[Federal Register Volume 88, Number 150 (Monday, August 7, 2023)]
[Notices]
[Pages 52179-52182]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-16812]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-3032]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Bromazolam;
Flubromazepam; Butonitazene; 3-Chloromethcathinone (3-CMC);
Dipentylone; 2-Fluorodeschloroketamine (2-FDCK); Nitrous Oxide (N2O);
Carisoprodol; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
-----------------------------------------------------------------------
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 eight 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, 2023.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 24, 2023. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
[[Page 52180]]
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
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 https://www.regulations.gov.
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:
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.
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-2023-N-3032 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs;
Bromazolam; Flubromazepam; Butonitazene; 3-Chloromethcathinone (3-CMC);
Dipentylone; 2-Fluorodeschloroketamine (2-FDCK); Nitrous oxide
(N2O); Carisoprodol; 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 https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
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 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 https://www.regulations.gov.
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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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. 5110, Silver
Spring, MD 20993-0002, 301-796-0727, [email protected].
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.
Paragraph (d)(2)(A) of the CSA (21 U.S.C. 811) (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.22.2023
The World Health Organization (WHO) presents its compliments to
Member States and Associate Members and has the pleasure of
announcing that the 46th Expert Committee on Drug Dependence (ECDD)
will meet from 16 to 20 October 2023, 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 46th ECDD, which are in the Annex I file, 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 46th
ECDD Information Session on 16 October 2023. 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 46th
Expert Committee
[[Page 52181]]
for consideration in its deliberations. Registration information
will be made available on the ECDD website in due course: https://www.who.int/news-room/events/detail/2023/10/16/default-calendar/forty-sixth-expert-committee-on-drug-dependence.
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 up to date and
accurate information concerning the substances under review in
advance of the meeting. For this purpose, and as per previous
practice, 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.
The World Health Organization takes this opportunity to renew to
Member States and Associate Members the assurance of its highest
consideration.
GENEVA, 27 June 2023
\1\ https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=90.
Annex I
46th Expert Committee on Drug Dependence (ECDD) Substances for
Review 16-20 October 2023
Critical reviews: The substances listed below have been proposed
by WHO for critical review 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.
Benzodiazepines
1. Bromazolam
2. Flubromazepam
Novel Synthetic Opioids
3. Butonitazene
Cathinones/stimulants
4. 3-Chloromethcathinone (3-CMC)
5. Dipentylone
Dissociative-type substances
6. 2-fluorodeschloroketamine (2-FDCK)
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
7. Nitrous oxide
8. Carisoprodol
FDA has verified the website addresses contained in the WHO notice
as of the date this document publishes in the Federal Register;
however, websites are subject to change over time. Access to view the
WHO questionnaire can be found at https://www.who.int/groups/who-expert-committee-on-drug-dependence/46th-ecdd-documents.
III. Substances Under WHO Review
Bromazolam is a triazolobenzodiazepine that produces agonist
effects on gamma-aminobutyric acid (GABA) type-A channels through the
benzodiazepine site. Through this mechanism of action, bromazolam can
produce sedative and anxiolytic effects similar to other drugs of the
benzodiazepine class. According to the National Forensic Laboratory
Information System (NFLIS) database, there were 2,881 drug seizures of
bromazolam in the United States from 2016 to May of 2023; however, some
case reports are still pending for 2022 and 2023, so this number is
increasing. Toxicology data indicate that bromazolam is typically
detected in samples that include other drugs such as stimulants and
opioids. This polydrug combination has led to the determination that
bromazolam has played at least a contributory role in 152 confirmed
deaths associated with the use of bromazolam. There are no commercial
or approved medical uses for bromazolam in the United States, and it is
not controlled under the CSA.
Flubromazepam is a compound of the benzodiazepine class that
produces agonist effects on GABAA channels and can produce
sedative and anxiolytic effects similar to other drugs of the class.
Law enforcement data indicate that flubromazepam has been detected in
169 biological samples from 2019 through 2022. In 2022, 87 percent of
those samples also contained fentanyl. There are no commercial or
approved medical uses for flubromazepam in the United States and it is
not controlled under the CSA.
Butonitazene is a novel synthetic mu-opioid receptor agonist of the
benzimidazole structural class. Law enforcement data indicates that
butonitazene appeared on the U.S. illicit markets as evidenced by their
identification in forensic drug seizures and biological samples. The
abuse liability of benzimidazole opioids is similar to other synthetic
opioids. Butonitazene has been identified in toxicological samples from
post-mortem cases. The public health risks attendant to the abuse of
mu-opioid receptor agonists are well established and can result in
drowsiness, nausea, vomiting, and respiratory depression leading to
death. Butonitazene has no approved medical uses in the United States
and is a schedule I substance under the CSA.
3-Chloromethcathinone (3-CMC) and dipentylone are synthetic
stimulant designer drugs structurally similar to schedule I synthetic
cathinones and schedule II stimulants like methamphetamine. Like other
schedule I synthetic cathinones, 3-MMC and dipentylone are abused for
their psychoactive effects. Adverse effects associated with the abuse
of synthetic cathinones include agitation, hypertension, tachycardia,
and death. According to NFLIS, dipentylone was first detected in the
United States in 2014, and in 2022 there were 4,901 law enforcement
seizures of the drug. Both 3-CMC and dipentylone have been detected in
biological samples from toxicological drug tests and from postmortem
samples. 3-CMC and dipentylone have no approved medical uses in the
United States and both are schedule I substances under the CSA.
2-Fluorodeschloroketamine (2-FDCK) is a dissociative anesthetic
related to ketamine. 2-FDCK is a novel psychoactive substance (NPS)
that is used as a research chemical and is sometimes marketed as a
legal high. In animals, 2-FDCK demonstrated a similar potential for
abuse as ketamine in studies that compare measurements of reinforcing
effects (e.g., self-administration) and discriminative stimulus effects
(e.g., drug discrimination and conditioned place preference). As a
result, 2-FDCK is presumed to produce psychoactive effects similar to
ketamine such as sensory dissociation, derealization, analgesia,
hallucinations, mania, and amnesia. 2-FDCK has been detected in
biological samples from toxicological drug tests and from postmortem
samples. 2-FDCK has no approved medical uses in the United States and
is not a controlled substance under the CSA, although it is controlled
in many European countries.
Nitrous oxide (N2O) is an inhalable gas that is also
known by the common names, laughing gas, nitrous, whippets, NOS, or
hippy-crack. It is part of the dissociative class of hallucinogens and
is thought to function through modulation of GABA and N-methyl-D-
aspartate (NMDA) receptors. N2O was first used in the late
1700s as an analgesic for dental and surgical operations. It is
approved by FDA as a medical gas but has seen increasing use around the
world for its subjective effects. These effects include, but are not
limited to, dizziness, loss of motor control, euphoria, perceptual
changes, numbness, amnesia, derealization, and altered acuity.
N2O is not controlled under the CSA.
[[Page 52182]]
Carisoprodol is a sedative-hypnotic that is used as a centrally
acting muscle relaxant and hypnotic. Carisoprodol is a prodrug that is
metabolized in the liver to form meprobamate which functions similarly
to benzodiazepines and barbiturates. It is approved for medical use in
the United States as a muscle relaxant and is typically prescribed in
combination with analgesics to treat muscle pain. Scientific studies
indicate that carisoprodol has a demonstrated abuse potential similar
to benzodiazepines, and it is controlled under schedule IV under the
CSA.
IV. Opportunity To Submit Domestic Information
As required by paragraph (d)(2)(A) of the CSA, FDA, on behalf of
HHS, invites interested persons to submit comments regarding the eight
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
2023. Any HHS position regarding international control of these drug
substances will be preceded by another Federal Register notice
soliciting public comments, as required by paragraph (d)(2)(B) of the
CSA (21 U.S.C. 811).
Dated: August 2, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-16812 Filed 8-4-23; 8:45 am]
BILLING CODE 4164-01-P