21556 Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 

1Though 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. 

2The 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. 

Matthew S. Borman, 

Deputy Assistant Secretary for Export 

Administration. 

[FR Doc. 2022–07836 Filed 4–8–22; 8:45 am] 

BILLING CODE 3510–33–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, NPyrrolidino etonitazene, and 

Protonitazene in Schedule I 

AGENCY: Drug Enforcement 

Administration, Department of Justice. 

ACTION: Temporary amendment; 

temporary scheduling order. 

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): 

• 2-(2-(4-butoxybenzyl)-5-nitro-1Hbenzimidazol-1-yl)-N,N-diethylethan-1- 

amine (butonitazene), 

• 2-(2-(4-ethoxybenzyl)-1Hbenzimidazol-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-1Hbenzimidazol-1-yl)ethan-1-amine 

(metonitazene), 

• 2-(4-ethoxybenzyl)-5-nitro-1-(2- 

(pyrrolidin-1-yl)ethyl)-1Hbenzimidazole (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. 

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, Npyrrolidino 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, 


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Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 21557 

3NFLIS 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. 

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, Npyrrolidino 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 benzimidazoleopioids 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 postmortem 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 threefactor 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 benzimidazoleopioids 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). 

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 


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21558 Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 

4Center 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. 

5While 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. 

6NSDUH, 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, noninstitutionalized 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). 

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-overdosedata.htm. 

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 coidentified with designer 

benzodiazepines (7), fentanyl (4), and 

methamphetamine (4). 

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, Npyrrolidino 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 underreporting as forensic laboratories try to 

secure reference standards for these 

substances. However, metodesnitazene 

has 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 

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, Npyrrolidino 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 on the illicit 

drug market. Data obtained from preclinical 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, Npyrrolidino 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 


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Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 21559 

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. 

9Center for Forensic Science Research and 

Education. NPS Opioids in the United States— 

Trend Report Q1, Q2, and Q3, 2021. 

(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 deathscene 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 (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. 

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, Npyrrolidino 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, Npyrrolidino 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, Npyrrolidino 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 


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21560 Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 

surrender all currently held quantities 

of these seven substances. 

3. Security. Butonitazene, 

etodesnitazene, flunitazene, 

metodesnitazene, metonitazene, Npyrrolidino 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. Nonpractitioners 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, Npyrrolidino 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, Npyrrolidino 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, Npyrrolidino 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. 


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Federal Register / Vol. 87, No. 70 / Tuesday, April 12, 2022 / Rules and Regulations 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 

■ 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 (h)(56) to read as follows: 

§ 1308.11 Schedule I 

* * * * * 

(h) * * * 

(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) .................................................................................................................................. 9751 

(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) ......................................................................................................................... 9765 

(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) .................................................................................................................................... 9756 

(53) N,N-diethyl-2-(2-(4-methoxybenzyl)-1H-benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers, salts, and salts of isomers, 

esters and ethers (Other name: Metodesnitazene) ...................................................................................................................................... 9764 

(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) ............................................................................................................................. 9757 

(55) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(pyrrolidin-1-yl)ethyl)-1H-benzimidazole, its isomers, esters, ethers, salts, and salts of isomers, 

esters and ethers (Other names: N-pyrrolidino etonitazene; etonitazepyne) ............................................................................................ 9758 

(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) ............................................................................................................................ 9759 

Anne Milgram, 

Administrator. 

[FR Doc. 2022–07640 Filed 4–11–22; 8:45 am] 

BILLING CODE 4410–09–P 

DEPARTMENT OF THE INTERIOR 

Office of Surface Mining Reclamation 

and Enforcement 

30 CFR Part 938 

[SATS No. PA–161–FOR; Docket ID: OSM– 

2012–0009; S1D1S SS08011000 SX064A000 

221S180110; S2D2S SS08011000 

SX064A000 22XS501520] 

Pennsylvania Regulatory Program 

AGENCY: Office of Surface Mining 

Reclamation and Enforcement, Interior. 

ACTION: Final rule; approval of 

amendment. 

SUMMARY: We, the Office of Surface 

Mining Reclamation and Enforcement 

(OSMRE), are approving an amendment 

to the approved Pennsylvania regulatory 

program (the Pennsylvania program) 

under the Surface Mining Control and 

Reclamation Act of 1977 (SMCRA or the 

Act). The amendment we are approving 

consists of revisions and additions to 

Pennsylvania’s regulations related to 

beneficial use of coal ash at active 

surface coal mining sites. 

DATES: The effective date is May 12, 

2022. 

FOR FURTHER INFORMATION CONTACT: Mr. 

Ben Owens, Acting Field Office 

Director, Pittsburgh Field Office, 

Telephone: (412) 937–2857; email: 

bowens@osmre.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background on the Pennsylvania Program 

and Federal Regulation of Coal 

Combustion Residues 

II. Submission of the Amendment 

III. OSMRE’s Findings 

IV. Summary and Disposition of Comments 

V. OSMRE’s Decision 

VI. Statutory and Executive Order Reviews 

I. Background on the Pennsylvania 

Program and Federal Regulation of 

Coal Combustion Residues 

The Pennsylvania Program 

Section 503(a) of the SMCRA permits 

a state to assume primacy for the 

regulation of surface coal mining and 

reclamation operations on non-Federal 

and non-Indian lands within its borders 

by demonstrating that its program 

includes, among other things, State laws 

and regulations that govern surface coal 

mining and reclamation operations in 

accordance with the Act and consistent 

with the Federal regulations. 30 U.S.C. 

1253(a)(1) and (7). On the basis of these 

criteria, the Secretary of the Interior 

conditionally approved the 

Pennsylvania program effective July 30, 

1982. You can find background 

information on the Pennsylvania 

program, including the Secretary’s 

findings, the disposition of comments, 

and the conditions of approval of the 

Pennsylvania program in the July 30, 

1982, Federal Register (47 FR 33050). 

You can also find later actions 


khammond on DSKJM1Z7X2PROD with RULES