[Federal Register Volume 89, Number 145 (Monday, July 29, 2024)]
[Rules and Regulations]
[Pages 60817-60823]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-16391]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1143]
Schedules of Controlled Substances: Temporary Placement of N-
Desethyl Isotonitazene and N-Piperidinyl Etonitazene in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Temporary amendment; temporary scheduling order.
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SUMMARY: The Administrator of the Drug Enforcement Administration is
issuing this temporary order to schedule two 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 two substances in schedule I
is necessary to avoid imminent hazard to the public safety. This order
imposes the regulatory controls and administrative, civil, and criminal
sanctions applicable to schedule I controlled substances on persons who
handle (manufacture, distribute, reverse distribute, import, export,
engage in research, conduct instructional activities or chemical
analysis with, or possess) or propose to handle these two specified
controlled substances.
[[Page 60818]]
DATES: This temporary scheduling order is effective July 29, 2024,
until July 29, 2026. 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 two substances, including their
isomers, esters, ethers, salts, and salts of isomers, esters, and
ethers whenever the existence of such isomers, esters, ethers, and
salts is possible, to schedule I under the Controlled Substances Act
(CSA):
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\1\ Though DEA has used the term ``final order'' with respect to
temporary scheduling orders in the past, this action adheres to the
statutory language of 21 U.S.C. 811(h), which refers to a
``temporary scheduling order.'' No substantive change is intended.
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N-ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H-benzimidazol-
1-yl)ethan-1-amine (commonly known as N-desethyl isotonitazene), and
2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1-yl)ethyl)-1H-
benzimidazole (commonly known as either N-piperidinyl etonitazene or
etonitazepipne).
Legal Authority
Under 21 U.S.C. 811(h)(1), the Attorney General, as delegated to
the Administrator of DEA (Administrator) pursuant to 28 CFR 0.100, has
the authority to temporarily place a substance in schedule I of the CSA
for two years without regard to the evaluation 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.\2\ 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.\3\
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\2\ 21 U.S.C. 811(h)(1).
\3\ 21 U.S.C. 811(h)(2).
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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, 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.\4\
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\4\ 21 U.S.C. 811(h)(1); 21 CFR part 1308.
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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).\5\ The Administrator transmitted the
required notice to the Assistant Secretary for Health of HHS (Assistant
Secretary),\6\ by letter dated April 3, 2023, regarding N-desethyl
isotonitazene and N-piperidinyl etonitazene. The Assistant Secretary
responded to this notice by letter dated May 11, 2023, 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 N-desethyl isotonitazene and N-
piperidinyl etonitazene. The Assistant Secretary also stated that HHS
had no objection to the temporary placement of these substances in
schedule I. N-Desethyl isotonitazene and N-piperidinyl etonitazene
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
substances.
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\5\ 21 U.S.C. 811(h)(4).
\6\ The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. 58 FR 35460 (July 1, 1993).
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DEA has taken into consideration the Assistant Secretary's comments
as required by subsection 811(h)(4). DEA has found the control of N-
desethyl isotonitazene and N-piperidinyl etonitazene 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 N-desethyl isotonitazene and N-
piperidinyl etonitazene on October 25, 2023.\7\ That NOI discussed
findings from DEA's three-factor analysis dated January 2023, which DEA
made available on www.regulations.gov.
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\7\ 88 FR 73293 (Oct. 25, 2023).
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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.\8\ Consideration of these factors
includes any information indicating actual abuse, diversion from
legitimate channels, and clandestine importation, manufacture, or
distribution of these substances.\9\
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\8\ 21 U.S.C. 811(h)(3).
\9\ Id.
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Substances meeting the statutory requirements for temporary
scheduling may only be placed in schedule I.\10\ Substances in schedule
I have 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.\11\
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\10\ 21 U.S.C. 811(h)(1).
\11\ 21 U.S.C. 812(b)(1).
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Two Benzimidazole-Opioids: N-desethyl isotonitazene and N-piperidinyl
etonitazene
The continued encounter of novel psychoactive substances (NPS) on
the recreational drug market poses a threat to public safety. Following
the class-wide scheduling of fentanyl-related substances,\12\ there has
been an increase in the emergence of synthetic opioids that are not
structurally related to fentanyl. Beginning in 2019, a new class of
synthetic opioids known as benzimidazole-opioids, commonly referred to
as ``nitazenes,'' emerged on the recreational drug market. This class
of substances was first synthesized in the 1950s by CIBA
Aktiengesellschaft in Switzerland, and it has a similar pharmacological
profile to fentanyl, morphine, and other mu-opioid receptor agonists.
Between August 2020 and April 2022, DEA temporarily controlled eight
benzimidazole-opioids because they posed a threat to public safety.\13\
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\12\ On February 6, 2018, pursuant to 21 U.S.C. 811(h), the then
Acting Administrator of Drug Enforcement Administration temporarily
placed fentanyl-related substances in schedule I of the Controlled
Substances Act (CSA) (83 FR 5188) to avoid an imminent hazard to
public safety. Through the Temporary Reauthorization and Study of
Emergency Scheduling of Fentanyl Analogues Act, Public Law 116-114,
which became law on February 6, 2020, Congress extended the
temporary control of fentanyl-related substances until May 6, 2021.
This temporary order was subsequently extended multiple times, most
recently through the Consolidated Appropriations Act of 2023, Public
Law 117-328, which extended the order until December 31, 2024.
\13\ Schedules of Controlled Substances: Temporary Placement of
Butonitazene, Etodesnitazene, flunitazene, Metodesnitazene,
Metonitazene, N-Pyrrolidino etonitazene, and Protonitazene in
Schedule I, 87 FR 21556 (Apr. 12, 2022); Schedules of Controlled
Substances: Temporary Placement of Isotonitazene in Schedule I, 85
FR 51342 (Aug. 20, 2020).
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Recently, additional benzimidazole-opioids have been identified
within the rapidly expanding class of ``nitazene'' compounds on the
recreational drug market. N-Desethyl isotonitazene and N-piperidinyl
etonitazene are some of the recently encountered ``nitazene''
[[Page 60819]]
synthetic opioids identified on the illicit drug market.
The continued trafficking and identification of benzimidazole-
opioids in toxicology cases pose a significant threat to public health
and safety. Adverse health effects associated with the misuse and abuse
of synthetic opioids have led to devastating consequences including
death. Preclinical pharmacology data demonstrate that N-desethyl
isotonitazene and N-piperidinyl etonitazene have pharmacological
profiles similar to those of the potent benzimidazole-opioids
etonitazene and isotonitazene, schedule I opioid substances.\14\ N-
Desethyl isotonitazene, an active metabolite of isotonitazene, has been
positively identified in at least ten toxicology cases.\15\ N-
Piperidinyl etonitazene has been positively identified in at least
three toxicology cases.\16\ As the United States continues to
experience a high number of opioid-involved overdoses and mortalities,
the introduction of new designer opioids further exacerbates the
current opioid epidemic.
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\14\ DEA-VA Interagency Agreement. ``In Vitro Receptor and
Transporter Assays for Abuse Liability Testing for the DEA by the
VA''. Binding and Functional Activity at Delta, Kappa and Mu Opioid
Receptors. 2022.
\15\ Walton SE, Krotulski AJ, Logan BK. A Forward-Thinking
Approach to Addressing the New Synthetic Opioid 2-
Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography-Tandem
Quadrupole Mass Spectrometry (LC-QQQ-MS). J Anal Toxicol. 2022 Mar
21;46(3):221-231.
\16\ Calello DP, Aldy K, Jefri M, Nguyen TT, Krotulski A, Logan
B, Brent J, Wax P, Walton S, Manini AF; ToxIC Fentalog Study Group.
Identification of a novel opioid, N-piperidinyl etonitazene
(etonitazepipne), in patients with suspected opioid overdose. Clin
Toxicol (Phila). 2022 Sep;60(9):1067-1069.
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Available data and information for N-desethyl isotonitazene and N-
piperidinyl etonitazene, summarized below, indicate that these
substances have high potentials for abuse, no currently accepted
medical uses in treatment in the United States,\17\ and a lack of
accepted safety for use under medical supervision. N-Desethyl
isotonitazene and N-piperidinyl etonitazene have been positively
identified toxicology cases. As the United States continues to
experience a high number of opioid-involved overdoses and mortalities,
the introduction of new designer opioids further exacerbates the
current opioid epidemic Thus, the Administrator concludes that N-
desethyl isotonitazene and N-piperidinyl etonitazene meet the statutory
requirements to be temporarily placed in schedule I under the CSA.
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-1143.
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\17\ When finding that placing a substance in schedule I on a
temporary basis is necessary to avoid imminent hazard to the public,
21 U.S.C. 811(h) does not require DEA to consider whether the
substance has a currently accepted medical use in treatment in the
United States. Nonetheless, there is no evidence suggesting that N-
desethyl isonitazene and etonitazepipne have a currently accepted
medical use in treatment in the United States. To determine whether
a drug or other substance has a currently accepted medical use, DEA
has traditionally applied a five-part test to a drug or substance
that has not been approved by the FDA: i. The drug's chemistry must
be known and reproducible; ii. there must be adequate safety
studies; iii. there must be adequate and well-controlled studies
proving efficacy; iv. the drug must be accepted by qualified
experts; and v. the scientific evidence must be widely available.
See Marijuana Scheduling Petition; Denial of Petition; Remand, 57 FR
10499 (Mar. 26, 1992), pet. for rev. denied, Alliance for Cannabis
Therapeutics v. Drug Enforcement Admin., 15 F.3d 1131, 1135 (D.C.
Cir. 1994). DEA and HHS applied the traditional five-part test for
currently accepted medical use in this matter. In a recent published
letter in a different context, HHS applied an additional two-part
test to determine currently accepted medical use for substances that
do not satisfy the five-part test: (1) whether there exists
widespread, current experience with medical use of the substance by
licensed health care practitioners operating in accordance with
implemented jurisdiction-authorized programs, where medical use is
recognized by entities that regulate the practice of medicine, and,
if so, (2) whether there exists some credible scientific support for
at least one of the medical conditions for which part (1) is
satisfied. On April 11, 2024, the Department of Justice's Office of
Legal Counsel (OLC) issued an opinion, which, among other things,
concluded that the HHS's two-part test would be sufficient to
establish that a drug has a currently accepted medical use. Office
of Legal Counsel, Memorandum for Merrick B. Garland Attorney General
Re: Questions Related to the Potential Rescheduling of Marijuana at
3 (April 11, 2024). For purposes of this temporary scheduling
action, there is no evidence that health care providers have
widespread experience with medical use of N-desethyl isonitazene and
etonitazepipne, or that the use of N-desethyl isonitazene and
etonitazepipne is recognized by entities that regulate the practice
of medicine under either the traditional five-part test or the two-
part test.
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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
structurally unique benzimidazole derivatives with analgesic
properties; however, the research effort did not produce any medically
approved analgesic products. These benzimidazole derivatives include
schedule I substances, such as synthetic opioids clonitazene,
etonitazene, and isotonitazene.
Since 2019, there has been an emergence of nitazene compounds on
the illicit drug market, which have been positively identified in
numerous cases of fatal overdose events. In August 2020, isotonitazene
was placed in schedule I of the CSA (85 FR 51342). Subsequently, seven
additional benzimidazole-opioids \18\ have been placed in schedule I of
the CSA.
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\18\ Butonitazene, etodesnitazene, flunitazene, metodesnitazene,
metonitazene, N-pyrrolidino etonitazene, and protonitazene. See 87
FR 21556 (Apr. 12, 2022).
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Recently, two additional benzimidazole-opioids have emerged on the
illicit drug market. Law enforcement officers have encountered N-
desethyl isotonitazene and N-piperidinyl etonitazene in several solid
forms (e.g., powder and tablets). These substances are not approved
pharmaceutical products and are not approved for medical use anywhere
in the world. The Assistant Secretary in a letter to DEA dated May 11,
2023, stated that there are no FDA-approved NDAs or INDs for N-desethyl
isotonitazene and N-piperidinyl etonitazene in the United States. There
are no legitimate channels for these substances as marketed drug
products.
The appearance of benzimidazole-opioids on the illicit drug market
is similar to other designer opioid drugs that are trafficked for their
psychoactive effects. These substances are likely to be abused in the
same manner as schedule I opioids, such as etonitazene, isotonitazene,
and heroin.
In 2022, N-desethyl isotonitazene was identified in counterfeit
tablets in the United States and United Kingdom. Recent reporting by
Center for Forensic Science Research and Education (CFSRE) indicates
that in the United States, N-desethyl isotonitazene was identified in
counterfeit oxycodone round blue tablets in Florida. Further, in
December 2022, N-desethyl isotonitazene was co-identified in ``dope''
samples containing xylazine, fentanyl, para-fluorofentanyl, and
designer benzodiazepines (e.g., flubromazepam and bromazolam).\19\
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\19\ CFSRE NPS Discovery Public Alert 2023. Case Example--N-
desethyl isotonitazene. January 2023.
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In 2021, N-piperidinyl etonitazene emerged on the illicit synthetic
drug market, as evidenced by its identification in toxicological
analysis of biological samples.\20\ In addition, there have been
encounters of N-piperidinyl etonitazene in Europe. As reported in
January 2022 by the European Monitoring Center for Drugs
[[Page 60820]]
and Drug Addiction (EMCDDA), the European Union Early Warning System
Network identified N-piperidinyl etonitazene in Germany in October
2021. As of January 23, 2023, a total of four European countries have
reported identifications of N-piperidinyl etonitazene in powder form to
the EMCDDA.\21\
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\20\ A partnership between the American College of Medical
Toxicology (ACMT) and the Center for Forensic Science Research and
Education (CFSRE) was established to comprehensively assess the role
and prevalence of synthetic opioids and other drugs among suspected
overdose events in the United States. CFSRE NPS Monograph. N-
Piperidinyl etonitazene. November 22, 2021.
\21\ Email communication with EMCDDA dated January 23, 2023.
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Factor 5. Scope, Duration and Significance of Abuse
N-Desethyl isotonitazene and N-piperidinyl etonitazene, similar to
etonitazene and isotonitazene (schedule I substances), have been
described as potent synthetic opioids, and evidence suggests they are
abused for their opioidergic effects. The abuse of these benzimidazole-
opioids, similar to other synthetic opioids, has resulted in serious
adverse health effects. Between October 2019 and January 2020, N-
desethyl isotonitazene was positively identified as a metabolite of
isotonitazene in 13 postmortem samples and 64 driving-under-the-
influence-of-drugs (DUID) in the United States. However, beginning in
2023, N-desethyl isotonitazene has been identified in 10 toxicology
cases.\22\ The pharmacological profile of N-desethyl isotonitazene
demonstrates it is a highly potent synthetic opioid similar to
etonitazene, isotonitazene, and fentanyl. As such, the identification
of this substance as a parent drug in the recreational drug market is
worrisome.
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\22\ CFSRE NPS Opioids Trend Report, 2023 Q1 and Q2. Accessed
September 15, 2023.
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Data from law enforcement suggest that N-desethyl isotonitazene and
N-piperidinyl etonitazene are being abused in the United States as
recreational drugs.\23\ Since 2022, there have been 14 reports to DEA's
National Forensic Laboratory Information System (NFLIS)-Drug \24\
(Federal, State, and local laboratories) database pertaining to the
trafficking, distribution, and abuse of N-desethyl isotonitazene (n =
5) and N-piperidinyl etonitazene (n = 9). These five encounters of N-
desethyl isotonitazene were reported to NFLIS-Drug from Pennsylvania
(2), Florida (2) and Kansas (1). Encounters of N-piperidinyl
etonitazene occurred in Tennessee (8) and Pennsylvania (1).
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\23\ While law enforcement data are 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).
\24\ NFLIS-Drug 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-
Drug, is currently 98.5 percent. NFLIS-Drug includes drug chemistry
results from completed analyses only. While NFLIS-Drug data is not
direct evidence of abuse, it can lead to an inference that a drug
has been diverted and abused. See Schedules of Controlled
Substances: Placement of Carisoprodol Into Schedule IV, 76 FR 77330,
77332 (Dec. 12, 2011). NFLIS-Drug data was queried on October 2,
2023.
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Based on information collected from NFLIS-Drug, N-desethyl
isotonitazene and N-piperidinyl etonitazene were identified in tablet
form or as residue. Reporting from CFSRE show that N-desethyl
isotonitazene was identified in a counterfeit oxycodone tablet in
Florida,\25\ suggesting that it might be present as a substitute for
heroin or fentanyl and likely abused in the same manner as either of
those substances.
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\25\ CFSRE NPS Discovery Public Alert January 2023. Accessed
January 25, 2023.
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The population likely to be harmed by these benzimidazole-opioids
appears to be the same as that harmed by prescription opioid
analgesics, fentanyl, and other synthetic drugs.\26\ This is evidenced
by the types of other drugs co-identified in biological samples and law
enforcement reports. Law enforcement and toxicology reports demonstrate
that N-desethyl isotonitazene and N-piperidinyl etonitazene are being
illicitly distributed and abused. Because users of N-desethyl
isotonitazene and N-piperidinyl etonitazene are likely to obtain these
substances through unregulated sources, the identity, purity, and
quantity of these substances are uncertain and inconsistent, thus
posing significant adverse health risks to the end user. 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/or death, similar to that of other opioid
analgesics (e.g., fentanyl, morphine, etc.).
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\26\ According to the most recent data from the National Survey
on Drug Use and Health, as of 2022, an estimated 8.9 million people
aged 12 years or older misused opioids in the past year, including
8.5 million prescription pain reliever misusers and 1.0 million
heroin users. This population abusing opioids is likely to be at
risk of abusing N-desethyl isotonitazene and N-piperidinyl
etonitazene.
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Factor 6. What, if Any, Risk There Is to the Public Health
The increase in opioid overdose deaths in the United States has
been exacerbated recently by the availability of potent synthetic
opioids on the illicit drug market. Data obtained from pre-clinical
studies demonstrate that N-desethyl isotonitazene and N-piperidinyl
etonitazene exhibit pharmacological profiles similar to that of
etonitazene, isotonitazene, and other mu-opioid receptor agonists.\27\
These two benzimidazole-opioids bind to and act as an agonist at the
mu-opioid receptors. It is well established that substances that act as
mu-opioid receptor agonists have a high potential for addiction and can
induce dose-dependent respiratory depression.
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\27\ DEA-VA Interagency Agreement. ``In Vitro Receptor and
Transporter Assays for Abuse Liability Testing for the DEA by the
VA''. Binding and Functional Activity at Delta, Kappa and Mu Opioid
Receptors. 2022. Unpublished data.
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Consistent with any mu-opioid receptor agonist, the potential
health and safety risks for users of N-desethyl isotonitazene and N-
piperidinyl etonitazene are high. N-Desethyl isotonitazene and N-
piperidinyl etonitazene have been positively 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.
N-Piperidinyl etonitazene was detected in suspected opioid overdose
cases in three patients from New Jersey over a period of three days in
July 2021. Of those patients, two reported the use of cocaine; one
reported the use of heroin and alprazolam. Similarly, according to a
2021 CFSRE report, N-piperidinyl etonitazene was co-identified with
fentanyl in two cases and para-fluorofentanyl in one other case.\28\
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\28\ NPS Discovery Program at the Center for Forensic Science
Research and Education: Monograph. N-Piperidinyl etonitazene
Toxicology Analytical Report. November 22, 2021.
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The pharmacological profile of this substance demonstrates that it
is a highly potent synthetic opioid similar to etonitazene,
isotonitazene, and fentanyl. As such, the identification of this
substance as a parent drug in the recreational drug market is
worrisome.
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 N-desethyl
isotonitazene and N-piperidinyl etonitazene 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.
[[Page 60821]]
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 N-
desethyl isotonitazene and N-piperidinyl etonitazene indicate that
these substances meet the three statutory criteria.
As required by 21 U.S.C. 811(h)(4), the Administrator transmitted
to the Assistant Secretary, via letter dated April 3, 2023, notice of
her intent to place N-desethyl isotonitazene and N-piperidinyl
etonitazene in schedule I on a temporary basis. HHS had no objection to
the temporary placement of these substances in schedule I. DEA
subsequently published a NOI in the Federal Register on October 25,
2023.\29\
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\29\ Schedules of Controlled Substances: Temporary Placement of
N-Desethyl Isotonitazene and N-Piperidinyl Etionitazene in Schedule
I, 88 FR 73293 (Oct. 25, 2023).
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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 schedule N-
desethyl isotonitazene and N-piperidinyl etonitazene 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.
This temporary placement of N-desethyl isotonitazene and N-
piperidinyl etonitazene in schedule I of the CSA will take effect 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.\30\
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\30\ 21 U.S.C. 811(h)(1) and (2).
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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.\31\ The regular scheduling process of formal
rulemaking affords interested parties appropriate process and the
government 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.\32\
Temporary scheduling orders are not subject to judicial review.\33\
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\31\ 21 U.S.C. 811.
\32\ 21 U.S.C. 877.
\33\ 21 U.S.C. 811(h)(6).
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Requirements for Handling
Upon the effective date of this temporary order, N-desethyl
isotonitazene and N-piperidinyl etonitazene will be subject to the
regulatory controls and administrative, civil, and criminal sanctions
applicable to the manufacture, distribution, reverse distribution,
importation, exportation, 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, N-desethyl isotonitazene or N-piperidinyl
etonitazene 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 July 29, 2024. Any person who thereafter
handles N-desethyl isotonitazene or N-piperidinyl etonitazene and is
not registered with DEA must submit an application for registration and
may not continue to handle N-desethyl isotonitazene and N-piperidinyl
etonitazene as of July 29, 2024, 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 July 29, 2024 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 N-desethyl isotonitazene
or N-piperidinyl etonitazene must surrender all currently held
quantities of these substances.
3. Security. N-Desethyl isotonitazene and N-piperidinyl etonitazene
are subject to schedule I security requirements and must be handled in
accordance with 21 CFR 1301.71-1301.93, as of July 29, 2024.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of N-desethyl isotonitazene and N-piperidinyl
etonitazene 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 July 29,
2024 to comply with all labeling and packaging requirements.
5. Inventory. Every DEA registrant who possesses any quantity of N-
desethyl isotonitazene or N-piperidinyl etonitazene 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 N-desethyl isotonitazene and N-piperidinyl etonitazene) 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 N-desethyl isotonitazene and N-piperidinyl etonitazene pursuant to
21 U.S.C. 827 and 958(e) and in accordance with 21 CFR parts 1304,
1312, and 1317, and section 1307.11. Current DEA registrants authorized
to handle these two 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
N-desethyl isotonitazene and N-piperidinyl etonitazene 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 July 29, 2024.
Manufacturers and distributors must also submit reports regarding these
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 N-desethyl
isotonitazene or N-piperidinyl etonitazene must comply with order form
requirements pursuant to 21 U.S.C. 828 and in accordance with 21 CFR
part 1305 as of July 29, 2024.
9. Importation and Exportation. All importation and exportation of
N-desethyl isotonitazene and N-piperidinyl etonitazene must be in
compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance
with 21 CFR part 1312 as of July 29, 2024.
10. Quota. Only DEA-registered manufacturers may manufacture N-
desethyl isotonitazene and N-piperidinyl etonitazene in accordance
[[Page 60822]]
with a quota assigned pursuant to 21 U.S.C. 826 and in accordance with
21 CFR part 1303, as of July 29, 2024.
11. Liability. Any activity involving N-desethyl isotonitazene or
N-piperidinyl etonitazene not authorized by or in violation of the CSA,
occurring as of July 29, 2024, 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 an imminent hazard to the public safety. Under 21
U.S.C. 811(h)(1), 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, as
delegated by the Secretary of HHS.\34\
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\34\ 21 U.S.C. 811(h)(1).
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Inasmuch as section 811(h) directs that temporary scheduling
actions be issued by order (as distinct from a rule) and sets forth the
procedures by which such orders are to be issued, DEA believes the
notice-and-comment requirements of section 553 of the Administrative
Procedure Act (APA), 5 U.S.C. 553, which are applicable to rulemaking,
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). This contrasts with
permanent scheduling actions, which are subject to formal rulemaking
procedures done ``on the record after opportunity for a hearing,'' and
final decisions that conclude the scheduling process and are subject to
judicial review. 21 U.S.C. 811(a) and 877. 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)(1), Congress authorized the issuance of temporary
scheduling actions by order rather than by rule.
Assuming for the sake of argument that this action 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 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. Therefore, in this instance,
since DEA believes this temporary scheduling action is not a ``rule,''
it is not subject to the requirements of the Regulatory Flexibility Act
when issuing this temporary action.
In accordance with the principles of Executive Orders (E.O.) 12866,
13563, and 14094, 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, sec. 3(f),
as amended by E.O. 14094, sec. 1(b), provides the definition of a
``significant regulatory action,'' requiring review by the Office of
Management and Budget. 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, it is
determined that this action does not have sufficient federalism
implications to warrant the preparation of a Federalism Assessment.
Signing Authority
This document of the Drug Enforcement Administration was signed on
July 16, 2024, by Administrator Anne Milgram. That document with the
original signature and date is maintained by DEA. For administrative
purposes only, and in compliance with requirements of the Office of the
Federal Register, the undersigned DEA Federal Register Liaison Officer
has been authorized to sign and submit the document in electronic
format for publication, as an official document of DEA. This
administrative process in no way alters the legal effect of this
document upon publication in the Federal Register.
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, DEA amends 21 CFR part 1308 as
follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for part 1308 continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. In Sec. 1308.11, add paragraphs (h)(68) and (69) to read as
follows:
Sec. 1308.11 Schedule I
* * * * *
(h) * * *
[[Page 60823]]
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* * * * * * *
(68) N-ethyl-2-(2-(4-isopropoxybenzyl)-5-nitro-1H- 9760
benzimidazol-1-yl)ethan-1-amine, its isomers, esters,
ethers, salts, and salts of isomers, esters and ethers
(Other name: N-desethyl isotonitazene).................
(69) 2-(4-ethoxybenzyl)-5-nitro-1-(2-(piperidin-1- 9761
yl)ethyl)-1H-benzimidazole, its isomers, esters,
ethers, salts, and salts of isomers, esters and ethers
(Other names: N-piperidinyl etonitazene;
etonitazepipne)........................................
* * * * * * *
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* * * * *
[FR Doc. 2024-16391 Filed 7-26-24; 8:45 am]
BILLING CODE 4410-09-P