[Federal Register Volume 88, Number 142 (Wednesday, July 26, 2023)]
[Rules and Regulations]
[Pages 48112-48118]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-15748]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-989]
Schedules of Controlled Substances: Temporary Placement of
Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam 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 five synthetic benzodiazepine
substances: etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam, in schedule I of the Controlled Substances Act. This action
is based on a finding by the Administrator that the placement of these
five 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
[[Page 48113]]
analysis with, or possess) or propose to handle these five specified
controlled substances.
DATES: This temporary scheduling order is effective July 26, 2023,
until July 26, 2025. 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 five substances, including their salts,
isomers, and salts of isomers, whenever the existence of such salts,
isomers, and salts of isomers is possible, to schedule I under the
Controlled Substances Act (CSA):
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\1\ Though DEA has used the term ``final order'' with respect to
temporary scheduling orders in the past, this order adheres to the
statutory language of 21 U.S.C. 811(h), which refers to a
``temporary scheduling order.'' No substantive change is intended.
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4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-
f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as etizolam),
8-chloro-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as
flualprazolam),
6-(2-chlorophenyl)-1-methyl-8-nitro-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (commonly known as
clonazolam),
8-bromo-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine (alternate chemical name:
8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-
a][1,4]benzodiazepine and commonly known as, flubromazolam), and
7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-
benzo[e][1,4]diazepin-2-one (commonly known as diclazepam).
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 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 Administrator
transmitted the required notice to the Assistant Secretary for Health
of HHS (Assistant Secretary),\2\ by letter dated October 27, 2021,
regarding etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam. The Assistant Secretary responded to this notice by letter
dated January 3, 2022, 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 (NDA)
for etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam.
The Assistant Secretary also stated that HHS had no objection to the
temporary placement of these substances in schedule I.
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\2\ The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. 58 FR 35460, July 1, 1993.
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DEA has taken into consideration the Assistant Secretary's comments
as required by subsection 811(h)(4). DEA has found that the control of
these five benzodiazepines in schedule I on a temporary basis is
necessary to avoid an imminent hazard to the public safety. Etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam 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 five
benzodiazepine substances.
As required by 21 U.S.C. 811(h)(1)(A), DEA published a notice of
intent (NOI) to temporarily schedule etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam on December 23, 2022. 87 FR
78887. That NOI discussed findings from DEA's three-factor analysis
dated October 2022, 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, risk
there is to the public health. 21 U.S.C. 811(h)(3). Consideration of
these factors 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 are those that 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. 21
U.S.C. 812(b)(1).
DEA's October 2022 three-factor analysis and the Assistant
Secretary's January 3, 2022 letter are available in their entirety
under the tab ``Supporting Documents'' of the public docket of this
action at www.regulations.gov.
Five Benzodiazepine Substances: Etizolam, Flualprazolam, Clonazolam,
Flubromazolam, and Diclazepam
The dramatic increase in trafficking and abuse associated with
novel psychoactive substances (NPS) of the benzodiazepine class, also
known as designer benzodiazepines, in the United States has become a
national public health concern in recent years. The availability of NPS
benzodiazepine substances in the illicit drug market continues to pose
an imminent hazard to the public safety. The Centers for Disease
Control and Prevention (CDC) highlights this issue in their Morbidity
and Mortality Weekly Report (MMWR) published on August 27, 2021.\3\ CDC
indicated that from April 2019 to June 2020 prescription and illicit
benzodiazepine-involved overdose deaths increased by 21.8 percent and
519.6 percent respectively. Additionally, benzodiazepines were involved
in nearly 7,000 overdose
[[Page 48114]]
deaths in 23 states from January 2019 to June 2020, accounting for 17
percent of all drug overdose deaths. Adverse health effects associated
with the abuse of such substances, their continued evolution, and
increased popularity of these substances have been a serious concern in
recent years.
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\3\ Centers for Disease Control and Prevention Morbidity and
Mortality Weekly Report: Trends in Nonfatal and Fatal Overdoses
Involving Benzodiazepines--38 States and the District of Columbia,
2019-2020. Vol. 70, No. 34. August 27, 2021.
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The increase in the co-use of opioids with designer benzodiazepines
has become a particular concern as the United States continues to
experience an unprecedented epidemic of opioid misuse and abuse.\4\
CDC's 2021 MMWR further states that between January and June 2020, 92.7
percent of benzodiazepine-involved deaths also involved opioids and
66.7 percent involved illicitly manufactured fentanyl. The combination
of benzodiazepines with opioids substantially enhances the potential
for lethality. Etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam are benzodiazepine substances recently identified on the
illicit drug market in the United States.
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\4\ Centers for Disease Control and Prevention Morbidity and
Mortality Weekly Report: Trends in Nonfatal and Fatal Overdoses
Involving Benzodiazepines--38 States and the District of Columbia,
2019-2020. Vol. 70, No. 34. August 27, 2021.
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The abuse of etizolam, flualprazolam, clonazolam, flubromazolam,
and diclazepam has been associated with fatalities in recent years in
the United States. The positive identification of these five substances
in post-mortem cases is a serious concern to the public safety.
Additionally, law enforcement data indicate that the substances at
issue here have significant presence in the illicit drug market found
in the United States. In light of the law enforcement encounters and
fatalities associated with the abuse of etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam, these substances pose an
imminent hazard to public safety.
Available data and information for etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam, summarized below, indicate
that these substances have high potential for abuse, no currently
accepted medical use in treatment in the United States, and lack of
accepted safety for use under medical supervision. DEA's three-factor
analysis is available in its entirety under ``Supporting and Related
Material'' of the public docket for this action at www.regulations.gov
under Docket Number DEA-989.
Factor 4. History and Current Pattern of Abuse
The chemical synthesis of etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam was previously reported in the scientific
literature; however, the research did not lead to any medically
approved products in the United States. Since 2012, synthetic drugs
belonging to the benzodiazepine class have begun to emerge in the
illicit drug market as evidenced by the identification of these drugs
in forensic drug exhibits reported to the National Forensic Laboratory
Information System (NFLIS-Drug) \5\ and toxicology samples. Beginning
in 2012, etizolam emerged on the illicit synthetic drug market as
evidenced by its identification in drug seizures in the United States.
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\5\ 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 more than 96 percent of an estimated 1.0
million distinct annual state and local drug analysis cases. 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 76 FR
77330, 77332, Dec. 12, 2011.
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In recent years, there has been a rise in the recreational use of
etizolam. As evidenced by their identification in NFLIS-Drug,
diclazepam emerged in the United States' illicit drug market in 2014,
flubromazolam and clonazolam in 2015, and flualprazolam in 2017. While
these substances are not approved for medical use in the United States,
etizolam is approved for medical use in Italy, India, and Japan.\6\ In
a letter dated January 3, 2022, the Assistant Secretary informed DEA
that there are no INDs or FDA-approved NDAs for etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam in the United
States. Hence, there are no legitimate channels for these substances as
marketed drug products in the United States. These five benzodiazepine
substances are likely to be abused in the same manner as other sedative
hypnotics. They have been identified in tablet form, as white to beige
powders, or in liquid forms, typically of unknown purity or
concentration.
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\6\ Although there is no evidence suggesting that etizolam,
flualprazolam, clonazolam, flubromazolam, or diclazepam has a
currently accepted medical use in treatment in the United States, it
bears noting that a drug cannot be found to have such medical use
unless DEA concludes that it satisfies a five-part test.
Specifically, with respect to a drug that has not been approved by
FDA, to have a currently accepted medical use in treatment in the
United States, all of the following must be demonstrated: 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. 57 FR 10499 (1992), pet. for rev. denied, Alliance for
Cannabis Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
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Based on data from NFLIS-Drug, law enforcement often encounters
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam in
counterfeit pills, liquid, or powder form. Substances often found in
combination with some of these benzodiazepines include substances of
abuse such as heroin (schedule I), fentanyl (schedule II), substances
structurally related to fentanyl, other benzodiazepines (both FDA-
approved schedule IV benzodiazepines and other novel non-controlled
benzodiazepines), and tramadol (schedule IV). Evidence suggests that
individuals are using these substances to obtain ``legal highs'' \7\ or
to self-medicate. Information gathered from case histories and autopsy
findings shows that deaths involving etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam were predominantly associated
with poly-drug use.
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\7\ Substances used as ``legal highs'' are psychoactive
substances that are not controlled under the CSA, but can be used to
obtain a desired psychoactive effect.
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Factor 5. Scope, Duration, and Significance of Abuse
Etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
are novel benzodiazepines and evidence suggests they are abused for
their sedative effects (see Factor 6). In death investigations
involving polysubstance use, the co-appearance of benzodiazepines and
opioids in toxicological analysis was common. Between August 2019 and
January 2020, flualprazolam and etizolam were identified in seven and
six postmortem blood specimens, respectively, out of 18 deaths
associated with the abuse of isotonitazene, a schedule I opioid that
was recently controlled.\8\ These cases corresponded to four states--
Illinois (9), Indiana (7), Minnesota (1), and Wisconsin (1). Most (12)
of the decedents were male. The ages ranged from 24 to 66 years old
with an average age of 41 years.\9\
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\8\ 85 FR 51342 and 86 FR 60761.
\9\ Krotulski AJ, Papsun DM, Kacinko SL, and Logan BK.
Isotonitazene Quantitation and Metabolite Discovery in Authentic
Forensic Casework. Journal of Analytical Toxicology, 2020,
44(6):521-530.
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In another recent publication, 20 forensic postmortem cases were
reviewed and analyzed for the presence of metonitazine, NPS
benzodiazepines, and opioids. Clonazolam was positively identified in
four cases, etizolam in two cases, flualprazolam in two cases, and
[[Page 48115]]
pyrazolam in one case.\10\ Law enforcement encounters of etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam as reported to
NFLIS-Drug include 34,781 drug reports since 2014 (queried 01/13/2022).
NFLIS-Drug registered three encounters of etizolam in 2012 (first year
of encounter) and 3,022 reports in 2021. Flualprazolam was first
encountered in 2017 when one report was identified in NFLIS-Drug, and
then in 2021, 1,305 encounters were reported. A similar trend was seen
with clonazolam. During 2015 (its first year of encounter), 57 cases
were reported in NFLIS-Drug, while 3,994 drug reports were identified
in 2021. NFLIS-Drug registered five diclazepam encounters in 2014 (its
first year of encounter) and 54 encounters in 2021. Flubromazolam
encounters totaled 14 in 2015 (its first year of encounter) and 414 in
2021.
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\10\ Krotulski AJ, Papsun DM, Walton SE, and Logan BK.
Metonitazene in the United States-Forensic toxicology assessment of
a potent new synthetic opioid using liquid chromatography mass
spectrometry. Drug Testing Analysis, 2021, 13(10):1697-1711.
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The population likely to abuse etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam appears to be the same as those abusing
prescription benzodiazepines, barbiturates, and other sedative hypnotic
substances. This is evidenced by drug user reports associated with
these substances. Because abusers of etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam 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.
The misuse and abuse of benzodiazepines have been demonstrated and
are well-characterized.\11\ According to the most recent data from the
National Survey on Drug Use and Health (NSDUH),\12\ as of 2020, an
estimated 4.8 million people aged 12 years or older misused
prescription benzodiazepines in the past year. This included 1.1
million young adults aged 18 to 25, 3.5 million adults aged 26 or
older, and 157,000 adolescents aged 12 to 17. This population abusing
prescription benzodiazepines is likely to be at risk of abusing
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam.
Individuals who initiate use of these five substances (i.e., use a drug
for the first time) are likely to be at risk of developing substance
use disorder, overdose, and death at rates similar to that of other
sedative hypnotics (e.g., alprazolam, etc.). Law enforcement or
toxicology reports demonstrate that the five substances at issue are
being distributed and abused.
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\11\ Votaw VR, Geyer R, Rieselbach MM, and McHugh RK. The
epidemiology of benzodiazepine misuse: A systematic review. Drug
Alcohol Dependence, 2019, 200:95-114.
\12\ The National Survey on Drug Use and Health (NSDUH),
formerly known as the National Household Survey on Drug Abuse
(NHSDA), is conducted annually by the Department of Health and Human
Services Substance Abuse and Mental Health Services Administration
(SAMHSA). It is the primary source of estimates of the prevalence
and incidence of 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 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 2020 NSDUH annual report is available at https://www.samhsa.gov/data/ (last accessed February 8, 2022).
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Factor 6. What, if Any, Risk There Is to the Public Health
The increase in benzodiazepine-related overdose deaths in the
United States has been exacerbated recently by the availability of NPS
benzodiazepines in the illicit drug market. Etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam have been described as
derivatives of other known benzodiazepines, each possessing various
degrees of potency. Evidence suggests these substances are being abused
for their sedative/hypnotic effects (see DEA 3-Factor Analysis). Public
health risks associated with the five substances at issue here relate
to their pharmacological similarities with known benzodiazepines. Thus,
risk to the public health is associated with adverse reactions in
humans, which are expected to include CNS depressant-like effects, such
as slurred speech, ataxia, altered mental state, and respiratory
depression.
Etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
have been increasingly identified in toxicology reports, death
investigations, and driving under the influence of drugs (DUID) cases
since their first appearance in law enforcement seizures. According to
the Center for Forensic Science Research and Education (CFSRE), a non-
profit organization in collaboration with the Department of Justice and
CDC between 2020 and 2021, etizolam was the most identified NPS
benzodiazepine accounting for 697 total toxicology cases in 2020, many
of which were co-identified with fentanyl. In 2021, etizolam was
identified in 1,012 toxicology cases, while flualprazolam, clonazolam,
flubromazolam, and diclazepam were associated with 432, 331, 170, and
four toxicology cases, respectively (CSFRE Quarterly Trend Reports: NPS
Benzodiazepines in the United States).
Death investigations associated with four of the five NPS
benzodiazepines at issue here have increased in recent years. In a 2021
publication by the Orange County Crime Lab in Santa Ana, California,
flualprazolam was identified as serving a contributory role in the
death of 13 of 24 cases analyzed in the study.\13\ In another recently
published study, between August 2019 and January 2020, flualprazolam
and etizolam were identified in seven and six postmortem blood
specimens respectively, out of 18 deaths associated with the abuse of
isotonitazene, a schedule I opioid.\14\ Then, a study published in 2021
which compiled data from 254 reports published between 2008 and 2021,
identified: 33 deaths associated with etizolam, 20 flualprazolam-
related deaths, six emergency department (ED) visits associated with
clonazolam, 14 flubromazolam-related ED visits, and one death, 12 DUID
cases, and four ED visits associated with diclazepam.\15\ Additionally,
in 2020, the European Monitoring Centre for Drugs and Drug Addiction
reported 34 deaths associated with diclazepam use, which were
determined through the analysis of biological samples.\16\ Furthermore,
the National Poison Data System reported that between January 2014 and
December 2017, clonazolam was the second most common benzodiazepine
associated with poison control center calls, accounting for 50
incidents.\17\
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\13\ Ha HH and Mata DC. Flualprazolam distribution in postmortem
samples. Journal of Forensic Sciences, 2022, 67(1): 297-308.
\14\ Krotulski AJ, Papsun DM, Kacinko SL, and Logan BK.
Isotonitazene Quantitation and Metabolite Discovery in Authentic
Forensic Casework. Journal of Analytical Toxicology, 2020, 44(6):
521-530.
\15\ Brunetti P, Giorgetti R, Tagliabracci A, Huestis MA,
Busard[ograve] FP. Designer Benzodiazepines: A Review of Toxicology
and Public Health Risks. Pharmaceuticals (Basel). 2021 Jun
11;14(6):560.
\16\ EMCDDA (2020). EMCDDA response to WHO request for
information on the new psychoactive substances, eutylone, [alpha]-
PHiP, 4F-furanylfentanyl, 2-methyl-AP-237, and, diclazepam.
\17\ Carpenter JE, Murray BP, Dunkley C, Kazzi ZN, Gittinger MH.
Designer benzodiazepines: a report of exposures recorded in the
National Poison Data System, 2014-2017. Clin Toxicol (Phila). 2019
Apr;57(4):282-286.
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Impaired driving is another risk factor associated with the use and
abuse of etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam. In a recent published report from the
[[Page 48116]]
Sedgwick County Regional Forensic Science Center in Wichita, Kansas, 12
DUID case samples were analyzed. Etizolam was positively identified in
three cases, while flubromazolam was identified in nine of these
cases.\18\ In a 2021 publication, similar involvement of flubromazolam
in drug-impaired driving was reported in Canada where flubromazolam was
detected in 10 percent of 113 case samples.\19\ Diclazepam has also
been implicated in DUID cases domestically and internationally. In a
Norwegian study conducted between July 2013 and May 2016, diclazepam
was identified in 15 of 77 analyzed samples taken from impaired drivers
and individuals involved in other criminal offenses. Then, in 2019, a
study of Norwegian drivers was conducted using 575 samples taken
predominantly from intoxicated drivers and individuals who committed
other criminal offenses.\20\ Notably, 334 samples were found to contain
diclazepam. Additionally, in a 2021 publication from Orange County
Crime Laboratory in Santa Ana, California, researchers identified 22
samples that tested positive for flualprazolam in samples obtained from
DUID investigations between August 2018 and September 2020.\21\
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\18\ Rohrig TP, Osawa KA, Baird TR, Youso KB. Driving Impairment
Cases Involving Etizolam and Flubromazolam. J Anal Toxicol. 2021 Feb
6;45(1):93-98.
\19\ Vaillancourt L, Viel E, Dombrowski C, Desharnais B,
Mireault P. Drugs and driving prior to cannabis legalization: A 5-
year review from DECP (DRE) cases in the province of Quebec, Canada.
Accid Anal Prev. 2021 Jan;149:105832.
\20\ Heide G, H[oslash]iseth G, Middelkoop G, and [Oslash]iestad
[Aring]ML. Blood concentrations of designer benzodiazepines:
Relation to impairment and findings in forensic cases. Journal of
Analytical Toxicology, 2020, 44(8): 905-914.
\21\ Ha HH and Mata DC. Flualprazolam distribution in postmortem
samples. Journal of Forensic Sciences, 2022, 67(1): 297-308.
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Finding of Necessity of Schedule I Placement To Avoid Imminent Hazard
to Public Safety
In accordance with 21 U.S.C. 811(h)(3), based on the available data
and information summarized above, the uncontrolled manufacture,
distribution, reverse distribution, importation, exportation, conduct
of research and chemical analysis, possession, and/or abuse of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam 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,
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 etizolam, flualprazolam, clonazolam, flubromazolam, and
diclazepam indicate that these five synthetic benzodiazepine substances
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.
As required by 21 U.S.C. 811(h)(4), the Administrator transmitted
to the Assistant Secretary for Health, via a letter dated October 27
2021, notice of her intent to place etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam 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 on December 23, 2022. 87 FR 78887.
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
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam 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. Permanent 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 permanent scheduling
process of formal rulemaking affords interested parties with an
appropriate process and the government any additional relevant
information needed to make determinations. Final decisions that
conclude the permanent 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, etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam 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, etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam 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 26, 2023. Any
person who currently handles etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam and is not registered with DEA must
submit an application for registration and may not continue to handle
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam as
of July 26, 2023, 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 26, 2023 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 etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam must surrender all currently
held quantities of these five substances.
3. Security. Etizolam, flualprazolam, clonazolam, flubromazolam,
and diclazepam are subject to schedule I security requirements and must
be handled in accordance with 21 CFR 1301.71-1301.93, as of July 26,
2023.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of etizolam, flualprazolam,
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clonazolam, flubromazolam, and diclazepam 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 26, 2023 to comply with all labeling and
packaging requirements.
5. Inventory. Every DEA registrant who possesses any quantity of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam 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 etizolam, flualprazolam, clonazolam,
flubromazolam, and diclazepam) 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 etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
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 five 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
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam
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 26,
2023. Manufacturers and distributors must also submit reports regarding
these five 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 etizolam,
flualprazolam, clonazolam, flubromazolam, and diclazepam must comply
with order form requirements pursuant to 21 U.S.C. 828 and in
accordance with 21 CFR part 1305 as of July 26, 2023.
9. Importation and Exportation. All importation and exportation of
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam 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 26, 2023.
10. Quota. Only DEA-registered manufacturers may manufacture
etizolam, flualprazolam, clonazolam, flubromazolam, and diclazepam in
accordance with a quota assigned pursuant to 21 U.S.C. 826 and in
accordance with 21 CFR part 1303, as of July 26, 2023.
11. Liability. Any activity involving etizolam, flualprazolam,
clonazolam, flubromazolam, and diclazepam not authorized by or in
violation of the CSA, occurring as of July 26, 2023, 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 schedule 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 (as distinct from a rule) 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, 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). 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 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, 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
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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.
Signing Authority
This document of the Drug Enforcement Administration was signed on
July 18, 2023, 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.
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)(57) through (h)(61) to read as
follows:
Sec. 1308.11 Schedule I.
* * * * *
(h) * * *
(57) 4-(2-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-
f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and salts
of isomers (Other name: etizolam) 2780
(58) 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: flualprazolam) 2785
(59) 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: clonazolam) 2786
(60) 8-bromo-6-(2-fluorophenyl)-1-methyl-4H-
benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine, its salts, isomers, and
salts of isomers (Other name: flubromazolam) 2788
(61) 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-
benzo[e][1,4]diazepin-2-one, its salts, isomers, and salts of isomers
(Other name: diclazepam) 2789
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2023-15748 Filed 7-25-23; 8:45 am]
BILLING CODE 4410-09-P