[Federal Register Volume 87, Number 183 (Thursday, September 22, 2022)]
[Proposed Rules]
[Pages 57852-57859]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-19974]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1310

[Docket No. DEA-951]


Designation of 4-Piperidone as a List I Chemical

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration is proposing the control 
of 4-piperidone, its acetals, its amides, its carbamates, its salts, 
and salts of its acetals, its amides, and its carbamates, whenever the 
existence of such is possible, as a list I chemical under the 
Controlled Substances Act. The Drug Enforcement Administration finds 
that 4-piperidone is used in the illicit manufacture of the controlled 
substance fentanyl, and is important to the manufacture of the 
controlled substance fentanyl because it cannot be replaced by other 
chemicals in its respective synthetic pathways which are used in the 
illicit manufacture of fentanyl. If finalized, this action would 
subject handlers of 4-piperidone to the chemical regulatory provisions 
of the Controlled Substances Act and its implementing regulations. This 
rulemaking does not establish a threshold for domestic and 
international transactions of 4-piperidone. As such, all transactions 
of chemical mixtures containing 4-piperidone will be regulated at any 
concentration and will be subject to control under the Controlled 
Substances Act.

DATES: Comments must be submitted electronically or postmarked on or 
before October 24, 2022. Commenters should be aware that the electronic 
Federal Docket Management System will not accept any comments after 
11:59 p.m. Eastern Time on the last day of the comment period.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-951'' on all electronic and written correspondence, 
including any attachments.

[[Page 57853]]

     Electronic comments: The Drug Enforcement Administration 
encourages that all comments be submitted electronically through the 
Federal eRulemaking Portal which provides the ability to type short 
comments directly into the comment field on the web page or attach a 
file for lengthier comments. Please go to https://www.regulations.gov 
and follow the online instructions at that site for submitting 
comments. Upon completion of your submission, you will receive a 
Comment Tracking Number for your comment. Please be aware that 
submitted comments are not instantaneously available for public view on 
Regulations.gov. If you have received a Comment Tracking Number, your 
comment has been successfully submitted and there is no need to 
resubmit the same comment.
     Paper comments: Paper comments that duplicate electronic 
submissions are not necessary. Should you wish to mail a paper comment, 
in lieu of an electronic comment, it should be sent via regular or 
express mail to: Drug Enforcement Administration, Attn: DEA Federal 
Register Representative/DPW, 8701 Morrissette Drive, Springfield, 
Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical 
Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

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

Legal Authority

    The Controlled Substances Act (CSA) gives the Attorney General the 
authority to specify, by regulation, chemicals as list I chemicals.\1\ 
A ``list I chemical'' is a chemical that is used in manufacturing a 
controlled substance in violation of the CSA and is important to the 
manufacture of the controlled substances.\1\ The current list of all 
listed chemicals is published at 21 CFR 1310.02. Pursuant to 28 CFR 
0.100(b), the Attorney General has delegated his authority to designate 
list I chemicals to the Administrator of DEA (Administrator). DEA 
regulations set forth the process by which DEA may add a chemical as a 
listed chemical. As set forth in 21 CFR 1310.02(c), the agency may do 
so by publishing a final rule in the Federal Register following a 
published notice of proposed rulemaking with at least 30 days for 
public comments.
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    \1\ 21 U.S.C. 802(34).
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Background

    The clandestine manufacture of fentanyl remains extremely 
concerning as the distribution of illicit fentanyl continues to drive 
drug-related overdose deaths in the United States. Fentanyl is a 
synthetic opioid and was first synthesized in Belgium in the late 
1950s. Fentanyl was introduced into medical practice and is approved 
for medical practitioners in the United States to prescribe lawfully 
for anesthesia and analgesia. Yet, due to its pharmacological effects, 
fentanyl can be used as a substitute for heroin, oxycodone, and other 
opioids in opioid dependent individuals. Therefore, despite its 
accepted medical use in treatment in the United States, the DEA 
controls fentanyl as a schedule II controlled substance due to its high 
potential for abuse and dependence.\2\
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    \2\ 21 U.S.C. 812(c) Schedule II(b)(6) and 21 CFR 1308.12(c).
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    The unlawful trafficking of fentanyl in the United States continues 
to pose an imminent hazard to the public safety. Since 2012, fentanyl 
has shown a dramatic increase in the illicit drug supply as a single 
substance, in mixtures with other illicit drugs (i.e., heroin, cocaine, 
and methamphetamine), or in forms that mimic pharmaceutical 
preparations including prescription opiates and benzodiazepines.\3\
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    \3\ United Nations Office on Drugs and Crime, Global SMART 
Update Volume 17, March 2017. 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 (which includes fentanyl), are 
predominantly responsible for drug overdose deaths in recent years. 
According to CDC data, drug-induced overdose deaths involving synthetic 
opioids (excluding methadone) in the United States increased from 
36,359 in 2019 to 56,516 in 2020 to 57,802 in 2021 (provisional).\4\ Of 
the drug overdose death data (106,854) predicted for the 12 month-
ending November 2021, synthetic opioids were involved in about 65.9 
percent of all drug-induced overdose deaths.\5\ The increase in 
overdose fatalities involving synthetic opioids coincides with a 
dramatic increase in law enforcement encounters of fentanyl. According 
to the National Forensic Laboratory Information System (NFLIS-Drug),\6\ 
reports from forensic

[[Page 57854]]

laboratories of drug items containing fentanyl increased dramatically 
since 2014, as shown in Table 1.
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    \4\ Centers for Disease Control and Prevention, National Center 
for Health Statistics. National Vital Statistics System, Provisional 
Mortality on CDC WONDER Online Database. Data are from the final 
Multiple Cause of Death Files, 2018-2020, and from provisional data 
for years 2021-2022, as compiled from data provided by the 57 vital 
statistics jurisdictions through the Vital Statistics Cooperative 
Program. Accessed at https://wonder.cdc.gov/mcd-icd10-provisional.html on May 5, 2022.
    \5\ 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.
    \6\ The National Forensic Laboratory Information System (NFLIS-
Drug) is a national forensic laboratory reporting system that 
systematically collects results from drug chemistry analyses 
conducted by Federal, State and local forensic laboratories in the 
United States. While NFLIS-Drug data is not direct evidence of 
abuse, it can lead to an inference that a drug has been diverted and 
abused. See 76 FR 77330, 77332 (December 12, 2011). NFLIS-Drug data 
was queried on January 13, 2022.

                        Table 1--Annual Reports of Fentanyl Identified in Drug Encounters
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            Year                 2014        2015        2016        2017        2018        2019        2020
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Reports.....................      5,535      15,456      37,142      61,604      89,764     107,080     115,762
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Role of 4-Piperidone in the Synthesis of Fentanyl

    Fentanyl is not a naturally occurring substance. As such, the 
manufacture of fentanyl requires it to be produced through synthetic 
organic chemistry. Synthetic organic chemistry is the process in which 
a new organic molecule is created through a series of chemical 
reactions, which involve precursor chemicals. Through chemical 
reactions, the chemical structures of precursor chemicals are modified 
in a desired fashion. These chemical reaction sequences, also known as 
synthetic pathways, are designed to create a desired substance. Several 
synthetic pathways to fentanyl have been identified in clandestine 
laboratory settings; these include the original ``Janssen method,'' the 
``Siegfried method,'' and the ``Gupta method.'' In response to the 
illicit manufacture of fentanyl using these methods, DEA controlled N-
phenethyl-4-piperidone (NPP),\7\ N-(1-benzylpiperidin-4-yl)-N-
phenylpropionamide (benzylfentanyl) and N-phenylpiperidin-4-amine (4-
anilinopiperidine) \8\ as list I chemicals, and 4-anilino-N-
phenethylpiperidine (ANPP) \9\ and N-phenyl-N-(piperidin-4-
yl)propionamide (norfentanyl) \10\ as schedule II immediate precursors 
under the CSA.
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    \7\ 72 FR 20039 (April 23, 2007).
    \8\ 85 FR 20822 (May 15, 2020).
    \9\ 75 FR 37295 (August 30, 2010).
    \10\ 85 FR 21320 (May 18, 2020).
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    In 2017, the United Nations Commission on Narcotic Drugs placed NPP 
and ANPP in Table I of the Convention Against Illicit Traffic in 
Narcotic Drugs and Psychotropic Substances of 1988 (1988 Convention) in 
response to the international reintroduction of fentanyl on the illicit 
drug market. As such, member states of the United Nations were required 
to regulate these precursor chemicals at the national level. 
Importantly, the People's Republic of China regulated NPP and ANPP on 
February 1, 2018.\11\
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    \11\ 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.\12\
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    \12\ 72 FR 20039 (April 23, 2007) and 85 FR 20822 (April 15, 
2020).
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    In addition to the continuous exploration of viable precursors to 
manufacture fentanyl, illicit manufacturers also employ protecting 
group strategies on known fentanyl precursors. These protecting group 
strategies modify the chemical structure of a known precursor and are 
specifically designed to disguise the known precursor to evade law 
enforcement detection or to enhance the manufacturing process of the 
controlled substance the known precursor is used to make. These 
modified precursors are sometimes referred to as ``masked precursors.'' 
For example, 1-boc-4-anilinopiperidine (tert-butyl 4-
(phenylamino)piperidine-1-carboxylate, 1-boc-4-AP), a carbamate of 4-
anilinopiperidine and a list I chemical, was identified as a ``masked'' 
precursor chemical used in the illicit manufacture of fentanyl. 
Likewise, 1-boc-4-piperidone (tert-butyl 4-oxopiperidine-1-
carboxylate), a carbamate of 4-piperidone, and 4,4-piperidinediol 
(piperidine-4,4-diol) have also been identified as ``masked'' 
precursors. As a carbamate of 4-piperidone, 1-boc-4-piperidone would be 
controlled as a list I chemical upon completion of this rulemaking, as 
proposed. Similarly, 4,4-piperidinediol (Chemical Abstract Service 
Registry Number (CAS RN) 73390-11-1 for the free base and CAS RN 40064-
34-4 for the hydrochloride salt) is 4-piperidone with the inclusion of 
one water molecule of hydration and is known as a hydrate of 4-
piperidone. As a hydrate of 4-piperidone, 4,4-piperidinediol would also 
be subject to control under the listing of 4-piperidone upon completion 
of this rulemaking, as proposed. These masked precursors serve both a 
role in attempts to evade law enforcement detection as well as a 
strategic synthesis advantage compared to their unprotected 
counterparts, namely 4-anilinopiperidine and 4-piperidone.

4-Piperidone

    The original published synthetic pathway to fentanyl, known as the 
Janssen method, does not involve NPP or ANPP as precursor chemicals. 
This synthetic pathway involves the important precursors, 
benzylfentanyl and norfentanyl. 4-Piperidone serves as a precursor 
chemical to benzylfentanyl, a list I chemical under the CSA,\8\ which 
is converted to norfentanyl, the schedule II immediate precursor in 
this synthetic pathway. Norfentanyl is then subjected to one simple 
chemical reaction to complete the synthesis of fentanyl. Norfentanyl is 
controlled in schedule II of the CSA.\10\
    Like the Janssen method, 4-piperidone serves as an early-stage 
precursor chemical in the Siegfried method. 4-Piperidone is a precursor 
to NPP, a known fentanyl precursor and list I chemical, in the 
Siegfried method. NPP, a list I chemical under the CSA,\7\ is then 
converted to ANPP, the schedule II immediate precursor in this 
synthetic pathway. ANPP is then subjected to a simple one step chemical 
reaction to complete the synthesis of fentanyl. ANPP is controlled as a 
schedule II immediate precursor under the CSA.\9\
    In addition to the Janssen and Siegfried methods, clandestine 
manufacturers are using other methods to synthesize fentanyl, one of 
which is known as the Gupta method. 4-

[[Page 57855]]

Piperidone can be used to synthesize 4-anilinopiperidine, a list I 
chemical under the CSA \8\ and key precursor in the Gupta method. 4-
Anilinopiperidine serves as an alternative precursor chemical to NPP in 
the synthesis of ANPP, albeit through a different synthetic process. 
The resulting ANPP is then used as the immediate precursor chemical in 
the illicit manufacture of the schedule II controlled substance, 
fentanyl.
    DEA has determined that 4-piperidone is commercially available from 
both domestic and foreign suppliers. DEA is aware of at least 38 
domestic suppliers and 19 foreign suppliers. 4-Piperidone is attractive 
to illicit manufacturers due to the lack of regulations on this 
chemical, it is readily available from chemical suppliers, and it can 
be easily converted to known fentanyl precursors, including NPP, 
benzylfentanyl, and 4-anilinopiperidine.
    4-Piperidone and 1-boc-4-piperidone have been imported and 
identified in law enforcement encounters in the United States. 
According to law enforcement information, between March 2016 and 
October 2021, there have been three seizures of 4-piperidone (2) and 1-
boc-4-piperidone (1) totaling 357 kilograms (kg) at ports of entry in 
the United States. In addition to these encounters, a query of DEA's 
Laboratory Information Management System (LIMS) resulted in three 
domestic reports of 4-piperidone (1) and 1-boc-4-piperidone (2) from 
analyses conducted on submitted drug evidence by DEA forensic 
laboratories. 4-Piperidone was also identified at clandestine 
laboratories located in Arizona and Pennsylvania, which were involved 
in the illicit manufacture of fentanyl.
    As of May 2019, in addition to domestic encounters, the 
International Narcotics Control Board of the United Nations reported 
eight international transactions of 4-piperidone (6) and 1-boc-4-
piperidone (2) through the Precursors Incident Communication System 
(PICS) \13\ reporting system. These incidents reported to PICS totaled 
approximately 1,900 kg and had destinations located in North America 
and Europe. Along with the incidents reported to PICS, DEA is aware of 
ten additional seizures of 4-piperidone (9) and 1-boc-4-piperidone (1) 
at international ports of entry since May 2019, totaling approximately 
1,335 kg.
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    \13\ PICS is a platform that allows Governments to exchange 
operational and investigative intelligence and to generate strategic 
intelligence on precursors trafficking. PICS reports were collected 
up to December 16, 2021.
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    These recent law enforcement encounters of 4-piperidone coincide 
with the placement of NPP and ANPP in Table I of the 1988 Convention, 
the People's Republic of China regulating NPP and ANPP as of February 
1, 2018, and the regulation of benzylfentanyl and 4-anilinopiperidine 
as list I chemicals and the designation of norfentanyl as a schedule II 
immediate precursor to fentanyl in the United States. The domestic and 
international encounters of 4-piperidone at ports of entry and the 
identification of 4-piperidone at domestic fentanyl clandestine 
laboratories indicate a change in illicit fentanyl manufacturing 
methods in efforts to evade international controls on NPP and ANPP and 
additional controls on benzylfentanyl, 4-anilinopiperidine, and 
norfentanyl in the United States.

Regulation of 4-Piperidone, Including Its Acetals, Its Amides, Its 
Carbamates, Its Salts, and Salts of Its Acetals, Its Amides, and Its 
Carbamates, Whenever the Existence of Such Is Possible, as a List I 
Chemical

    The CSA, specifically 21 U.S.C. 802(34), and its implementing 
regulations at 21 CFR 1310.02(c), provide the Attorney General with the 
authority to specify, by regulation, additional precursor or essential 
chemicals as listed chemicals if they are used in the manufacture of 
controlled substances in violation of the CSA. Recent law enforcement 
encounters indicate 4-piperidone is being used in the illicit 
manufacture of the schedule II controlled substance fentanyl. This 
proposed rule would regulate 4-piperidone as a list I chemical because 
DEA finds that 4-piperidone is used in the illicit manufacture of the 
controlled substance fentanyl, and is important to the manufacture of 
the controlled substance fentanyl because it cannot be replaced by 
other chemicals in its respective synthetic pathways which are used in 
the illicit manufacture of fentanyl.

Chemical Mixtures of 4-Piperidone

    This proposed rulemaking, if finalized, would specify that chemical 
mixtures containing 4-piperidone would not be exempt from regulatory 
requirements at any concentration, unless an application for exemption 
of a chemical mixture is submitted by a 4-piperidone manufacturer and 
the application is reviewed and accepted by DEA under 21 CFR 1310.13 
(Exemption by Application Process). The control of chemical mixtures 
containing any amount of 4-piperidone is necessary to prevent the 
extraction, isolation, and use of 4-piperidone in the illicit 
manufacture fentanyl. This proposed rule would modify the Table of 
Concentration Limits in 21 CFR 1310.12(c) to reflect the fact that 
chemical mixtures containing any amount of 4-piperidone are subject to 
the CSA chemical control provisions.

Exemption by Application Process

    DEA has implemented an application process to exempt mixtures from 
the requirements of the CSA and its implementing regulations.\14\ Under 
the application process, manufacturers may submit an application for 
exemption for those mixtures that do not qualify for automatic 
exemption. Exemption status can be granted if DEA determines that the 
mixture is formulated in such a way that it cannot be easily used in 
the illicit production of a controlled substance and that the listed 
chemical cannot be readily recovered.\15\
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    \14\ 21 CFR 1310.13.
    \15\ 21 CFR U.S.C. 802(39)(A)(vi).
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Requirements for Handling List I Chemicals

    If this rule is finalized as proposed, 4-piperidone will be subject 
to all of the regulatory controls and administrative, civil, and 
criminal sanctions applicable to the manufacture, distribution, 
importing, and exporting of list I chemicals. Upon publication of a 
final rule, persons potentially handling 4-piperidone, including 
regulated chemical mixtures containing 4-piperidone, will be required 
to comply with list I chemical regulations, including the following:
    1. Registration. Any person who manufactures, distributes, imports, 
or exports 4-piperidone, including chemical mixtures containing 4-
piperidone, or proposes to engage in the manufacture, distribution, 
importation, or exportation of 4-piperidone, including chemical 
mixtures containing 4-piperidone, must obtain a registration pursuant 
to 21 U.S.C. 822, 823, 957, and 958. Regulations describing 
registration for list I chemical handlers are set forth in 21 CFR part 
1309. DEA regulations require separate registrations for manufacturing, 
distributing, importing, and exporting of list I chemicals. 21 CFR 
1309.21. Further, a separate registration is required for each 
principal place of business at one general physical location where list 
I chemicals are manufactured, distributed, imported, or exported by a 
person. 21 U.S.C. 822(e)(1) and 21 CFR 1309.23(a).
    DEA notes that under the CSA, ``warehousemen'' are not required to 
register and may lawfully possess list I chemicals, if the possession 
of those

[[Page 57856]]

chemicals is in the usual course of business or employment. Under DEA 
implementing regulations, the warehouse in question must receive the 
list I chemical from a DEA registrant and shall only distribute the 
list I chemical back to the DEA registrant and registered location from 
which it was received. A warehouse that distributes list I chemicals to 
persons other than the registrant and registered location from which 
they were obtained is conducting distribution activities and is 
required to register as such.
    Upon publication of a final rule, any person manufacturing, 
distributing, importing, or exporting 4-piperidone or a chemical 
mixture containing 4-piperidone would become subject to the 
registration requirement under the CSA. DEA recognizes, however, that 
it is not possible for persons who are subject to the registration 
requirements to immediately complete and submit an application for 
registration, and for DEA to immediately issue registrations for those 
activities. Therefore, to allow any continued legitimate commerce in 4-
piperidone or a chemical mixture containing 4-piperidone, DEA is 
proposing to establish in 21 CFR 1310.09, a temporary exemption from 
the registration requirement for persons desiring to engage in 
activities with 4-piperidone or a chemical mixture containing 4-
piperidone, provided that DEA receives a properly completed application 
for registration or application for exemption of a chemical mixture 
under 21 CFR 1310.13 on or before 30 days after publication of a final 
rule implementing regulations regarding 4-piperidone. The temporary 
exemption for such persons will remain in effect until DEA takes final 
action on their application for registration or application for 
exemption of a chemical mixture.
    The temporary exemption applies solely to the registration 
requirement; all other chemical control requirements, including 
recordkeeping and reporting, would become effective on the effective 
date of the final rule. This is necessary because a delay in regulating 
these transactions could result in increased diversion of chemicals 
desirable to drug traffickers.
    Additionally, the temporary exemption for registration does not 
suspend applicable Federal criminal laws relating to 4-piperidone, nor 
does it supersede State or local laws or regulations. All handlers of 
4-piperidone must comply with applicable State and local requirements 
in addition to the CSA regulatory controls.
    2. Records and Reports. Every DEA registrant would be required to 
maintain records and submit reports with respect to 4-piperidone 
pursuant to 21 U.S.C. 830 and in accordance with 21 CFR part 1310.04 
and 1310.05. Pursuant to 21 CFR 1310.04, a record must be kept for two 
years after the date of a transaction involving a listed chemical, 
provided the transaction is a regulated transaction.
    Each regulated bulk manufacturer of a listed chemical will be 
required to submit manufacturing, inventory, and use data on an annual 
basis. 21 CFR 1310.05(d). Existing standard industry reports containing 
the required information are acceptable, provided the information is 
separate or readily retrievable from the report.
    The CSA and its implementing regulations require that each 
regulated person must report to DEA any regulated transaction involving 
an extraordinary quantity of a listed chemical, an uncommon method of 
payment or delivery, or any other circumstance that the regulated 
person believes may indicate that the listed chemical will be used in 
violation of subchapter I of the CSA. In addition, regulated persons 
must report any proposed regulated transaction with a person whose 
description or other identifying characteristics DEA has previously 
furnished to the regulated person, any unusual or excessive loss or 
disappearance of a listed chemical under the control of the regulated 
person, and any in-transit loss in which the regulated person is the 
supplier. 21 U.S.C. 830(b) and 21 CFR 1310.05(a) and (b). Importation 
and Exportation. All importation and exportation of 4-piperidone or a 
chemical mixture containing 4-piperidone would need to be done in 
compliance with 21 U.S.C. 957, 958, and 971 and in accordance with 21 
CFR part 1313.
    3. Security. All applicants and registrants would be required to 
provide effective controls against theft and diversion of list I 
chemicals in accordance with 21 CFR 1309.71-1309.73.
    4. Administrative Inspection. Places, including factories, 
warehouses, or other establishments and conveyances, where registrants 
or other regulated persons may lawfully hold, manufacture, distribute, 
or otherwise dispose of a list I chemical or where records relating to 
those activities are maintained, are controlled premises as defined in 
21 U.S.C. 880(a) and 21 CFR 1316.02(c). The CSA allows for 
administrative inspections of these controlled premises as provided in 
21 CFR part 1316, subpart A. 21 U.S.C. 880.
    5. Liability. Any activity involving 4-piperidone not authorized 
by, or in violation of, the CSA, would be unlawful, and would subject 
the person to administrative, civil, and/or criminal action.

Solicitation for Information

    As part of this proposed rulemaking, DEA is soliciting information 
on any possible legitimate uses of 4-piperidone unrelated to fentanyl 
production (including industrial uses) in order to assess the potential 
economic impact of controlling 4-piperidone. DEA has searched 
information in the public domain for legitimate uses of this chemical, 
and has not documented a legitimate commercial or industrial use for 4-
piperidone other than as an intermediary chemical in the production of 
fentanyl. DEA seeks, however, to document any unpublicized use(s) and 
other proprietary use(s) of 4-piperidone that are not in the public 
domain. Therefore, DEA is soliciting comment on the uses of 4-
piperidone in the legitimate marketplace.
    DEA is soliciting input from all potentially affected parties 
regarding: (1) The types of legitimate industries using 4-piperidone; 
(2) the legitimate uses of 4-piperidone, if any; (3) the size of the 
domestic market for 4-piperidone; (4) the number of manufacturers of 4-
piperidone; (5) the number of distributors of 4-piperidone; (6) the 
level of import and export of 4-piperidone; (7) the potential burden 
these proposed regulatory controls of 4-piperidone may have on any 
legitimate trade; (8) the potential number of individuals/firms that 
may be adversely affected by these proposed regulatory controls 
(particularly with respect to the impact on small businesses); and (9) 
any other information on the manner of manufacturing, distribution, 
consumption, storage, disposal, and uses of 4-piperidone by industry 
and others. DEA invites all interested parties to provide any 
information on any legitimate uses of 4-piperidone in industry, 
commerce, academia, research and development, or other applications. 
DEA seeks both quantitative and qualitative data.

Handling of Confidential or Proprietary Information

    Confidential or proprietary information may be submitted as part of 
a comment regarding this Notice of Proposed Rulemaking. Please see the 
``POSTING OF PUBLIC COMMENTS'' section above for a discussion of the 
identification and redaction of confidential business information and 
personally identifying information.

[[Page 57857]]

Regulatory Analyses

Executive Orders 12866 and 13563, Regulatory Planning and Review, 
Improving and Regulation and Regulatory Review

    This proposed rule was developed in accordance with the principles 
of Executive Orders (E.O.) 12866 and 13563. E.O. 12866 directs agencies 
to assess all costs and benefits of available regulatory alternatives 
and, if regulation is necessary, to select regulatory approaches that 
maximize net benefits (including potential economic, environmental, 
public health, and safety effects; distributive impacts; and equity). 
E.O. 13563 is supplemental to and reaffirms the principles, structures, 
and definitions governing regulatory review as established in E.O. 
12866. E.O. 12866 classifies a ``significant regulatory action,'' 
requiring review by the Office of Management and Budget (OMB), as any 
regulatory action that is likely to result in a rule that may: (1) have 
an annual effect on the economy of $100 million or more or adversely 
affect in a material way the economy, a sector of the economy, 
productivity, competition, jobs, the environment, public health or 
safety, or State, local, or tribal Governments or communities; (2) 
create a serious inconsistency or otherwise interfere with an action 
taken or planned by another agency; (3) materially alter the budgetary 
impact of entitlements, grants, user fees, or loan programs or the 
rights and obligations of recipients thereof; or (4) raise novel legal 
or policy issues arising out of legal mandates, the President's 
priorities, or the principles set forth in the E.O.
    A review of the 38 domestic suppliers of 4-piperidone indicates 
that 37 entities are not registered with DEA to handle list I 
chemicals. DEA anticipates that this proposed rule will impose minimal 
or no economic impact on affected entities; and thus, will not have a 
significant economic impact on any of the 37 affected small entities. 
Therefore, DEA has concluded that this proposed rule will not have a 
significant effect on a substantial number of small entities. If 
finalized as proposed, 4-piperidone will be subject to all of the 
regulatory controls and administrative, civil, and criminal sanctions 
applicable to the manufacture, distribution, importing, and exporting 
of list I chemicals. 4-Piperidone is a precursor chemical used in, and 
is important to, the illicit manufacture of the schedule II controlled 
substance fentanyl. The distribution of illicitly manufactured fentanyl 
has caused an unprecedented outbreak of thousands of fentanyl-related 
overdoses in the United States in recent years.
    DEA has searched information in the public domain for any 
legitimate uses of 4-piperidone, and has not documented a use for 4-
piperidone other than as an intermediary chemical in the production of 
fentanyl. Based on the review of import and quota information for NPP, 
ANPP, and fentanyl, DEA believes the vast majority of, if not all, 
legitimate pharmaceutical fentanyl is produced via a synthetic route 
involving NPP and ANPP as intermediaries. The quantities of NPP 
indicated in import data and quantities of ANPP indicated in import and 
quota data generally correspond with the quantities of legitimate 
pharmaceutical fentanyl produced in the United States. Therefore, DEA 
concludes the vast majority of, if not all, 4-piperidone undergoing 
chemical transactions is being used for the manufacturing of illicit 
fentanyl. DEA cannot rule out the possibility that minimal quantities 
of 4-piperidone is being used for the manufacturing of legitimate 
pharmaceutical fentanyl. However, if there are any quantities of 4-
piperidone used for the manufacturing of legitimate pharmaceutical 
fentanyl, the quantities are believed to be small and economically 
insignificant. DEA welcomes any public comment on these quantities and 
their economic significance.
    DEA evaluated the costs and benefits of this proposed action.
Costs
    DEA believes the market for 4-piperidone for the legitimate 
manufacturing of pharmaceutical fentanyl is minimal. As stated above, 
the only use for 4-piperidone of which DEA is aware is as an 
intermediary for the manufacturing of fentanyl. Any manufacturer, 
distributor, importer, or exporter of 4-piperidone for the production 
of legitimate pharmaceutical fentanyl, if they exist at all, would 
incur costs if this proposed rule were finalized. The primary costs 
associated with this proposed rule would be the annual registration 
fees for list I chemicals ($3,699 for manufacturers and $1,850 for 
distributors, importers, and exporters). However, any manufacturer that 
uses 4-piperidone for legitimate pharmaceutical fentanyl production 
would already be registered with DEA and have all security and other 
handling processes in place because of the controls already in place on 
fentanyl, resulting in minimal cost to those entities. While different 
forms of handling the scheduled substance versus the list I chemical 
(distribution of fentanyl vs exporting 4-piperidone) could require a 
separate registration for the different handling of the substances, if 
an entity is already registered to handle, manufacture, import, or 
export a scheduled substance, the entity would not need an additional 
registration for the list I chemical, provided it is handling the list 
I chemical in the same manner that it is registered for with the 
scheduled substance, or as a coincident activity permitted by Sec.  
1309.21. Even with the possibility of these additional registrations, 
DEA believes that the cost will be minimal.
    DEA has identified 38 domestic suppliers of 4-piperidone. Only one 
is registered to handle list I chemicals, the remaining 37 are not 
registered with DEA to handle list I chemicals. It is difficult to 
estimate how much 4-piperidone is distributed by these suppliers. It is 
common for chemical distributors to have items in their catalog while 
not actually having any material level of sales. Based on the review of 
import and quota information for NPP, ANPP, and fentanyl, where the 
quantities of NPP and ANPP imported and manufactured generally 
correspond with the quantities of fentanyl produced, DEA believes any 
quantity of sales from these distributors for legitimate pharmaceutical 
fentanyl manufacturing is minimal. If this proposed rule is finalized, 
suppliers for the legitimate use of 4-piperidone are expected to choose 
the least-cost option, and stop selling the minimal quantities, if any, 
of 4-piperidone, rather than incur the registration cost. Because DEA 
believes the quantities of 4-piperidone supplied for the legitimate 
manufacturing of pharmaceutical fentanyl are minimal, DEA estimates 
that the cost of foregone sales is minimal; and thus, the cost of this 
proposed rule is minimal. DEA welcomes any public comment regarding 
this estimate.
    This analysis excludes consideration of any economic impact to 
those businesses that facilitate the manufacturing and distribution of 
4-piperidone for the manufacturing of illicit fentanyl. As a law 
enforcement organization and as a matter of principle, DEA believes 
considering the economic utility of facilitating the manufacture of 
illicit fentanyl would be improper.

[[Page 57858]]

Benefits
    Controlling 4-piperidone is expected to prevent, curtail, and limit 
the unlawful manufacture and distribution of the controlled substance, 
fentanyl. As a list I chemical, handling of 4-piperidone would require 
registration with DEA and various controls and monitoring as required 
by the CSA. This proposed rule is also expected to assist preventing 
the possible theft or diversion of 4-piperidone from any legitimate 
firms. DEA also believes control is necessary to prevent unscrupulous 
chemists from synthesizing 4-piperidone and selling it (as an 
unregulated material) through the internet and other channels, to 
individuals who may wish to acquire unregulated intermediary chemicals 
for the purpose of illicitly manufacturing fentanyl.
    In summary, DEA conducted a qualitative analysis of costs and 
benefits. DEA believes this proposed action, if finalized, will 
minimize the diversion of 4-piperidone. DEA believes the market for 4-
piperidone for the legitimate manufacturing of pharmaceutical fentanyl 
is minimal. Therefore, any potential cost as a result of this 
regulation is minimal.

Executive Order 12988, Civil Justice Reform

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of E.O. 12988 Civil Justice Reform to 
eliminate drafting errors and ambiguity, minimize litigation, provide a 
clear legal standard for affected conduct, and promote simplification 
and burden reduction.

Executive Order 13132, Federalism

    This proposed rulemaking does not have federalism implications 
warranting the application of E.O. 13132. The proposed rule does not 
have substantial direct effects on the States, on the relationship 
between the national Government and the States, or the distribution of 
power and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This proposed rule does not have tribal implications warranting the 
application of E.O. 13175. This proposed rule does not have substantial 
direct effects on one or more Indian tribes, on the relationship 
between the Federal Government and Indian tribes, or on the 
distribution of power and responsibilities between the Federal 
Government and Indian tribes.

Regulatory Flexibility Act

    The Administrator, in accordance with the Regulatory Flexibility 
Act (5 U.S.C. 601-612), has reviewed this proposed rule and by 
approving it certifies that it will not have a significant economic 
impact on a substantial number of small entities. As discussed above, 
if finalized as proposed, 4-piperidone or a chemical mixture containing 
4-piperidone will be subject to all of the regulatory controls and 
administrative, civil, and criminal sanctions applicable to the 
manufacture, distribution, importing, and exporting of list I 
chemicals. 4-Piperidone is a precursor chemical used in, and is 
important to, the illicit manufacture of the schedule II controlled 
substance fentanyl. The distribution of illicitly manufactured fentanyl 
has caused an unprecedented outbreak of thousands of fentanyl-related 
overdoses in the United States in recent years. DEA has not identified 
any legitimate industrial use for 4-piperidone other than its role as 
an intermediary chemical in the production of fentanyl. However, DEA 
believes the vast majority, if not all, of legitimate pharmaceutical 
fentanyl is produced via a synthetic route involving NPP and ANPP as 
intermediaries, not 4-piperidone. The review of import and quota 
information for fentanyl, ANPP, and NPP supports this belief. 
Therefore, DEA believes the vast majority, if not all, of 4-piperidone 
is used for the illicit manufacturing of fentanyl. The primary costs 
associated with this proposed rule are the annual registration fees 
($3,699 for manufacturers and $1,850 for distributors, importers, and 
exporters). Additionally, any manufacturer that uses 4-piperidone for 
legitimate pharmaceutical fentanyl production would already be 
registered with DEA and have all security and other handling processes 
in place, resulting in minimal cost. DEA has identified 38 domestic 
suppliers of 4-piperidone, 37 of which are not registered with DEA to 
handle list I chemicals. All non-registered domestic suppliers are 
affected and are estimated to be small entities (based on Small 
Business Administration size standard for chemical distributors and 
Statistics of U.S. Business data).\16\ It is impossible to know how 
much 4-piperidone is distributed by these suppliers. It is common for 
chemical distributors to have items in their catalog while not actually 
having any material level of sales. Based on the review of import and 
quota information for NPP, ANPP, and fentanyl, where the quantities of 
NPP and ANPP imported and manufactured generally correspond with the 
quantities of fentanyl produced, DEA believes any quantity of sales 
from these distributors for legitimate pharmaceutical fentanyl 
manufacturing is minimal. Therefore, DEA estimates the cost of this 
rule on any affected small entity is minimal. DEA welcomes any public 
comment regarding this estimate. Based on these factors, DEA projects 
that this rule, if promulgated, will not result in a significant 
economic impact on a substantial number of small entities.
---------------------------------------------------------------------------

    \16\ 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.

Paperwork Reduction Act

    This proposed action does not impose a new collection of 
information requirement under the Paperwork Reduction Act, 44 U.S.C. 
3501-3521. This proposed action would not impose recordkeeping or 
reporting requirements on State or local Governments, individuals, 
businesses, or organizations. An agency may not conduct or sponsor, and 
a person is not required to respond to, a collection of information 
unless it displays a currently valid OMB control number.

List of Subjects in 21 CFR Part 1310

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, DEA proposes to amend 21 CFR part 
1310 as follows:

PART 1310--RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN 
MACHINES; IMPORTATION AND EXPORTATION OF CERTAIN MACHINES

0
1. The authority citation for 21 CFR part 1310 continues to read as 
follows:

    Authority: 21 U.S.C. 802, 827(h), 830, 871(b), 890.


[[Page 57859]]


0
2. In Sec.  1310.02, add paragraph (a)(38) to read as follows:


Sec.  1310.02   Substances covered.

* * * * *
    (a) * * *

 (38) 4-piperidone (piperidin-4-one), its acetals, its amides,      8330
 its carbamates, its salts, and salts of its acetals, its amides,
 and its carbamates, whenever the existence of such is possible..
 

* * * * *
0
3. In Sec.  1310.04:
0
a. Redesignate paragraphs (g)(1)(xvi) and (xvii) as paragraphs 
(g)(1)(xvii) and (xviii) respectively; and
0
b. Add a new paragraph (g)(1)(xvi).
    The revision reads as follows:


Sec.  1310.04   Maintenance of records.

* * * * *
    (g) * * *
    (1) * * *
    (xvi) 4-piperidone (piperidin-4-one), its acetals, its amides, its 
carbamates, its salts, and salts of its acetals, its amides, and its 
carbamates, whenever the existence of such is possible
* * * * *
0
4. In Sec.  1310.09, add paragraph (s) to read as follows:


Sec.  1310.09  Temporary exemption from registration.

* * * * *
    (s)(1) Each person required under 21 U.S.C. 822 and 21 U.S.C. 957 
to obtain a registration to manufacture, distribute, import, or export 
regulated 4-piperidone (piperidin-4-one), its acetals, its amides, its 
carbamates, its salts, and salts of its acetals, its amides, and its 
carbamates, whenever the existence of such is possible, including 
regulated chemical mixtures pursuant to Sec.  1310.12, is temporarily 
exempted from the registration requirement, provided that DEA receives 
a properly completed application for registration or application for 
exemption for a chemical mixture containing 4-piperidone pursuant to 
Sec.  1310.13 on or before 30 days after the publication of a rule 
finalizing this action. The exemption would remain in effect for each 
person who has made such application until the Administration has 
approved or denied that application. This exemption applies only to 
registration; all other chemical control requirements set forth in the 
Act and parts 1309, 1310, 1313, and 1316 of this chapter remain in full 
force and effect.
    (2) Any person who manufactures, distributes, imports, or exports a 
chemical mixture containing 4-piperidone (piperidin-4-one), its 
acetals, its amides, its carbamates, its salts, and salts of its 
acetals, its amides, and its carbamates, whenever the existence of such 
is possible whose application for exemption is subsequently denied by 
DEA must obtain a registration with DEA. A temporary exemption from the 
registration requirement will also be provided for those persons whose 
application for exemption is denied, provided that DEA receives a 
properly completed application for registration on or before 30 days 
following the date of official DEA notification that the application 
for exemption has been denied. The temporary exemption for such persons 
will remain in effect until DEA takes final action on their 
registration application.
0
5. In 1310.12(c), amend the table by adding in alphabetical order an 
entry for ``4-piperidone (piperidin-4-one), its acetals, its amides, 
its carbamates, its salts, and salts of its acetals, its amides, and 
its carbamates, whenever the existence of such is possible'' to read as 
follows:


Sec.  1310.12   Exempt chemical mixtures.

* * * * *
    (c) * * *

                                          Table of Concentration Limits
----------------------------------------------------------------------------------------------------------------
                                              DEA
                                            chemical          Concentration              Special conditions
                                            code No.
----------------------------------------------------------------------------------------------------------------
                                                List I Chemicals
----------------------------------------------------------------------------------------------------------------
 
                                                  * * * * * * *
4-piperidone (piperidin-4-one), its             8330  Not exempt at any             Chemical mixtures containing
 acetals, its amides, its carbamates, its              concentration.                any amount of 4-piperidone
 salts, and salts of its acetals, its                                                are not exempt.
 amides, and its carbamates, whenever the
 existence of such is possible.
 
                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------

* * * * *

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
September 8, 2022, by Administrator Anne Milgram. That document with 
the original signature and date is maintained by DEA. For 
administrative purposes only, and in compliance with requirements of 
the Office of the Federal Register, the undersigned DEA Federal 
Register Liaison Officer has been authorized to sign and submit the 
document in electronic format for publication, as an official document 
of DEA. This administrative process in no way alters the legal effect 
of this document upon publication in the Federal Register.

Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2022-19974 Filed 9-21-22; 8:45 am]
BILLING CODE 4410-09-P