[Federal Register Volume 86, Number 232 (Tuesday, December 7, 2021)]
[Proposed Rules]
[Pages 69182-69187]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-26263]


=======================================================================
-----------------------------------------------------------------------

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):
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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-

[[Page 69183]]

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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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).

[[Page 69184]]

    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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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

[[Page 69185]]

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.
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \9\ Center for Forensic Science Research and Education. NPS 
Opioids in the United States--Trend Report Q1 and Q2, 2021.
---------------------------------------------------------------------------

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

[[Page 69186]]

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

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 (56) to read as 
follows:


Sec.  1308.11  Schedule I.

* * * * *
    (h) * * *

[[Page 69187]]



(50) 2-(2-(4-butoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)-N,N-       9654
 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-               9665
 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-     9656
 1-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-          9664
 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-                 9657
 benzimidazol-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)-       9658
 1H-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-                 9659
 benzimidazol-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. 2021-26263 Filed 12-6-21; 8:45 am]
BILLING CODE 4410-09-P