[Federal Register Volume 88, Number 70 (Wednesday, April 12, 2023)]
[Rules and Regulations]
[Pages 21902-21910]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07538]
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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: Final rule.
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SUMMARY: The Drug Enforcement Administration (DEA) is finalizing the
control of 4-piperidone, its acetals, its amides, its carbamates, its
salts, and salts of its acetals, its amides, and its carbamates, and
any combination thereof, whenever the existence of such is possible, as
a list I chemical under the Controlled Substances Act. DEA proposed
control of 4-piperidone due to its use in clandestine laboratories to
illicitly manufacture the schedule II controlled substance fentanyl.
This rulemaking finalizes the control of 4-piperidone as a list I
chemical.
DATES: This rulemaking is effective on May 12, 2023. Persons seeking
registration must apply on or before May 12, 2023, to continue their
business pending final action by DEA on their application.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION: The Drug Enforcement Administration (DEA) is
[[Page 21903]]
extremely concerned with the recent increase in the illicit manufacture
and distribution of fentanyl. Therefore, on September 22, 2022, DEA
published a Notice of Proposed Rulemaking (NPRM) to control the
precursor chemical 4-piperidone as a list I chemical.\1\ This
rulemaking finalizes that NPRM.
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\1\ 87 FR 57852.
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This action subjects handlers of 4-piperidone to the chemical
regulatory provisions of the Controlled Substances Act (CSA) and its
implementing regulations. This rulemaking does not establish a
threshold for domestic and international transactions of 4-piperidone.
As such, all transactions involving 4-piperidone, regardless of size,
shall be regulated and are subject to control under the CSA. In
addition, chemical mixtures containing 4-piperidone are not exempt from
regulatory requirements at any concentration. Therefore, all
transactions of chemical mixtures containing any quantity of 4-
piperidone shall be regulated pursuant to the CSA.
Legal Authority
The CSA gives the Attorney General the authority to specify, by
regulation, chemicals as list I chemicals.\2\ The Attorney General
delegated his authority to designate list I chemicals to the
Administrator of DEA (Administrator).\3\ A ``list I chemical'' is a
chemical that is used in manufacturing a controlled substance in
violation of subchapter I (Control and Enforcement) of the CSA and is
important to the manufacture of the controlled substances.\2\ The
current list of all list I chemicals is published at 21 CFR 1310.02(a).
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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\2\ 21 U.S.C. 802(34).
\3\ 28 CFR 0.100(b).
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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 also 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.\4\
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\4\ 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.\5\
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\5\ 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 in the United States in recent years.
According to the Centers for Disease Control and Prevention (CDC),
opioids, mainly synthetic opioids (including 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).\6\ Of
the drug overdose death data (106,854) predicted for the 12-month
period ending November 2021, synthetic opioids were involved in about
65.9 percent of all drug-induced overdose deaths.\7\ 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),\8\
reports from forensic laboratories of drug items containing fentanyl
increased dramatically since 2014, as shown in Table 1.
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\6\ 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 https://wonder.cdc.gov/mcd-icd10-provisional.html on May 5, 2022.
\7\ Ahmad FB, Rossen LM, Sutton P. Provisional drug overdose
death counts. National Center for Health Statistics. 2021. Accessed
at https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm on May
5, 2022.
\8\ 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
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),\9\ N-(1-benzylpiperidin-4-yl)-N-
phenylpropionamide (benzylfentanyl) and N-phenylpiperidin-4-amine (4-
anilinopiperidine) \10\ as list I chemicals, and 4-anilino-N-
phenethylpiperidine
[[Page 21904]]
(ANPP) \11\ and N-phenyl-N-(piperidin-4-yl)propionamide (norfentanyl)
\12\ as schedule II immediate precursors under the CSA.
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\9\ 72 FR 20039 (April 23, 2007).
\10\ 85 FR 20822 (May 15, 2020).
\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 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.\13\
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\13\ https://www.dea.gov/press-release/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals.
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.\14\
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\14\ 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 is
subject to this rulemaking. 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 is also subject to this rulemaking. These masked
precursors serve both as a role in attempts to evade law enforcement
detection as well as a strategic synthesis advantage compared to their
unprotected counterparts (precursors without protecting groups), 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 in the Janssen method, 4-piperidone also 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-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 two seizures of 4-piperidone and one
seizure of 1-boc-4-piperidone, amounting to a total of 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 a total of 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 a
total of eight international transactions of 4-piperidone (6) and 1-
boc-4-piperidone (2) through the Precursors Incident Communication
System (PICS).\15\ 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
a total 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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\15\ 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
[[Page 21905]]
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, and Any Combination Thereof, 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 rule
regulates 4-piperidone, including its acetals, its amides, its
carbamates, its salts, and salts of its acetals, its amides, and its
carbamates, and any combination thereof, whenever the existence of such
is possible, 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. In effort to make clear DEA's intent in the
NPRM published on September 22, 2022 \16\ that combinations of
functional group definitions are included in the control of 4-
piperidone, DEA is including, ``and any combination thereof'' in the
definitions of 4-piperidone in this final rule. This amendment is not a
substantive change from the NPRM; it only clarifies DEA's intent of
this action.
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\16\ 87 FR 57852.
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Comments Received
As part of the NPRM published on September 22, 2022,\17\ DEA
specifically solicited comment on any possible legitimate uses of 4-
piperidone unrelated to fentanyl production (including industrial uses)
in order to assess the potential commercial impact of controlling 4-
piperidone. DEA had searched information in the public domain for
legitimate uses of this chemical and had not documented a legitimate
commercial use for 4-piperidone other than as intermediary chemicals in
the production of fentanyl. DEA sought, however, to document any
unpublicized use(s) and other proprietary use(s) of 4-piperidone that
are not in the public domain. Therefore, DEA solicited comment on the
uses of 4-piperidone in the legitimate marketplace.
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\17\ Id.
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DEA solicited 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 regulatory controls of 4-piperidone may have on any legitimate
commercial activities; (8) the potential number of individuals/firms
that may be adversely affected by these 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 invited 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 sought both quantitative and qualitative data. DEA did not receive
any responses to these specific solicitations.
In response to the NPRM, DEA received three comments. Two
commenters were in support of controlling 4-piperidone as a list I
chemical. One commenter submitted a response that was outside the scope
of the action.
Comment: One commenter stated that designating 4-piperidone as a
list I chemical is in the best interest of the public due to the rise
in synthetic opioid issues in the United States. The commenter compared
the regulation of 4-piperidone to the regulation of methamphetamine
precursors in the past, which ultimately led to difficulty in obtaining
methamphetamine precursor chemicals. The commenter also stated that
consequences, such as foreign production of drugs, be considered and
that work with partner nations to reduce availability of illicit
narcotics.
DEA response: DEA agrees with the comment in support of controlling
4-piperidone as a list I chemical. DEA is concerned with the abuse of
illicitly manufactured fentanyl in the United States and believes this
rule will help to control the illicit manufacture of fentanyl. DEA also
agrees that the illicit manufacture of fentanyl and other drugs is a
global challenge and necessitates cooperation with international
partners. As a list I chemical, imports and exports of 4-piperidone
will be regulated per 21 CFR part 1313.
Comment: One commenter stated that controlling 4-piperidone would
limit the unlawful manufacture and distribution of fentanyl.
Controlling 4-piperidone will reduce theft, which leads to the
unregulated sale of illicitly manufactured fentanyl. The control of 4-
piperidone would lead to a decrease in overdose deaths.
DEA response: DEA agrees with the comment in support of controlling
4-piperidone as a list I chemical. DEA is concerned with the abuse of
illicitly manufactured fentanyl in the United States and believes this
rule will help to control the illicit manufacture of fentanyl.
Comment: One commenter stated that the Drug Enforcement Agency
[sic] does not have the constitutional authority to ban and prosecute
American citizens for selling, obtaining, and using drugs not involved
in interstate commerce. The commenter further states that the Drug
Enforcement Agency [sic] has ruined the lives of thousands for
possession of a substance and that possession of a substance is not a
morally justifiable reason for imprisonment. The commenter stated that
DEA needs to stop arbitrary regulations and allow Americans to live
freely. The commenter further states that the criminalization of drugs
has given a monopoly to drug cartels. Lastly, the commenter states that
drug consumption would be safer, Americans would be freer, and cartels
would lose their income stream if companies were allowed to sell drugs.
DEA response: This comment is outside the scope of this rule.
Congress has provided, in the CSA, the mechanism to regulate precursor
chemicals, which is the authority utilized in this rule.\18\
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\18\ 21 U.S.C. 802(34).
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Chemical Mixtures of 4-Piperidone
Under this rulemaking, chemical mixtures containing 4-piperidone
are
[[Page 21906]]
not 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 rule modifies 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.\19\ 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.\20\
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\19\ 21 CFR 1310.13.
\20\ 21 U.S.C. 802(39)(A)(vi).
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Requirements for Handling List I Chemicals
This final rule subjects 4-piperidone 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 the effective date of this final rule, persons 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\
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).
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\21\ 21 CFR 1309.21.
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DEA notes that under the CSA, ``warehousemen'' are not required to
register and may lawfully possess list I chemicals, if the possession
of those chemicals is in the usual course of business or
employment.\22\ 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.\23\
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\22\ 21 U.S.C. 822(c)(2)
\23\ 21 U.S.C. 822(a)(1).
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Upon the effective date of this final rule, any person
manufacturing, distributing, importing, or exporting 4-piperidone or a
chemical mixture containing 4-piperidone will 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
establishing 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 May 12, 2023. 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 this 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 must 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 must submit
manufacturing, inventory, and use data on an annual basis. Existing
standard industry reports containing the required information are
acceptable, provided the information is separate or readily retrievable
from the report.\24\
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\24\ 21 CFR 1310.05(d).
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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 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.\25\
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\25\ 21 U.S.C. 830(b) and 21 CFR 1310.05(a) and (b).
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3. Importation and Exportation. All importation and exportation of
4-piperidone or a chemical mixture containing 4-piperidone must be done
in compliance with 21 U.S.C. 957, 958, and 971 and in accordance with
21 CFR part 1313.
4. Security. All applicants and registrants must provide effective
controls against theft and diversion of list I chemicals in accordance
with 21 CFR 1309.71-1309.73.
[[Page 21907]]
5. 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 U.S.C. 880 and 21 CFR part 1316, subpart A.
6. 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.
Regulatory Analyses
Executive Orders 12866 and 13563, Regulatory Planning and Review,
Improving and Regulation and Regulatory Review
This final rulemaking, which adds 4-piperidone as a list 1
chemical, 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.
DEA has reviewed this rule under the foregoing principles and has
determined that this rule is not a ``significant regulatory action''
under E.O. 12866. Accordingly, the Office of Information and Regulatory
Affairs has not reviewed this rule.
This final rulemaking subjects 4-piperidone 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, not 4-piperidone. 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 requested public comment
regarding this estimate; however, no public comment was received during
the notice and comment period.
DEA evaluated the costs and benefits of this 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, will incur
costs. The primary costs associated with this 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. 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 rule is minimal. DEA requested
public comment regarding this estimate; however, no public comment was
received during the notice and comment period.
[[Page 21908]]
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.
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 requires
registration with DEA and various controls and monitoring as required
by the CSA. This 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 action 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 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 rulemaking does not have federalism implications warranting
the application of E.O. 13132. The 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 rule does not have tribal implications warranting the
application of E.O. 13175. This 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 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, 4-piperidone
or a chemical mixture containing 4-piperidone shall 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 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).\26\ 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 did not receive
public comment regarding this estimate. Based on these factors, DEA
projects that this rule will not result in a significant economic
impact on a substantial number of small entities.
---------------------------------------------------------------------------
\26\ https://www.sba.gov/sites/default/files/2018-07/NAICS%202017%20Table%20of%20Size%20Standards.pdf.
---------------------------------------------------------------------------
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.
Congressional Review Act
This rule is not a major rule as defined by the Congressional
Review Act (CRA), 5 U.S.C. 804. However, pursuant to the CRA, DEA is
submitting a copy of this final rule to both Houses of Congress and to
the Comptroller General.
Signing Authority
This document of the Drug Enforcement Administration was signed on
April 3, 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
[[Page 21909]]
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.
List of Subjects in 21 CFR Part 1310
Administrative practice and procedure, Drug traffic control,
Exports, Imports, Reporting and recordkeeping requirements.
For the reasons set out above, DEA amends 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 part 1310 continues to read as follows:
Authority: 21 U.S.C. 802, 827(h), 830, 871(b), 890.
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, and any combination thereof,
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 addition 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, and any combination thereof, 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, and any combination thereof, 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 May 12,
2023. 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, and any combination thereof,
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, amend the table in paragraph (c) 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, and any combination thereof,
whenever the existence of such is possible'' to read as follows:
Sec. 1310.12 Exempt chemical mixtures.
* * * * *
(c) * * *
Table of Concentration Limits
----------------------------------------------------------------------------------------------------------------
DEA chemical
code No. Concentration Special conditions
----------------------------------------------------------------------------------------------------------------
List I Chemicals
----------------------------------------------------------------------------------------------------------------
* * * * * * *
4-piperidone (piperidin-4-one), its 8330 Not exempt at any Chemical mixtures
acetals, its amides, its carbamates, concentration. containing any amount of
its salts, and salts of its acetals, 4-piperidone are not
its amides, and its carbamates, and exempt.
any combination thereof, whenever the
existence of such is possible.
* * * * * * *
----------------------------------------------------------------------------------------------------------------
[[Page 21910]]
* * * * *
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2023-07538 Filed 4-11-23; 8:45 am]
BILLING CODE 4410-09-P