[Federal Register Volume 87, Number 70 (Tuesday, April 12, 2022)]
[Rules and Regulations]
[Pages 21556-21561]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07640]
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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: Temporary amendment; temporary scheduling order.
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SUMMARY: The Administrator of the Drug Enforcement Administration is
issuing this temporary order to schedule seven synthetic benzimidazole-
opioid substances, as identified in this order, in schedule I of the
Controlled Substances Act. This action is based on a finding by the
Administrator that the placement of these seven substances in schedule
I is necessary to avoid imminent hazard to the public safety. As a
result of this order, the regulatory controls and administrative,
civil, and criminal sanctions applicable to schedule I controlled
substances will be imposed 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 these seven specified controlled substances.
DATES: This temporary scheduling order is effective April 12, 2022,
until April 12, 2024. If this order is extended or made permanent, DEA
will publish a document in the Federal Register.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., 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 Drug Enforcement Administration (DEA)
issues 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):
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\1\ Though DEA has used the term ``final order'' with respect to
temporary scheduling orders in the past, this order adheres to the
statutory language of 21 U.S.C. 811(h), which refers to a
``temporary scheduling order.'' No substantive change is intended.
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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-
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).
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
the Administrator 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 Administrator 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
21 U.S.C. 812, and 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 regarding 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 (INDs) or approved new drug
applications (NDAs) 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
of the CSA.
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\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.
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DEA has taken into consideration the Assistant Secretary's comments
as required by subsection 811(h)(4). 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. DEA has found that the control
of these seven benzimidazole-opioids in schedule I on a temporary basis
is necessary to avoid an imminent hazard to the public safety.
As required by 21 U.S.C. 811(h)(1)(A), DEA published a notice of
intent (NoI) to temporarily schedule butonitazene, etodesnitazene,
flunitazene, metodesnitazene, metonitazene, N-pyrrolidino etonitazene,
and protonitazene on December 7, 2021. 86 FR 69182. That NoI discussed
findings from DEA's three-factor analysis dated November 2021, which
DEA made available on www.regulations.gov.
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,
[[Page 21557]]
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). DEA's
November 2021 three-factor analysis and the Assistant Secretary's July
7 and September 10, 2021, letters are available in their entirety under
the tab ``Supporting Documents'' of the public docket of this action at
www.regulations.gov.
Since the publication of the NoI, DEA discovered that the NoI
inadvertently assigned duplicate drug codes to butonitazene,
etodesnitazene, flunitazene, and protonitazene. Accordingly, with this
temporary scheduling order, DEA hereby corrects those errors by
assigning new drug codes to all seven substances: butonitazene (9751),
etodesnitazene (9765), flunitazene (9756), metodesnitazene (9764),
metonitazene (9757), N-pyrrolidino etonitazene (9758), and
protonitazene (9759).
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 on 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 20 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).
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 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).
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\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.
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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. These seven substances are likely
to be abused in the same manner as schedule I
[[Page 21558]]
opioids such as isotonitazene and heroin.
Factor 5. Scope, Duration, and Significance of Abuse
Butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene are
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 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).
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\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.
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Data from law enforcement encounters suggests that etodesnitazene,
flunitazene, metonitazene, butonitazene, N-pyrrolidino etonitazene, and
protonitazene are abused \5\ in the United States as recreational
drugs. Law enforcement encounters of etodesnitazene, flunitazene,
metonitazene, butonitazene, N-pyrrolidino etonitazene, and
protonitazene as reported to NFLIS (Federal, State, and local
laboratories) include 417 exhibits since 2020 (queried 11/23/2021).
NFLIS registered two encounters of etodesnitazene from two states, five
encounters of flunitazene from four states, 399 encounters of
metonitazene from eighteen states, three encounters of butonitazene
from one state, five encounters of N-pyrrolidino etonitazene from three
states, and three encounters of protonitazene from three states. Data
from NFLIS show that at least 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 metodesnitazene 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, metodesnitazene has been identified in
toxicology cases.
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\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.
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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 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.
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\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).
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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 on 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
[[Page 21559]]
(36,359) of all drug-involved overdose deaths.
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\7\ 12 Month-ending (April, 2021) Provisional Number of Drug
Overdose Deaths. Reported provisional data as of November 7, 2021.
https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm.
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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.
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\8\ Krotulski A.J, Papsun D.M, Walton S.E, Logan B.K.
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.
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According to recent reports, butonitazene (1 instance),
etodesnitazene (11), flunitazene (4), metodesnitazene (1), metonitazene
(43), protonitazene (10), and N-pyrrolidino etonitazene (16) have been
identified in toxicology cases in the United States.\9\ For some 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.
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\9\ Center for Forensic Science Research and Education. NPS
Opioids in the United States--Trend Report Q1, Q2, and Q3, 2021.
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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 an
imminent hazard to the 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 temporarily place
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, and protonitazene in schedule I. In a letter to the
Assistant Secretary for Health dated August 25, 2021, the Administrator
transmitted notice of her intent to temporarily place N-pyrrolidino
etonitazene in schedule I. DEA subsequently published a NoI on December
7, 2021. 86 FR 69182.
Conclusion
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 place
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene in schedule
I of the CSA and finds that such placement is necessary to avoid an
imminent hazard to the public safety.
This temporary order scheduling these substances will be effective
on the date the order is published in the Federal Register and remain
in effect for two 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 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).
Requirements for Handling
Upon the effective date of this temporary order, butonitazene,
etodesnitazene, flunitazene, metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and protonitazene will be subject to the
regulatory controls and administrative, civil, and criminal sanctions
applicable to the manufacture, distribution, reverse distribution,
importation, exportation, and possession of, and engagement in research
and conduct of instructional activities or chemical analysis with,
schedule I controlled substances, including the following:
1. Registration. Any person who handles (possesses, manufactures,
distributes, reverse distributes, imports, exports, engages in
research, or conducts instructional activities or chemical analysis
with) or desires to handle, butonitazene, etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-pyrrolidino etonitazene, and
protonitazene must be registered with DEA to conduct such activities,
pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21
CFR parts 1301 and 1312, as of April 12, 2022. Any person who currently
handles butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene and is not
registered with DEA must submit an application for registration and may
not continue to handle butonitazene, etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-pyrrolidino etonitazene, and
protonitazene as of April 12, 2022, unless DEA has approved that
application for registration pursuant to 21 U.S.C. 822, 823, 957, and
958, and in accordance with 21 CFR parts 1301 and 1312. Retail sales of
schedule I controlled substances to the general public are not allowed
under the CSA. Possession of any quantity of these substances in a
manner not authorized by the CSA on or after April 12, 2022 is
unlawful, and those in possession of any quantity of these substances
may be subject to prosecution pursuant to the CSA.
2. Disposal of stocks. Any person who does not desire or is unable
to obtain a schedule I registration to handle butonitazene,
etodesnitazene, flunitazene, metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and protonitazene must
[[Page 21560]]
surrender all currently held quantities of these seven substances.
3. Security. Butonitazene, etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-pyrrolidino etonitazene, and
protonitazene are subject to schedule I security requirements and must
be handled and stored pursuant to 21 U.S.C. 821, 823, and 871(b), and
in accordance with 21 CFR 1301.71-1301.76, as of April 12, 2022. Non-
practitioners handling these seven substances must also comply with the
employee screening requirements of 21 CFR 1301.90-1301.93.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of butonitazene, etodesnitazene, flunitazene,
metodesnitazene, metonitazene, N-pyrrolidino etonitazene, and
protonitazene must comply with 21 U.S.C. 825 and 958(e) and 21 CFR part
1302. Current DEA registrants will have 30 calendar days from April 12,
2022 to comply with all labeling and packaging requirements.
5. Inventory. Every DEA registrant who possesses any quantity of
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene on the
effective date of this order must take an inventory of all stocks of
these substances on hand pursuant to 21 U.S.C. 827 and 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11. Current DEA
registrants will have 30 calendar days from the effective date of this
order to comply with all inventory requirements. After the initial
inventory, every DEA registrant must take an inventory of all
controlled substances (including butonitazene, etodesnitazene,
flunitazene, metodesnitazene, metonitazene, N-pyrrolidino etonitazene,
and protonitazene) on hand on a biennial basis pursuant to 21 U.S.C.
827 and 958 and in accordance with 21 CFR 1304.03, 1304.04, and
1304.11.
6. Records. All DEA registrants must maintain records with respect
to butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene pursuant to
21 U.S.C. 827 and 958 and in accordance with 21 CFR parts 1304, 1312,
and 1317, and section 1307.11. Current DEA registrants authorized to
handle these seven substances shall have 30 calendar days from the
effective date of this order to comply with all recordkeeping
requirements.
7. Reports. All DEA registrants must submit reports with respect to
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene pursuant to
21 U.S.C. 827 and in accordance with 21 CFR parts 1304, 1312, and 1317,
and sections 1301.74(c) and 1301.76(b), as of April 12, 2022.
Manufacturers and distributors must also submit reports regarding these
seven substances to the Automation of Reports and Consolidated Order
System pursuant to 21 U.S.C. 827 and in accordance with 21 CFR parts
1304 and 1312.
8. Order Forms. All DEA registrants who distribute butonitazene,
etodesnitazene, flunitazene, metodesnitazene, metonitazene, N-
pyrrolidino etonitazene, and protonitazene must comply with order form
requirements pursuant to 21 U.S.C. 828 and in accordance with 21 CFR
part 1305 as of April 12, 2022.
9. Importation and Exportation. All importation and exportation of
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene must be in
compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance
with 21 CFR part 1312 as of April 12, 2022.
10. Quota. Only DEA-registered manufacturers may manufacture
butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene in
accordance with a quota assigned pursuant to 21 U.S.C. 826 and in
accordance with 21 CFR part 1303, as of April 12, 2022.
11. Liability. Any activity involving butonitazene, etodesnitazene,
flunitazene, metodesnitazene, metonitazene, N-pyrrolidino etonitazene,
and protonitazene not authorized by or in violation of the CSA,
occurring as of April 12, 2022, is unlawful and may subject the person
to administrative, civil, and/or criminal sanctions.
Regulatory Matters
The CSA provides for expedited temporary scheduling actions where
necessary to avoid imminent hazards 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 temporary scheduling order. 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.
Alternatively, even if this action was 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
imminent hazards to public safety.
Although DEA believes this 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.
[[Page 21561]]
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 amends 21 CFR part 1308 as
follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
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.
0
2. In Sec. 1308.11, add paragraphs (h)(50) through (h)(56) to read as
follows:
Sec. 1308.11 Schedule I
* * * * *
(h) * * *
(50) 2-(2-(4-butoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N,N- 9751
diethylethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other name: Butonitazene).
(51) 2-(2-(4-ethoxybenzyl)-1H-benzimidazol-1-yl)-N,N- 9765
diethylethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other names:
Etodesnitazene; etazene).......................................
(52) N,N-diethyl-2-(2-(4-fluorobenzyl)-5-nitro-1H-benzimidazol-1- 9756
yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts
of isomers, esters and ethers (Other name: Flunitazene)........
(53) N,N-diethyl-2-(2-(4-methoxybenzyl)-1H-benzimidazol-1- 9764
yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts
of isomers, esters and ethers (Other name: Metodesnitazene)....
(54) N,N-diethyl-2-(2-(4-methoxybenzyl)-5-nitro-1H-benzimidazol- 9757
1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other name: Metonitazene).
(55) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H- 9758
benzimidazole, its isomers, esters, ethers, salts, and salts of
isomers, esters and ethers (Other names: N-pyrrolidino
etonitazene; etonitazepyne)....................................
(56) N,N-diethyl-2-(5-nitro-2-(4-propoxybenzyl)-1H-benzimidazol- 9759
1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and
salts of isomers, esters and ethers (Other name: Protonitazene)
Anne Milgram,
Administrator.
[FR Doc. 2022-07640 Filed 4-11-22; 8:45 am]
BILLING CODE 4410-09-P