[Federal Register Volume 85, Number 150 (Tuesday, August 4, 2020)]
[Notices]
[Pages 47217-47220]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-16905]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-N-1680]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Isotonitazene; MDMB-
4en-PINACA; CUMYL-PEGACLONE; Flubromazolam; Clonazolam; Diclazepam; 3-
MeO-PCP; DIPHENIDINE; 2-MEO-DIPHENIDINE; 5-MEO-DALT; and 3-
FLUOROPHENMETRAZINE (3-FPM); 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 the Agency) is
requesting interested persons to submit comments concerning abuse
potential, actual abuse, medical usefulness, trafficking, and impact of
scheduling
[[Page 47218]]
changes on availability for medical use of 11 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: Submit either electronic or written comments by August 28, 2020.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before August 28, 2020. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of August 28, 2020. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are postmarked or the delivery
service acceptance receipt is on or before that date.
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-2020-N-1680 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs;
Isotonitazene; MDMB-4en-PINACA; CUMYL-PEGACLONE; Flubromazolam;
Clonazolam; Diclazepam; 3-MeO-PCP; DIPHENIDINE; 2-MEO-DIPHENIDINE; 5-
MEO-DALT; and 3-FLUOROPHENMETRAZINE (3-FPM); 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: James R. Hunter, 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, 301-796-3156, [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 (the 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 (non-
relevant text removed):
Ref.: C.L.22.2020
The World Health Organization (WHO) presents its compliments to
Member States and Associate Members and in reference to C.L.14.2019
has the pleasure of informing
[[Page 47219]]
that the 43rd Expert Committee on Drug Dependence (ECDD) will meet
from 12 to 16 October 2020 in Geneva, Switzerland. In the event that
the meeting should be held virtually due to exceptional
circumstances, corresponding arrangements will be made. Given that
ECDD meetings are of a closed nature, this letter serves to notify
Member States of the substances under review at the 43rd ECDD, which
are in the Annex I 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 the appropriate control of a
psychoactive substance, 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 scientific and 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 43rd
ECDD Open Session on 12 October 2020. The Open Session will allow
interested parties to present information concerning substances
under review to the Expert Committee. Registration information will
be made available on the ECDD website: https://www.who.int/medicines/access/controlled-substances/en/.
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 43rd
ECDD by emailing [email protected] with the subject ``Ref:
C.L.22.2020''.
The World Health Organization takes this opportunity to renew to
Member States and Associate Members the assurance of its highest
consideration.
GENEVA, 23 June 2020
\1\ https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58.
Annex I
43nd Expert Committee on Drug Dependence (ECDD), 12-16 October 2020,
Substances for Review
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.
Critical Review
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Synthetic Opioids......................... 1. Isotonitazene
Synthetic Cannabinoid Receptor Agonists... 2. MDMB-4en-PINACA
3. CUMYL-PEGALONE
Benzodiazepines........................... 4. Flubromazolam
5. Clonazolam
6. Diclazepam
Dissociative-type substances.............. 7. 3-MeO-PCP
8. DIPHENIDINE
9. 2-MEO-DIPHENIDINE
Hallucinogen.............................. 10. 5-MEO-SALT
Synthetic Stimulant....................... 11. 3-FLUROPHENMETRAZINE (3-
FPM)
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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 https://www.who.int/teams/health-product-and-policy-standards/controlled-substances/ecdd-member-state-questionnaire.
III. Substances Under WHO Review
Isotonitazene (chemical name: N,N-diethyl-2-(2-(4
isopropoxybenzyl)-5-nitro-1H-benzimidazol-1-yl)ethan-1-amine) is a
potent synthetic opioid that is abused similar to other synthetic
opioids. Its use has resulted in adverse health effects, including
positively identified in 49 death investigation cases in the United
States between August 2019 and April 2020. Law enforcement data
indicate that isotonitazene has appeared in the United States' illicit
drug market. According to the National Forensic Laboratory Information
System (NFLIS) database, there have been 53 encounters of isotonitazene
in the United States (as of June 2020). There are no commercial or
approved medical uses for isotonitazene. On June 18, 2020, the Drug
Enforcement Administration issued a notice of intent to temporarily
control isotonitazene as a schedule I substance under the CSA.
MDMB-4en-PINACA is a synthetic cannabinoid that has been sold
online and used to mimic the biological effects of tetrahydrocannabinol
(THC), the 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 NFLIS database, MDMB-4en-PINACA was first encountered
in the United States in January 2019. There have been 1,436 encounters
of MDMB-4en-PINACA in the United States (as of July 6, 2020). MDMB-4en-
PINACA has also been encountered mixed with opioids including heroin
and fentanyl, with some incidents resulting in violent behaviors,
tachycardia, and hypertension. There are no commercial or approved
medical uses for MDMB-4en-PINACA and MDMB-4en-PINACA is not a
controlled substance under the CSA.
CUMYL-PEGACLONE is a synthetic cannabinoid that has been sold
online and used to mimic the biological effects of THC, the 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. In vitro studies
demonstrate that CUMYL-PEGALCONE binds to and activates the cannabinoid
one receptor. CUMYL-PEGALCONE has not been encountered within the
United States according to the NFLIS database (as of July 6, 2020).
There are no commercial or approved medical uses for CUMYL-PEGALCONE
and is not a controlled substance under the CSA.
Flubromazolam, clonazolam, and diclazepam belong to a class of
substances known as benzodiazepines. Benzodiazepines produce central
nervous system depression and are commonly used to treat insomnia,
anxiety, and seizure disorders. Flubromazolam is a triazole analogue of
the designer benzodiazepine, flubromazepam. Flubromazolam can be
purchased on the internet and is used as a recreational substance in
the United States. Flubromazolam has been identified in an increasing
number of law enforcement seizures and has been associated with an
increasing number of drug overdose deaths. It is abused by a broad
range of groups including youths, young adults, and older adults.
Clonazolam has been involved in an increasing number of drug seizure
events as well as drug overdose deaths, alone and in combination with
alcohol. Diclazepam is a designer benzodiazepine sold on the internet
and
[[Page 47220]]
most often found as a liquid solution, but it may be sold as a powder,
tablet, blotter paper, or pellet. In 2018, flubromazolam, clonazolam,
and dicalazepam were all identified by law enforcement in driving under
the influence of drugs cases in the United States. Flubromazolam,
clonazolam, and diclazepam are not approved for medical use in the
United States and are not controlled substances under the CSA.
3-MeO-PCP (3-methoxyphencyclidine; chemical name: 1-(1-(3-
methoxyphenyl)cyclohexyl)piperidine) is a novel N-methyl-D-aspartate
(NMDA) receptor antagonist with structural and biochemical similarities
to phencyclcycidine (PCP) and other arylcyclohexylamines. 3-MeO-PCP is
classified as an arylcyclohexylamine and produces dissociative
anesthetic and hallucinogenic effects. Use of this substance is
associated with intoxication and published case reports of both fatal
and non-fatal overdose. 3-MeO-PCP is encountered by law enforcement in
drug seizure reports. 3-MeO-PCP is an analogue of the Schedule II
hallucinogen PCP. There is no approved medical use for 3-MeO-PCP in the
United States. 3-MeO-PCP is not a controlled substance under the CSA.
If intended for human consumption, 3-MeO-PCP may be treated as a
``controlled substance analogue'' under the CSA pursuant to 21 U.S.C
802(32) (A) and 813.
DIPHENIDINE (chemical name: 1-(1,2-diphenylethyl) piperidine) is a
non-competitive NMDA receptor antagonist classified as a
diarylethylamine and produces dissociative anesthetic and
hallucinogenic effects. It was originally synthesized in the 1920s, but
reports of abuse started in the last decade. Use of this substance is
associated with intoxication and published case reports of both fatal
and non-fatal overdose outside of the United States. DIPHENIDINE is
encountered by law enforcement in drug seizure reports. DIPHENIDINE is
not approved for medical use in the United States and is not a
controlled substance under the CSA.
2-MeO-DIPHENIDINE (2-methoxy-diphenidine, methoxphenidine) is a
non-competitive NMDA receptor antagonist classified as a
diarylethylamine and produces dissociative anesthetic and
hallucinogenic effects that may produce effects similar to high doses
of dextromethorphan. Use of this substance is associated with
intoxication and non-fatal overdose in published case reports outside
the United States. 2-MeO-DIPHENIDINE is encountered by law enforcement
in drug seizure reports. There is no approved medical use for 2-MeO-
DIPHENIDINE in the United States and 2-MeO-DIPHENIDINE is not a
controlled substance under the CSA.
5-MeO-DALT (chemical name: N,N-Diallyl-5-methoxytryptamine) is a
tryptamine hallucinogen and is an agonist of the serotonin (5-HT) 5-
HT2A receptor. 5-MeO-DALT appears to produce hallucinogenic
effects similar to other tryptamine hallucinogens and fully substituted
for 2,5-dimethoxy-4-methylamphetamine (DOM) in DOM-trained rats. 5-MeO-
DALT is an analogue of the Schedule I controlled substance 5methoxy-
N,N-diisopropyltryptamine (5-MeO-DiPT). 5-MeO-DALT has been encountered
by law enforcement in drug seizure reports. 5-MeO-DALT is not approved
for medical use in the United States and is not controlled under the
CSA.
3-FLUOROPHENMETRAZINE (3-FPM) (chemical name: 1-(3-fluorophenyl)-2-
(methylamino)propan-1-one) shares substantial chemical structural
similarity to phenmetrazine, a Schedule II controlled substance that
was prescribed as an appetite suppressant before being withdrawn from
the pharmaceutical drug market in the United States because of its
abuse potential. 3-FPM, which is similar to phenmetrazine and other
stimulant drugs of abuse, increases extracellular concentrations of the
neurotransmitter dopamine by inhibiting the uptake of this
neurotransmitter at the dopamine transporter. Elevated extracellular
dopamine concentrations have been implicated in the mechanism of action
of stimulant drugs of abuse. There is no approved medical use for 3-FPM
in the United States and 3-FPM is not a controlled substance 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 11
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-
2020. 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.
Dated: July 29, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-16905 Filed 8-3-20; 8:45 am]
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