentanyl, DEA believes the vast majority of, if not all,
legitimate pharmaceutical fentanyl is produced via a synthetic route
involving NPP and ANPP as intermediaries. The quantities of NPP
indicated in import data and quantities of ANPP indicated in import and
quota data generally correspond with the quantities of legitimate
pharmaceutical fentanyl produced in the United States. Therefore, DEA
concludes the vast majority of, if not all, 4-piperidone undergoing
chemical transactions is being used for the manufacturing of illicit
fentanyl. DEA cannot rule out the possibility that minimal quantities
of 4-piperidone is being used for the manufacturing of legitimate
pharmaceutical fentanyl. However, if there are any quantities of 4-
piperidone used for the manufacturing of legitimate pharmaceutical
fentanyl, the quantities are believed to be small and economically
insignificant. DEA welcomes any public comment on these quantities and
their economic significance.
DEA evaluated the costs and benefits of this proposed action.
Costs
DEA believes the market for 4-piperidone for the legitimate
manufacturing of pharmaceutical fentanyl is minimal. As stated above,
the only use for 4-piperidone of which DEA is aware is as an
intermediary for the manufacturing of fentanyl. Any manufacturer,
distributor, importer, or exporter of 4-piperidone for the production
of legitimate pharmaceutical fentanyl, if they exist at all, would
incur costs if this proposed rule were finalized. The primary costs
associated with this proposed rule would be the annual registration
fees for list I chemicals ($3,699 for manufacturers and $1,850 for
distributors, importers, and exporters). However, any manufacturer that
uses 4-piperidone for legitimate pharmaceutical fentanyl production
would already be registered with DEA and have all security and other
handling processes in place because of the controls already in place on
fentanyl, resulting in minimal cost to those entities. While different
forms of handling the scheduled substance versus the list I chemical
(distribution of fentanyl vs exporting 4-piperidone) could require a
separate registration for the different handling of the substances, if
an entity is already registered to handle, manufacture, import, or
export a scheduled substance, the entity would not need an additional
registration for the list I chemical, provided it is handling the list
I chemical in the same manner that it is registered for with the
scheduled substance, or as a coincident activity permitted by Sec.
1309.21. Even with the possibility of these additional registrations,
DEA believes that the cost will be minimal.
DEA has identified 38 domestic suppliers of 4-piperidone. Only one
is registered to handle list I chemicals, the remaining 37 are not
registered with DEA to handle list I chemicals. It is difficult to
estimate how much 4-piperidone is distributed by these suppliers. It is
common for chemical distributors to have items in their catalog while
not actually having any material level of sales. Based on the review of
import and quota information for NPP, ANPP, and fentanyl, where the
quantities of NPP and ANPP imported and manufactured generally
correspond with the quantities of fentanyl produced, DEA believes any
quantity of sales from these distributors for legitimate pharmaceutical
fentanyl manufacturing is minimal. If this proposed rule is finalized,
suppliers for the legitimate use of 4-piperidone are expected to choose
the least-cost option, and stop selling the minimal quantities, if any,
of 4-piperidone, rather than incur the registration cost. Because DEA
believes the quantities of 4-piperidone supplied for the legitimate
manufacturing of pharmaceutical fentanyl are minimal, DEA estimates
that the cost of foregone sales is minimal; and thus, the cost of this
proposed rule is minimal. DEA welcomes any public comment regarding
this estimate.
This analysis excludes consideration of any economic impact to
those businesses that facilitate the manufacturing and distribution of
4-piperidone for the manufacturing of illicit fentanyl. As a law
enforcement organization and as a matter of principle, DEA believes
considering the economic utility of facilitating the manufacture of
illicit fentanyl would be improper.
[[Page 57858]]
Benefits
Controlling 4-piperidone is expected to prevent, curtail, and limit
the unlawful manufacture and distribution of the controlled substance,
fentanyl. As a list I chemical, handling of 4-piperidone would require
registration with DEA and various controls and monitoring as required
by the CSA. This proposed rule is also expected to assist preventing
the possible theft or diversion of 4-piperidone from any legitimate
firms. DEA also believes control is necessary to prevent unscrupulous
chemists from synthesizing 4-piperidone and selling it (as an
unregulated material) through the internet and other channels, to
individuals who may wish to acquire unregulated intermediary chemicals
for the purpose of illicitly manufacturing fentanyl.
In summary, DEA conducted a qualitative analysis of costs and
benefits. DEA believes this proposed action, if finalized, will
minimize the diversion of 4-piperidone. DEA believes the market for 4-
piperidone for the legitimate manufacturing of pharmaceutical fentanyl
is minimal. Therefore, any potential cost as a result of this
regulation is minimal.
Executive Order 12988, Civil Justice Reform
This proposed regulation meets the applicable standards set forth
in sections 3(a) and 3(b)(2) of E.O. 12988 Civil Justice Reform to
eliminate drafting errors and ambiguity, minimize litigation, provide a
clear legal standard for affected conduct, and promote simplification
and burden reduction.
Executive Order 13132, Federalism
This proposed rulemaking does not have federalism implications
warranting the application of E.O. 13132. The proposed rule does not
have substantial direct effects on the States, on the relationship
between the national Government and the States, or the distribution of
power and responsibilities among the various levels of government.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This proposed rule does not have tribal implications warranting the
application of E.O. 13175. This proposed rule does not have substantial
direct effects on one or more Indian tribes, on the relationship
between the Federal Government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
Government and Indian tribes.
Regulatory Flexibility Act
The Administrator, in accordance with the Regulatory Flexibility
Act (5 U.S.C. 601-612), has reviewed this proposed rule and by
approving it certifies that it will not have a significant economic
impact on a substantial number of small entities. As discussed above,
if finalized as proposed, 4-piperidone or a chemical mixture containing
4-piperidone will be subject to all of the regulatory controls and
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, importing, and exporting of list I
chemicals. 4-Piperidone is a precursor chemical used in, and is
important to, the illicit manufacture of the schedule II controlled
substance fentanyl. The distribution of illicitly manufactured fentanyl
has caused an unprecedented outbreak of thousands of fentanyl-related
overdoses in the United States in recent years. DEA has not identified
any legitimate industrial use for 4-piperidone other than its role as
an intermediary chemical in the production of fentanyl. However, DEA
believes the vast majority, if not all, of legitimate pharmaceutical
fentanyl is produced via a synthetic route involving NPP and ANPP as
intermediaries, not 4-piperidone. The review of import and quota
information for fentanyl, ANPP, and NPP supports this belief.
Therefore, DEA believes the vast majority, if not all, of 4-piperidone
is used for the illicit manufacturing of fentanyl. The primary costs
associated with this proposed rule are the annual registration fees
($3,699 for manufacturers and $1,850 for distributors, importers, and
exporters). Additionally, any manufacturer that uses 4-piperidone for
legitimate pharmaceutical fentanyl production would already be
registered with DEA and have all security and other handling processes
in place, resulting in minimal cost. DEA has identified 38 domestic
suppliers of 4-piperidone, 37 of which are not registered with DEA to
handle list I chemicals. All non-registered domestic suppliers are
affected and are estimated to be small entities (based on Small
Business Administration size standard for chemical distributors and
Statistics of U.S. Business data).\16\ It is impossible to know how
much 4-piperidone is distributed by these suppliers. It is common for
chemical distributors to have items in their catalog while not actually
having any material level of sales. Based on the review of import and
quota information for NPP, ANPP, and fentanyl, where the quantities of
NPP and ANPP imported and manufactured generally correspond with the
quantities of fentanyl produced, DEA believes any quantity of sales
from these distributors for legitimate pharmaceutical fentanyl
manufacturing is minimal. Therefore, DEA estimates the cost of this
rule on any affected small entity is minimal. DEA welcomes any public
comment regarding this estimate. Based on these factors, DEA projects
that this rule, if promulgated, will not result in a significant
economic impact on a substantial number of small entities.
---------------------------------------------------------------------------
\16\ <a href="https://www.sba.gov/sites/default/files/2018-07/NAICS%202017%20Table%20of%20Size%20Standards.pdf">https://www.sba.gov/sites/default/files/2018-07/NAICS%202017%20Table%20of%20Size%20Standards.pdf</a>.
---------------------------------------------------------------------------
Unfunded Mandates Reform Act of 1995
On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, DEA has determined and certifies
pursuant to the Unfunded Mandates Reform Act of 1995 (UMRA), 2 U.S.C.
1501 et seq., that this action would not result in any Federal mandate
that may result ``in the expenditure by State, local, and tribal
Governments, in the aggregate, or by the private sector, of
$100,000,000 or more (adjusted for inflation) in any one year . . . .
.'' Therefore, neither a Small Government Agency Plan nor any other
action is required under provisions of UMRA.
Paperwork Reduction Act
This proposed action does not impose a new collection of
information requirement under the Paperwork Reduction Act, 44 U.S.C.
3501-3521. This proposed action would not impose recordkeeping or
reporting requirements on State or local Governments, individuals,
businesses, or organizations. An agency may not conduct or sponsor, and
a person is not required to respond to, a collection of information
unless it displays a currently valid OMB control number.
List of Subjects in 21 CFR Part 1310
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, DEA proposes to amend 21 CFR part
1310 as follows:
PART 1310--RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN
MACHINES; IMPORTATION AND EXPORTATION OF CERTAIN MACHINES
0
1. The authority citation for 21 CFR part 1310 continues to read as
follows:
Authority: 21 U.S.C. 802, 827(h), 830, 871(b), 890.
[[Page 57859]]
0
2. In Sec. 1310.02, add paragraph (a)(38) to read as follows:
Sec. 1310.02 Substances covered.
* * * * *
(a) * * *
(38) 4-piperidone (piperidin-4-one), its acetals, its amides, 8330
its carbamates, its salts, and salts of its acetals, its amides,
and its carbamates, whenever the existence of such is possible..
* * * * *
0
3. In Sec. 1310.04:
0
a. Redesignate paragraphs (g)(1)(xvi) and (xvii) as paragraphs
(g)(1)(xvii) and (xviii) respectively; and
0
b. Add a new paragraph (g)(1)(xvi).
The revision reads as follows:
Sec. 1310.04 Maintenance of records.
* * * * *
(g) * * *
(1) * * *
(xvi) 4-piperidone (piperidin-4-one), its acetals, its amides, its
carbamates, its salts, and salts of its acetals, its amides, and its
carbamates, whenever the existence of such is possible
* * * * *
0
4. In Sec. 1310.09, add paragraph (s) to read as follows:
Sec. 1310.09 Temporary exemption from registration.
* * * * *
(s)(1) Each person required under 21 U.S.C. 822 and 21 U.S.C. 957
to obtain a registration to manufacture, distribute, import, or export
regulated 4-piperidone (piperidin-4-one), its acetals, its amides, its
carbamates, its salts, and salts of its acetals, its amides, and its
carbamates, whenever the existence of such is possible, including
regulated chemical mixtures pursuant to Sec. 1310.12, is temporarily
exempted from the registration requirement, provided that DEA receives
a properly completed application for registration or application for
exemption for a chemical mixture containing 4-piperidone pursuant to
Sec. 1310.13 on or before 30 days after the publication of a rule
finalizing this action. The exemption would remain in effect for each
person who has made such application until the Administration has
approved or denied that application. This exemption applies only to
registration; all other chemical control requirements set forth in the
Act and parts 1309, 1310, 1313, and 1316 of this chapter remain in full
force and effect.
(2) Any person who manufactures, distributes, imports, or exports a
chemical mixture containing 4-piperidone (piperidin-4-one), its
acetals, its amides, its carbamates, its salts, and salts of its
acetals, its amides, and its carbamates, whenever the existence of such
is possible whose application for exemption is subsequently denied by
DEA must obtain a registration with DEA. A temporary exemption from the
registration requirement will also be provided for those persons whose
application for exemption is denied, provided that DEA receives a
properly completed application for registration on or before 30 days
following the date of official DEA notification that the application
for exemption has been denied. The temporary exemption for such persons
will remain in effect until DEA takes final action on their
registration application.
0
5. In 1310.12(c), amend the table by adding in alphabetical order an
entry for ``4-piperidone (piperidin-4-one), its acetals, its amides,
its carbamates, its salts, and salts of its acetals, its amides, and
its carbamates, whenever the existence of such is possible'' to read as
follows:
Sec. 1310.12 Exempt chemical mixtures.
* * * * *
(c) * * *
Table of Concentration Limits
----------------------------------------------------------------------------------------------------------------
DEA
chemical Concentration Special conditions
code No.
----------------------------------------------------------------------------------------------------------------
List I Chemicals
----------------------------------------------------------------------------------------------------------------
* * * * * * *
4-piperidone (piperidin-4-one), its 8330 Not exempt at any Chemical mixtures containing
acetals, its amides, its carbamates, its concentration. any amount of 4-piperidone
salts, and salts of its acetals, its are not exempt.
amides, and its carbamates, whenever the
existence of such is possible.
* * * * * * *
----------------------------------------------------------------------------------------------------------------
* * * * *
Signing Authority
This document of the Drug Enforcement Administration was signed on
September 8, 2022, 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.
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2022-19974 Filed 9-21-22; 8:45 am]
BILLING CODE 4410-09-P
</pre></body>
</html>Indexed from Federal Register on September 22, 2022.
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.