Schedules of Controlled Substances: Temporary Placement of Butonitazene, Etodesnitazene, Flunitazene, Metodesnitazene, Metonitazene, N-pyrrolidino etonitazene, and Protonitazene in Schedule I

CourtDrug Enforcement Administration
Citation86 FR 69182
Record Number2021-26263
Publication Date07 December 2021
69182
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
1
Though DEA has used the term ‘‘final order’’
with respect to temporary scheduling orders in the
past, this notice of intent adheres to the statutory
language of 21 U.S.C. 811(h), which refers to a
‘‘temporary scheduling order.’’ No substantive
change is intended.
in the
ADDRESSES
section of this
document. FAA Order JO 7400.11F lists
Class A, B, C, D, and E airspace areas,
air traffic service routes, and reporting
points.
The Proposal
The FAA proposes an amendment to
14 CFR part 71 to amend Class E
airspace extending upward from 700
feet above the surface at Atlanta
Speedway Airport (formerly Clayton
County-Tara Field), Hampton, GA by
updating the airports name and
updating the geographical coordinates
of the airport to coincide with the FAA’s
database. This action would also
increase the radius to 9.2 miles
(formerly 6.8 miles) and eliminate
excessive verbiage in the legal
description.
Class E airspace designations are
published in Paragraphs 6005 of FAA
Order JO 7400.11F, dated August 10,
2021, and effective September 15, 2021,
which is incorporated by reference in 14
CFR 71.1. The Class E airspace
designations listed in this document
will be published subsequently in FAA
Order JO 7400.11.
FAA Order JO 7400.11, Airspace
Designations and Reporting Points, is
published yearly and effective on
September 15.
Regulatory Notices and Analyses
The FAA has determined that this
proposed regulation only involves an
established body of technical
regulations for which frequent and
routine amendments are necessary to
keep them operationally current. It,
therefore: (1) Is not a ‘‘significant
regulatory action’’ under Executive
Order 12866; (2) is not a ‘‘significant
rule’’ under DOT Regulatory Policies
and Procedures (44 FR 11034; February
26, 1979); and (3) does not warrant
preparation of a Regulatory Evaluation
as the anticipated impact is so minimal.
Since this is a routine matter that will
only affect air traffic procedures and air
navigation, it is certified that this
proposed rule, when promulgated, will
not have a significant economic impact
on a substantial number of small entities
under the criteria of the Regulatory
Flexibility Act.
Environmental Review
This proposal will be subject to an
environmental analysis in accordance
with FAA Order 1050.1F,
‘‘Environmental Impacts: Policies and
Procedures’’, prior to any FAA final
regulatory action.
Lists of Subjects in 14 CFR Part 71
Airspace, Incorporation by reference,
Navigation (air).
The Proposed Amendment
In consideration of the foregoing, the
Federal Aviation Administration
proposes to amend 14 CFR part 71 as
follows:
PART 71—DESIGNATION OF CLASS A,
B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND
REPORTING POINTS
1. The authority citation for part 71
continues to read as follows:
Authority: 49 U.S.C. 106(f), 106(g); 40103,
40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR,
1959–1963 Comp., p. 389.
§ 71.1 [Amended]
2. The incorporation by reference in
14 CFR 71.1 of FAA Order JO 7400.11F,
Airspace Designations and Reporting
Points, dated August 10, 2021, and
effective September 15, 2021, is
amended as follows:
Paragraph 6005 Class E Airspace Areas
Extending Upward From 700 feet or More
Above the Surface of the Earth.
* * * * *
ASO GA E5 Hampton, GA [Amended]
Atlanta Speedway Airport, GA
(Lat. 33°2324N. long. 84°1952W)
That airspace extending upward from 700
feet above the surface within a 9.2-mile
radius of Atlanta Speedway Airport.
Issued in College Park, Georgia, on
December 1, 2021.
Andreese C. Davis,
Manager, Airspace & Procedures Team South,
Eastern Service Center, Air Traffic
Organization.
[FR Doc. 2021–26418 Filed 12–6–21; 8:45 am]
BILLING CODE 4910–13–P
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA–900]
Schedules of Controlled Substances:
Temporary Placement of Butonitazene,
Etodesnitazene, Flunitazene,
Metodesnitazene, Metonitazene, N-
pyrrolidino etonitazene, and
Protonitazene in Schedule I
AGENCY
: Drug Enforcement
Administration, Department of Justice.
ACTION
: Proposed amendment; notice of
intent.
SUMMARY
: The Administrator of the Drug
Enforcement Administration is issuing
this notice of intent to publish a
temporary order to schedule seven
synthetic benzimidazole-opioid
substances, including their isomers,
esters, ethers, salts, and salts of isomers,
esters, and ethers whenever the
existence of such isomers, esters, ethers,
and salts is possible, in schedule I of the
Controlled Substances Act. When it is
issued, the temporary scheduling order
will impose the regulatory controls and
administrative, civil, and criminal
sanctions applicable to schedule I
controlled substances on persons who
handle (manufacture, distribute, reverse
distribute, import, export, engage in
research, conduct instructional
activities or chemical analysis, or
possess) or propose to handle these
seven specified controlled substances.
DATES
: December 7, 2021.
ADDRESSES
: Drug Enforcement
Administration, 8701 Morrissette Drive,
Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT
:
Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control
Division, Drug Enforcement
Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia
22152; Telephone: (571) 362–3249.
SUPPLEMENTARY INFORMATION
: The notice
of intent contained in this document is
issued pursuant to the temporary
scheduling provisions of 21 U.S.C.
811(h). The Drug Enforcement
Administration (DEA) intends to issue a
temporary scheduling order
1
(in the
form of a temporary amendment) to add
the following seven substances,
including their isomers, esters, ethers,
salts, and salts of isomers, esters, and
ethers whenever the existence of such
isomers, esters, ethers, and salts is
possible, to schedule I under the
Controlled Substances Act (CSA):
2-(2-(4-butoxybenzyl)-5-nitro-1H-
benzimidazol-1-yl)-N,N-diethylethan-1-
amine (butonitazene),
2-(2-(4-ethoxybenzyl)-1H-
benzimidazol-1-yl)-N,N-diethylethan-1-
amine (etodesnitazene; etazene),
N,N-diethyl-2-(2-(4-fluorobenzyl)-5-
nitro-1H-benzimidazol-1-yl)ethan-1-
amine) (flunitazene),
N,N-diethyl-2-(2-(4-
methoxybenzyl)-1H-benzimidazol-1-
yl)ethan-1-amine (metodesnitazene),
N,N-diethyl-2-(2-(4-
methoxybenzyl)-5-nitro-1H-
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00002 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1
69183
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
2
The Secretary of HHS has delegated to the
Assistant Secretary for Health of HHS the authority
to make domestic drug scheduling
recommendations. 58 FR 35460, July 1, 1993.
benzimidazol-1-yl)ethan-1-amine
(metonitazene),
2-(4-ethoxybenzyl)-5-nitro-1-(2-
(pyrrolidin-1-yl)ethyl)-1H-
benzimidazole (N-pyrrolidino
etonitazene; etonitazepyne), and
N,N-diethyl-2-(5-nitro-2-(4-
propoxybenzyl)-1H-benzimidazol-1-
yl)ethan-1-amine (protonitazene).
The temporary scheduling order will
be published in the Federal Register on
or after January 6, 2022.
Legal Authority
The CSA provides the Attorney
General (as delegated to the
Administrator of DEA (Administrator)
pursuant to 28 CFR 0.100) with the
authority to temporarily place a
substance in schedule I of the CSA for
two years without regard to the
requirements of 21 U.S.C. 811(b), if he
finds that such action is necessary to
avoid an imminent hazard to the public
safety. 21 U.S.C. 811(h)(1). In addition,
if proceedings to control a substance are
initiated under 21 U.S.C. 811(a)(1) while
the substance is temporarily controlled
under section 811(h), the Attorney
General may extend the temporary
scheduling for up to one year. 21 U.S.C.
811(h)(2).
Where the necessary findings are
made, a substance may be temporarily
scheduled if it is not listed in any other
schedule under section 202 of the CSA,
21 U.S.C. 812, or if there is no
exemption or approval in effect for the
substance under section 505 of the
Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 355. 21 U.S.C. 811(h)(1); 21
CFR part 1308.
Background
The CSA requires the Administrator
to notify the Secretary of the
Department of Health and Human
Services (HHS) of an intent to place a
substance in schedule I of the CSA
temporarily (i.e., to issue a temporary
scheduling order). 21 U.S.C. 811(h)(4).
The then-Acting Administrator
transmitted the required notice to the
Assistant Secretary for Health of HHS
(Assistant Secretary),
2
by letter dated
June 16, 2021, regarding butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, and
protonitazene. In a subsequent letter
dated August 25, 2021, the
Administrator transmitted the required
notice to the Assistant Secretary for N-
pyrrolidino etonitazene. The Assistant
Secretary responded to these notices by
letters dated July 7 and September 10,
2021, and advised that based on a
review by the Food and Drug
Administration (FDA), there are
currently no investigational new drug
applications (IND) or approved new
drug applications (NDA) for
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene. The
Assistant Secretary also stated that HHS
had no objection to the temporary
placement of these substances in
schedule I. Butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene currently are not listed in
any schedule under the CSA, and no
exemptions or approvals under 21
U.S.C. 355 are in effect for these seven
benzimidazole-opioids.
To find that temporarily placing a
substance in schedule I of the CSA is
necessary to avoid an imminent hazard
to the public safety, the Administrator
must consider three of the eight factors
set forth in 21 U.S.C. 811(c): The
substance’s history and current pattern
of abuse; the scope, duration and
significance of abuse; and what, if any,
risk there is to the public health. 21
U.S.C. 811(h)(3). This consideration
includes any information indicating
actual abuse, diversion from legitimate
channels, and clandestine importation,
manufacture, or distribution of these
substances. 21 U.S.C. 811(h)(3).
Substances meeting the statutory
requirements for temporary scheduling
may only be placed in schedule I. 21
U.S.C. 811(h)(1). Substances in schedule
I have high potential for abuse, no
currently accepted medical use in
treatment in the United States, and no
accepted safety for use under medical
supervision. 21 U.S.C. 812(b)(1).
Seven Benzimidazole-Opioids:
Butonitazene, Etodesnitazene,
Flunitazene, Metodesnitazene,
Metonitazene, N-Pyrrolidino
Etonitazene, and Protonitazene
The United States currently is
experiencing an opioid overdose
epidemic, and the presence of synthetic
opioids in the illicit drug market
threatens to exacerbate this. The
trafficking, continued evolution, and
abuse of new synthetic opioids are
deadly trends posing imminent hazards
to public safety. Adverse health effects
associated with abuse of synthetic
opioids and increased popularity of
these substances have been serious
concerns in recent years. Butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene are synthetic opioids
recently identified on the illicit drug
market in the United States.
Data obtained from preclinical
pharmacology studies show that
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene have
pharmacological profiles similar to
those of the potent benzimidazole-
opioids etonitazene and isotonitazene,
both schedule I controlled substances.
Because of their pharmacological
similarities, use of these seven
benzimidazole-opioid substances
presents a high risk of abuse and may
negatively affect users and
communities. They have been identified
in at least 44 toxicology and post-
mortem cases in the United States
between November 2020 and July 2021.
Specifically, butonitazene has been
identified in one case, etodesnitazene in
five cases, flunitazene in four cases,
metodesnitazene in one case,
metonitazene in twenty cases, N-
pyrrolidino etonitazene in eight cases,
and protonitazene in five cases, which
together create serious public safety
concerns.
Available data and information for
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene,
summarized below, indicate that these
substances have high potential for
abuse, no currently accepted medical
use in treatment in the United States,
and lack of accepted safety for use
under medical supervision. DEA’s three-
factor analysis is available in its entirety
under ‘‘Supporting and Related
Material’’ of the public docket for this
action at www.regulations.gov under
Docket Number DEA–900.
Factor 4. History and Current Pattern of
Abuse
In the late 1950s, pharmaceutical
research laboratories of the Swiss
chemical company CIBA
Aktiengesellschaft synthesized a group
of benzimidazole derivatives with
analgesic properties; however, the
research did not lead to any medically
approved analgesic products. These
benzimidazole derivatives include
schedule I substances such as synthetic
opioids clonitazene, etonitazene, and
isotonitazene. In 2019, isotonitazene
emerged on the illicit drug market and
was involved in numerous fatal
overdose events. In August 2020, DEA
temporarily controlled it as a schedule
I substance under the CSA (85 FR
51342).
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00003 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1
69184
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
3
NFLIS represents an important resource in
monitoring illicit drug trafficking, including the
diversion of legally manufactured pharmaceuticals
into illegal markets. NFLIS is a comprehensive
information system that includes data from forensic
laboratories that handle more than 96% of an
estimated 1.0 million distinct annual state and local
drug analysis cases. NFLIS includes drug chemistry
results from completed analyses only. While NFLIS
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.
4
Center for Forensic Science Research and
Education. Public Alert: New High Potency
Synthetic Opioid N-Pyrrolidino Etonitazene
(Etonitazepyne) Linked to Overdoses across United
States. June 17, 2021.
5
While law enforcement data are not direct
evidence of abuse, they can lead to an inference that
drugs have been diverted and abused. See 76 FR
77330, 77332, Dec. 12, 2011.
6
NSDUH, formerly known as the National
Household Survey on Drug Abuse (NHSDA), is
conducted annually by the Department of Health
and Human Services’ Substance Abuse and Mental
Health Services Administration (SAMHSA). It is the
primary source of estimates of the prevalence and
incidence of non-medical use of pharmaceutical
drugs, illicit drugs, alcohol, and tobacco use in the
United States. The survey is based on a nationally
representative sample of the civilian, non-
institutionalized population 12 years of age and
older. The survey excludes homeless people who
do not use shelters, active military personnel, and
residents of institutional group quarters such as
jails and hospitals. The NSDUH provides yearly
national and state level estimates of drug abuse, and
includes prevalence estimates by lifetime (i.e., ever
used), past year, and past month abuse or
dependence. The 2019 NSDUH Annual Report.
(Last accessed July 26, 2021).
Subsequently, the benzimidazole-
opioids at issue here have emerged on
the illicit drug market. Law enforcement
agencies have encountered
etodesnitazene, flunitazene,
metonitazene, and protonitazene in
several solid (e.g., powder and rock) and
liquid forms. These substances are not
approved for medical use anywhere in
the world. The Assistant Secretary, by
letters dated July 7 and September 10,
2021, informed DEA that there are no
FDA-approved NDAs or INDs for them
in the United States. Hence, there are no
legitimate channels for these substances
as marketed drug products. Their
appearance on the illicit drug market is
similar to other synthetic opioids
trafficked for their psychoactive effects.
These seven opioid substances are likely
to be abused in the same manner as
schedule I opioids such as etonitazene,
isotonitazene, and heroin. They have
been identified as white to beige
powders or in liquid forms, typically of
unknown purity or concentration.
In 2020 and 2021, butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, and
protonitazene emerged on the illicit
synthetic drug market as evidenced by
their identification in forensic drug
seizures or biological samples. In July
2020, metonitazene was first reported
seized as a white powdery substance in
a North Carolina case. Based on data
from the National Forensic Laboratory
Information System (NFLIS),
3
law
enforcement often encounters
etodesnitazene, flunitazene,
metonitazene, and protonitazene in
mixtures. Substances found in
combination with some of these
benzimidazole-opioids include cutting
agents (caffeine, xylazine, etc.) or other
substances of abuse such as heroin,
fentanyl (schedule II), fentanyl analogs,
and tramadol (schedule IV).
In the United States, butonitazene,
etodesnitazene, flunitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene have
been identified alone or in combination
with other substances such as designer
benzodiazepines and fentanyl (see
Factors 5 and 6). Evidence suggests that
individuals are using these substances
as a replacement for other opioids,
either knowingly or unknowingly.
Information gathered from case histories
and autopsy findings show that deaths
involving metonitazene were similar to
those of opioid-related deaths.
Identified material or paraphernalia
from death-scene investigations also
were consistent with opioid use. The
seven substances are likely to be abused
in the same manner as schedule I
opioids such as isotonitazene and
heroin.
Factor 5. Scope, Duration, and
Significance of Abuse
The subject substances have been
described as synthetic opioids, and
evidence suggests they are abused for
their opioidergic effects (see Factor 6).
Their abuse has resulted in their
identification in toxicology and post-
mortem cases. Between January and
February of 2021, metonitazene has
been positively identified in 20 forensic
post-mortem cases from seven different
states: Tennessee (10), Illinois (5),
Florida (1), Iowa (1), Ohio (1), South
Carolina (1), and Wisconsin (1). Most
(18) of the decedents were male, with
ages ranging from 19 to 63 years and an
average age of 41 years. Metonitazene
was identified as the sole drug detected
in only three cases, and the only opioid
in six cases.
Detection of N-pyrrolidino
etonitazene in a toxicology case first
was reported
4
in May 2021. It has been
identified in a total of eight post-mortem
cases from five different states (Colorado
(1), Florida (1), New York (1),
Pennsylvania (1), and West Virginia (4))
between January and April 2021. The
decedents’ ages spanned their 20s to
50s. N-Pyrrolidino etonitazene was the
only drug of interest in one of these
cases. In the other cases, it was co-
identified with designer
benzodiazepines (7), fentanyl (4), and
methamphetamine (4). Data from law
enforcement encounters suggests that
etodesnitazene, flunitazene,
metonitazene, and protonitazene are
abused
5
in the United States as
recreational drugs. Law enforcement
encounters of etodesnitazene,
flunitazene, metonitazene, and
protonitazene as reported to NFLIS
(Federal, State, and local laboratories)
includes 270 exhibits since 2020
(queried 08/04/2021). NFLIS registered
one encounter of etodesnitazene from
one state, five encounters of flunitazene
from four states, 262 encounters of
metonitazene from eight states, and two
encounters of protonitazene from two
states. Data from NFLIS show that
561.55 grams of metonitazene has been
encountered by law enforcement since
2020, and it was often suspected as
heroin or fentanyl. This suggests that
metonitazene might be presented as a
substitute for heroin or fentanyl and
likely abused in the same manner as
either of these substances. The lack of
identification of butonitazene,
metodesnitazene, and N-pyrrolidino
etonitazene in law enforcement reports
might be due to the rapid appearance of
these benzimidazole-opioids and under-
reporting as forensic laboratories try to
secure reference standards for these
substances. However, butonitazene,
metodesnitazene, and N-pyrrolidino
etonitazene have been identified in
toxicology cases.
The population likely to abuse these
seven benzimidazole-opioids appears to
be the same as those abusing other
opioid substances such as heroin,
tramadol, fentanyl, and other synthetic
opioids. This is evidenced by the types
of other drugs co-identified in biological
samples and law enforcement
encounters. Because abusers are likely
to obtain these substances through
unregulated sources, their identity,
purity, and quantity are uncertain and
likely to be inconsistent, thus posing
significant adverse health risks to the
end user. The misuse and abuse of
opioids have been demonstrated and are
well-characterized. According to the
most recent data from the National
Survey on Drug Use and Health
(NSDUH),
6
as of 2019, an estimated 10.1
million people aged 12 years or older
misused opioids in the past year,
including 9.7 million prescription pain
reliever misusers and 745,000 heroin
users. In 2019, an estimated 1.6 million
people had an opioid use disorder,
including 1.4 million people with a
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00004 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1
69185
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
7
12 Month-ending Provisional Number of Drug
Overdose Deaths. Reported provisional data as of
July 4, 2021. https://www.cdc.gov/nchs/nvss/vsrr/
drug-overdose-data.htm.
8
Krotulski AJ, Papsun DM, Walton SE, Logan BK.
Metonitazene in the United States-Forensic
toxicology assessment of a potent new synthetic
opioid using liquid chromatography mass
spectrometry. Drug Test Anal. 2021 Jun 16. doi:
10.1002/dta.3115. Epub ahead of print.
9
Center for Forensic Science Research and
Education. NPS Opioids in the United States—
Trend Report Q1 and Q2, 2021.
prescription pain reliever use disorder
and 438,000 people with heroin use
disorder. This population likely is at
risk of abusing butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene. Individuals who initiate
(i.e., use a drug for the first time) use of
these benzimidazole-opioids are likely
to be at risk of developing substance use
disorder, overdose, and death similar to
that of other opioid analgesics (e.g.,
fentanyl, morphine, etc.). Law
enforcement or toxicology reports
demonstrate that the seven substances at
issue are being distributed illicitly and
abused.
Factor 6. What, if Any, Risk There Is to
the Public Health
The increase in opioid overdose
deaths in the United States has been
exacerbated recently by the availability
of potent synthetic opioids in the illicit
drug market. Data obtained from pre-
clinical studies demonstrate that
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene exhibit
pharmacological profiles similar to that
of schedule I substances such as
etonitazene, isotonitazene, and other
mu-opioid receptor agonists. These
seven benzimidazole-opioids bind to
and act as agonists at the mu-opioid
receptors. It is well established that
substances that act as mu-opioid
receptor agonists have a high potential
for abuse and addiction and can induce
dose-dependent respiratory depression.
As with any mu-opioid receptor
agonist, the potential health and safety
risks for users of butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene are high. Consistently,
these substances have been identified in
toxicology cases. The public health risks
attendant to the abuse of mu-opioid
receptor agonists are well established.
These risks include large numbers of
drug treatment admissions, emergency
department visits, and fatal overdoses.
According to the Centers for Disease
Control and Prevention (CDC), opioids,
mainly synthetic opioids other than
methadone, are predominantly
responsible for drug overdose deaths in
recent years. According to CDC data,
synthetic opioid-related overdose deaths
in the United States increased from
36,359 in 2019, to 56,688 in 2020 (CDC,
2021).
7
Of the drug overdose death data
(70,630) for 2019, synthetic opioids
were involved in about 51.4 percent
(36,359) of all drug-involved overdose
deaths.
According to a recent publication,
since November 2020, there has been an
increase in metonitazene-related
adverse events, including deaths.
8
Metonitazene has been co-identified
with other substances in biological
samples from 20 post-mortem cases
from seven different states: Florida (1),
Illinois (5), Iowa (1), Ohio (1), South
Carolina (1), Tennessee (10), and
Wisconsin (1). Information gathered
from case histories and autopsy findings
show that deaths involving
metonitazene were similar to those of
opioid-related deaths. Identified
material or paraphernalia from death-
scene investigations were consistent
with opioid use. Reports obtained from
autopsy findings showed that deaths
involving metonitazene presented
pulmonary and cerebral edema, as well
as distended bladder and signs of
intravenous drug use. Of the cases for
which death certificate data were
available, metonitazene was reported as
a cause of death in four cases, of which
three cases listed metonitazene as the
only cause.
According to recent reports,
butonitazene (1 instance),
etodesnitazene (5), flunitazene (4),
metodesnitazene (1), metonitazene (20),
protonitazene (5), and N-pyrrolidino
etonitazene (10) have been identified in
toxicology cases in the United States.
9
For cases involving N-pyrrolidino
etonitazene, it was co-identified with
fentanyl in four cases and with novel
benzodiazepines (e.g., flualprazolam,
etizolam, and clonazolam) in six others.
Finding of Necessity of Schedule I
Placement To Avoid Imminent Hazard
to Public Safety
In accordance with 21 U.S.C.
811(h)(3), based on the available data
and information summarized above, the
uncontrolled manufacture, distribution,
reverse distribution, importation,
exportation, conduct of research and
chemical analysis, possession, and
abuse of butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene pose
imminent hazards to public safety. DEA
is not aware of any currently accepted
medical uses for these substances in the
United States. A substance meeting the
statutory requirements for temporary
scheduling, found in 21 U.S.C.
811(h)(1), may only be placed in
schedule I. Substances in schedule I
must have a high potential for abuse, no
currently accepted medical use in
treatment in the United States, and a
lack of accepted safety for use under
medical supervision. Available data and
information for butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene indicate that these
substances meet the three statutory
criteria. As required by 21 U.S.C.
811(h)(4), the then-Acting Administrator
transmitted to the Assistant Secretary
for Health, via letter dated June 16,
2021, notice of his intent to place
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, and protonitazene in
schedule I on a temporary basis. In a
letter to the Assistant Secretary for
Health dated August 25, 2021, the
Administrator transmitted notice of her
intent to place N-pyrrolidino
etonitazene in schedule I on a
temporary basis.
Conclusion
This Notice of Intent provides the 30-
day notice pursuant to 21 U.S.C.
811(h)(1) of DEA’s intent to issue a
temporary scheduling order. In
accordance with 21 U.S.C. 811(h)(1) and
(3), the Administrator considered
available data and information, herein
set forth the grounds for her
determination that it is necessary to
temporarily schedule butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene in schedule I of the CSA,
and finds that placement of these
substances in schedule I is necessary to
avoid an imminent hazard to the public
safety.
The temporary placement of
butonitazene, etodesnitazene,
flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino
etonitazene, and protonitazene in
schedule I of the CSA will take effect
pursuant to a temporary scheduling
order, which will not be issued before
January 6, 2022. Because the
Administrator hereby finds this
temporary scheduling order necessary to
avoid an imminent hazard to the public
safety, it will take effect on the date the
order is published in the Federal
Register, and remain in effect for two
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00005 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1
69186
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
years, with a possible extension of one
year, pending completion of the regular
(permanent) scheduling process. 21
U.S.C. 811(h)(1) and (2). The
Administrator intends to issue a
temporary scheduling order as soon as
possible after the expiration of 30 days
from the date of publication of this
document. Upon the temporary order’s
publication, butonitazene,
etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and
protonitazene will then be subject to the
CSA’s schedule I regulatory controls
and to administrative, civil, and
criminal sanctions applicable to their
manufacture, distribution, reverse
distribution, importation, exportation,
research, conduct of instructional
activities and chemical analysis, and
possession.
The CSA sets forth specific criteria for
scheduling drugs or other substances.
Regular scheduling actions in
accordance with 21 U.S.C. 811(a) are
subject to formal rulemaking procedures
‘‘on the record after opportunity for a
hearing’’ conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. 21
U.S.C. 811. The regular scheduling
process of formal rulemaking affords
interested parties appropriate process
and the government any additional
relevant information needed to make
determinations. Final decisions that
conclude the regular scheduling process
of formal rulemaking are subject to
judicial review. 21 U.S.C. 877.
Temporary scheduling orders are not
subject to judicial review. 21 U.S.C.
811(h)(6).
Regulatory Analyses
The CSA provides for expedited
temporary scheduling actions where
necessary to avoid an imminent hazard
to the public safety. Under 21 U.S.C.
811(h), the Administrator, as delegated
by the Attorney General, may, by order,
temporarily place substances in
schedule I. Such orders may not be
issued before the expiration of 30 days
from: (1) The publication of a notice in
the Federal Register of the intent to
issue such order and the grounds upon
which such order is to be issued, and (2)
the date that notice of the proposed
temporary scheduling order is
transmitted to the Assistant Secretary
for Health of HHS, as delegated by the
Secretary of HHS. 21 U.S.C. 811(h)(1).
Inasmuch as section 811(h) directs
that temporary scheduling actions be
issued by order and sets forth the
procedures by which such orders are to
be issued, including the requirement to
publish in the Federal Register a Notice
of Intent, the notice-and-comment
requirements of section 553 of the
Administrative Procedure Act (APA), 5
U.S.C. 553, do not apply to this Notice
of Intent. The APA expressly
differentiates between orders and rules,
as it defines an ‘‘order’’ to mean a ‘‘final
disposition, whether affirmative,
negative, injunctive, or declaratory in
form, of an agency in a matter other
than rule making.’’ 5 U.S.C. 551(6)
(emphasis added). The specific language
chosen by Congress indicates its intent
that DEA issue orders instead of
proceeding by rulemaking when
temporarily scheduling substances.
Given that Congress specifically
requires the Administrator (as delegated
by the Attorney General) to follow
rulemaking procedures for other kinds
of scheduling actions, see 21 U.S.C.
811(a), it is noteworthy that, in section
811(h), Congress authorized the
issuance of temporary scheduling
actions by order rather than by rule.
Even assuming that this Notice of
Intent is subject to section 553 of the
APA, the Administrator finds that there
is good cause to forgo its notice-and-
comment requirements, as any further
delays in the process for issuing
temporary scheduling orders would be
impracticable and contrary to the public
interest given the manifest urgency to
avoid an imminent hazard to the public
safety.
Although DEA believes this Notice of
Intent to issue a temporary scheduling
order is not subject to the notice-and-
comment requirements of section 553 of
the APA, DEA notes that in accordance
with 21 U.S.C. 811(h)(4), the
Administrator took into consideration
comments submitted by the Assistant
Secretary in response to the notices that
DEA transmitted to the Assistant
Secretary pursuant to such subsection.
Further, DEA believes that this
temporary scheduling action is not a
‘‘rule’’ as defined by 5 U.S.C. 601(2),
and, accordingly, is not subject to the
requirements of the Regulatory
Flexibility Act. The requirements for the
preparation of an initial regulatory
flexibility analysis in 5 U.S.C. 603(a) are
not applicable where, as here, DEA is
not required by section 553 of the APA
or any other law to publish a general
notice of proposed rulemaking.
In accordance with the principles of
Executive Orders (E.O.) 12866 and
13563, this action is not a significant
regulatory action. 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, 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.
Because this is not a rulemaking action,
this is not a significant regulatory action
as defined in Section 3(f) of E.O. 12866.
This action will not have substantial
direct effects on the States, on the
relationship between the National
Government and the States, or on the
distribution of power and
responsibilities among the various
levels of government. Therefore, in
accordance with E.O. 13132
(Federalism), it is determined that this
action does not have sufficient
federalism implications to warrant the
preparation of a Federalism Assessment.
List of Subjects in 21 CFR Part 1308
Administrative practice and
procedure, Drug traffic control,
Reporting and recordkeeping
requirements.
For the reasons set out above, DEA
proposes to amend 21 CFR part 1308 as
follows:
PART 1308—SCHEDULES OF
CONTROLLED SUBSTANCES
1. The authority citation for part 1308
continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b),
956(b), unless otherwise noted.
2. In § 1308.11, add paragraphs (h)(50)
through (56) to read as follows:
§ 1308.11 Schedule I.
* * * * *
(h) * * *
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00006 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1
69187
Federal Register / Vol. 86, No. 232 / Tuesday, December 7, 2021 / Proposed Rules
(50) 2-(2-(4-butoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N,N-diethylethan-1-amine, its isomers, esters, ethers, salts, and salts of
isomers, esters and ethers (Other name: butonitazene) .......................................................................................................................... 9654
(51) 2-(2-(4-ethoxybenzyl)-1H-benzimidazol-1-yl)-N,N-diethylethan-1-amine, its isomers, esters, ethers, salts, and salts of isomers,
esters and ethers (Other names: etodesnitazene; etazene) ..................................................................................................................... 9665
(52) N,N-diethyl-2-(2-(4-fluorobenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts of
isomers, esters and ethers (Other name: flunitazene) ............................................................................................................................. 9656
(53) N,N-diethyl-2-(2-(4-methoxybenzyl)-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts of iso-
mers, esters and ethers (Other name: metodesnitazene) ........................................................................................................................ 9664
(54) N,N-diethyl-2-(2-(4-methoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts of
isomers, esters and ethers (Other name: metonitazene) ......................................................................................................................... 9657
(55) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzimidazole, its isomers, esters, ethers, salts, and salts of iso-
mers, esters and ethers (Other names: N-pyrrolidino etonitazene; etonitazepyne) .............................................................................. 9658
(56) N,N-diethyl-2-(5-nitro-2-(4-propoxybenzyl)-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts of
isomers, esters and ethers (Other name: protonitazene) ........................................................................................................................ 9659
Anne Milgram,
Administrator.
[FR Doc. 2021–26263 Filed 12–6–21; 8:45 am]
BILLING CODE 4410–09–P
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA–568]
Schedules of Controlled Substances:
Placement of Methoxetamine (MXE) in
Schedule I
AGENCY
: Drug Enforcement
Administration, Department of Justice.
ACTION
: Notice of proposed rulemaking.
SUMMARY
: The Drug Enforcement
Administration proposes placing 2-
(ethylamino)-2-(3-
methoxyphenyl)cyclohexan-1-one
(methoxetamine, MXE), including its
salts, isomers, and salts of isomers
whenever the existence of such salts,
isomers, and salts of isomers is possible
within the specific chemical
designation, in schedule I of the
Controlled Substances Act. This action
is being taken to enable the United
States to meet its obligations under the
1971 Convention on Psychotropic
Substances. If finalized, this action
would impose the regulatory controls
and administrative, civil, and criminal
sanctions applicable to schedule I
controlled substances on persons who
handle (manufacture, distribute, reverse
distribute, import, export, engage in
research, conduct instructional
activities or chemical analysis with, or
possess), or propose to handle,
methoxetamine.
DATES
: Comments must be submitted
electronically or postmarked on or
before February 7, 2022.
Interested persons may file a request
for hearing or waiver of hearing
pursuant to 21 CFR 1308.44 and in
accordance with 21 CFR 1316.45 and/or
1316.47, as applicable. Requests for
hearing and waivers of an opportunity
for a hearing or to participate in a
hearing, together with a written
statement of position on the matters of
fact and law asserted in the hearing,
must be received on or before January 6,
2022.
ADDRESSES
: Interested persons may file
written comments on this proposal in
accordance with 21 CFR 1308.43(g). The
electronic Federal Docket Management
System will not accept comments after
11:59 p.m. Eastern Time on the last day
of the comment period. To ensure
proper handling of comments, please
reference ‘‘Docket No. DEA–568’’ on all
electronic and written correspondence,
including any attachments.
Electronic comments: DEA
encourages commenters to submit all
comments 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 on-line instructions at that site for
submitting comments. Upon completion
of your submission, you will receive a
Comment Tracking Number. Submitted
comments are not instantaneously
available for public view on
regulations.gov. If you have received a
Comment Tracking Number, you have
submitted your comment successfully
and there is no need to resubmit the
same comment.
Paper comments: Paper comments
that duplicate electronic submissions
are not necessary and are discouraged.
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.
Hearing requests: All requests for a
hearing and waivers of participation,
together with a written statement of
position on the matters of fact and law
asserted in the hearing, must be sent to:
Drug Enforcement Administration, Attn:
Administrator, 8701 Morrissette Drive,
Springfield, Virginia 22152. All requests
for hearing and waivers of participation
should also be sent to: (1) Drug
Enforcement Administration, Attn:
Hearing Clerk/LJ, 8701 Morrissette
Drive, Springfield, Virginia 22152; and
(2) Drug Enforcement Administration,
Attn: DEA Federal Register
Representative/DPW, 8701 Morrissette
Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT
:
Terrence L. Boos, Drug & Chemical
Evaluation Section, Diversion Control
Division, Drug Enforcement
Administration; Telephone: (571) 362–
3249.
SUPPLEMENTARY INFORMATION
:
Posting of Public Comments
All comments received in response to
this docket are considered part of the
public record. The Drug Enforcement
Administration (DEA) will make
comments available, unless reasonable
cause is given, 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
DEA to make it 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 DEA to make
it publicly available, you must include
the phrase ‘‘CONFIDENTIAL BUSINESS
INFORMATION’’ in the first paragraph
of your comment. You must also
VerDate Sep<11>2014 16:37 Dec 06, 2021 Jkt 256001 PO 00000 Frm 00007 Fmt 4702 Sfmt 4702 E:\FR\FM\07DEP1.SGM 07DEP1
lotter on DSK11XQN23PROD with PROPOSALS1

VLEX uses login cookies to provide you with a better browsing experience. If you click on 'Accept' or continue browsing this site we consider that you accept our cookie policy. ACCEPT