[Federal Register Volume 85, Number 162 (Thursday, August 20, 2020)]
[Rules and Regulations]
[Pages 51342-51346]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-17951]


-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-631]


Schedules of Controlled Substances: Temporary Placement of 
Isotonitazene in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Temporary amendment; temporary scheduling order.

-----------------------------------------------------------------------

SUMMARY: The Acting Administrator of the Drug Enforcement 
Administration is issuing this temporary order to schedule N,N-diethyl-
2-(2-(4 isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine 
(commonly known as isotonitazene), including its 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. This action is based on a finding by the Acting 
Administrator that the placement of isotonitazene in schedule I of the 
Controlled Substances Act is necessary to avoid an 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 isotonitazene.

DATES: This temporary scheduling order is effective August 20, 2020, 
until August 20, 2022. If this order is extended or made permanent, DEA 
will publish a document in the Federal Register.

FOR FURTHER INFORMATION CONTACT: Scott A. Brinks, Regulatory Drafting 
and Policy Support Section, Diversion Control Division, Drug 
Enforcement Administration; Mailing Address: 8701 Morrissette Drive, 
Springfield, Virginia 22152; Telephone: (571) 362-3261.

SUPPLEMENTARY INFORMATION:

Legal Authority

    The Controlled Substances Act (CSA) provides the Attorney General 
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 permanently 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 \1\ for up to one year. 21 U.S.C. 811(h)(2).
---------------------------------------------------------------------------

    \1\ Though the Drug Enforcement Administration (DEA) has used 
the term ``final order'' with respect to temporary scheduling orders 
in the past, this document adheres to the statutory language of 21 
U.S.C. 811(h), which refers to a ``temporary scheduling order.'' No 
substantive change is intended.
---------------------------------------------------------------------------

    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 (FDCA), 21 U.S.C. 355. 21 U.S.C. 
811(h)(1); 21 CFR part 1308. The Attorney General has delegated 
scheduling authority under 21 U.S.C. 811 to the Administrator of DEA 
(Administrator). 28 CFR 0.100.

Background

    21 U.S.C. 811(h)(4) requires the Administrator to notify the 
Secretary of the Department of Health and Human Services (HHS) of his 
intention to temporarily place a substance in schedule I of the CSA.\2\ 
The Acting Administrator transmitted notice of his intent to place 
isotonitazene in schedule I on a temporary basis to the Assistant 
Secretary for Health of HHS (Assistant Secretary) by letter dated March 
2, 2020. The Assistant Secretary responded to this notice by letter 
dated March 31, 2020, 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 isotonitazene. The Assistant Secretary also stated that HHS had no 
objection to the temporary placement of isotonitazene in schedule I of 
the CSA.
---------------------------------------------------------------------------

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

    The Drug Enforcement Administration (DEA) has taken into 
consideration the Assistant Secretary's comments as required by 21 
U.S.C. 811(h)(4). Isotonitazene is not currently listed in any schedule 
under the CSA, and no exemptions or approvals are in effect for 
isotonitazene under section 505 of the FDCA, 21 U.S.C. 355. DEA has 
found that the control of isotonitazene 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 to temporarily schedule isotonitazene in the Federal Register on 
June 18, 2020. 85 FR 38619. That notice of intent discussed findings 
from DEA's three-factor analysis dated May 2020, which DEA made 
available on www.regulations.gov contemporaneously with the publication 
of the notice of intent. This temporary scheduling order discusses 
updated findings on isotonitazane for one of the three factors (Factor 
5) in DEA's July 2020 analysis related to law enforcement seizures, 
overdoses, and regulatory status.
    To find that placing a substance temporarily in schedule I of the 
CSA is necessary to avoid an imminent hazard to the public safety, the 
Administrator is required to 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). 
Consideration of these factors includes actual abuse, diversion from 
legitimate channels, and clandestine importation, manufacture, or 
distribution. 21 U.S.C. 811(h)(3).
    A substance 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 are those that 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. 21 U.S.C. 812(b)(1).
    Available data and information for isotonitazene summarized below 
indicate that it has 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. DEA's May and July 2020 
three-factor analyses and the Assistant Secretary's March 31, 2020, 
letter are available in their entirety under the tab ``Supporting 
Documents'' of the public docket of this action at www.regulations.gov.

[[Page 51343]]

Isotonitazene

    The availability of synthetic opioids in the illicit drug market 
continues to pose an imminent hazard to the public safety. Adverse 
health effects associated with the abuse of synthetic opioids and the 
continued evolution and increased popularity of these substances have 
been a serious concern in recent years. As the United States continues 
to experience an unprecedented epidemic of opioid misuse and abuse, the 
presence of new synthetic opioids with no approved medical use 
exacerbates the epidemic. The trafficking and abuse of new synthetic 
opioids are deadly new trends.
    The identification of isotonitazene, chemically known as N,N-
diethyl-2-(2-(4 isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-
amine (other name: N,N-diethyl-2-[[4-(1-methylethoxy)phenyl]methyl]-5-
nitro-1H-benzimidazole-1-ethanamine), in the illicit drug market has 
been reported in Canada, Estonia, Germany, Latvia, Sweden, and the 
United States (see Factor 4 below). Data obtained from preclinical 
pharmacology studies shows that isotonitazene has a pharmacological 
profile similar to that of the potent synthetic opioid etonitazene, a 
schedule I controlled substance. Because of the pharmacological 
similarities of isotonitazene to etonitazene, the use of isotonitazene 
presents a high risk of abuse and may negatively affect users and 
communities. The abuse of isotonitazene has been associated with at 
least 19 fatalities in the United States (see Factor 5 below). The 
positive identification of this substance in overdose and post-mortem 
cases is a serious concern for public safety. Thus, isotonitazene poses 
an imminent hazard to public safety.
    Available data and information for isotonitazene, as summarized 
below, indicates that this substance has 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. 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-631.

Factor 4. History and Current Pattern of Abuse

    The chemical syntheses of isotonitazene (a benzimidazole 
derivative) and other benzimidazole derivatives (including schedule I 
substances such as synthetic opioids etonitazene and clonitazene) were 
first reported in the scientific literature in 1957. Isotonitazene is 
not an approved pharmaceutical product and is not approved for medical 
use anywhere in the world. As discussed in the background section, the 
Assistant Secretary stated in a March 31, 2020, letter to DEA that 
there are no INDs or FDA-approved NDAs for isotonitazene in the United 
States. Hence, DEA notes there is no legitimate channel for 
isotonitazene as a marketed drug product.
    Since 2014, numerous synthetic opioids structurally related to 
fentanyl and several opioids from other structural classes have begun 
to emerge in the illicit drug market, as evidenced by the 
identification of these drugs in forensic drug exhibits and toxicology 
samples. Beginning in April 2019, isotonitazene emerged on the illicit 
synthetic drug market in the United States, as evidenced by its 
identification in drug seizures and in biological samples collected and 
submitted to National Medical Services (NMS) Laboratory \3\ in August 
2019. In August 2019, isotonitazene was first reported in a drug case 
in Belgium and in toxicology casework in Canada (a toxicological sample 
was collected in March 2019). In the United States, the Center for 
Forensic Science Research and Education (under the novel psychoactive 
substances discovery program) first reported isotonitazene in November 
2019.
---------------------------------------------------------------------------

    \3\ NMS Labs, in collaboration with the Center for Forensic 
Science Research and Education at the Fredric Rieders Family 
Foundation and the Organized Crime Drug Enforcement Task Force at 
the U.S. Department of Justice, has received funding from the 
Centers for Disease Control and Prevention to develop systems for 
the early identification and notification of novel psychoactive 
substances in the drug supply within the United States.
---------------------------------------------------------------------------

    According to a report by the European Monitoring Center for Drugs 
and Drug addiction and Europol,\4\ between April 2019 and January 2020, 
four member-states (Estonia, Latvia, Germany, and Sweden) have reported 
24 isotonitazene cases involving 109.6 grams of powder (22 cases) and 
4.5 grams of liquid (two cases). Isotonitazene has been encountered by 
United States law enforcement primarily in powder form. In March 2020, 
Canada law enforcement also encountered isotonitazene in a tablet form, 
as a white triangular tablet with `M' logo on one side and `8' logo on 
the other side, and as a blue tablet in Dilaudid counterfeit pills. 
Identification of isotonitazene in counterfeit pills is deeply 
concerning because the identity, purity, and quantity of isotonitazene 
in this formulation are uncertain, thus presenting additional safety 
concerns for unsuspecting users.
---------------------------------------------------------------------------

    \4\ European Monitoring Centre for Drugs and Drug Addiction and 
Europol (2020), EMCDDA initial report on the new psychoactive 
substance N,N-diethyl-2-[[4-(1-methylethoxy)phenyl]methyl]-5-nitro-
1H-benzimidazole-1-ethanamine (isotonitazene). In accordance with 
Article 5b of Regulation (EC) No 1920/2006 (as amended), 
Publications Office of the European Union, Luxembourg.
---------------------------------------------------------------------------

    In the United States, isotonitazene has been identified as a single 
substance or in combination with other substances. In April 2019, the 
United States Customs and Border Protection (CBP) seized 1.6 grams of 
isotonitazene in California. In addition, Wisconsin State Crime 
Laboratories identified isotonitazene mixed with heroin and bromazolam, 
a nonscheduled benzodiazepine, in seized powder. Further, isotonitazene 
was identified in a substance obtained from the scene of a death 
investigation in Iowa. Evidence suggests that individuals are using 
isotonitazene as a replacement to heroin or other opioids, either 
knowingly or unknowingly.

Factor 5. Scope, Duration, and Significance of Abuse

    Isotonitazene, similar to etonitazene (schedule I), has been 
described as a potent synthetic opioid and evidence suggests it is 
being abused for its opioidergic effects (see Factor 6). The abuse of 
isotonitazene, similar to other synthetic opioids, has resulted in 
adverse health effects. Isotonitazene has been positively identified in 
18 death investigations between August 2019 and January 2020. These 
reports were from four states--Illinois (9), Indiana (7), Minnesota 
(1), and Wisconsin (1). Most (n = 12) of the decedents were male. The 
ages ranged from 24 to 66 years old with an average age of 41. Other 
substances identified in postmortem blood specimens obtained from these 
decedents include etizolam (6); flualprazolam, a nonscheduled 
benzodiazepine (7); fentanyl (6); heroin (3); tramadol, a schedule IV 
narcotic (2); and U-47700, a schedule I synthetic opioid (1). The 
average concentration of isotonitazene in these biological samples 
(blood) was 2.2  2.1 nanogram/milliliter (ng/ml) (range 0.4 
to 9.5 ng/ml). Isotonitazene was detected as the only opioid in 50 
percent (n = 9) of the specimens for these decedents. DEA \5\ is aware 
of another postmortem case that occurred in January 2020 in 
Pennsylvania where isotonitazene was identified in a biological sample. 
In total, isotonitazene has been positively identified in 19 postmortem 
cases.

[[Page 51344]]

Recent communication from Minnesota Department of Health \6\ reports 
the positive identification of isotonitazene in two overdose cases.
---------------------------------------------------------------------------

    \5\ Email communication from DEA Philadelphia Field Division on 
March 4, 2020.
    \6\ Email communication from Minnesota Department of Health: 
Biomonitoring and Emerging Contaminants Unit; received May 26, 2020.
---------------------------------------------------------------------------

    Law enforcement data indicate that isotonitazene has appeared in 
the United States' illicit drug market. According to the National 
Forensic Laboratory Information System (NFLIS) \7\ database, which 
collects drug identification results from drug cases submitted to and 
analyzed by Federal, State, and local forensic laboratories, there have 
been 48 encounters of isotonitazene in the United States (queried May 
14, 2020). These 48 encounters occurred in 2019 and 2020 in five 
states: California (1), Iowa (5), Ohio (4), Tennessee (13), and 
Wisconsin (25). One of these encounters consisted of 1.6 grams of 
isotonitazene seized by the CBP in California in April 2019.
---------------------------------------------------------------------------

    \7\ NFLIS represents an important resource in monitoring illicit 
drug trafficking, including the diversion of legally manufactured 
pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive 
information system that includes data from forensic laboratories 
that handle the nation's drug analysis cases. NFLIS-Drug 
participation rate, defined as the percentage of the national drug 
caseload represented by laboratories that have joined NFLIS, is 
currently 98.5 percent. 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. NFLIS data was 
queried on May 14, 2020.
---------------------------------------------------------------------------

    As of May 2020, Ohio and Wisconsin enacted emergency legislation to 
control isotonitazene as a schedule I controlled substance. 
Internationally, isotonitazene is controlled under Estonia, Latvia, 
Poland, and Sweden drug control legislation. In the United Kingdom, 
isotonitazene is controlled under the Psychoactive Substances Act 2016. 
Further, isotonitazene is controlled under the Norwegian Medicines Act 
and Lithuania medicine legislation.\8\
---------------------------------------------------------------------------

    \8\ The Medicines Act, LOVDATA, https://lovdata.no/dokument/NL/lov/1992-12-04-132, 1992.
---------------------------------------------------------------------------

    The population likely to abuse isotonitazene appears to be the same 
as those abusing prescription opioid analgesics, heroin, tramadol, 
fentanyl, and other synthetic opioid substances. This is evidenced by 
the types of other drugs co-identified in isotonitazene fatal overdose 
cases. Because abusers of isotonitazene are likely to obtain it through 
unregulated sources, the identity, purity, and quantity are uncertain 
and 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),\9\ as of 2018, an 
estimated 10.3 million people aged 12 years or older had misused 
opioids in the past year, including 9.9 million prescription pain 
reliever misusers and 808,000 heroin users. In 2018, an estimated 2.0 
million people had an opioid use disorder which included 1.7 million 
people with a prescription pain reliever use disorder and 0.5 million 
people with heroin use disorder. This population abusing opioids is 
likely to be at risk of abusing isotonitazene. Individuals who initiate 
(i.e., use a drug for the first time) use of isotonitazene are likely 
to be at risk of developing substance use disorders, overdoses, and 
death similar to that of other opioid analgesics (e.g., fentanyl, 
morphine, etc.). Law enforcement and toxicology reports demonstrate 
that isotonitazene is being illicitly distributed and abused.
---------------------------------------------------------------------------

    \9\ The National Survey on Drug Use and Health (NSDUH), formerly 
known as the National Household Survey on Drug Abuse (NHSDA), is 
conducted annually by HHS' Substance Abuse and Mental Health 
Services Administration (SAMHSA). It is the primary source of 
estimates of the prevalence and incidence of nonmedical 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 twelve 
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 2018 NSDUH annual 
report is available at https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHNationalFindingsReport2018/NSDUHNationalFindingsReport2018.pdf (last accessed June 18, 2020).
---------------------------------------------------------------------------

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 isotonitazene exhibits a pharmacological 
profile similar to that of etonitazene and other mu-opioid receptor 
agonists. In an in vivo (in mice) study, isotonitazene was 500 times 
more potent than morphine as an analgesic in a tail-flick assay. The 
tail-flick assay is useful in evaluating antinociceptive effect. Data 
from in vitro studies showed that isotonitazene activated the mu-opioid 
receptor and acted as a mu-opioid receptor agonist. Isotonitazene, 
similar to hydromorphone and fentanyl, activated the mu-opioid receptor 
and acted as an agonist via interaction at the mu-opioid receptor with 
[beta]-arrestin-2, a regulatory protein, in a live cell-based receptor 
assay. Naloxone, an opioid receptor antagonist, blocked isotonitazene's 
activation of the mu-opioid receptor. Substances that act as an agonist 
at the mu-opioid receptors have a high potential for addiction and can 
induce dose-dependent respiratory depression.
    As with any mu-opioid receptor agonist, the potential health and 
safety risks for users are high. The public health risks attendant to 
the abuse of heroin and other mu-opioid receptor agonists are well 
established and have resulted in 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. A CDC report 
shows that from 2013 to 2018,\10\ opioid-related overdose deaths in the 
United States increased from 25,052 to 46,802. Of the drug overdose 
death data for 2018, opioids were involved in about 69.5 percent of all 
drug-involved overdose deaths.
---------------------------------------------------------------------------

    \10\ CDC National Center for Health Statistics (NCHS), National 
Vital Statistics System, Mortality. NCHS Data Brief, Number 356, 
January 2020.
---------------------------------------------------------------------------

    In the United States, isotonitazene has been co-identified with 
other substances in 18 postmortem cases, and DEA is aware of an 
additional death in January 2020, involving isotonitazene. These deaths 
associated with isotonitazene occurred in five states: Illinois (9), 
Indiana (7), Minnesota (1), Pennsylvania (1), and Wisconsin (1). 
Information gathered from case histories and autopsy findings shows 
that isotonitazene use is similar to that of classic opioid agonists. 
Evidence obtained from reported cases of death scenarios suggests that 
isotonitazene, similar to heroin, can be used intravenously.\11\
---------------------------------------------------------------------------

    \11\ Krotulski AJ, Papsun DM, Kacinko SL, and Logan BK (2020). 
Isotonitazene Quantitation and Metabolite Discovery in Authentic 
Forensic Casework. Journal of Analytical Toxicology. [Epub ahead of 
print].
---------------------------------------------------------------------------

    The introduction of potent synthetic opioids such as isotonitazene 
into the illicit market exacerbates problematic opioid use for those 
seeking these powerful opioids. As documented by a published toxicology 
report, poly-substance abuse remains common in fatalities associated 
with the abuse of isotonitazene.\12\
---------------------------------------------------------------------------

    \12\ Id.

---------------------------------------------------------------------------

[[Page 51345]]

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 
isotonitazene pose an imminent hazard to the public safety. DEA is not 
aware of any currently accepted medical uses for isotonitazene 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 are those that 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 isotonitazene indicate 
that this substance has 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. As required by 21 
U.S.C. 811(h)(4), by a letter dated March 2, 2020, the Acting 
Administrator notified the Assistant Secretary for Health of DEA's 
intention to temporarily place isotonitazene in schedule I. DEA 
subsequently published a Notice of Intent in the Federal Register on 
June 18, 2020. 85 FR 38619.

Conclusion

    In accordance with the provisions of 21 U.S.C. 811(h), the Acting 
Administrator considered available data and information, and herein 
sets forth the grounds for his determination that it is necessary to 
temporarily schedule N,N-diethyl-2-(2-(4 isopropoxybenzyl)-5-nitro-1H-
benzimidazol-1-yl)ethan-1-amine (commonly known as: Isotonitazene) in 
schedule I of the CSA to avoid an imminent hazard to the public safety.
    Because the Acting Administrator hereby finds it necessary to 
temporarily place isotonitazene in schedule I to avoid an imminent 
hazard to the public safety, this temporary order scheduling this 
substance is effective on the date of publication in the Federal 
Register, and will be in effect for a period of two years, with a 
possible extension of one additional 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 a drug or other 
substance. Regular scheduling actions in accordance with 21 U.S.C. 
811(a) are subject to formal rulemaking procedures done ``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 with appropriate 
process and the government with any additional relevant information 
needed to make a determination. 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, isotonitazene will 
be subject to the regulatory controls and administrative, civil, and 
criminal sanctions applicable to the manufacture, distribution, reverse 
distribution, importation, exportation, engagement in research, and 
conduct of instructional activities or chemical analysis with, and 
possession of schedule I controlled substances, including the 
following:
    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, imports, exports, engages in research, or conducts 
instructional activities or chemical analysis with, or possesses), or 
who desires to handle, isotonitazene 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 August 20, 
2020. Any person who currently handles isotonitazene, and is not 
registered with DEA, must submit an application for registration and 
may not continue to handle isotonitazene as of August 20, 2020, 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 August 20, 2020, 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 not 
able to obtain a schedule I registration to handle isotonitazene must 
surrender all currently held quantities of isotonitazene.
    3. Security. Isotonitazene is subject to schedule I security 
requirements and must be handled and stored pursuant to 21 U.S.C. 821, 
823, 871(b), and in accordance with 21 CFR 1301.71-1301.93, as of 
August 20, 2020. Non-practitioners handling isotonitazene 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 isotonitazene must be in compliance with 21 
U.S.C. 825, 958(e), and be in accordance with 21 CFR part 1302. Current 
DEA registrants shall have 30 calendar days from August 20, 2020, to 
comply with all labeling and packaging requirements.
    5. Inventory. Every DEA registrant who possesses any quantity of 
isotonitazene 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 shall have 30 calendar days from the 
effective date of this order to be in compliance with all inventory 
requirements. After the initial inventory, every DEA registrant must 
take an inventory of all controlled substances (including 
isotonitazene) 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 isotonitazene pursuant to 21 U.S.C. 827 and 958, and in accordance 
with 21 CFR parts 1304, 1312, 1317, and Sec.  1307.11. Current DEA 
registrants authorized to handle isotonitazene shall have 30 calendar 
days from the effective date of this order to be in compliance with all 
recordkeeping requirements.
    7. Reports. All DEA registrants who manufacture or distribute 
isotonitazene must submit reports pursuant to 21 U.S.C. 827 and in 
accordance with 21 CFR parts 1304 and 1312 as of August 20, 2020.
    8. Order Forms. All DEA registrants who distribute isotonitazene 
must comply with order form requirements pursuant to 21 U.S.C. 828 and 
in accordance with 21 CFR part 1305 as of August 20, 2020.
    9. Importation and Exportation. All importation and exportation of 
isotonitazene must be in compliance with 21 U.S.C. 952, 953, 957, 958, 
and in accordance with 21 CFR part 1312 as of August 20, 2020.
    10. Quota. Only DEA registered manufacturers may manufacture 
isotonitazene in accordance with a quota assigned pursuant to 21 U.S.C. 
826 and in accordance with 21 CFR part 1303 as of August 20, 2020.

[[Page 51346]]

    11. Liability. Any activity involving isotonitazene not authorized 
by, or in violation of the CSA, occurring as of August 20, 2020, is 
unlawful, and may subject the person to administrative, civil, and/or 
criminal sanctions.

Regulatory Matters

    21 U.S.C. 811(h) provides for a temporary scheduling action where 
such action is necessary to avoid an imminent hazard to the public 
safety. As provided in this subsection, the Attorney General may, by 
order, schedule a substance in schedule I on a temporary basis. Such an 
order may not be issued before the expiration of 30 days from: (1) The 
publication of a notice in the Federal Register of the intention 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 of HHS. 21 U.S.C. 811(h)(1).
    Inasmuch as 21 U.S.C. 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 of a publication in 
the Federal Register of 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 an order and a rule, 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 an intention for DEA to proceed through 
the issuance of an order instead of proceeding by rulemaking. Given 
that Congress specifically requires 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 21 U.S.C. 811(h), Congress 
authorized the issuance of temporary scheduling actions by order rather 
than by rule.
    In the alternative, even assuming that this action might be subject 
to section 553 of the APA, the Acting Administrator finds that there is 
good cause to forgo the notice-and-comment requirements of section 553, 
as any further delays in the process for issuance of temporary 
scheduling orders would be impracticable and contrary to the public 
interest in view of the manifest urgency to avoid an imminent hazard to 
the 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 Acting 
Administrator took into consideration comments submitted by the 
Assistant Secretary in response to the notice 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 (OMB), as any regulatory action that is likely to 
result in a rule that may: (1) Have an annual effect on the economy of 
$100 million or more or adversely affect in a material way the economy; 
a sector of the economy; productivity; competition; jobs; the 
environment; public health or safety; or State, local, or tribal 
governments or communities; (2) create a serious inconsistency or 
otherwise interfere with an action taken or planned by another agency; 
(3) materially alter the budgetary impact of entitlements, grants, user 
fees, or loan programs, or the rights and obligations of recipients 
thereof; or (4) raise novel legal or policy issues arising out of legal 
mandates, the President's priorities, or the principles set forth in 
the E.O. Because this is not a rulemaking action, this is not a 
significant regulatory action as defined in Section 3(f) of E.O. 12866. 
In addition, because this action is not considered an E.O. 12866 
``significant regulatory action,'' it does not meet the definition of 
an E.O. 13771 regulatory action. Therefore, the repeal and cost offset 
requirements of E.O. 13771 have not been triggered.
    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 paragraph (h)(48) to read as follows:


Sec.  1308.11   Schedule I

* * * * *
    (h) * * *

(48) N,N-diethyl-2-(2-(4 isopropoxybenzyl)-5-nitro-1H-              9614
 benzimidazol-1-yl)ethan-1-amine, its isomers, esters, ethers,
 salts and salts of isomers, esters and ethers (Other names:
 isotonitazene; N,N-diethyl-2-[[4-(1-
 methylethoxy)phenyl]methyl]-5-nitro-1H-benzimidazole-1-
 ethanamine)
 

* * * * *

Timothy J. Shea,
Acting Administrator.
[FR Doc. 2020-17951 Filed 8-19-20; 8:45 am]
BILLING CODE 4410-09-P