Schedules of Controlled Substances: Temporary Placement of Brorphine in Schedule I, 11862-11867 [2021-04242]
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Federal Register / Vol. 86, No. 38 / Monday, March 1, 2021 / Rules and Regulations
impact is so minimal. Since this is a
routine matter that will only affect air
traffic procedures and air navigation, it
is certified that this rule, when
promulgated, would not have a
significant economic impact on a
substantial number of small entities
under the criteria of the Regulatory
Flexibility Act.
Environmental Review
The FAA has determined that this
action qualifies for categorical exclusion
under the National Environmental
Policy Act in accordance with FAA
Order 1050.1F, ‘‘Environmental
Impacts: Policies and Procedures,’’
paragraph 5–6.5a. This airspace action
is not expected to cause any potentially
significant environmental impacts, and
no extraordinary circumstances exist
that warrant preparation of an
environmental assessment.
List of Subjects in 14 CFR Part 71
Airspace, Incorporation by reference,
Navigation (air).
Adoption of the Amendment
In consideration of the foregoing, the
Federal Aviation Administration
amends 14 CFR part 71 as follows:
PART 71—DESIGNATION OF CLASS A,
B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND
REPORTING POINTS
1. The authority citation for 14 CFR
part 71 continues to read as follows:
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AWP CA E5 Palmdale, CA [Amended]
Palmdale USAF Plant 42 Airport, CA
(Lat. 34°37′46″ N, long. 118°05′04″ W)
That airspace extending upward from 700
feet above the surface within a 6.8-mile
radius of the airport, and within 6.1 miles
each side of the 080° bearing from the airport,
extending from the 6.8-mile radius to 12.9
miles east of the airport, and within 4 miles
north and 8 miles south of the 086° bearing
from the airport, extending from the airport
to 14.3 miles east of the airport, and within
2 miles each side of the 274° bearing from the
airport, extending from the 6.8-mile radius to
13.4 miles west of Palmdale USAF Plant 42
Airport.
Issued in Seattle, Washington, on February
16, 2021.
B.G. Chew,
Acting Group Manager, Operations Support
Group, Western Service Center.
BILLING CODE 4910–13–P
DEPARTMENT OF JUSTICE
[Amended]
Drug Enforcement Administration
2. The incorporation by reference in
14 CFR 71.1 of FAA Order 7400.11E,
Airspace Designations and Reporting
Points, dated July 21, 2020, and
effective September 15, 2020, is
amended as follows:
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Paragraph 5000
Class D Airspace.
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21 CFR Part 1308
[Docket No. DEA–716]
Schedules of Controlled Substances:
Temporary Placement of Brorphine in
Schedule I
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AWP CA D Palmdale, CA [Amended]
Palmdale USAF Plant 42 Airport, CA
(Lat. 34°37′46″ N, long. 118°05′04″ W)
That airspace extending upward from the
surface to and including 5,000 feet MSL
within a 4.3-mile radius of Palmdale USAF
Plant 42 Airport. This Class D airspace area
is effective during the specific dates and
times established, in advance, by a Notice to
Airmen. The effective date and time will
thereafter be continuously published in the
Chart Supplement.
Paragraph 6004 Class E Airspace Areas
Designated as an Extension to a Class D or
Class E Surface Area.
*
Paragraph 6005 Class E Airspace Areas
Extending Upward From 700 Feet or More
Above the Surface of the Earth.
[FR Doc. 2021–03904 Filed 2–26–21; 8:45 am]
Authority: 49 U.S.C. 106(f), 106(g), 40103,
40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR,
1959–1963 Comp., p. 389.
§ 71.1
AWP CA E4 Palmdale, CA [Amended]
Palmdale USAF Plant 42 Airport, CA
(Lat. 34°37′46″ N, long. 118°05′04″ W)
That airspace extending upward from the
surface within 1 mile each side of the 270°
bearing from the airport, extending from the
4.3-mile radius to 7.5 miles west of Palmdale
USAF Plant 42 Airport. This Class E airspace
area is effective during the specific dates and
times established, in advance, by a Notice to
Airmen. The effective date and time will
thereafter be continuously published in the
Chart Supplement.
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Drug Enforcement
Administration, Department of Justice.
ACTION: Temporary amendment;
temporary scheduling order.
AGENCY:
The Acting Administrator of
the Drug Enforcement Administration is
issuing this temporary order to schedule
1-(1-(1-(4-bromophenyl)ethyl)piperidin4-yl)-1,3-dihydro-2H-benzo[d]imidazol2-one (commonly known as brorphine),
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 of the Controlled
SUMMARY:
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Substances Act . This action is based on
a finding by the Acting Administrator
that the placement of brorphine 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 brorphine.
DATES: This temporary scheduling order
is effective March 1, 2021, until March
1, 2023. If this order is extended or
made permanent, DEA will publish a
document in the Federal Register.
FOR FURTHER INFORMATION CONTACT:
Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control
Division, Drug Enforcement
Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia
22152; Telephone: (571) 362–3249.
SUPPLEMENTARY INFORMATION:
Legal Authority
The Controlled Substances Act (CSA)
provides the Attorney General (as
delegated to the Administrator of Drug
Enforcement Administrator (DEA)
pursuant to 28 CFR 0.100) with the
authority to temporarily place a
substance in schedule I of the CSA for
two years without regard to the
requirements of 21 U.S.C. 811(b), if he
finds that such action is necessary to
avoid an imminent hazard to the public
safety. 21 U.S.C. 811(h)(1). In addition,
if proceedings to control a substance are
initiated under 21 U.S.C. 811(a)(1) while
the substance is temporarily controlled 1
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, or if there
is no exemption or approval in effect for
the substance under section 505 of the
Federal Food, Drug, and Cosmetic Act,
21 U.S.C. 355. 21 U.S.C. 811(h)(1); 21
CFR part 1308.
Background
The CSA requires the Administrator
to notify the Secretary of the
1 Though 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.
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Department of Health and Human
Services (HHS) of his intention to
temporarily place a substance in
schedule I.2 21 U.S.C. 811(h)(4). The
Acting Administrator transmitted such
notice regarding brorphine to the
Assistant Secretary for Health of HHS
(Assistant Secretary) by letter dated
September 22, 2020. The Assistant
Secretary responded to this notice by
letter dated October 27, 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 brorphine. The Assistant Secretary
also stated that HHS had no objection to
the temporary placement of brorphine
in schedule I of the CSA.
DEA has taken into consideration the
Assistant Secretary’s comments as
required by subsection 811(h)(4).
Brorphine is not currently listed in any
schedule under the CSA, and no
exemptions or approvals are in effect for
brorphine under 21 U.S.C. 355. DEA has
found that the control of brorphine 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 brorphine on
December 3, 2020. 85 FR 78047. That
notice of intent discussed findings from
DEA’s three-factor analysis dated
August 2020, which DEA made
available on www.regulations.gov.
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 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).
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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Available data and information for
brorphine 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 August
2020 three-factor analysis and the
Assistant Secretary’s October 27, 2020,
letter are available in their entirety
under the tab ‘‘Supporting Documents’’
of the public docket of this action at
www.regulations.gov.
Brorphine
The availability of synthetic opioids
on 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 increased popularity of these
substances have posed serious health
concerns in recent years. The presence
of new synthetic opioids with no
approved medical use exacerbates the
unprecedented opioid epidemic in the
United States continues to experience.
The trafficking and abuse of new
synthetic opioids are deadly new trends.
The identification of brorphine on the
illicit drug market has been reported in
the United States, Canada, Belgium, and
Sweden. Data obtained from preclinical
pharmacology studies show that
brorphine has a pharmacological profile
similar to that of other potent opioids
such as morphine and fentanyl,
schedule II controlled substances.
Because of the pharmacological
similarities between brorphine and
other potent opioids, the use of
brorphine presents a high risk of abuse
and may negatively affect users and
their communities. The positive
identification of this substance in law
enforcement seizures and post-mortem
toxicology reports is a serious concern
to the public safety. The abuse of
brorphine has been associated with at
least seven fatalities between June and
July 2020 in the United States. Thus,
brorphine poses an imminent hazard to
public safety.
Available data and information for
brorphine, 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–716.
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Factor 4. History and Current Pattern of
Abuse
Brorphine is part of a structural class
of compounds known as substituted
piperidine benzimidazolones. The
general synthesis of brorphine was first
reported in the literature in 2018.
Brorphine is not an approved
pharmaceutical product and is not
approved for medical use anywhere in
the world. The Assistant Secretary, by a
letter to DEA dated October 27, 2020,
stated that there are no FDA-approved
NDAs or INDs for brorphine in the
United States. Hence, DEA notes there
is no legitimate channel for brorphine as
a marketed drug product. The
appearance of brorphine on the illicit
drug market is similar to other designer
drugs trafficked for their psychoactive
effects.
Since 2014, numerous synthetic
opioids structurally related to fentanyl
and several synthetic opioids from other
structural classes have begun to emerge
on the illicit drug market as evidenced
by the identification of these drugs in
forensic drug exhibits and toxicology
samples. Beginning in June 2019,
brorphine emerged in the United States
illicit, synthetic drug market as
evidenced by brorphine’s identification
in drug seizures. Authorities Between
July and September 2019, brorphine was
first reported in drug casework in
Canada and was first reported in police
seizures in Sweden in March 2020.3
Brorphine has been encountered by
United States law enforcement in
powder form. In the United States,
brorphine has been identified as a single
substance and in combination with
other substances. Between June 2019
and August 2020, there are twenty
reports of brorphine in the National
Forensic Laboratory Information System
(NFLIS) from three different states (see
Factor 5).4 In several NFLIS encounters,
brorphine was found in combination
3 Health Canada Drug Analysis Service (2019);
Analyzed Drug Report Canada 2019—Q3 (July to
September); European Monitoring Centre for Drugs
and Drug Addiction (EMCDDA) (2020); EU Early
Warning System Situation Report, Situation report
1—June 2020.
4 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,
December 12, 2011. NFLIS data was queried on
August 18, 2020.
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with heroin (a schedule I substance) and
fentanyl (a schedule II substance). In
reports from the Northeastern Illinois
Regional Crime Laboratory, suspected
heroin/fentanyl powders were analyzed
and found to be brorphine in
combination with flualprazolam, a nonscheduled benzodiazepine, and
diphenhydramine, an over-the-counter
antihistamine.5
Post-mortem toxicology samples
collected and submitted to National
Medical Services (NMS) Laboratory 6 in
June and July 2020 verified the
identification of brorphine. Brorphine
was first reported by the Center for
Forensic Science Research and
Education (CFSRE)—Novel
Psychoactive Substance (NPS)
Discovery Program (under the novel
psychoactive substances discovery
program, in collaboration with NMS
Labs) in July 2020. In seven postmortem toxicology reports in June and
July 2020, brorphine was found in
combination with fentanyl,
flualprazolam, and heroin. Evidence
suggests that individuals are using
brorphine as a replacement to heroin or
other opioids, either knowingly or
unknowingly.
Factor 5. Scope, Duration, and
Significance of Abuse
Brorphine has been described as a
potent synthetic opioid, and evidence
suggests it is being abused for its
opioidergic effects (see Factor 6).
According to a recent publication by
CFSRE—NPS Discovery Program,
brorphine has been positively identified
in seven death investigation cases
spanning between June and July 2020.
These cases occurred in three states—
Illinois (3), Minnesota (3), and Arizona
(1). Most (n=6) of the decedents were
male. The decedents’ ages ranged
between 40’s and 60’s with an average
age of 52 years. Other substances
identified in postmortem blood
specimens obtained from these
decedents include flualprazolam, a
nonscheduled benzodiazepine (n=5),
fentanyl, a schedule II substance (n=7),
and heroin, a schedule I substance
(n=4). The appearance of
5 Email communications with Northeastern
Illinois Regional Crime Laboratory, dated 7/1/2020
and 6/11/2020.
6 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 United States 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.
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benzodiazepines and other opioids is
common with polysubstance abuse.
NFLIS registered 20 reports of
brorphine from Ohio (4), Pennsylvania
(1), and Wisconsin (15) in 2019 and
2020. NFLIS was queried on August 18,
2020, for brorphine. Due to the rapid
appearance of the drug, brorphine is
most likely under reported as forensic
laboratories secure reference standards
for the confirmative identification and
reporting of this substance.
The population likely to abuse
brorphine 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 samples obtained
from brorphine seizures and postmortem toxicology reports. Because
abusers of brorphine are likely to obtain
it through unregulated sources, the
identity, purity, and quantity of
brorphine 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 wellcharacterized. According to the most
recent data from the National Survey on
Drug Use and Health (NSDUH),7 as of
2019, an estimated 10.1 million people
aged 12 years or older misused opioids
in the past year, including 9.7 million
prescription pain reliever misusers and
745,000 heroin users. In 2019, an
estimated 1.6 million people had an
opioid use disorder, which included 1.4
million people with a prescription pain
reliever use disorder and 438,000
people with heroin use disorder. In
2018, an estimated 10.3 million people
aged 12 years or older misused opioids
in the past year, including 9.9 million
prescription pain reliever misusers and
808,000 heroin users. In 2018, an
estimated 2 million people had an
opioid use disorder, which included 1.7
million people with a prescription pain
reliever use disorder and 500,000
people with heroin use disorder. This
7 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, noninstitutionalized population 12 years of age and
older. The survey excludes homeless people who
do not use shelters, active military personnel, and
residents of institutional group quarters such as
jails and hospitals. The NSDUH provides yearly
national and state level estimates of drug abuse, and
includes prevalence estimates by lifetime (i.e., ever
used), past year, and past month abuse or
dependence.
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population abusing opioids is likely to
be at risk of abusing brorphine.
Individuals who initiate use (i.e., use a
drug for the first time) of brorphine are
likely to be at risk of developing
substance use disorder, overdose, and
death similar to that of other opioid
analgesics (e.g., fentanyl, morphine,
etc.). Law enforcement reports
demonstrate that brorphine is being
illicitly distributed and abused.
Factor 6. What, if Any, Risk There Is to
the Public Health
The increase in opioid overdose
deaths in the United States has been
exacerbated recently by the availability
of potent synthetic opioids on the illicit
drug market. Data obtained from preclinical studies demonstrate that
brorphine exhibits a pharmacological
profile similar to that of other muopioid receptor agonists. Data from in
vitro studies showed that brorphine
binds to and activates the mu-opioid
receptors. In the [35S]GTPgS cell-based
receptor assay, brorphine, similar to
fentanyl, acted as a mu-opioid receptor
agonist. Brorphine’s activation of the
mu-opioid receptor was also shown to
involve recruitment of beta-arrestin-2, a
regulatory protein whose interaction
with the mu-opioid receptor has been
implicated in the adverse effects of muopioid receptor activation. Brorphine
binds to and activates the mu-opioid
receptor and has efficacy on scale with
fentanyl in in vitro studies. 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.
As with any mu-opioid receptor
agonist, the potential health and safety
risks for users of brorphine are high.
The public health risks associated to the
abuse of heroin and other m-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, opioid-related
overdose deaths in the United States
increased from 25,052 to 46,802. Of the
drug overdose deaths for 2018, opioids
were involved in about 69.5 percent of
all drug-involved overdose deaths.
In the United States, the abuse of
opioid analgesics has resulted in large
numbers of treatment admissions,
emergency department visits, and fatal
overdoses. The introduction of potent
synthetic opioids such as brorphine into
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the illicit market may serve as a portal
to problematic opioid use for those
seeking these powerful opioids.
Brorphine has been co-identified with
other substances in seven post-mortem
toxicology cases in June and July 2020.
These substances include other opioids
such as fentanyl and heroin, and other
substance classes such as
benzodiazepines. These deaths occurred
in three states: Illinois, Arizona, and
Minnesota. Information gathered from
case history findings shows that
brorphine use is similar to that of classic
opioid agonists. As documented by
toxicology reports, poly-substance abuse
remains common in fatalities associated
with the abuse of brorphine.
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 brorphine pose an imminent
hazard to the public safety. DEA is not
aware of any currently accepted medical
uses for brorphine in the United States.8
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 brorphine 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), the Acting
8 Although
there is no evidence suggesting that
brorphine 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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Administrator, through a letter dated
September 22, 2020, notified the
Assistant Secretary of DEA’s intention
to temporarily place brorphine in
schedule I. DEA subsequently published
a notice of intent on December 3, 2020.
85 FR 78047.
Conclusion
In accordance with 21 U.S.C.
811(h)(1) and (3), the Acting
Administrator considered available data
and information, herein set forth the
grounds for his determination that it is
necessary to temporarily schedule
brorphine in schedule I of the CSA and
finds that placement of this substance in
schedule I of the CSA is necessary in
order to avoid an imminent hazard to
the public safety.
This temporary order scheduling this
substance will be effective on the date
the order is published 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, brorphine 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, brorphine must be
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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
March 1, 2021. Any person who
currently handles brorphine, and is not
registered with DEA, must submit an
application for registration and may not
continue to handle brorphine as of
March 1, 2021, 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 this substance in a manner
not authorized by the CSA on or after
March 1, 2021 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
brorphine must surrender all currently
held quantities of brorphine.
3. Security. Brorphine 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 March 1, 2021. Nonpractitioners handling brorphine 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 brorphine must be in
compliance with 21 U.S.C. 825, 958(e)
and be in accordance with 21 CFR part
1302. Current DEA registrants will have
30 calendar days from March 1, 2021 to
comply with all labeling and packaging
requirements.
5. Inventory. Every DEA registrant
who possesses any quantity of
brorphine 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
be in compliance with all inventory
requirements. After the initial
inventory, every DEA registrant must
take an inventory of all controlled
substances (including brorphine) 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
brorphine, pursuant to 21 U.S.C. 827
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and 958 and in accordance with 21 CFR
parts 1304, 1312, and 1317, and section
1307.11. Current DEA registrants
authorized to handle brorphine 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 brorphine
must submit reports pursuant to 21
U.S.C. 827 and in accordance with 21
CFR parts 1304 and 1312 as of March 1,
2021.
8. Order Forms. All DEA registrants
who distribute brorphine must comply
with order form requirements pursuant
to 21 U.S.C. 828 and in accordance with
21 CFR part 1305 as of March 1, 2021.
9. Importation and Exportation. All
importation and exportation of
brorphine must be in compliance with
21 U.S.C. 952, 953, 957, and 958, and
in accordance with 21 CFR part 1312 as
of March 1, 2021.
10. Quota. Only DEA registered
manufacturers may manufacture
brorphine in accordance with a quota
assigned pursuant to 21 U.S.C. 826 and
in accordance with 21 CFR part 1303 as
of March 1, 2021.
11. Liability. Any activity involving
brorphine not authorized by, or in
violation of the CSA, occurring as of
March 1, 2021, is unlawful and may
subject the person to administrative,
civil, and/or criminal sanctions.
Regulatory Matters
The CSA provides for a temporary
scheduling action where such action is
necessary to avoid an imminent hazard
to the public safety. 21 U.S.C. 811(h)(1).
As provided in this subsection, the
Administrator (as delegated by the
Attorney General) by order may
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 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
Administrator to follow rulemaking
procedures for other kinds of scheduling
actions, see 21 U.S.C. 811(a), note that
in 21 U.S.C. 811(h)(1), 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
Acting Administrator finds that there is
good cause to forgo the notice-andcomment 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 here, as DEA is not
required by section 553 of the APA or
any other law to publish a general
notice of proposed rulemaking.
In accordance with the principles of
Executive Orders (E.O.) 12866 and
13563, this action is not a significant
regulatory action. E.O. 12866 directs
agencies to assess all costs and benefits
of available regulatory alternatives and,
if regulation is necessary, to select
regulatory approaches that maximize
net benefits (including potential
economic, environmental, public health,
and safety effects; distributive impacts;
and equity). E.O. 13563 is supplemental
to and reaffirms the principles,
structures, and definitions governing
regulatory review as established in E.O.
12866. E.O. 12866 classifies a
‘‘significant regulatory action,’’
requiring review by the Office of
Management and Budget, as any
regulatory action that is likely to result
in a rule that may: (1) Have an annual
effect on the economy of $100 million
or more or adversely affect in a material
way the economy; a sector of the
economy; productivity; competition;
jobs; the environment; public health or
safety; or State, local, or tribal
governments or communities; (2) create
a serious inconsistency or otherwise
interfere with an action taken or
planned by another agency; (3)
materially alter the budgetary impact of
entitlements, grants, user fees, or loan
programs, or the rights and obligations
of recipients thereof; or (4) raise novel
legal or policy issues arising out of legal
mandates, the President’s priorities, or
the principles set forth in the E.O.
Because this is not a rulemaking action,
this is not a significant regulatory action
as defined in Section 3(f) of E.O. 12866.
This action will not have substantial
direct effects on the states, on the
relationship between the national
government and the states, or on the
distribution of power and
responsibilities among the various
levels of government. Therefore, in
accordance with E.O. 13132
(Federalism), it is determined that this
action does not have sufficient
federalism implications to warrant the
preparation of a Federalism Assessment.
List of Subjects in 21 CFR Part 1308
Administrative practice and
procedure, Drug traffic control,
Reporting and recordkeeping
requirements.
For the reasons set out above, DEA
amends 21 CFR part 1308 as follows:
PART 1308—SCHEDULES OF
CONTROLLED SUBSTANCES
1. The authority citation for part 1308
continues to read as follows:
■
Authority: 21 U.S.C. 811, 812, 871(b),
956(b), unless otherwise noted.
2. In § 1308.11, add paragraph (h)(49)
to read as follows:
■
§ 1308.11
*
Schedule I
*
*
(h) * * *
*
*
(49) 1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one, its isomers, esters, ethers, salts and salts of
isomers, esters and ethers (Other names: brorphine; 1-[1-[1-(4-bromophenyl)ethyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2one) ..................................................................................................................................................................................................................
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*
*
*
*
*
D. Christopher Evans,
Acting Administrator.
[FR Doc. 2021–04242 Filed 2–26–21; 8:45 am]
BILLING CODE 4410–09–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 52
[EPA–R04–OAR–2019–0613; FRL–10019–
20–Region 4]
Air Plan Approval; North Carolina:
Revisions to Annual Emissions
Reporting
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
The Environmental Protection
Agency (EPA) is approving a State
Implementation Plan (SIP) revision
submitted by the State of North
Carolina, through the North Carolina
Department of Environmental Quality,
Division of Air Quality (DAQ), on July
10, 2019. The SIP revision modifies the
State’s annual emissions reporting
regulation by removing the annual
emissions reporting requirement for
certain non-Title V facilities in
geographic areas that have been
redesignated to attainment for the 1979
1-hour ozone national ambient air
quality standards (‘‘NAAQS’’ or
‘‘standards’’) and in the areas listed in
the rule that have been redesignated to
attainment for the 1997 8-hour ozone
NAAQS, with the exception of the
geographic areas that have been
redesignated to attainment for the 2008
8-hour ozone NAAQS. The SIP revision
also makes minor changes that do not
significantly alter the meaning of the
regulation. EPA is approving this
revision pursuant to the Clean Air Act
(CAA or Act).
DATES: This rule is effective March 31,
2021.
ADDRESSES: EPA has established a
docket for this action under Docket
Identification No. EPA–R04–OAR–
2019–0613. All documents in the docket
are listed on the www.regulations.gov
website. Although listed in the index,
some information may not be publicly
available, i.e., Confidential Business
Information or other information whose
disclosure is restricted by statute.
Certain other material, such as
copyrighted material, is not placed on
the internet and will be publicly
available only in hard copy form.
Publicly available docket materials can
either be retrieved electronically via
SUMMARY:
VerDate Sep<11>2014
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www.regulations.gov or in hard copy at
the Air Regulatory Management Section,
Air Planning and Implementation
Branch, Air and Radiation Division,
U.S. Environmental Protection Agency,
Region 4, 61 Forsyth Street SW, Atlanta,
Georgia 30303–8960. EPA requests that,
if at all possible, you contact the person
listed in the FOR FURTHER INFORMATION
CONTACT section to schedule your
inspection. The Regional Office’s
official hours of business are Monday
through Friday 8:30 a.m. to 4:30 p.m.,
excluding Federal holidays.
FOR FURTHER INFORMATION CONTACT:
Tiereny Bell, Air Regulatory
Management Section, Air Planning and
Implementation Branch, Air and
Radiation Division, Region 4, U.S.
Environmental Protection Agency, 61
Forsyth Street SW, Atlanta, Georgia
30303–8960. The telephone number is
(404) 562–9088. Ms. Bell can also be
reached via electronic mail at
bell.tiereny@epa.gov.
SUPPLEMENTARY INFORMATION:
I. Background
In 1979, EPA promulgated a NAAQS
for ozone, setting the standard at 0.12
parts per million (ppm) averaged over a
1-hour time frame. See 44 FR 8202
(February 8, 1979). In 1997, EPA
promulgated a revised NAAQS for
ozone, setting the standard at 0.08 ppm
averaged over an 8-hour time frame. See
62 FR 38856 (July 18, 1997).1 In 2008,
EPA revised the level of the 8-hour
ozone standard to 0.075 ppm. See 73 FR
16436 (March 27, 2008).2 The
promulgation of a new or revised
NAAQS triggers a CAA requirement for
EPA to designate as nonattainment any
area that violates the NAAQS or
contributes to a violation in a nearby
area. On November 6, 1991, EPA
published designations and
classifications for the 1979 1-hour ozone
NAAQS.3 See 56 FR 56694. EPA initially
published designations and
classifications for the revised 1997 8hour and revised 2008 8-hour ozone
standards on April 30, 2004 (69 FR
23858) and May 21, 2012 (77 FR 30088),
1 EPA has revoked the 1979 and 1997 ozone
standards. See 69 FR 23951 (April 30, 2004) and 80
FR 12264 (March 6, 2015), respectively.
2 EPA revised the level of the 8-hour ozone
standard to 0.070 ppm in 2015 and designated the
entire state as attainment/unclassifiable for that
NAAQS in 2017. See 80 FR 65296 (October 22,
2015) and 82 FR 54232 (November 16, 2017).
3 EPA designated the following geographic areas
in North Carolina as nonattainment for the 1979
ozone standard: Davidson, Durham, Forsyth,
Gaston, Guilford, Mecklenburg, and Wake Counties,
the Dutchville Township in Granville County, and
that part of Davie County bounded by the Yadkin
River, Dutchmans Creek, North Carolina Highway
801, Fulton Creek and back to the Yadkin River.
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11867
respectively. The geographic areas
designated as nonattainment in North
Carolina for the 1997 8-hour ozone
standard included the CharlotteGastonia-Rock Hill, NC-SC Area (the
North Carolina portion is hereinafter the
‘‘1997 Charlotte Area’’).4 The geographic
areas designated as nonattainment in
North Carolina for the 2008 ozone
standard are part of an area known as
the Charlotte-Rock Hill, NC-SC Area
(the North Carolina portion is
hereinafter the ‘‘2008 Charlotte Area’’).5
EPA redesignated North Carolina’s 1979
ozone nonattainment areas to
attainment in a series of actions from
1993 to 1995,6 redesignated the 1997
Charlotte Area to attainment on
December 2, 2013 (78 FR 72036), and
redesignated the 2008 Charlotte Area to
attainment on July 28, 2015 (80 FR
44873).
North Carolina was required to
develop nonattainment SIP revisions
addressing the CAA requirements for its
ozone nonattainment areas. Among
other things, North Carolina was
required to address the annual
emissions reporting requirement in CAA
section 182(a)(3)(B), which requires
each state with an ozone nonattainment
area to submit a SIP revision requiring
stationary sources that emit 25 tons per
year (tpy) or more of nitrogen oxides
(NOX) or volatile organic compounds
(VOC) within the nonattainment area to
provide certified annual emissions
statements to the state showing actual
annual NOX and VOC emissions from
the sources.
4 The geographic areas designated as
nonattainment in North Carolina for the 1997 ozone
standard included all geographic areas designated
as nonattainment for the 1979 ozone standard as
well as additional areas. The 1997 Charlotte Area
consists of Cabarrus, Gaston, Lincoln, Mecklenburg,
Rowan, and Union Counties and Davidson
Township and Coddle Creek Township in Iredell
County.
5 The 2008 Charlotte Area is a subset of the 1997
Charlotte Area and consists of Central Cabarrus
Township, Concord Township, Georgeville
Township, Harrisburg Township, Kannapolis
Township, Midland Township, Mount Pleasant
Township, New Gilead Township, Odell Township,
Poplar Tent Township, and Rimertown Township
in Cabarrus County; Crowders Mountain Township,
Dallas Township, Gastonia Township, Riverbend
Township, and South Point Township in Gaston
County; Davidson Township and Coddle Creek
Township in Iredell County; Catawba Springs
Township, Ironton Township, and Lincolnton
Township in Lincoln County; Atwell Township,
China Grove Township, Franklin Township, Gold
Hill Township, Litaker Township, Locke Township,
Providence Township, Salisbury Township, Steele
Township, and Unity Township in Rowan County;
and Goose Creek Township, Marshville Township,
Monroe Township, Sandy Ridge Township, and
Vance Township in Union County.
6 See 58 FR 47391 (November 9, 1993), 59 FR
18300 (April 18, 1994), and 60 FR 34859 (July 5,
1995).
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[Federal Register Volume 86, Number 38 (Monday, March 1, 2021)]
[Rules and Regulations]
[Pages 11862-11867]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-04242]
=======================================================================
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-716]
Schedules of Controlled Substances: Temporary Placement of
Brorphine 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 1-(1-(1-(4-
bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
(commonly known as brorphine), 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
of the Controlled Substances Act . This action is based on a finding by
the Acting Administrator that the placement of brorphine 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 brorphine.
DATES: This temporary scheduling order is effective March 1, 2021,
until March 1, 2023. If this order is extended or made permanent, DEA
will publish a document in the Federal Register.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Mailing Address: 8701 Morrissette Drive, Springfield,
Virginia 22152; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
Legal Authority
The Controlled Substances Act (CSA) provides the Attorney General
(as delegated to the Administrator of Drug Enforcement Administrator
(DEA) pursuant to 28 CFR 0.100) with the authority to temporarily place
a substance in schedule I of the CSA for two years without regard to
the requirements of 21 U.S.C. 811(b), if he finds that such action is
necessary to avoid an imminent hazard to the public safety. 21 U.S.C.
811(h)(1). In addition, if proceedings to control a substance are
initiated under 21 U.S.C. 811(a)(1) while the substance is temporarily
controlled \1\ under section 811(h), the Administrator may extend the
temporary scheduling for up to one year. 21 U.S.C. 811(h)(2).
---------------------------------------------------------------------------
\1\ Though 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
21 U.S.C. 812, or if there is no exemption or approval in effect for
the substance under section 505 of the Federal Food, Drug, and Cosmetic
Act, 21 U.S.C. 355. 21 U.S.C. 811(h)(1); 21 CFR part 1308.
Background
The CSA requires the Administrator to notify the Secretary of the
[[Page 11863]]
Department of Health and Human Services (HHS) of his intention to
temporarily place a substance in schedule I.\2\ 21 U.S.C. 811(h)(4).
The Acting Administrator transmitted such notice regarding brorphine to
the Assistant Secretary for Health of HHS (Assistant Secretary) by
letter dated September 22, 2020. The Assistant Secretary responded to
this notice by letter dated October 27, 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 brorphine. The Assistant Secretary also stated
that HHS had no objection to the temporary placement of brorphine 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.
---------------------------------------------------------------------------
DEA has taken into consideration the Assistant Secretary's comments
as required by subsection 811(h)(4). Brorphine is not currently listed
in any schedule under the CSA, and no exemptions or approvals are in
effect for brorphine under 21 U.S.C. 355. DEA has found that the
control of brorphine 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 brorphine on December 3, 2020. 85 FR
78047. That notice of intent discussed findings from DEA's three-factor
analysis dated August 2020, which DEA made available on
www.regulations.gov.
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 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 brorphine 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 August 2020 three-
factor analysis and the Assistant Secretary's October 27, 2020, letter
are available in their entirety under the tab ``Supporting Documents''
of the public docket of this action at www.regulations.gov.
Brorphine
The availability of synthetic opioids on 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
increased popularity of these substances have posed serious health
concerns in recent years. The presence of new synthetic opioids with no
approved medical use exacerbates the unprecedented opioid epidemic in
the United States continues to experience. The trafficking and abuse of
new synthetic opioids are deadly new trends.
The identification of brorphine on the illicit drug market has been
reported in the United States, Canada, Belgium, and Sweden. Data
obtained from preclinical pharmacology studies show that brorphine has
a pharmacological profile similar to that of other potent opioids such
as morphine and fentanyl, schedule II controlled substances. Because of
the pharmacological similarities between brorphine and other potent
opioids, the use of brorphine presents a high risk of abuse and may
negatively affect users and their communities. The positive
identification of this substance in law enforcement seizures and post-
mortem toxicology reports is a serious concern to the public safety.
The abuse of brorphine has been associated with at least seven
fatalities between June and July 2020 in the United States. Thus,
brorphine poses an imminent hazard to public safety.
Available data and information for brorphine, 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-716.
Factor 4. History and Current Pattern of Abuse
Brorphine is part of a structural class of compounds known as
substituted piperidine benzimidazolones. The general synthesis of
brorphine was first reported in the literature in 2018. Brorphine is
not an approved pharmaceutical product and is not approved for medical
use anywhere in the world. The Assistant Secretary, by a letter to DEA
dated October 27, 2020, stated that there are no FDA-approved NDAs or
INDs for brorphine in the United States. Hence, DEA notes there is no
legitimate channel for brorphine as a marketed drug product. The
appearance of brorphine on the illicit drug market is similar to other
designer drugs trafficked for their psychoactive effects.
Since 2014, numerous synthetic opioids structurally related to
fentanyl and several synthetic opioids from other structural classes
have begun to emerge on the illicit drug market as evidenced by the
identification of these drugs in forensic drug exhibits and toxicology
samples. Beginning in June 2019, brorphine emerged in the United States
illicit, synthetic drug market as evidenced by brorphine's
identification in drug seizures. Authorities Between July and September
2019, brorphine was first reported in drug casework in Canada and was
first reported in police seizures in Sweden in March 2020.\3\
---------------------------------------------------------------------------
\3\ Health Canada Drug Analysis Service (2019); Analyzed Drug
Report Canada 2019--Q3 (July to September); European Monitoring
Centre for Drugs and Drug Addiction (EMCDDA) (2020); EU Early
Warning System Situation Report, Situation report 1--June 2020.
---------------------------------------------------------------------------
Brorphine has been encountered by United States law enforcement in
powder form. In the United States, brorphine has been identified as a
single substance and in combination with other substances. Between June
2019 and August 2020, there are twenty reports of brorphine in the
National Forensic Laboratory Information System (NFLIS) from three
different states (see Factor 5).\4\ In several NFLIS encounters,
brorphine was found in combination
[[Page 11864]]
with heroin (a schedule I substance) and fentanyl (a schedule II
substance). In reports from the Northeastern Illinois Regional Crime
Laboratory, suspected heroin/fentanyl powders were analyzed and found
to be brorphine in combination with flualprazolam, a non-scheduled
benzodiazepine, and diphenhydramine, an over-the-counter
antihistamine.\5\
---------------------------------------------------------------------------
\4\ 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, December 12, 2011. NFLIS data was
queried on August 18, 2020.
\5\ Email communications with Northeastern Illinois Regional
Crime Laboratory, dated 7/1/2020 and 6/11/2020.
---------------------------------------------------------------------------
Post-mortem toxicology samples collected and submitted to National
Medical Services (NMS) Laboratory \6\ in June and July 2020 verified
the identification of brorphine. Brorphine was first reported by the
Center for Forensic Science Research and Education (CFSRE)--Novel
Psychoactive Substance (NPS) Discovery Program (under the novel
psychoactive substances discovery program, in collaboration with NMS
Labs) in July 2020. In seven post-mortem toxicology reports in June and
July 2020, brorphine was found in combination with fentanyl,
flualprazolam, and heroin. Evidence suggests that individuals are using
brorphine as a replacement to heroin or other opioids, either knowingly
or unknowingly.
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\6\ 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 United States 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.
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Factor 5. Scope, Duration, and Significance of Abuse
Brorphine has been described as a potent synthetic opioid, and
evidence suggests it is being abused for its opioidergic effects (see
Factor 6). According to a recent publication by CFSRE--NPS Discovery
Program, brorphine has been positively identified in seven death
investigation cases spanning between June and July 2020. These cases
occurred in three states--Illinois (3), Minnesota (3), and Arizona (1).
Most (n=6) of the decedents were male. The decedents' ages ranged
between 40's and 60's with an average age of 52 years. Other substances
identified in postmortem blood specimens obtained from these decedents
include flualprazolam, a nonscheduled benzodiazepine (n=5), fentanyl, a
schedule II substance (n=7), and heroin, a schedule I substance (n=4).
The appearance of benzodiazepines and other opioids is common with
polysubstance abuse.
NFLIS registered 20 reports of brorphine from Ohio (4),
Pennsylvania (1), and Wisconsin (15) in 2019 and 2020. NFLIS was
queried on August 18, 2020, for brorphine. Due to the rapid appearance
of the drug, brorphine is most likely under reported as forensic
laboratories secure reference standards for the confirmative
identification and reporting of this substance.
The population likely to abuse brorphine 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 samples obtained from
brorphine seizures and post-mortem toxicology reports. Because abusers
of brorphine are likely to obtain it through unregulated sources, the
identity, purity, and quantity of brorphine 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),\7\ as of 2019, an estimated 10.1
million people aged 12 years or older misused opioids in the past year,
including 9.7 million prescription pain reliever misusers and 745,000
heroin users. In 2019, an estimated 1.6 million people had an opioid
use disorder, which included 1.4 million people with a prescription
pain reliever use disorder and 438,000 people with heroin use disorder.
In 2018, an estimated 10.3 million people aged 12 years or older
misused opioids in the past year, including 9.9 million prescription
pain reliever misusers and 808,000 heroin users. In 2018, an estimated
2 million people had an opioid use disorder, which included 1.7 million
people with a prescription pain reliever use disorder and 500,000
people with heroin use disorder. This population abusing opioids is
likely to be at risk of abusing brorphine. Individuals who initiate use
(i.e., use a drug for the first time) of brorphine are likely to be at
risk of developing substance use disorder, overdose, and death similar
to that of other opioid analgesics (e.g., fentanyl, morphine, etc.).
Law enforcement reports demonstrate that brorphine is being illicitly
distributed and abused.
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\7\ 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.
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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 brorphine exhibits a pharmacological profile
similar to that of other mu-opioid receptor agonists. Data from in
vitro studies showed that brorphine binds to and activates the mu-
opioid receptors. In the [\35\S]GTP[gamma]S cell-based receptor assay,
brorphine, similar to fentanyl, acted as a mu-opioid receptor agonist.
Brorphine's activation of the mu-opioid receptor was also shown to
involve recruitment of beta-arrestin-2, a regulatory protein whose
interaction with the mu-opioid receptor has been implicated in the
adverse effects of mu-opioid receptor activation. Brorphine binds to
and activates the mu-opioid receptor and has efficacy on scale with
fentanyl in in vitro studies. 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.
As with any mu-opioid receptor agonist, the potential health and
safety risks for users of brorphine are high. The public health risks
associated 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, opioid-related overdose
deaths in the United States increased from 25,052 to 46,802. Of the
drug overdose deaths for 2018, opioids were involved in about 69.5
percent of all drug-involved overdose deaths.
In the United States, the abuse of opioid analgesics has resulted
in large numbers of treatment admissions, emergency department visits,
and fatal overdoses. The introduction of potent synthetic opioids such
as brorphine into
[[Page 11865]]
the illicit market may serve as a portal to problematic opioid use for
those seeking these powerful opioids.
Brorphine has been co-identified with other substances in seven
post-mortem toxicology cases in June and July 2020. These substances
include other opioids such as fentanyl and heroin, and other substance
classes such as benzodiazepines. These deaths occurred in three states:
Illinois, Arizona, and Minnesota. Information gathered from case
history findings shows that brorphine use is similar to that of classic
opioid agonists. As documented by toxicology reports, poly-substance
abuse remains common in fatalities associated with the abuse of
brorphine.
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 brorphine
pose an imminent hazard to the public safety. DEA is not aware of any
currently accepted medical uses for brorphine in the United States.\8\
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 brorphine 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), the Acting Administrator, through a letter dated September
22, 2020, notified the Assistant Secretary of DEA's intention to
temporarily place brorphine in schedule I. DEA subsequently published a
notice of intent on December 3, 2020. 85 FR 78047.
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\8\ Although there is no evidence suggesting that brorphine 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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Conclusion
In accordance with 21 U.S.C. 811(h)(1) and (3), the Acting
Administrator considered available data and information, herein set
forth the grounds for his determination that it is necessary to
temporarily schedule brorphine in schedule I of the CSA and finds that
placement of this substance in schedule I of the CSA is necessary in
order to avoid an imminent hazard to the public safety.
This temporary order scheduling this substance will be effective on
the date the order is published 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, brorphine 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, brorphine 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 March 1, 2021. Any
person who currently handles brorphine, and is not registered with DEA,
must submit an application for registration and may not continue to
handle brorphine as of March 1, 2021, 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 this substance in a manner
not authorized by the CSA on or after March 1, 2021 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 brorphine must
surrender all currently held quantities of brorphine.
3. Security. Brorphine 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 March
1, 2021. Non-practitioners handling brorphine 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 brorphine must be in compliance with 21 U.S.C.
825, 958(e) and be in accordance with 21 CFR part 1302. Current DEA
registrants will have 30 calendar days from March 1, 2021 to comply
with all labeling and packaging requirements.
5. Inventory. Every DEA registrant who possesses any quantity of
brorphine 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 be in compliance with all inventory requirements.
After the initial inventory, every DEA registrant must take an
inventory of all controlled substances (including brorphine) 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 brorphine, pursuant to 21 U.S.C. 827
[[Page 11866]]
and 958 and in accordance with 21 CFR parts 1304, 1312, and 1317, and
section 1307.11. Current DEA registrants authorized to handle brorphine
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
brorphine must submit reports pursuant to 21 U.S.C. 827 and in
accordance with 21 CFR parts 1304 and 1312 as of March 1, 2021.
8. Order Forms. All DEA registrants who distribute brorphine must
comply with order form requirements pursuant to 21 U.S.C. 828 and in
accordance with 21 CFR part 1305 as of March 1, 2021.
9. Importation and Exportation. All importation and exportation of
brorphine must be in compliance with 21 U.S.C. 952, 953, 957, and 958,
and in accordance with 21 CFR part 1312 as of March 1, 2021.
10. Quota. Only DEA registered manufacturers may manufacture
brorphine in accordance with a quota assigned pursuant to 21 U.S.C. 826
and in accordance with 21 CFR part 1303 as of March 1, 2021.
11. Liability. Any activity involving brorphine not authorized by,
or in violation of the CSA, occurring as of March 1, 2021, is unlawful
and may subject the person to administrative, civil, and/or criminal
sanctions.
Regulatory Matters
The CSA provides for a temporary scheduling action where such
action is necessary to avoid an imminent hazard to the public safety.
21 U.S.C. 811(h)(1). As provided in this subsection, the Administrator
(as delegated by the Attorney General) by order may 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 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 Administrator to follow rulemaking procedures for other kinds of
scheduling actions, see 21 U.S.C. 811(a), note that in 21 U.S.C.
811(h)(1), 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 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 here, as DEA is not
required by section 553 of the APA or any other law to publish a
general notice of proposed rulemaking.
In accordance with the principles of Executive Orders (E.O.) 12866
and 13563, this action is not a significant regulatory action. E.O.
12866 directs agencies to assess all costs and benefits of available
regulatory alternatives and, if regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential
economic, environmental, public health, and safety effects;
distributive impacts; and equity). E.O. 13563 is supplemental to and
reaffirms the principles, structures, and definitions governing
regulatory review as established in E.O. 12866. E.O. 12866 classifies a
``significant regulatory action,'' requiring review by the Office of
Management and Budget, as any regulatory action that is likely to
result in a rule that may: (1) Have an annual effect on the economy of
$100 million or more or adversely affect in a material way the economy;
a sector of the economy; productivity; competition; jobs; the
environment; public health or safety; or State, local, or tribal
governments or communities; (2) create a serious inconsistency or
otherwise interfere with an action taken or planned by another agency;
(3) materially alter the budgetary impact of entitlements, grants, user
fees, or loan programs, or the rights and obligations of recipients
thereof; or (4) raise novel legal or policy issues arising out of legal
mandates, the President's priorities, or the principles set forth in
the E.O. Because this is not a rulemaking action, this is not a
significant regulatory action as defined in Section 3(f) of E.O. 12866.
This action will not have substantial direct effects on the states,
on the relationship between the national government and the states, or
on the distribution of power and responsibilities among the various
levels of government. Therefore, in accordance with E.O. 13132
(Federalism), it is determined that this action does not have
sufficient federalism implications to warrant the preparation of a
Federalism Assessment.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, DEA 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)(49) to read as follows:
Sec. 1308.11 Schedule I
* * * * *
(h) * * *
(49) 1-(1-(1-(4-bromophenyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H- 9098
benzo[d]imidazol-2-one, its isomers, esters, ethers, salts and
salts of isomers, esters and ethers (Other names: brorphine; 1-
[1-[1-(4-bromophenyl)ethyl]-4-piperidinyl]-1,3-dihydro-2H-
benzimidazol-2-one).............................................
[[Page 11867]]
* * * * *
D. Christopher Evans,
Acting Administrator.
[FR Doc. 2021-04242 Filed 2-26-21; 8:45 am]
BILLING CODE 4410-09-P
