[Federal Register Volume 88, Number 72 (Friday, April 14, 2023)]
[Proposed Rules]
[Pages 22955-22962]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07454]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1310
[Docket No. DEA-1098]
Designation of Halides of 4-Anilinopiperidine as List I Chemicals
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: The Drug Enforcement Administration is proposing to modify the
listing of the list I chemical, N-phenylpiperidin-4-amine (also known
as 4-anilinopiperidine; N-phenyl-4-piperidinamine; 4-AP) (hereinafter
referred to as 4-anilinopiperidine), to include halides of 4-
anilinopiperidine. The current listing of 4-anilinopiperidine includes
its amides, its carbamates, and its salts, as list I chemicals under
the Controlled Substances Act. The Drug Enforcement Administration
proposes the new listing to read as follows: N-phenylpiperidin-4-amine
(4-anilinopiperidine; N-phenyl-4-piperidinamine; 4-AP), its amides, its
carbamates, its halides, its salts, and any combination thereof,
whenever the existence of such is possible, as a list I chemical under
the Controlled Substances Act.
DATES: Comments must be submitted electronically or postmarked on or
before May 15, 2023. Commenters should be aware that the electronic
Federal Docket Management System will not accept any comments after
11:59 p.m. Eastern Time on the last day of the comment period.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-1098'' on all electronic and written correspondence,
including any attachments.
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.\2\ The current list of all
listed chemicals is published at 21 CFR 1310.02. Pursuant to 28 CFR
0.100(b), the Attorney General has delegated his authority to designate
list I chemicals to the Administrator of DEA (Administrator). DEA
regulations set forth the process by which DEA may add a chemical as a
listed chemical. As set forth in 21 CFR 1310.02(c), the agency may do
so by publishing a final rule in the Federal Register following a
published notice of proposed rulemaking with at least 30 days for
public comments.
---------------------------------------------------------------------------
\1\ 21 U.S.C. 802(34).
\2\ Id.
---------------------------------------------------------------------------
Background
DEA previously found that 4-anilinopiperidine is used in the
illicit manufacture of the controlled substance fentanyl (a schedule II
substance under the CSA) and fentanyl analogues controlled in schedule
I of the CSA, and is important to the manufacture of the controlled
substance fentanyl and fentanyl analogues, because it cannot be
replaced by other chemicals in its respective synthetic pathways that
are used in the illicit manufacture of
[[Page 22956]]
fentanyl and fentanyl analogues.\3\ On this basis, DEA previously
specified that 4-anilinopiperidine is a list I chemical.\4\ DEA has now
found that halides of 4-anilinopiperidine are also used in the illicit
manufacture of schedule I controlled substances, such as para-
fluorofentanyl, ortho-fluorofentanyl, and para-chlorofentanyl.
Accordingly, if finalized, this action would add halides of 4-
anilinopiperidine to the prior listing of 4-anilinopiperidine and
thereby subject handlers of halides of 4-anilinopiperidine to the
chemical regulatory provisions of the CSA and its implementing
regulations.
---------------------------------------------------------------------------
\3\ 85 FR 20822 (Apr. 15, 2020).
\4\ Id.
---------------------------------------------------------------------------
This proposed rule would not affect current handlers of 4-
anilinopiperidine, including its amides, its carbamates, and its salts,
as they would already be registered to handle 4-anilinopiperidine. This
rulemaking does not establish a threshold for domestic and
international transactions of halides of 4-anilinopiperidine. As such,
all transactions of chemical mixtures containing halides of 4-
anilinopiperidine will be regulated at any concentration and will be
subject to control under the CSA.
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. 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.\5\
---------------------------------------------------------------------------
\5\ 21 U.S.C. 812(c), Schedule II(b)(6); 21 CFR 1308.12(c).
---------------------------------------------------------------------------
The unlawful trafficking and distribution of fentanyl and fentanyl
analogues in the United States continues to pose an imminent hazard to
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.\6\
---------------------------------------------------------------------------
\6\ 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.
---------------------------------------------------------------------------
In recent years, the United States has experienced a significant
increase in overdoses and overdose fatalities from fentanyl and
fentanyl analogues. According to the Centers for Disease Control and
Prevention (CDC), drug-induced overdose deaths involving synthetic
opioids (excluding methadone) in the United States increased from
36,359 in 2019, to 56,516 in 2020, and to 70,589 in 2021
(provisional).\7\ Further, CDC reports that opioids, mainly synthetic
opioids (which includes fentanyl), are predominately responsible for
drug overdose fatalities, as the drug overdose death data (109,247)
predicted for the 12 month-ending March 2022, synthetic opioids were
involved in about 67.3 percent of all drug-induced overdose deaths.\8\
---------------------------------------------------------------------------
\7\ 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 August 15, 2022.
\8\ 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.
---------------------------------------------------------------------------
The increase in overdose fatalities involving synthetic opioids
coincides with a dramatic increase in law enforcement encounters of
fentanyl and fentanyl analogues. According to the National Forensic
Laboratory Information System (NFLIS-Drug),\9\ reports from forensic
laboratories of drug items containing fentanyl and several schedule I
fentanyl analogues increased dramatically since 2014, as shown in Table
1.
---------------------------------------------------------------------------
\9\ 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 (Dec. 12, 2011). NFLIS-Drug data was
queried on August 15, 2022.
Table 1--Annual Reports of Fentanyl and Halogenated Fentanyl Analogues Identified in Drug Encounters
--------------------------------------------------------------------------------------------------------------------------------------------------------
Year 2014 2015 2016 2017 2018 2019 2020 2021
--------------------------------------------------------------------------------------------------------------------------------------------------------
Fentanyl........................................ 5,553 15,461 37,144 61,628 89,890 107,928 124,773 156,629
Halogenated Fentanyl Analogues \10\............. 1 10 435 2,628 2,960 1,013 743 19,831
--------------------------------------------------------------------------------------------------------------------------------------------------------
Role of 4-Anilinopiperidine in the Synthesis of Fentanyl and Fentanyl
Analogues
Fentanyl and its analogues are not naturally occurring substances.
As such, the manufacture of these substances requires them to be
produced through synthetic organic chemistry. Synthetic organic
chemistry is the process in which a new organic molecule is created
through a series of chemical reactions, which involve precursor
chemicals. Through chemical reactions, the chemical structures of
precursor chemicals are modified in a desired fashion. These chemical
reaction sequences, also known as synthetic pathways, are designed to
create a desired substance. Several synthetic pathways to fentanyl and
fentanyl analogues have been identified in clandestine laboratory
settings, including the original ``Janssen method,'' the ``Siegfried
method,'' and the ``Gupta method,'' which are further explained below.
In response to the illicit manufacture of fentanyl using these
methods, DEA controlled N-phenethyl-4-piperidone (NPP); \11\ N-(1-
benzylpiperidin-4-yl)-N-phenylpropionamide (benzylfentanyl), N-
phenylpiperidin-4-amine (4-anilinopiperidine); \12\ and proposed
control of 4-piperidone \13\ as list I chemicals. DEA also controlled
4-anilino-N-phenethylpiperidine
[[Page 22957]]
(ANPP) \14\ and N-phenyl-N-(piperidin-4-yl)propionamide (norfentanyl)
\15\ as schedule II immediate precursors to fentanyl under the CSA.
---------------------------------------------------------------------------
\10\ Halogenated fentanyl analogues reported to NFLIS-Drug
include: meta-fluorofentanyl, meta-fluoroisobutyryl fentanyl, para-
fluoroisobutyryl fentanyl, chlorofentanyl, fluoro furanyl fentanyl,
fluorobutyryl fentanyl, fluorobutyryl/fluoroisobutyryl fentanyl,
fluorofentanyl, fluoroisobutyryl fentanyl, meta-fluoro furanyl
fentanyl, ortho-fluorobutyryl fentanyl, ortho-fluoroisobutyryl
fentanyl, ortho-fluoro acrylfentanyl, ortho-fluoro furanyl fentanyl,
ortho-fluorofentanyl, ortho-chlorofentanyl, para-chlorofentanyl,
para-fluoro furanyl fentanyl, para-fluoro valeryl fentanyl, para-
fluorobutyryl fentanyl, and para-fluorofentanyl.
\11\ 72 FR 20039 (Apr. 23, 2007).
\12\ 85 FR 20822 (Apr. 15, 2020).
\13\ 87 FR 57852 (Sept. 22, 2022).
\14\ 75 FR 37295 (Aug. 30, 2010).
\15\ 85 FR 21320 (Apr. 17, 2020).
---------------------------------------------------------------------------
In 2017, the United Nations Commission on Narcotic Drugs (CND)
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.\16\ As such, member states of the United
Nations were required to regulate these precursor chemicals at the
national level. In addition, the People's Republic of China regulated
NPP and ANPP on February 1, 2018.\17\
---------------------------------------------------------------------------
\16\ 60th Session of the CND Dec/60/12 (ANPP) and Dec/60/13
(NPP).
\17\ https://www.dea.gov/press-release/2018/01/05/china-announces-scheduling-controls-two-fentanyl-precursor-chemicals.
Accessed March 9, 2022.
---------------------------------------------------------------------------
Following the international control of NPP and ANPP under the 1988
Convention, illicit fentanyl manufacturers moved to unregulated
precursor chemicals. These included 4-anilinopiperidine, 1-boc-4-AP,
and norfentanyl. In response, the CND placed 4-anilinopiperidine, 1-
boc-4-AP, and norfentanyl in Table I of the 1988 Convention.\18\
---------------------------------------------------------------------------
\18\ In a letter dated May 27, 2022, the United Nations Office
on Drugs and Crime, in accordance with Article 12, paragraph 6 of
the 1988 Convention, informed the Permanent Mission of the United
States of America to the United Nations (Vienna) that the CND
decided to place the chemical 4-AP in Table I of the 1988 Convention
(CND Dec/65/4) and the chemical 1-boc-4-AP in Table I of the 1988
Convention (CND Dec/65/5) at its 65th Session on March 16, 2022.
---------------------------------------------------------------------------
On May 15, 2020, 4-anilinopiperidine became a list I chemical in
the United States due to its role in the illicit manufacture of
fentanyl.\19\ Since that control action, DEA has observed an increase
in identifications of certain fentanyl analogues by law enforcement and
public health officials. Many of these fentanyl analogues contain a
halogen atom on the aniline ring of its respective chemical structure.
The presence of the halogen atom suggests that the fentanyl analogue
was synthesized from a halogenated precursor chemical. Indeed,
halogenated fentanyl precursors have been identified by law
enforcement, such as tert-butyl 4-((4-fluorophenyl)amino)piperidine-1-
carboxylate (para-fluoro 1-boc 4-AP). The chemical structure of this
precursor defines it as a halide and carbamate of 4-anilinopiperidine.
As such, it falls outside of the current definitions of a list I
chemical, simply due to the presence of the fluorine (a halogen) atom.
Although it is not regulated as a list I chemical, it can be used in
the synthesis of fentanyl analogues, such as the schedule I substances
para-fluorofentanyl, para-fluoroisobutyryl fentanyl, para-fluorobutyryl
fentanyl, and para-fluoro furanyl fentanyl.
---------------------------------------------------------------------------
\19\ 85 FR 20822 (April 15, 2020).
---------------------------------------------------------------------------
In addition, fentanyl analogues with both meta- and ortho-fluoro
substitutions have been identified, such as ortho-fluorofuranyl
fentanyl and meta-fluorofuranyl fentanyl. The identification of these
substances suggests illicit fentanyl analogue manufacturers attempt to
utilize unregulated precursor chemicals to evade law enforcement
detection and precursor chemical controls. This strategy allows for the
synthesis of a variety of fentanyl analogues by simply moving the
fluorine atom around the aniline ring while maintaining the same
synthetic methodology used to synthesize fentanyl and fentanyl
analogues.
Likewise, other halogenated fentanyl analogues, such as those
containing a chlorine atom, have been reported by forensic
laboratories. According to NFLIS-Drug, para-chlorofentanyl and ortho-
chlorofentanyl were reported for the first time in 2020. The
identification of these substances suggests that illicit fentanyl
analogue manufacturers utilize precursor chemicals containing a
chlorine atom as an alternative to a fluorine atom in effort to evade
law enforcement detection.
4-Anilinopiperidine
The original published synthetic pathway to fentanyl, known as the
Janssen method, involves the two important precursors, benzylfentanyl
and norfentanyl. 4-Piperidone,\20\ a chemical proposed for list I
control under the CSA, serves as a precursor chemical to
benzylfentanyl, a list I chemical under the CSA,\21\ 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.\22\
---------------------------------------------------------------------------
\20\ 87 FR 57852 (Sept. 22, 2022).
\21\ 85 FR 20822 (Apr. 15, 2020).
\22\ 85 FR 21320 (Apr. 17, 2020).
---------------------------------------------------------------------------
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 under the
CSA,\23\ in the Siegfried method. NPP 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.\24\
---------------------------------------------------------------------------
\23\ 72 FR 20039 (Apr. 23, 2007).
\24\ 75 FR 37295 (Aug. 30, 2010).
---------------------------------------------------------------------------
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-Anilinopiperidine, a list I
chemical under the CSA,\25\ is the 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 fentanyl.
---------------------------------------------------------------------------
\25\ 85 FR 20822 (Apr. 15, 2020).
---------------------------------------------------------------------------
Recent encounters of precursor chemicals related to 4-
anilinopiperidine in chemical structure have occurred. These precursor
chemicals contain a halogen atom on the aniline ring of 4-
anilinopiperidine. Modifications have included the addition of a
fluorine atom, a chlorine atom, or a bromine atom at different
positions on the aniline ring of the 4-anilinopiperidine structure. The
use of these halogenated 4-anilinopiperidine precursor chemicals in
place of 4-anilinopiperidine has resulted in the illicit manufacturing
of schedule I fentanyl analogues.
Halogenated 4-anilinopiperidines \26\ are commercially available
from both domestic and foreign suppliers. DEA is aware of at least 25
domestic suppliers and 14 foreign suppliers. Substituted versions of 4-
anilinopiperidine, such as para-fluoro 1-boc-4-AP, are attractive to
illicit manufacturers because they are readily available from chemical
suppliers and the lack of regulations on these substituted precursor
chemicals.
---------------------------------------------------------------------------
\26\ Chemicals included the folowing: ortho-fluoro 4-AP, ortho-
chloro 4-AP, ortho-bromo 4-AP, meta-fluoro 4-AP, meta-chloro 4-AP,
meta-bromo 4-AP, para-fluoro 4-AP, para-chloro 4-AP, para-bromo 4-
AP, ortho-fluoro 1-boc-4-AP, ortho-chloro 1-boc-4-AP, ortho-bromo 1-
boc-4-AP, meta-fluoro 1-boc-4-AP, meta-chloro 1-boc-4-AP, meta-bromo
1-boc-4-AP, para-fluoro 1-boc-4-AP, para-chloro 1-boc-4-AP, and
para-bromo 1-boc-4-AP.
---------------------------------------------------------------------------
[[Page 22958]]
para-Fluoro 1-boc-4-AP has been identified in law enforcement
encounters in the United States. According to NFLIS-Drug, beginning in
2020, there have been at least nine reports of para-fluoro 1-boc-4-AP
from forensic laboratories in the United States. A query of DEA's
STARLiMS \27\ database provided 16 reports of para-fluoro 1-boc-4-AP
from analyses conducted on submitted drug evidence by DEA forensic
laboratories. Of these 16 reports, para-fluoro 1-boc-4-AP was the only
substance reported in nine exhibits (totaling more than 29 kg),
suggesting that these seizures were intended to be used as precursor
chemicals in the synthesis of fentanyl analogues. Additionally, para-
fluoro 1-boc-4-AP was reported in combination with para-fluorofentanyl
in four of the seven exhibits containing a mixture of substances,
suggesting that para-fluoro 1-boc-4-AP was a precursor chemical
involved in the synthesis of para-fluorofentanyl, a schedule I
substance under the CSA.
---------------------------------------------------------------------------
\27\ On October 1, 2014, DEA implemented STARLiMS (a web-based,
commercial laboratory information management system) to replace the
System to Retrieve Information from Drug Evidence (STRIDE) as its
laboratory drug evidence data system of record. STARLiMS data was
queried on September 12, 2022.
---------------------------------------------------------------------------
As of August 2022, in addition to domestic encounters, the
International Narcotics Control Board of the United Nations reported
two international transactions of para-fluoro 1-boc-4-AP through the
Precursors Incident Communication System (PICS) \28\ reporting system.
These incidents reported to PICS totaled approximately 51 kg and had
destinations located in North America.
---------------------------------------------------------------------------
\28\ 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 August 23, 2022.
---------------------------------------------------------------------------
These recent law enforcement encounters of para-fluoro 1-boc-4-AP
coincide with the placement of NPP, ANPP, 4-anilinopiperidine, 1-boc-4-
AP (tert-butyl 4-(phenylamino)piperidine-1-carboxylate), and
norfentanyl 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 proposed control of 4-piperidone as
list I chemicals in the United States. The domestic encounters of para-
fluoro 1-boc-4-AP at ports of entry indicate a change in precursors
used in the illicit manufacture of fentanyl to substituted precursor
chemicals used in the illicit manufacture of fentanyl analogues in
efforts to evade international controls on NPP, ANPP, 4-
anilinopiperidine, 1-boc-4-AP, and norfentanyl and additional controls
on benzylfentanyl in the United States.
Regulation of 4-Anilinopiperidine, Including Its Amides, Its
Carbamates, Its Halides, Its Salts, 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 halides of 4-anilinopiperidine are being used in
the illicit manufacture of schedule I fentanyl analogues. This proposed
rule would modify the current regulations that regulate 4-
anilinopiperidine, including its amides, its carbamates, and its salts
to include halides of 4-anilinopiperidine. DEA finds that 4-
anilinopiperidine, including its amides, its carbamates, its halides,
its salts, and any combination thereof, whenever the existence of such
is possible, is used in the illicit manufacture of controlled
substances, such as fentanyl and fentanyl analogues, and is important
to the manufacture of these substances because it cannot be replaced by
other chemicals in their respective synthetic pathways that are used in
the illicit manufacture of fentanyl and fentanyl analogues.
Chemical Mixtures of 4-Anilinopiperidine
This proposed rulemaking, if finalized, would modify the current
regulations that regulate 4-anilinopiperidine, including its amides,
its carbamates, and its salts to include halides of 4-
anilinopiperidine. The regulations would specify that chemical mixtures
containing halides of 4-anilinopiperidine would not be exempt from
regulatory requirements at any concentration, unless an application for
exemption of a chemical mixture is submitted by a manufacturer of
halides of 4-anilinopiperidine 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
halides of 4-anilinopiperidine is necessary to prevent the extraction,
isolation, and use of halides of 4-anilinopiperidine in the illicit
manufacture of schedule I fentanyl analogues. 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-
anilinopiperidine, including its amides, its carbamates, its halides,
its salts, and any combination thereof, whenever the existence of such
is possible, 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.\29\ 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.\30\
---------------------------------------------------------------------------
\29\ 21 CFR 1310.13.
\30\ 21 U.S.C. 802(39)(A)(vi).
---------------------------------------------------------------------------
Requirements for Handling List I Chemicals
On May 15, 2020, DEA regulated 4-anilinopiperidine, including its
amides, its carbamates, and its salts, as a list I chemical under the
CSA. This proposed rule would expand the definitions of 4-
anilinopiperidine to include its halides. Halides of 4-
anilinopiperidine would become subject to the regulatory provisions of
the CSA upon publication of a final rule. Chemicals that meet the
current definition of 4-anilinopiperidine \31\ have been, and continue
to be, subject to the regulatory provisions of the CSA since May 15,
2020.
---------------------------------------------------------------------------
\31\ 85 FR 20822.
---------------------------------------------------------------------------
If this rule is finalized as proposed, halides of 4-
anilinopiperidine 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, just as 4-anilinopiperidine, including its amides, its
carbamates, and its salts are currently regulated. Upon publication of
a final rule, persons potentially handling halides of 4-
anilinopiperidine, including regulated chemical mixtures containing
halides of 4-anilinopiperidine, will be required to comply with list I
chemical regulations, including the following:
1. Registration. Any person who manufactures, distributes, imports,
or exports halides of 4-anilinopiperidine, including chemical mixtures
containing halides of 4-anilinopiperidine, or
[[Page 22959]]
proposes to engage in the manufacture, distribution, importation, or
exportation of halides of 4-anilinopiperidine, including chemical
mixtures containing halides of 4-anilinopiperidine, 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.\32\ 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.\33\
---------------------------------------------------------------------------
\32\ 21 CFR 1309.21.
\33\ 21 U.S.C. 822(e)(1); 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 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 halides of 4-anilinopiperidine or
a chemical mixture containing halides of 4-anilinopiperidine 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 halides of 4-anilinopiperidine or a
chemical mixture containing halides of 4-anilinopiperidine, DEA is
proposing to update the listing in 21 CFR 1310.09(p), to include the
proposed updated definitions of 4-anilinopiperidine to include a
temporary exemption from the registration requirement for persons
desiring to engage in activities with the proposed updated definitions
of halides of 4-anilinopiperidine or a chemical mixture containing
halides of 4-anilinopiperidine, 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 the
proposed updated definitions of 4-anilinopiperidine. 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 halides of 4-
anilinopiperidine, nor does it supersede State or local laws or
regulations. All handlers of halides of 4-anilinopiperidine 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 halides of 4-
anilinopiperidine 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.
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); 21 CFR 1310.05(a) and (b).
3. Importation and Exportation. All importation and exportation of
halides of 4-anilinopiperidine or a chemical mixture containing halides
of 4-anilinopiperidine would need to 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 would be required to
provide effective controls against theft and diversion of list I
chemicals in accordance with 21 CFR 1309.71-1309.73.
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 CFR part 1316, subpart A.\34\
---------------------------------------------------------------------------
\34\ 21 U.S.C. 880.
---------------------------------------------------------------------------
6. Liability. Any activity involving halides of 4-anilinopiperidine
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 halides of 4-anilinopiperidine
unrelated to fentanyl production (including industrial uses) in order
to assess the potential economic impact of controlling halides of 4-
anilinopiperidine as defined in this proposed rule. 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
halides of 4-anilinopiperidine. DEA seeks, however, to document any
unpublicized use(s) and other proprietary use(s) of halides of 4-
anilinopiperidine that are not in the public domain. Therefore, DEA is
soliciting comment on the uses of halides of 4-anilinopiperidine in the
legitimate marketplace.
DEA is soliciting input from all potentially affected parties
regarding: (1) The types of legitimate industries using halides of 4-
anilinopiperidine; (2) the legitimate uses of halides of 4-
anilinopiperidine, if any; (3) the size of the domestic market for
halides of 4-anilinopiperidine; (4) the number of manufacturers of
halides of 4-anilinopiperidine; (5) the number of
[[Page 22960]]
distributors of halides of 4-anilinopiperidine; (6) the level of import
and export of halides of 4-anilinopiperidine; (7) the potential burden
these proposed regulatory controls of halides of 4-anilinopiperidine
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 halides of 4-anilinopiperidine by industry and others. DEA invites
all interested parties to provide any information on any legitimate
uses of halides of 4-anilinopiperidine 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.
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 25 domestic suppliers of halides of 4-
anilinopiperidine indicates that these entities are not registered with
DEA to handle list I chemicals. These 25 suppliers are entities that do
not also supply 4-anilinopiperidine as these entities would already be
registered to handle list I chemicals since 4-anilinopiperidine is
currently a list I chemical under the CSA. Therefore, the modified
definitions of 4-anilinopiperidine in this proposed rule would
potentially affect 25 entities. 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 25
affected small entities. Therefore, DEA concludes this proposed rule is
not a significant regulatory action under E.O. 12866. If finalized as
proposed, halides of 4-anilinopiperidine 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, just as 4-anilinopiperidine, including its amides,
its carbamates, and its salts, is currently regulated. 4-
Anilinopiperidine is a precursor chemical used in, and is important to,
the illicit manufacture of the schedule II controlled substance
fentanyl and schedule I fentanyl analogues. The distribution of
illicitly manufactured fentanyl and fentanyl analogues 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 halides of 4-anilinopiperidine, and has not
documented a use for halides of 4-anilinopiperidine. 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 halides of 4-anilinopiperidine for the
legitimate manufacturing of pharmaceutical fentanyl is minimal because
halides of 4-anilinopiperidine are not used to synthesize fentanyl or
any schedule II fentanyl analogue currently used in medical practice.
As stated above, DEA is not aware of any legitimate uses of halides of
4-anilinopiperidine. Any manufacturer, distributor, importer, or
exporter of halides of 4-anilinopiperidine, 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, DEA believes that the
cost will be minimal.
DEA has identified 25 domestic suppliers of halides of 4-
anilinopiperidine. None of these 25 suppliers are registered to handle
list I chemicals. It is difficult to estimate the quantity of
distribution of halides of 4-anilinopiperidine by these suppliers. It
is common for chemical distributors to have items in their catalog
while not actually having any material level of sales. If this proposed
rule is finalized, suppliers for the legitimate use of halides of 4-
anilinopiperidine are expected to choose the least-cost option, and
stop selling the minimal quantities, if any, of halides of 4-
anilinopiperidine, rather than incur the registration cost. Because DEA
believes the quantities of halides of 4-anilinopiperidine supplied for
the legitimate manufacturing of pharmaceutical fentanyl are minimal,
DEA estimates that the cost of foregone sales is minimal; 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
halides of 4-anilinopiperidine for the manufacturing of illicit
fentanyl and fentanyl analogues. 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 halides of 4-anilinopiperidine is expected to prevent,
curtail, and limit the unlawful manufacture and distribution of
fentanyl and fentanyl analogues. As a list I chemical, handling of
halides of 4-anilinopiperidine 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
[[Page 22961]]
possible theft or diversion of halides of 4-anilinopiperidine from any
legitimate firms. DEA also believes control is necessary to prevent
unscrupulous chemists from synthesizing halides of 4-anilinopiperidine
and selling them (as unregulated materials) through the internet and
other channels, to individuals who may wish to acquire unregulated
intermediary chemicals for the purpose of illicitly manufacturing
fentanyl and fentanyl analogues.
In summary, DEA conducted a qualitative analysis of costs and
benefits. DEA believes this proposed action, if finalized, will
minimize the diversion of halides of 4-anilinopiperidine. DEA believes
the market for halides of 4-anilinopiperidine for the legitimate
manufacturing of fentanyl or schedule II fentanyl analogues currently
used in medical practice is minimal since halides of 4-
anilinopiperidine are not used to synthesize fentanyl or any schedule
II fentanyl analogue currently used in medical practice. 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, halides of 4-anilinopiperidine or a chemical
mixture containing halides of 4-anilinopiperidine 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. Halides of 4-anilinopiperidine are
precursor chemicals used in, and important to, the illicit manufacture
of the schedule I fentanyl analogues. The distribution of illicitly
manufactured fentanyl and fentanyl analogues 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 halides of 4-anilinopiperidine.
Therefore, DEA believes the vast majority, if not all, of halides of 4-
anilinopiperidine is used for the illicit manufacturing of schedule I
fentanyl analogues. 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). DEA has identified
25 domestic suppliers of halides of 4-anilinopiperidineall 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).\35\ It is
impossible to know how much halides of 4-anilinopiperidine 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. Therefore, DEA estimates the cost of this proposed rule
on any affected small entity is minimal. DEA welcomes any public
comment regarding this estimate. Based on these factors, DEA projects
that this proposed rule, if promulgated, will not result in a
significant economic impact on a substantial number of small entities.
---------------------------------------------------------------------------
\35\ 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.
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.
0
2. In Sec. 1310.02, revise paragraph (a)(33) to read as follows:
Sec. 1310.02 Substances covered.
* * * * *
(a) * * *
(33) N-phenylpiperidin-4-amine (4-anilinopiperidine; N-phenyl-4- 8335
piperidinamine; 4-AP), its amides, its carbamates, its halides,
its salts, and any combination thereof, whenever the existence
of such is possible............................................
* * * * *
0
3. In Sec. 1310.04, revise paragraph (g)(1)(xiii) to read as follows:
Sec. 1310.04 Maintenance of records.
* * * * *
(g) * * *
(1) * * *
(xiii) N-phenylpiperidin-4-amine (4-anilinopiperidine; N-phenyl-4-
[[Page 22962]]
piperidinamine; 4-AP), its amides, its carbamates, its halides, its
salts, and any combination thereof, whenever the existence of such is
possible
* * * * *
0
4. In Sec. 1310.09, revise paragraph (p) to read as follows:
Sec. 1310.09 Temporary exemption from registration.
* * * * *
(p)(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 N-phenylpiperidin-4-amine (4-anilinopiperidine; N-phenyl-4-
piperidinamine; 4-AP), its amides, its carbamates, its halides, its
salts, 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 halides of 4-anilinopiperidine 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 N-phenylpiperidin-4-amine (4-
anilinopiperidine; N-phenyl-4-piperidinamine; 4-AP), its amides, its
carbamates, its halides, its salts, 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 Sec. 1310.12, in the table in paragraph (c), revise the entry
for N-phenylpiperidin-4-amine to read as follows:
Sec. 1310.12 Exempt chemical mixtures.
* * * * *
(c) * * *
Table of Concentration Limits
----------------------------------------------------------------------------------------------------------------
DEA chemical code
number Concentration Special conditions
----------------------------------------------------------------------------------------------------------------
List I Chemicals
----------------------------------------------------------------------------------------------------------------
* * * * * *
N-phenylpiperidin-4-amine (4- 8335................... Not exempt at any Chemical mixtures
anilinopiperidine; N-phenyl-4- concentration. containing any amount
piperidinamine; 4-AP), its amides, of 4-anilinopiperidine
its carbamates, its halides, its are not exempt.
salts, and any combination thereof,
whenever the existence of such is
possible.
* * * * * *
----------------------------------------------------------------------------------------------------------------
* * * * *
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 RegisterLiaison 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. 2023-07454 Filed 4-13-23; 8:45 am]
BILLING CODE 4410-09-P