Notice2022-16572
International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-BUTINACA; Adinazolam; Bromazolam; Protonitazene (Propoxynitazene); Etazene (Etodesnitazene); Etonitazepyne (N-Pyrrolidino etonitazene); 2-Methyl-AP-237; Alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone; Request for Comments
Primary source
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Published
August 3, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is inviting interested persons to submit comments concerning abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of 10 drug substances. These comments will be considered in preparing a response from the United States to the World Health Organization (WHO) regarding the abuse liability and diversion of these drugs. WHO will use this information to consider whether to recommend that certain international restrictions be placed on these drug substances. This notice requesting comments is required by the Controlled Substances Act (CSA).
Full Text
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<title>Federal Register, Volume 87 Issue 148 (Wednesday, August 3, 2022)</title>
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[Federal Register Volume 87, Number 148 (Wednesday, August 3, 2022)]
[Notices]
[Pages 47428-47431]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-16572]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-N-1625]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; ADB-BUTINACA;
Adinazolam; Bromazolam; Protonitazene (Propoxynitazene); Etazene
(Etodesnitazene); Etonitazepyne (N-Pyrrolidino etonitazene); 2-Methyl-
AP-237; Alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone; Request
for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is inviting
interested persons to submit comments concerning abuse potential,
actual abuse, medical usefulness, trafficking, and impact of scheduling
changes on availability for medical use of 10 drug substances. These
comments will be considered in preparing a response from the United
States to the World Health Organization (WHO) regarding the abuse
liability and diversion of these drugs. WHO will use this information
to consider whether to recommend that certain international
restrictions be placed on these drug substances. This notice requesting
comments is required by the Controlled Substances Act (CSA).
DATES: Either electronic or written comments must be submitted by
August 24, 2022.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 24, 2022. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2022-N-1625 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-
BUTINACA; Adinazolam; Bromazolam; Protonitazene (propoxynitazene);
Etazene (etodesnitazene); Etonitazepyne (N-pyrrolidino etonitazene); 2-
Methyl-AP-237; alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone;
Request for Comments'' Received comments, those filed in a timely
manner (see ADDRESSES), will be placed in the docket and, except for
those submitted as ``Confidential Submissions,'' publicly viewable at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management Staff between
9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including
[[Page 47429]]
the claimed confidential information, in its consideration of comments.
The second copy, which will have the claimed confidential information
redacted/blacked out, will be available for public viewing and posted
on <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Submit both copies to the Dockets
Management Staff. If you do not wish your name and contact information
to be made publicly available, you can provide this information on the
cover sheet and not in the body of your comments and you must identify
this information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Edward (Greg) Hawkins, Center for Drug
Evaluation and Research, Controlled Substance Staff, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5150, Silver
Spring, MD 20993-0002, 301-796-0727, <a href="/cdn-cgi/l/email-protection#f1949586908395df9990869a989f82b1979590df999982df969e87"><span class="__cf_email__" data-cfemail="f89d9c8f998a9cd690998f9391968bb89e9c99d690908bd69f978e">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic
Substances (Psychotropic Convention). Article 2 of the Psychotropic
Convention provides that if a party to the convention or WHO has
information about a substance, which in its opinion may require
international control or change in such control, it shall so notify the
Secretary-General of the United Nations (U.N. Secretary-General) and
provide the U.N. Secretary-General with information in support of its
opinion.
Section 201(d)(2)(A) of the CSA (21 U.S.C. 811(d)(2)(A)) (Title II
of the Comprehensive Drug Abuse Prevention and Control Act of 1970)
provides that when WHO notifies the United States under Article 2 of
the Psychotropic Convention that it has information that may justify
adding a drug or other substances to one of the schedules of the
Psychotropic Convention, transferring a drug or substance from one
schedule to another, or deleting it from the schedules, the Secretary
of State must transmit the notice to the Secretary of Health and Human
Services (Secretary of HHS). The Secretary of HHS must then publish the
notice in the Federal Register and provide opportunity for interested
persons to submit comments that will be considered by HHS in its
preparation of the scientific and medical evaluations of the drug or
substance.
II. WHO Notification
The Secretary of HHS received the following notice from WHO
(nonrelevant text removed):
Ref.: C.L.27.2022
The World Health Organization (WHO) presents its compliments to
Member States and Associate Members and has the pleasure of
announcing that the 45th Expert Committee on Drug Dependence (ECDD)
will meet from 10 to 14 October 2022, in Geneva, Switzerland. Given
that WHO Expert Committee meetings are of a closed nature, this
letter serves to notify Member States of the substances under review
at the 45th ECDD, which are in the Annex I, attached for reference.
WHO is mandated by the 1961 and 1971 International Drug Control
Conventions to make recommendations to the UN Secretary-General on
the need for and level of international control of psychoactive
substances based on the advice of its independent scientific
advisory body, the ECDD. To assess whether or not a psychoactive
substance should be placed under international control, the ECDD
convenes annually to review the potential of this substance to cause
dependence, abuse and harm to health, as well as any therapeutic
applications. In order to perform this review and make evidence-
based decisions, the ECDD conducts medical, scientific, and public
health evaluations of the selected psychoactive substances using the
best available information.
Although the meetings are of a closed nature, Member States are
invited to contribute to the ECDD review process by joining the 45th
ECDD Open Session on 10 October 2022. The Information Session will
be held virtually and allow interested parties to learn about
present and future activities of the ECDD Secretariat, and to
present information concerning substances under review to the Expert
Committee for consideration in its deliberations. Registration
information will be made available on the ECDD website in due
course: <a href="https://www.who.int/medicines/access/controlled-substances/en/">https://www.who.int/medicines/access/controlled-substances/en/</a>.
As in the past and in line with the publication ``Guidance on
the WHO review of psychoactive substances for international
control'' (EB126/2010/REC1, Annex 6) \1\, Member States can also
contribute to the ECDD review process by providing accurate
information concerning the substances under review in advance of the
meeting. For this purpose, a questionnaire will be sent to Member
States to gather country information on the legitimate use, harmful
use, status of national control and potential impact of
international control for each substance under evaluation.
In addition to the questionnaire, Member States are also
encouraged to provide any additional relevant information
(unpublished or published) on substances to be reviewed by the 45th
ECDD.
The World Health Organization takes this opportunity to renew to
Member States and Associate Members the assurance of its highest
consideration.
GENEVA, 10 June 2021
\1\ <a href="https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58">https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58</a>.
Annex I
45th Expert Committee on Drug Dependence (ECDD) Substances For Review
10-14 October 2022
Critical reviews: The substances listed below have never been
formally reviewed by WHO and are not currently under international
control. Information was brought to WHO's attention that these
substances are clandestinely manufactured, of especially serious
risk to public health and society, and of no recognized therapeutic
use by any Party. The Expert Committee will consider whether
information presented during a critical review may justify the
scheduling or a change in the scheduling of the substance in the
1961 or 1971 Conventions.
Synthetic cannabinoid receptor agonists
1. ADB-BUTINACA
Benzodiazepines
2. Adinazolam
3. Bromazolam
Novel synthetic opioids
4. Protonitazene (propoxynitazene)
5. Etazene (etodesnitazene)
6. Etonitazepyne (N-pyrrolidino etonitazene)
7. 2-Methyl-AP-237
Cathinones/stimulants
8. alpha-PiHP
9. 3-Methylmethcathinone (3-MMC)
Pre-reviews: The substances listed below have been proposed for
a pre-review. The purpose of a pre-review is to determine whether
current information justifies an Expert Committee critical review. A
pre-review is a preliminary analysis and findings at this stage
should not determine whether the control status of a substance
should be changed.
Medicines
1. Zopiclone
FDA has verified the website addresses contained in the WHO
notice, as of the date this document publishes in the Federal
Register, but websites are subject to change over time. Access to
view the WHO questionnaire can be found at <a href="https://www.who.int/publications/m/item/45th-ecdd-questionnaire">https://www.who.int/publications/m/item/45th-ecdd-questionnaire</a>.
III. Substances Under WHO Review
ADB-BUTINACA is a synthetic cannabinoid that has been sold online
and is used to mimic the biological effects of tetrahydrocannabinol,
the
[[Page 47430]]
main psychoactive constituent in marijuana. Research and clinical
reports have demonstrated that synthetic cannabinoids are applied onto
plant material so that the material may be smoked as users attempt to
obtain a euphoric and psychoactive ``high.'' Synthetic cannabinoids
have been marketed under the guise of ``herbal incense,'' and promoted
by drug traffickers as legal alternatives to marijuana. According to
the National Forensic Laboratory Information System (NFLIS-Drug)
database,\1\ ADB-BUTINACA was first reported in 2020, and there were
4,358 reports in 2021. There are toxicology reports identifying ADB-
BUTINACA in at least six deaths and eight non-fatal emergency room
visits. There are no commercial or approved medical uses for ADB-
BUTINACA. As a positional isomer of AB-PINACA, ADB-BUTINACA is
controlled in schedule I of the CSA.
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\1\ NFLIS-Drug is a national forensic laboratory reporting
system that systematically collects drug identification results from
drug cases submitted to and analyzed by Federal, State and local
forensic laboratories in the United States. NFLIS-Drug data were
queried on June 29, 2022.
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Adinazolam is a designer benzodiazepine (i.e., a structural or
functional analog of other drugs in the benzodiazepine class) and is
expected to have central nervous system (CNS) depressant-like effects
similar to that of other known benzodiazepines. Adinazolam was first
reported to NFLIS-Drug in 2019, and there were 87 reports in 2021.
Adinazolam has appeared in toxicology reports in the United States.
Adinazolam is not currently controlled in the United States.
Bromazolam is a designer benzodiazepine and is expected to have CNS
depressant-like effects similar to that of other known benzodiazepines.
Bromazolam was first reported to NFLIS-Drug in 2016, and there were 743
reports in 2021. Bromazolam has appeared in at least two overdose death
reports in the United States and adverse effects associated with the
use of bromazolam have been reported. Bromazolam is not currently
controlled in the United States.
Protonitazene (propoxynitazene), etazene (etodesnitazene), and
etonitazepyne (N-pyrrolidino etonitazene) are novel synthetic opioid
receptor agonists of the benzimidazole structural class. Law
enforcement data indicates that these substances have appeared on the
U.S. illicit markets as evidenced by their identification in forensic
drug seizures and biological samples. Etazene was first reported to
NFLIS-Drug in 2020, and there were 41 reports in 2021. Protonitazene
and etonitazepyne were both first reported to NFLIS-Drug in 2021 with
20 and 129 reports in that year, respectively. The abuse of these
benzimidazole opioids are similar to other synthetic opioids.
Protonitazene, etazene, and etonitazepyne have been identified in
toxicology and several post-mortem cases. The public health risks
attendant to the abuse of mu-opioid receptor agonists are well
established. These risks included large numbers of drug treatment
admissions, emergency department visits, and fatal overdoses. On April
12, 2022, the U.S. Drug Enforcement Administration issued a temporary
order to control these substances as schedule I substances under the
CSA.
2-Methyl-AP-237 is a novel synthetic mu-opioid receptor agonist. It
was first reported to NFLIS-Drug in 2019, and there were 45 reports in
2021. Abuse of 2-methyl-AP-237 is similar to other synthetic opioids,
and has been associated with adverse health effects, including death.
In the United States, there are at least 10 confirmed reports of fatal
poisonings and several reports of emergency room visits, and non-fatal
poisonings associated with 2-methyl-AP-237. 2-Methyl-AP-237 is not
currently controlled in the United States. There are no commercial or
approved medical uses of 2-methyl-AP-237.
Alpha-PiHP is a synthetic stimulant designer drug structurally
similar to other schedule I synthetic cathinones. Alpha-PiHP is a
monoamine transporter (dopamine transporter and norepinephrine
transporter) uptake inhibitor. Adverse effects associated with
synthetic cathinones abuse include agitation, hypertension,
tachycardia, and death. Alpha-PiHP was first reported to NFLIS-Drug in
2017, and there were 332 reports in 2021. Alpha-PiHP has been confirmed
to have played a role in fatal and non-fatal overdose events in the
United States. Alpha-PiHP has no approved medical uses in the United
States. As a positional isomer of alpha-PHP, alpha-PiHP is controlled
in schedule I of the CSA.
3-Methylmethcathinone (3-MMC) is a designer drug of the
phenethylamine class, which is structurally and pharmacologically
similar to amphetamine, 3,4-methylenedioxymethamphetamine, cathinone
and other related substances. 3-MMC is a monoamine transporter
(dopamine transporter, serotonin transporter, and norepinephrine
transporter) uptake inhibitor. Like other schedule I synthetic
cathinones, 3-MMC is abused for its psychoactive effects. Adverse
effects associated with synthetic cathinones abuse include agitation,
hypertension, tachycardia, and death. 3-MMC was first reported to
NFLIS-Drug in 2012, and there were three reports in 2021. 3-MMC has no
approved medical uses in the United States. As a positional isomer of
mephedrone, 3-MMC is controlled in schedule I of the CSA.
Zopiclone is a nervous system depressant drug used in the treatment
of insomnia. Its mechanism of action is based on modulating
benzodiazepine receptors. Zopiclone is approved for medical use in the
United States as (S)-zopiclone (or eszopiclone), the active (S) isomer
of zopiclone. Zopiclone has abuse potential and may be misused due to
its ability to produce euphoric effects at high doses. Amnesia and
hallucinations have been reported with higher doses. Zopiclone is
controlled in schedule IV of the CSA.
IV. Opportunity To Submit Domestic Information
As required by section 201(d)(2)(A) of the CSA, FDA, on behalf of
HHS, invites interested persons to submit comments regarding the 10
drug substances. Any comments received will be considered by HHS when
it prepares a scientific and medical evaluation for drug substances
that is responsive to the WHO Questionnaire for these drug substances.
HHS will forward such evaluation of these drug substances to WHO, for
WHO's consideration in deciding whether to recommend international
control/decontrol of any of these drug substances. Such control could
limit, among other things, the manufacture and distribution (import/
export) of these drug substances and could impose certain recordkeeping
requirements on them.
Although FDA is, through this notice, requesting comments from
interested persons, which will be considered by HHS when it prepares an
evaluation of these drug substances, HHS will not now make any
recommendations to WHO regarding whether any of these drugs should be
subjected to international controls. Instead, HHS will defer such
consideration until WHO has made official recommendations to the
Commission on Narcotic Drugs, which are expected to be made in late
2022. Any HHS position regarding international control of these drug
substances will be preceded by another Federal Register notice
soliciting public comments, as required by section 201(d)(2)(B) of the
CSA.
[[Page 47431]]
Dated: July 28, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-16572 Filed 8-2-22; 8:45 am]
BILLING CODE 4164-01-P
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