[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