International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-FUBINACA; ADB-CHMINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; para-Fluoro Butyrfentanyl; Tramadol; Pregabalin; Cannabis Plant and Resin; and Eight Additional Substances; Request for Comments, 50938-50942 [2018-21954]
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Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
RPG CROSS-SITE EVALUATION ANNUALIZED BURDEN ESTIMATES—Continued
Total
number of
respondents
Data collection activity
Partner survey ......................................................................
Number of
responses per
respondent
(each year)
135
Average
burden hours
per response
(in hours)
.33
Estimated
total
burden hours
Total
annual
burden hours
0.42
56.3
18.8
2
43
43
33
2,288
16.5
0.25
0.017
0.017
0.03
2,673
2,612.3
174.2
133.7
37,065
891
870.8
58.1
44.6
12,355
27
27
1
2
42.6
144
3,450.6
23,328
1150.2
7,776
27
27
27
.33
130
2
8
1.25
25
216
13,162.5
4,050
72
4,387.5
1,350
Data entry for comparison study sites (22 grantees) ..........
22
130
1.25
10,725
3,575
Estimated Total Burden Hours .....................................
........................
........................
........................
97,827
32,609
Enrollment, client and service data
Semi-annual progress reports .............................................
Case enrollment data ...........................................................
Case closure ........................................................................
Case closure—prenatal .......................................................
Service log entries ...............................................................
27
81
81
81
162
Outcome and impact data
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Administrative Data:
Obtain access to administrative data ...........................
Report administrative data ............................................
Standardized instruments:
Review and adopt reporting templates .........................
Data entry for standardized instruments ......................
Review records and submit .................................................
In compliance with the requirements
of Section 3506(c)(2)(A) of the
Paperwork Reduction Act of 1995, the
Children’s Bureau within the
Administration for Children and
Families is soliciting public comment
on the specific aspects of the
information collection described above.
Copies of the proposed collection of
information can be obtained and
comments may be forwarded by writing
to Administration for Children and
Families, Office of Administration,
Office of Planning, Research and
Evaluation, 330 C Street SW,
Washington, DC 20201, Attn: ACF
Reports Clearance Officer. Email
address: infocollection@acf.hhs.gov. All
requests should be identified by the title
of the information collection.
The Department specifically requests
comments on: (a) Whether the proposed
collection of information is necessary
for the proper performance of the
function of the agency, including
whether the information shall have
practical utility; (b) the accuracy of the
agency’s estimate of the burden of the
proposed collection of information; (c)
the quality, utility, and clarity of the
information to be collected; and (d)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques or
other forms of information technology.
Consideration will be given to
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comments and suggestions within 60
days of this publication.
Robert Sargis,
Reports Clearance Officer.
[FR Doc. 2018–22020 Filed 10–9–18; 8:45 am]
BILLING CODE 4184–29–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–N–3685]
International Drug Scheduling;
Convention on Psychotropic
Substances; Single Convention on
Narcotic Drugs; ADB–FUBINACA;
ADB–CHMINACA; Cyclopropyl
Fentanyl; Methoxyacetyl Fentanyl;
para-Fluoro Butyrfentanyl; Tramadol;
Pregabalin; Cannabis Plant and Resin;
and Eight Additional Substances;
Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice; request for comments.
The Food and Drug
Administration (FDA) is requesting
interested persons to submit comments
concerning abuse potential, actual
abuse, medical usefulness, trafficking,
and impact of scheduling changes on
availability for medical use of 16 drug
substances. These comments will be
considered in preparing a response from
the United States to the World Health
SUMMARY:
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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 drugs. This notice
requesting comments is required by the
Controlled Substances Act (the CSA).
DATES: Submit either electronic or
written comments by October 31, 2018.
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 (enter date),
2018. The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of October 31, 2018.
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
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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–
2018–N–3685 for ‘‘International Drug
Scheduling; Convention on
Psychotropic Substances; Single
Convention on Narcotic Drugs; ADB–
FUBINACA; FUB–AMB(MMB–
FUBINACA_AMB–FUBINACA); ADB–
CHMINACA; CUMYL–4CN–BINACA;
Cyclopropyl Fentanyl; Methoxyacetyl
Fentanyl; Ortho-Fluorofentanyl; ParaFluoro Butyrfentanyl; ParaMethoxybutyrfentanyl; NEthylnorpentylone; Tramadol;
Pregabalin; Cannabis Plant and Resin;
Extracts and Tinctures of Cannabis;
Delta-9-Tetrahydrocannabinol;
Stereoisomers of Tetrahydrocannabinol;
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.
• 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
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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.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.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.
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:
james.hunter@fda.hhs.gov.
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
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50939
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.26.2018
The World Health Organization (WHO)
presents its compliments to Member States
and Associate Members and has the pleasure
of informing that the 41th Expert Committee
on Drug Dependence (ECDD) will meet in
Geneva from 12 to 16 November 2018. The
41th ECDD will convene to review
psychoactive substances on their potential to
cause dependence, abuse and harm to health,
and their potential therapeutic applications.
WHO will make recommendations to the UN
Secretary-General on the need for and level
of international control of these substances.
Member States are invited to collaborate, as
in the past, in this process by providing
pertinent information as requested in the
questionnaire and concerning substances
under review. At its 126th session in January
2010, the Executive Board approved the
publication ‘‘Guidance on the WHO review
of psychoactive substances for international
control’’ (EB126/2010/REC1, Annex 6) which
requires the Secretariat to request relevant
information from Ministers of Health in
Member States to prepare a report for
submission to the ECDD.
For this purpose, a questionnaire was
designed to gather information on the
legitimate use, harmful use, status of national
control and potential impact of international
control for each substance under evaluation.
A list of substances for which Member States
will receive questionnaires is attached.
Kindly note that Member States who
submitted questionnaire responses that were
reviewed at the 40th ECDD on cannabis and
cannabis-related substances will not be
requested to re-submit questionnaires for
those substances for the 41st ECDD.
However, if Member States would like to
amend their responses or submit additional
information on cannabis and cannabisrelated substances, it is requested that they
inform the Secretariat.
It would be appreciated if a person from
the Ministry of Health could be designated as
the focal point responsible for coordinating
answers to the questionnaires. A list of focal
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Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
points designated by Member States for the
40th ECDD in June 2018 is attached. It is
requested that if a focal point’s contact
details including email address are to be
added or amended, that Member States
inform the Secretariat by 17 September 2018.
Any additions or amendments to focal point
designations should be emailed to
ecddsecretariat@who.int.
If no additions or amendments to focal
point details are made by this date, the focal
point from 2018 will be approached by the
Secretariat for questionnaire completion.
Where there is a competent National
Authority under the International Drug
Control Treaties, it is kindly requested that
the questionnaires be completed in
collaboration with such body.
Once the Secretariat has received the
contact details, focal points will be given
further instructions and direct access to an
online questionnaire. The questionnaires will
be analysed by the Secretariat and prepared
as a report that will be shared with the
Committee for review.
Member States are also encouraged to
provide any additional relevant information
(unpublished or published) that is available
on these substances to: ecddsecretariat@
who.int. This information will be an
invaluable contribution to the ECDD and all
submissions will be treated as confidential.
The WHO takes this opportunity to renew
to Member States and Associate Members the
assurance of its highest consideration.
GENEVA, 21 August 2018
Attachment:
41st WHO Expert Committee on Drug
Dependence
Member State Questionnaire Substances
SYNTHETIC CANNABINOIDS
ADB–FUBINACA
FUB–AMB (MMB–FUBINACA, AMB–
FUBINACA)
ADB–CHMINACA
CUMYL–4CN–BINACA
FENTANYLS
Cyclopropyl Fentanyl
Methoxyacetyl Fentanyl
Ortho-Fluorofentanyl
Para-Fluoro Butyrfentanyl
Para-Methoxybutyrfentanyl
(METH)CATHINONE
N-Ethylnorpentylone
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MEDICINES
Tramadol
Pregabalin
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/medicines/
access/controlled-substances/ecdd_41_
meeting/en/.
III. Substances Under WHO Review
ADB–FUBINACA (chemical name:
N-[1-(aminocarbonyl)-2,2-
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dimethylpropyl]-1-[(4fluorophenyl)methyl]-1H-indazole-3carboxamide) is an indazole-based
synthetic cannabinoid that is a potent,
full agonist at CB1 receptors. This
substance functionally (biologically)
mimics the effects of the structurally
unrelated delta-9-tetrahydrocannabinol
(THC), a Schedule I substance, and the
main psychoactive chemical constituent
in the cannabis (marijuana) plant.
Synthetic cannabinoids have been
marketed under the guise of ‘‘herbal
incense,’’ and promoted by drug
traffickers as legal alternatives to
marijuana. ADB–FUBINACA use has
been associated with serious adverse
events including death in the United
States. There are no commercial or
approved medical uses for ADB–
FUBINACA. On April 10, 2017, ADB–
FUBINACA was temporarily controlled
as a Schedule I substance under the
CSA.
FUB–AMB (other names: MMB–
FUBINACA; AMB–FUBINACA;
chemical name: methyl 2-(1-(4fluorobenzyl)-1H-indazole-3carboxamido)-3-methylbutanoate) is an
indazole-based synthetic cannabinoid
that is a potent full agonist at CB1
receptors. This substance functionally
(biologically) mimics the effects of the
structurally unrelated THC, a Schedule
I substance, and the main psychoactive
chemical constituent in marijuana.
Synthetic cannabinoids have been
marketed under the guise of ‘‘herbal
incense,’’ and promoted by drug
traffickers as legal alternatives to
marijuana. FUB–AMB use has been
associated with serious adverse events
including death in the United States.
There are no commercial or approved
medical uses for FUB–AMB. On
November 3, 2017, FUB–AMB was
temporarily controlled as a Schedule I
substance under the CSA.
ADB–CHMINACA (other name:
MAB–CHMINACA; chemical name:
N-(1-amino-3,3-dimethyl-1-oxobutan-2yl)-1-(cyclohexylmethyl)-1H-indole-3carboxamide) is an indazole-based
synthetic cannabinoid that is a potent
full agonist at CB1 receptors. This
substance functionally (biologically)
mimics the effects of the structurally
THC, a Schedule I substance, and the
main psychoactive chemical constituent
in marijuana. Synthetic cannabinoids
have been marketed under the guise of
‘‘herbal incense,’’ and promoted by drug
traffickers as legal alternatives to
marijuana. ADB–CHMINACA use has
been associated with serious adverse
events including death in the United
States. There are no commercial or
approved medical uses for ADB–
CHMINACA. On February 5, 2016,
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ADB–CHMINACA was temporarily
controlled as a Schedule I substance
under the CSA.
CUMYL–4CN–BINACA (chemical
name: 1-(4-cyanobutyl)-N-(2phenylpropan-2-yl)-1 H-indazole-3carboxamide) is a clandestinely
produced indazole-3-carboxamide based
synthetic cannabinoid that has been
sold online and used to mimic the
biological effects of THC, the main
psychoactive chemical constituent in
marijuana. Synthetic cannabinoids have
been marketed under the guise of
‘‘herbal incense,’’ and promoted by drug
traffickers as legal alternatives to
marijuana. Hospital, scientific
publications and law enforcement
reports show that CUMYL–4CN–
BINACA is abused for its psychoactive
properties. CUMYL–4CN–BINACA has
been associated with serious adverse
events in the United States, in addition
to multiple deaths in Europe. CUMYL–
4CN–BINACA has no commercial or
medical uses. On July 10, 2018,
CUMYL–4CN–BINACA was temporarily
controlled as a Schedule I substance
under the CSA.
Cyclopropyl fentanyl is a synthetic
opioid that has a pharmacological
profile similar to other Schedule I and
II controlled opioid substances such as
acetyl fentanyl, fentanyl, and other
related mu-opioid receptor agonist
substances. This clandestinely produced
analog of fentanyl is associated with
adverse events typically associated with
opioid use such as respiratory
depression, anxiety, constipation,
tiredness, hallucinations, and
withdrawal. Cyclopropyl fentanyl has
been associated with numerous
fatalities. At least 115 confirmed
overdose deaths involving cyclopropyl
fentanyl abuse have been reported in the
United States. Cyclopropyl fentanyl has
no commercial or currently accepted
medical uses in the United States. On
January 4, 2018, cyclopropyl fentanyl
was temporarily placed into Schedule I
of the CSA.
Methoxyacetyl fentanyl has a
pharmacological profile similar to other
Schedule I and II opioid substances
such as acetyl fentanyl, fentanyl, and
other related mu-opioid receptor agonist
substances. Evidence suggests that the
pattern of abuse of fentanyl analogues,
including methoxyacetyl fentanyl is
similar to heroin and prescription
opioid analgesics. Law enforcement and
public health reports demonstrate that
methoxyacetyl fentanyl is being illicitly
distributed and abused. The Drug
Enforcement Administration (DEA) is
aware of at least two overdose deaths
associated with the abuse of
methoxyacetyl fentanyl in the United
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States. Methoxyacetyl fentanyl has no
currently accepted medical use in
treatment in the United States. On
October 26, 2017, methoxyacetyl
fentanyl was temporarily placed into
Schedule I of the CSA.
Ortho-fluorofentanyl has a
pharmacological profile similar to
fentanyl and other related mu-opioid
receptor agonist. Ortho-fluorofentanyl
has no currently accepted medical use
in treatment in the United States. Orthofluorofentanyl has been encountered by
law enforcement and public health
officials. The DEA has received reports
for at least 13 confirmed overdose
deaths involving ortho-fluorofentanyl
abuse in the United States. On October
26, 2017, ortho-fluorofentanyl was
temporarily placed into Schedule I of
the CSA.
Para-fluorobutyrfentanyl shares
pharmacological profile with other
Schedule I (e.g., butyryl fentanyl) and II
(e.g., fentanyl) opioid substances. Parafluorobutyrfentanyl has no currently
accepted medical use in treatment in the
United States. The abuse of parafluorobutyrfentanyl carries public
health risks similar to that of heroin,
fentanyl, and prescription opioid
analgesics. On February 1, 2018, parafluorobutyrfentanyl was temporarily
placed into Schedule I of the CSA.
Para-methoxybutyrfentanyl shares
pharmacological profile with other
Schedule I (e.g., butyryl fentanyl) and II
(e.g., fentanyl) opioid substances. Paramethoxybutyrfentanyl has no currently
accepted medical use in treatment in the
United States. The abuse of paramethoxybutyrfentanyl carries public
health risks similar to that of heroin,
fentanyl, and prescription opioid
analgesics. On February 1, 2018, paramethoxybutyrfentanyl was temporarily
placed into Schedule I of the CSA.
N-ethylnorpentylone (other name: Nethylpentylone) is a synthetic cathinone
with stimulant and psychoactive
properties similar to cathinone, a
Schedule I substance. N-ethylpentylone
abuse has been associated with adverse
health effects leading to emergency
department admissions, and deaths. Nethylpentylone has no currently
accepted medical use in treatment in the
United States. On August 31, 2018, Nethylnorpentylone was temporarily
controlled as a Schedule I substance
under the CSA.
Tramadol, an opioid analgesic, was
first approved by the FDA for medical
use in March of 1995 for the treatment
of moderate to moderately severe pain.
It is available as immediate-release,
extended-release, and combination
products containing acetaminophen.
Tramadol has been abused alone or in
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combination with other psychoactive
substances. On July 2, 2014, the DEA
issued a Final Rule controlling tramadol
as a Schedule IV substance under the
CSA with effective date of August 18,
2014.
The ECDD pre-reviewed tramadol at
its 39th meeting in November 2017
noting growing evidence of abuse of
tramadol in many countries, in some
cases serious, accompanied by adverse
reactions and tramadol-associated
deaths and recommending that tramadol
be subject to a critical review at a
subsequent meeting.
Pregabalin is an FDA-approved
medication in the United States and is
available as an oral capsule and oral
solution and approved for the
management of neuropathic pain
associated with diabetic peripheral
neuropathy, postherpetic neuralgia, and
adjunctive therapy for partial onset
seizures, fibromyalgia, and neuropathic
pain associated with spinal cord injury.
Although the mechanism of action of
pregabalin is unknown, pregabalin is
thought to produce its therapeutic
effects on neuropathic pain via binding
with high affinity to the alpha 2-delta
receptor site (a subunit of voltage gated
calcium channels) within the central
nervous system. Reports indicate that
patients are self-administering higher
than recommended doses to achieve
euphoria, especially patients who have
a history of substance abuse,
particularly opioids. While effects of
excessively high doses are generally
non-lethal, gabapentinoids such as
pregabalin are increasingly being
identified in postmortem toxicology
analyses. Pregabalin is a Schedule V
controlled substance in the United
States under the CSA. At its 39th
meeting in November 2017, the WHO
Expert Committee on Drug Dependence
(ECDD) pre-reviewed pregabalin and,
noting increasing evidence of misuse
and abuse in many countries, the ECDD
recommended that pregabalin be subject
to a future critical review.
Cannabis, also known as marijuana, is
a plant known by biological names
Cannabis sativa or Cannabis indica. It is
a complex plant substance containing
multiple cannabinoids and other
compounds, including the psychoactive
chemical THC and other structurally
similar compounds. Cannabinoids are
defined as having activity at
cannabinoid 1 and 2 (CB1 and CB2
respectively) receptors. Agonists of CB1
receptors are widely abused and are
known to modulate motor coordination,
memory processing, pain, and
inflammation, and have anxiolytic
effects.
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50941
The principal cannabinoids in the
cannabis plant include THC,
cannabidiol (CBD), and cannabinol.
These substances are controlled in
Schedule I under the CSA. The
synthetically derived single pure
stereoisomer, (¥)-trans-delta-9-THC
(also known as dronabinol) is the active
ingredient in two approved drug
products in the United States,
MARINOL (dronabinol) capsules (and
generics) and SYNDROS (dronabinol)
oral solution. MARINOL is controlled in
Schedule III, while SYNDROS is
controlled in Schedule II under the
CSA. Both MARINOL and SYNDROS
are approved to treat anorexia
associated with weight loss in patients
with acquired immunodeficiency
syndrome (AIDS), and nausea and
vomiting associated with cancer
chemotherapy in patients who have
failed to respond adequately to
conventional treatment.
CBD is another cannabinoid
constituent of the cannabis plant. In the
United States, one CBD-containing
product, Epidiolex oral solution, has
received marketing approval by FDA for
the treatment of seizures associated with
two rare and severe forms of epilepsy,
Lennox-Gastaut syndrome and Dravet
syndrome, in patients 2 years of age and
older. The CBD in Epidiolex is extracted
and purified from the cannabis plant.
Currently, CBD is controlled generally
as a Schedule I substance under the
CSA. However, the recent scheduling
action on September 28, 2018, by the
DEA for Epidiolex, and any future,
similar formulations of CBD that
become FDA-approved medications,
places these FDA-approved CBD
formulations in Schedule V under the
CSA.1 CBD is not specifically listed in
the schedules of the 1961, 1971, or 1988
International Drug Control conventions.
At the 40th (2018) meeting of the
ECDD, the committee criticallyreviewed CBD and pre-reviews of
cannabis plant and resin; extracts and
tinctures of cannabis; THC; and isomers
of THC. The 40th ECDD recommended
that preparations considered to be pure
CBD should not be scheduled within the
International Drug Control Conventions,
and that cannabis plant and resin;
extracts and tinctures of cannabis; THC;
and isomers of THC proceed to a Critical
Review.
IV. Opportunity To Submit Domestic
Information
As required by paragraph (d)(2)(A) of
the CSA, FDA, on behalf of HHS, invites
1 https://www.ecfr.gov/cgi-bin/text-idx?SID=f43ff6
b6883b0b81774fab03dcea8fa5&mc=true&node=
pt21.9.1308&rgn=div5#se21.9.1308_115.
E:\FR\FM\10OCN1.SGM
10OCN1
50942
Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
interested persons to submit comments
regarding the 16 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 mid-2018.
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: October 3, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–21954 Filed 10–9–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA 2016–D–1254]
Assessing Adhesion With Transdermal
and Topical Delivery Systems for
Abbreviated New Drug Applications;
Revised Draft Guidance for Industry;
Availability
AGENCY:
Food and Drug Administration,
HHS.
amozie on DSK3GDR082PROD with NOTICES1
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a revised
draft guidance for industry entitled
‘‘Assessing Adhesion With Transdermal
and Topical Delivery Systems for
ANDAs.’’ This revised draft guidance
supersedes the draft guidance entitled
SUMMARY:
VerDate Sep<11>2014
21:20 Oct 09, 2018
Jkt 247001
‘‘Assessing Adhesion with Transdermal
Delivery Systems and Topical Patches
for ANDAs,’’ which was announced in
the Federal Register on June 1, 2016.
This revised draft guidance provides
recommendations for the design and
conduct of studies evaluating the
adhesive performance of a transdermal
or a topical delivery system (collectively
referred to as TDS). Depending on the
objectives of a TDS product
development program, applicants may
choose to evaluate TDS adhesion in
clinical studies performed to evaluate
TDS adhesion only or in clinical studies
performed with a combined purpose
(e.g., for the simultaneous evaluation of
adhesion and bioequivalence (BE) with
pharmacokinetic (PK) endpoints). The
recommendations in this revised draft
guidance relate exclusively to studies
submitted in support of an abbreviated
new drug application (ANDA).
DATES: Submit either electronic or
written comments on the revised draft
guidance by December 10, 2018 to
ensure that the Agency considers your
comment on this revised draft guidance
before it begins work on the final
version of the guidance.
ADDRESSES: You may submit comments
on any guidance at any time as follows:
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:
PO 00000
Frm 00059
Fmt 4703
Sfmt 4703
• 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 2016–
D–1254 for ‘‘Assessing Adhesion With
Transdermal and Topical Delivery
Systems for ANDAs.’’ Received
comments 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.
• 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.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.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
E:\FR\FM\10OCN1.SGM
10OCN1
]]>Agencies
[Federal Register Volume 83, Number 196 (Wednesday, October 10, 2018)]
[Notices]
[Pages 50938-50942]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-21954]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-N-3685]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; ADB-FUBINACA; ADB-
CHMINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; para-Fluoro
Butyrfentanyl; Tramadol; Pregabalin; Cannabis Plant and Resin; and
Eight Additional Substances; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is requesting
interested persons to submit comments concerning abuse potential,
actual abuse, medical usefulness, trafficking, and impact of scheduling
changes on availability for medical use of 16 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 drugs. This notice requesting comments
is required by the Controlled Substances Act (the CSA).
DATES: Submit either electronic or written comments by October 31,
2018.
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 (enter date), 2018. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of October 31, 2018. 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
[[Page 50939]]
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-2018-N-3685 for ``International Drug Scheduling; Convention on
Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-
FUBINACA; FUB-AMB(MMB-FUBINACA_AMB-FUBINACA); ADB-CHMINACA; CUMYL-4CN-
BINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; Ortho-
Fluorofentanyl; Para-Fluoro Butyrfentanyl; Para-Methoxybutyrfentanyl;
N-Ethylnorpentylone; Tramadol; Pregabalin; Cannabis Plant and Resin;
Extracts and Tinctures of Cannabis; Delta-9-Tetrahydrocannabinol;
Stereoisomers of Tetrahydrocannabinol; 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.
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.gpo.gov/fdsys/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.
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: [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.26.2018
The World Health Organization (WHO) presents its compliments to
Member States and Associate Members and has the pleasure of
informing that the 41th Expert Committee on Drug Dependence (ECDD)
will meet in Geneva from 12 to 16 November 2018. The 41th ECDD will
convene to review psychoactive substances on their potential to
cause dependence, abuse and harm to health, and their potential
therapeutic applications. WHO will make recommendations to the UN
Secretary-General on the need for and level of international control
of these substances.
Member States are invited to collaborate, as in the past, in
this process by providing pertinent information as requested in the
questionnaire and concerning substances under review. At its 126th
session in January 2010, the Executive Board approved the
publication ``Guidance on the WHO review of psychoactive substances
for international control'' (EB126/2010/REC1, Annex 6) which
requires the Secretariat to request relevant information from
Ministers of Health in Member States to prepare a report for
submission to the ECDD.
For this purpose, a questionnaire was designed to gather
information on the legitimate use, harmful use, status of national
control and potential impact of international control for each
substance under evaluation. A list of substances for which Member
States will receive questionnaires is attached.
Kindly note that Member States who submitted questionnaire
responses that were reviewed at the 40th ECDD on cannabis and
cannabis-related substances will not be requested to re-submit
questionnaires for those substances for the 41st ECDD. However, if
Member States would like to amend their responses or submit
additional information on cannabis and cannabis-related substances,
it is requested that they inform the Secretariat.
It would be appreciated if a person from the Ministry of Health
could be designated as the focal point responsible for coordinating
answers to the questionnaires. A list of focal
[[Page 50940]]
points designated by Member States for the 40th ECDD in June 2018 is
attached. It is requested that if a focal point's contact details
including email address are to be added or amended, that Member
States inform the Secretariat by 17 September 2018. Any additions or
amendments to focal point designations should be emailed to
[email protected].
If no additions or amendments to focal point details are made by
this date, the focal point from 2018 will be approached by the
Secretariat for questionnaire completion. Where there is a competent
National Authority under the International Drug Control Treaties, it
is kindly requested that the questionnaires be completed in
collaboration with such body.
Once the Secretariat has received the contact details, focal
points will be given further instructions and direct access to an
online questionnaire. The questionnaires will be analysed by the
Secretariat and prepared as a report that will be shared with the
Committee for review.
Member States are also encouraged to provide any additional
relevant information (unpublished or published) that is available on
these substances to: [email protected]. This information will
be an invaluable contribution to the ECDD and all submissions will
be treated as confidential.
The WHO takes this opportunity to renew to Member States and
Associate Members the assurance of its highest consideration.
GENEVA, 21 August 2018
Attachment:
41st WHO Expert Committee on Drug Dependence
Member State Questionnaire Substances
SYNTHETIC CANNABINOIDS
ADB-FUBINACA
FUB-AMB (MMB-FUBINACA, AMB-FUBINACA)
ADB-CHMINACA
CUMYL-4CN-BINACA
FENTANYLS
Cyclopropyl Fentanyl
Methoxyacetyl Fentanyl
Ortho-Fluorofentanyl
Para-Fluoro Butyrfentanyl
Para-Methoxybutyrfentanyl
(METH)CATHINONE
N-Ethylnorpentylone
MEDICINES
Tramadol
Pregabalin
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/medicines/access/controlled-substances/ecdd_41_meeting/en/.
III. Substances Under WHO Review
ADB-FUBINACA (chemical name: N-[1-(aminocarbonyl)-2,2-
dimethylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide)
is an indazole-based synthetic cannabinoid that is a potent, full
agonist at CB1 receptors. This substance functionally (biologically)
mimics the effects of the structurally unrelated delta-9-
tetrahydrocannabinol (THC), a Schedule I substance, and the main
psychoactive chemical constituent in the cannabis (marijuana) plant.
Synthetic cannabinoids have been marketed under the guise of ``herbal
incense,'' and promoted by drug traffickers as legal alternatives to
marijuana. ADB-FUBINACA use has been associated with serious adverse
events including death in the United States. There are no commercial or
approved medical uses for ADB-FUBINACA. On April 10, 2017, ADB-FUBINACA
was temporarily controlled as a Schedule I substance under the CSA.
FUB-AMB (other names: MMB-FUBINACA; AMB-FUBINACA; chemical name:
methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-
methylbutanoate) is an indazole-based synthetic cannabinoid that is a
potent full agonist at CB1 receptors. This substance functionally
(biologically) mimics the effects of the structurally unrelated THC, a
Schedule I substance, and the main psychoactive chemical constituent in
marijuana. Synthetic cannabinoids have been marketed under the guise of
``herbal incense,'' and promoted by drug traffickers as legal
alternatives to marijuana. FUB-AMB use has been associated with serious
adverse events including death in the United States. There are no
commercial or approved medical uses for FUB-AMB. On November 3, 2017,
FUB-AMB was temporarily controlled as a Schedule I substance under the
CSA.
ADB-CHMINACA (other name: MAB-CHMINACA; chemical name: N-(1-amino-
3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indole-3-
carboxamide) is an indazole-based synthetic cannabinoid that is a
potent full agonist at CB1 receptors. This substance functionally
(biologically) mimics the effects of the structurally THC, a Schedule I
substance, and the main psychoactive chemical constituent in marijuana.
Synthetic cannabinoids have been marketed under the guise of ``herbal
incense,'' and promoted by drug traffickers as legal alternatives to
marijuana. ADB-CHMINACA use has been associated with serious adverse
events including death in the United States. There are no commercial or
approved medical uses for ADB-CHMINACA. On February 5, 2016, ADB-
CHMINACA was temporarily controlled as a Schedule I substance under the
CSA.
CUMYL-4CN-BINACA (chemical name: 1-(4-cyanobutyl)-N-(2-
phenylpropan-2-yl)-1 H-indazole-3-carboxamide) is a clandestinely
produced indazole-3-carboxamide based synthetic cannabinoid that has
been sold online and used to mimic the biological effects of THC, the
main psychoactive chemical constituent in marijuana. Synthetic
cannabinoids have been marketed under the guise of ``herbal incense,''
and promoted by drug traffickers as legal alternatives to marijuana.
Hospital, scientific publications and law enforcement reports show that
CUMYL-4CN-BINACA is abused for its psychoactive properties. CUMYL-4CN-
BINACA has been associated with serious adverse events in the United
States, in addition to multiple deaths in Europe. CUMYL-4CN-BINACA has
no commercial or medical uses. On July 10, 2018, CUMYL-4CN-BINACA was
temporarily controlled as a Schedule I substance under the CSA.
Cyclopropyl fentanyl is a synthetic opioid that has a
pharmacological profile similar to other Schedule I and II controlled
opioid substances such as acetyl fentanyl, fentanyl, and other related
mu-opioid receptor agonist substances. This clandestinely produced
analog of fentanyl is associated with adverse events typically
associated with opioid use such as respiratory depression, anxiety,
constipation, tiredness, hallucinations, and withdrawal. Cyclopropyl
fentanyl has been associated with numerous fatalities. At least 115
confirmed overdose deaths involving cyclopropyl fentanyl abuse have
been reported in the United States. Cyclopropyl fentanyl has no
commercial or currently accepted medical uses in the United States. On
January 4, 2018, cyclopropyl fentanyl was temporarily placed into
Schedule I of the CSA.
Methoxyacetyl fentanyl has a pharmacological profile similar to
other Schedule I and II opioid substances such as acetyl fentanyl,
fentanyl, and other related mu-opioid receptor agonist substances.
Evidence suggests that the pattern of abuse of fentanyl analogues,
including methoxyacetyl fentanyl is similar to heroin and prescription
opioid analgesics. Law enforcement and public health reports
demonstrate that methoxyacetyl fentanyl is being illicitly distributed
and abused. The Drug Enforcement Administration (DEA) is aware of at
least two overdose deaths associated with the abuse of methoxyacetyl
fentanyl in the United
[[Page 50941]]
States. Methoxyacetyl fentanyl has no currently accepted medical use in
treatment in the United States. On October 26, 2017, methoxyacetyl
fentanyl was temporarily placed into Schedule I of the CSA.
Ortho-fluorofentanyl has a pharmacological profile similar to
fentanyl and other related mu-opioid receptor agonist. Ortho-
fluorofentanyl has no currently accepted medical use in treatment in
the United States. Ortho-fluorofentanyl has been encountered by law
enforcement and public health officials. The DEA has received reports
for at least 13 confirmed overdose deaths involving ortho-
fluorofentanyl abuse in the United States. On October 26, 2017, ortho-
fluorofentanyl was temporarily placed into Schedule I of the CSA.
Para-fluorobutyrfentanyl shares pharmacological profile with other
Schedule I (e.g., butyryl fentanyl) and II (e.g., fentanyl) opioid
substances. Para-fluorobutyrfentanyl has no currently accepted medical
use in treatment in the United States. The abuse of para-
fluorobutyrfentanyl carries public health risks similar to that of
heroin, fentanyl, and prescription opioid analgesics. On February 1,
2018, para-fluorobutyrfentanyl was temporarily placed into Schedule I
of the CSA.
Para-methoxybutyrfentanyl shares pharmacological profile with other
Schedule I (e.g., butyryl fentanyl) and II (e.g., fentanyl) opioid
substances. Para-methoxybutyrfentanyl has no currently accepted medical
use in treatment in the United States. The abuse of para-
methoxybutyrfentanyl carries public health risks similar to that of
heroin, fentanyl, and prescription opioid analgesics. On February 1,
2018, para-methoxybutyrfentanyl was temporarily placed into Schedule I
of the CSA.
N-ethylnorpentylone (other name: N-ethylpentylone) is a synthetic
cathinone with stimulant and psychoactive properties similar to
cathinone, a Schedule I substance. N-ethylpentylone abuse has been
associated with adverse health effects leading to emergency department
admissions, and deaths. N-ethylpentylone has no currently accepted
medical use in treatment in the United States. On August 31, 2018, N-
ethylnorpentylone was temporarily controlled as a Schedule I substance
under the CSA.
Tramadol, an opioid analgesic, was first approved by the FDA for
medical use in March of 1995 for the treatment of moderate to
moderately severe pain. It is available as immediate-release, extended-
release, and combination products containing acetaminophen. Tramadol
has been abused alone or in combination with other psychoactive
substances. On July 2, 2014, the DEA issued a Final Rule controlling
tramadol as a Schedule IV substance under the CSA with effective date
of August 18, 2014.
The ECDD pre-reviewed tramadol at its 39th meeting in November 2017
noting growing evidence of abuse of tramadol in many countries, in some
cases serious, accompanied by adverse reactions and tramadol-associated
deaths and recommending that tramadol be subject to a critical review
at a subsequent meeting.
Pregabalin is an FDA-approved medication in the United States and
is available as an oral capsule and oral solution and approved for the
management of neuropathic pain associated with diabetic peripheral
neuropathy, postherpetic neuralgia, and adjunctive therapy for partial
onset seizures, fibromyalgia, and neuropathic pain associated with
spinal cord injury. Although the mechanism of action of pregabalin is
unknown, pregabalin is thought to produce its therapeutic effects on
neuropathic pain via binding with high affinity to the alpha 2-delta
receptor site (a subunit of voltage gated calcium channels) within the
central nervous system. Reports indicate that patients are self-
administering higher than recommended doses to achieve euphoria,
especially patients who have a history of substance abuse, particularly
opioids. While effects of excessively high doses are generally non-
lethal, gabapentinoids such as pregabalin are increasingly being
identified in postmortem toxicology analyses. Pregabalin is a Schedule
V controlled substance in the United States under the CSA. At its 39th
meeting in November 2017, the WHO Expert Committee on Drug Dependence
(ECDD) pre-reviewed pregabalin and, noting increasing evidence of
misuse and abuse in many countries, the ECDD recommended that
pregabalin be subject to a future critical review.
Cannabis, also known as marijuana, is a plant known by biological
names Cannabis sativa or Cannabis indica. It is a complex plant
substance containing multiple cannabinoids and other compounds,
including the psychoactive chemical THC and other structurally similar
compounds. Cannabinoids are defined as having activity at cannabinoid 1
and 2 (CB1 and CB2 respectively) receptors. Agonists of CB1 receptors
are widely abused and are known to modulate motor coordination, memory
processing, pain, and inflammation, and have anxiolytic effects.
The principal cannabinoids in the cannabis plant include THC,
cannabidiol (CBD), and cannabinol. These substances are controlled in
Schedule I under the CSA. The synthetically derived single pure
stereoisomer, (-)-trans-delta-9-THC (also known as dronabinol) is the
active ingredient in two approved drug products in the United States,
MARINOL (dronabinol) capsules (and generics) and SYNDROS (dronabinol)
oral solution. MARINOL is controlled in Schedule III, while SYNDROS is
controlled in Schedule II under the CSA. Both MARINOL and SYNDROS are
approved to treat anorexia associated with weight loss in patients with
acquired immunodeficiency syndrome (AIDS), and nausea and vomiting
associated with cancer chemotherapy in patients who have failed to
respond adequately to conventional treatment.
CBD is another cannabinoid constituent of the cannabis plant. In
the United States, one CBD-containing product, Epidiolex oral solution,
has received marketing approval by FDA for the treatment of seizures
associated with two rare and severe forms of epilepsy, Lennox-Gastaut
syndrome and Dravet syndrome, in patients 2 years of age and older. The
CBD in Epidiolex is extracted and purified from the cannabis plant.
Currently, CBD is controlled generally as a Schedule I substance under
the CSA. However, the recent scheduling action on September 28, 2018,
by the DEA for Epidiolex, and any future, similar formulations of CBD
that become FDA-approved medications, places these FDA-approved CBD
formulations in Schedule V under the CSA.\1\ CBD is not specifically
listed in the schedules of the 1961, 1971, or 1988 International Drug
Control conventions.
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\1\ https://www.ecfr.gov/cgi-bin/text-idx?SID=f43ff6b6883b0b81774fab03dcea8fa5&mc=true&node=pt21.9.1308&rgn=div5#se21.9.1308_115.
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At the 40th (2018) meeting of the ECDD, the committee critically-
reviewed CBD and pre-reviews of cannabis plant and resin; extracts and
tinctures of cannabis; THC; and isomers of THC. The 40th ECDD
recommended that preparations considered to be pure CBD should not be
scheduled within the International Drug Control Conventions, and that
cannabis plant and resin; extracts and tinctures of cannabis; THC; and
isomers of THC proceed to a Critical Review.
IV. Opportunity To Submit Domestic Information
As required by paragraph (d)(2)(A) of the CSA, FDA, on behalf of
HHS, invites
[[Page 50942]]
interested persons to submit comments regarding the 16 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 mid-
2018. 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: October 3, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-21954 Filed 10-9-18; 8:45 am]
BILLING CODE 4164-01-P
