82_FR_38021 82 FR 37866 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Ocfentanil, Carfentanil, Pregabalin, Tramadol, Cannabidiol, Ketamine, and Eleven Other Substances; Request for Comments

82 FR 37866 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Ocfentanil, Carfentanil, Pregabalin, Tramadol, Cannabidiol, Ketamine, and Eleven Other Substances; Request for Comments

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 155 (August 14, 2017)

Page Range37866-37869
FR Document2017-17119

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 17 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).

Federal Register, Volume 82 Issue 155 (Monday, August 14, 2017)
[Federal Register Volume 82, Number 155 (Monday, August 14, 2017)]
[Notices]
[Pages 37866-37869]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-17119]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-4515]


International Drug Scheduling; Convention on Psychotropic 
Substances; Single Convention on Narcotic Drugs; Ocfentanil, 
Carfentanil, Pregabalin, Tramadol, Cannabidiol, Ketamine, and Eleven 
Other Substances; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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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 17 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 September 13, 
2017.

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 September 13, 2017. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of September 13, 2017. 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-2017-N-4515 for ``International Drug Scheduling; Convention on 
Psychotropic Substances; Single Convention on Narcotic Drugs; 
Ocfentanil; Furanyl fentanyl (Fu-F); Acryloylfentanyl (Acrylfentanyl); 
Carfentanil; 4-fluoroisobutyrfentanyl (4-FIBF); 
Tetrahydrofuranylfentanyl (THF-F); 4-fluoroamphetamine (4-FA); AB-
PINACA; AB-CHMINACA; 5F-PB-22; UR-144; 5F-ADB; Etizolam; Pregabalin; 
Tramadol; Cannabidiol; Ketamine; 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

[[Page 37867]]

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.thefederalregister.org/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.
    Section 201 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.xx.2017

    The World Health Organization (WHO) presents its compliments to 
Member States and Associate Members and has the pleasure of 
informing that the Thirty-ninth Expert Committee on Drug Dependence 
(ECDD) will meet in Geneva from 6 to 10 November 2017 to review a 
number of substances with potential for dependence, abuse and harm 
to health, and will make recommendations to the U.N. Secretary-
General, on the need for and level of international control of these 
substances.
    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. 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.
    It would be appreciated if a person from the Ministry of Health 
could be designated as the focal point responsible for coordinating 
and answering the questionnaire. (non relevant information from 
letter not shown, see letter for text not shown here) The designated 
focal point, and only this person, should access and complete the 
questionnaires:

1. Ocfentanil
2. Furanyl fentanyl (Fu-F)
3. Acryloylfentanyl (Acrylfentanyl)
4. Carfentanil
5. 4-fluoroisobutyrfentanyl (4-FIBF)
6. Tetrahydrofuranylfentanyl (THF-F)
7. 4-fluoroamphetamine (4-FA)
8. AB-PINACA
9. AB-CHMINACA
10. 5F-PB-22
11. UR-144
12. 5F-ADB
13. Etizolam
14. Pregabalin
15. Tramadol
16. Cannabidiol
17. Ketamine

    PDF versions of the questionnaire in English, French and Spanish 
may be downloaded from the link http://www.who.int/medicines/access/controlled-substances/ecdd/en/. Please note that these versions are 
for reference only and all questionnaires must be answered through 
the online system. Further clarification regarding the questionnaire 
may be obtained from the Secretariat by emailing: 
[email protected].
    Replies to the questionnaire must reach the Secretariat by 30 
September 2017 in order to facilitate analyses and preparation of 
the report before the planned meeting. Where there is a competent 
National Authority under the International Drug Control Treaties, it 
is kindly requested that the questionnaire be completed in 
collaboration with such body.
    The summary information from the questionnaire will be published 
online as part of the report on the Web site for the Thirty-ninth 
ECDD linked to the Department of Essential Medicines and Health 
Products (EMP). The provisional agenda of the Thirty-ninth ECDD and 
the list of psychoactive substances under review are also published 
on Thirty-ninth ECDD Web page: http://www.who.int/medicines/access/controlled-substances/ecdd/en/.
    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 World Health Organization takes this opportunity to renew to 
Member States and Associate Members the assurance of its highest 
consideration.

GENEVA, 7 July 2017

    FDA has verified the Web site addresses contained in the WHO 
notice, as of the date this document publishes in the Federal Register, 
but Web sites are subject to change over time.

III. Substances Under WHO Review

    Ocfentanil is a synthetically produced opioid that is structurally 
related to fentanyl and approximately equipotent in effect. Reported 
risks associated with use of ocfentanil include development of opioid 
use disorder, overdose, and fatal overdose. It has no approved medical 
use in the United States and is not a controlled substance in the 
United States under the CSA.
    Furanyl fentanyl (Fu-F) is a potent clandestinely produced 
synthetic opioid that is an analog of fentanyl. Evidence suggests that 
the pattern of abuse of fentanyl analogues, including furanyl fentanyl, 
parallels that of heroin and

[[Page 37868]]

prescription opioid analgesics. Fu-F produces the typical opioid 
effects that include respiratory depression and loss of consciousness. 
Seizures of Fu-F have been encountered in powder form. Fu-F has been 
connected to fatal overdoses, in which intravenous routes of 
administration are documented. It has no approved medical use in the 
United States. On November 29, 2016, the Drug Enforcement 
Administration (DEA) issued a final order to temporarily schedule Fu-F 
and its isomers, esters, ethers, salts and salts of isomers, esters and 
ethers, into Schedule I pursuant to the temporary scheduling provisions 
of the CSA.
    Acryloylfentanyl (Acrylfentanyl) belongs to the 4-anilidopiperidine 
class of synthetic opioids and is similar in structure to fentanyl. 
Acryloylfentanyl is a clandestinely produced analog of fentanyl and 
sold illegally as a research chemical on several Web sites. 
Acryloylfentanyl has also been associated with adverse events typically 
associated with opioid use such as respiratory depression, anxiety, 
constipation, tiredness, hallucinations, and withdrawal. The use of 
acryloylfentanyl has also been linked to the development of opioid use 
disorder, overdose, and fatal overdose. Acryloylfentanyl has no 
commercial or medical uses. On July 14, 2017, the DEA issued a 
temporary order to temporarily schedule acryloylfentanyl, its isomers, 
esters, ethers, salts and salts of isomers, esters, and ethers, into 
Schedule I pursuant to the temporary scheduling provisions of the CSA.
    Carfentanil, also known as 4-carbomethoxyfentanyl, is an extremely 
potent synthetic opioid that is similar in structure to and 
approximately 100 times more potent than fentanyl as an analgesic. At 
one time legitimately produced, carfentanil is no longer manufactured, 
marketed, or used in the United States; it is approved by FDA for use 
under restricted conditions by veterinarians as a immobilizing agent 
for certain large animals. Illicitly produced carfentanil is a 
particularly harmful fentanyl analogue that is also being laced into 
heroin or sold by itself and trafficked in the United States. It is not 
approved for human use. Drug seizure data indicate that carfentanil is 
typically used in small doses to cut heroin and other illicitly abused 
drugs. The significant risk to public health associated with 
carfentanil use stems from its respiratory depressive effects with very 
small amounts. Several fatalities have been reported as the result of 
carfentanil overdoses. On October 28, 1988, the DEA placed carfentanil 
in Schedule II of the CSA.
    4-fluoroisobutyrfentanyl is a clandestinely produced synthetic 
opioid that is an analog of fentanyl. It has [micro]-receptor agonist 
activity similar to that of fentanyl. This would result in effects 
associated with opioid agonists such as analgesia, respiratory 
depression, anxiety, constipation, tiredness, hallucinations, 
withdrawal, the development of opioid use disorder, overdose, and fatal 
overdose. The use of 4-fluoroisobutyrfentanyl has been implicated in 
several cases of overdose and fatal overdoses. 4-fluoroisobutyrfentanyl 
has not been approved for medical use in the U.S. On May 3, 2017, the 
DEA issued a temporary order to temporarily schedule 4-
fluoroisobutyrfentanyl, its isomers, esters, ethers, salts and salts of 
isomers, esters and ethers, into Schedule I pursuant to the temporary 
scheduling provisions of the CSA.
    Tetrahydrofuranylfentanyl (THF-F) is a synthetic opioid that is an 
analog of fentanyl. It has [micro]-receptor agonist activity similar to 
that of fentanyl, resulting in effects associated with opioid agonists 
such as analgesia, respiratory depression, anxiety, constipation, 
tiredness, hallucinations, withdrawal, the development of opioid use 
disorder, overdose, and fatal overdose. THF-F is not approved for 
medical use or controlled in the United States under the CSA.
    4-Fluoroamphetamine (4-FA) is a psychoactive substance of the 
phenethylamine and substituted amphetamine chemical classes and 
produces stimulant effects. WHO reports that 4-FA is clandestinely 
produced, and its use is associated with fatal and non-fatal 
intoxications. 4-FA was reviewed at the 37th ECDD (2015) and, while not 
placed under international control due to insufficient data, was kept 
under surveillance. 4-FA is not approved for medical use in the United 
States and it is not controlled under the CSA.
    AB-PINACA is a clandestinely produced synthetic cannabinoid agonist 
approximately 1.5 times as potent as delta-9-tetrahydrocannabinol. 
Adverse effects produced by cannabinoid agonists include tachycardia, 
agitation, hallucination, chest pain, seizure, anxiety, acute 
psychosis, and death. AB-PINACA has been detected in illicit synthetic 
cannabinoid substances, and reported in cases of overdose and 
hospitalizations. It has not been approved for medical use in the 
United States. On January 27, 2017, the DEA published a Notice of 
Proposed Rulemaking to permanently control AB-PINACA as a Schedule I 
substance under the CSA.
    AB-CHMINACA is a clandestinely produced synthetic cannabinoid 
agonist that is approximately 16 times more potent than delta-9-
tetrahydrocannabinol. Adverse effects produced by cannabinoid agonists 
include tachycardia, agitation, hallucination, chest pain, seizure, 
anxiety, acute psychosis, and death. AB-CHMINACA has been detected in 
illicit synthetic cannabinoid substances and found in cases of overdose 
and hospitalizations. AB-CHMINACA has not been pre-reviewed or 
critically reviewed by the WHO. On January 27, 2017, the DEA published 
a Notice of Proposed Rulemaking to permanently control AB-CHMINACA as a 
Schedule I substance under the CSA.
    5F-PB-22 is a synthetic cannabinoid agonist with similar effects to 
delta-9-tetrahydrocannabinol, one of the main psychoactive components 
of cannabis. Adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
acute psychosis, and death. 5F-PB-22 is clandestinely produced. It has 
been found laced on plant material and marketed as herbal products, and 
is smoked for its psychoactive effects. According to the WHO, 5F-PB-22 
has been associated with fatal intoxications. On September 6, 2016, the 
DEA issued a final rule to permanently place 5F-PB-22 into Schedule I 
of the CSA.
    UR-144 is a clandestinely produced synthetic cannabinoid agonist. 
In general, adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
and acute psychosis. UR-144 has been detected in herbal smoking blends 
that are sold as herbal incense. In June 2014, the 36th (2014) ECDD 
reviewed UR-144 and recommended that it be placed under surveillance. 
On May 11, 2016, the DEA issued a final rule to permanently schedule 
UR-144 into Schedule I of the CSA.
    5F-ADB is a clandestinely produced synthetic cannabinoid agonist. 
In general, adverse effects produced by cannabinoid agonists include 
tachycardia, agitation, hallucination, chest pain, seizure, anxiety, 
and acute psychosis. 5F-ADB has been identified in overdose and/or 
cases involving death attributed to their abuse. Adverse health effects 
reported from incidents involving 5F-ADB and other synthetic 
cannabinoids have included: Nausea, persistent vomiting, agitation, 
altered mental status, seizures, convulsions, loss of consciousness, 
and/or cardio toxicity. On April 10, 2017, the DEA issued a temporary 
scheduling order to

[[Page 37869]]

temporarily schedule 5F-ADB, its isomers, esters, ethers, salts and 
salts of isomers, esters, and ethers into Schedule I pursuant to the 
temporary scheduling provisions of the CSA.
    Etizolam belongs 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. 
Etizolam is currently prescribed in some countries to treat generalized 
anxiety disorder with depressive symptoms, but is not approved for 
medical use or controlled in the United States under the CSA. WHO 
reported that non-fatal intoxications that include cases of driving 
under the influence of drugs have been linked to etizolam. The ECDD at 
its 37th (2015 meeting reviewed etizolam and recommended that a 
critical review of etizolam is warranted.
    Pregabalin is an anticonvulsant-type drug used to treat pain 
generated from the nervous system. It is available as an oral capsule 
and oral solution and approved for medical use in the United States for 
the management of neuropathic pain associated with diabetic peripheral 
neuropathy, post-herpetic 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, studies in animals suggest that binding to the nervous system 
tissues may be involved in its pain-relieving and anti-seizure effects. 
Pregabalin binds with high affinity to the alpha 2-delta receptor site 
(a subunit of voltage-gated calcium channels) in the central nervous 
system. The binding of pregabalin at this site is thought to be 
responsible for its therapeutic effect on neuropathic pain. 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, and psychiatric illness. While 
effects of excessively high doses are generally non-lethal, 
gabapentinoids such as pregabalin are increasingly being identified in 
post-mortem toxicology analyses. Pregabalin is a Schedule V controlled 
substance in the United States under the CSA.
    Tramadol is an opioid analgesic that produces its primary opioid-
like action through an active metabolite referred to as the M1 
metabolite (O-desmethyltramadol). Tramadol was first approved for 
marketing in the United States in 1995 and is available as immediate-
release, extended-release, and combination products for the treatment 
of moderate to moderately severe pain. On July 2, 2014, the DEA 
published a final rule in the Federal Register controlling tramadol as 
a Schedule IV substance of the CSA effective from August 18, 2014. 
Tramadol was pre-reviewed by the ECDD at its 28th (1992) and 32nd 
(2000) meetings, and critically reviewed at the 33rd (2002) meeting and 
not recommended for international control but placed on surveillance. 
Tramadol was pre-reviewed again by the ECDD at its 34th (2006) meeting; 
however, the ECDD concluded that there was not sufficient evidence to 
justify a critical review. At the 36th (2014) meeting, the ECDD 
considered updated information on tramadol, but again concluded that 
there was insufficient evidence to warrant a critical review.
    Cannabidiol (CBD) is one of the active cannabinoids identified in 
cannabis. CBD has been shown to be beneficial in experimental models of 
several neurological disorders, including those of seizure and 
epilepsy. In the United States, CBD-containing products are in human 
clinical testing in three therapeutic areas, but no such products are 
approved by FDA for marketing for medical purposes in the United 
States. CBD is a Schedule I controlled substance under the CSA. At the 
37th (2015) meeting of the ECDD, the committee requested that the 
Secretariat prepare relevant documentation to conduct pre-reviews for 
several substances, including CBD.
    Ketamine is classified as a rapid-acting general anesthetic agent 
used for short diagnostic and surgical procedures that do not require 
skeletal muscle relaxation. It is marketed in the United States as a 
solution for injection. Ketamine is controlled in Schedule III of the 
CSA in the United States. It is not controlled internationally under 
the Convention on Psychotropic Substances or the Single Convention on 
Narcotic Drugs. The ECDD reviewed ketamine at its 34th (2006), 35th 
(2012), and 36th (2014) meetings. On March 13, 2015, the Commission on 
Narcotic Drugs (CND) decided by consensus to postpone the consideration 
of a proposal concerning the recommendation to place ketamine in 
Schedule IV of the Psychotropic Convention. The CND requested 
additional information from the WHO. The ECDD reviewed updated 
information at its 37th (2015) meeting and found no reason to recommend 
a new pre-review or critical review of ketamine that could potentially 
change its standing 2014 recommendation that ketamine should not be 
placed under international control.

IV. Opportunity To Submit Domestic Information

    As required by section 201(d)(2)(A) of the CSA, FDA, on behalf of 
HHS, invites interested persons to submit comments regarding the 17 
named drug substances. Any comments received will be considered by HHS 
when it prepares a scientific and medical evaluation of these drug 
substances. HHS will forward a scientific and medical evaluation of 
these drug substances to WHO, through the Secretary of State, 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 early 
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 section 201(d)(2)(B) of the 
CSA.

V. Electronic Access

    Persons with access to the Internet may obtain the document at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: August 9, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-17119 Filed 8-11-17; 8:45 am]
 BILLING CODE 4164-01-P



                                                37866                             Federal Register / Vol. 82, No. 155 / Monday, August 14, 2017 / Notices

                                                the Commonwealth of Northern Mariana
                                                Islands.

                                                                                                                        ANNUAL BURDEN ESTIMATES
                                                                                                                                                                         Number of           Average
                                                                                                                                                       Number of                                          Total burden
                                                                                          Instrument                                                                   responses per       burden hours
                                                                                                                                                      respondents                                            hours
                                                                                                                                                                         respondent        per response

                                                Post-Expenditure Reporting Form ...................................................................               56                1               110          6,160
                                                Use of Post-Expenditure Reporting Form as Part of the Intended Use Plan                                           56                1                 2            112



                                                  Estimated Total Annual Burden                                 concerning abuse potential, actual                       comments, that information will be
                                                Hours: 6,272.                                                   abuse, medical usefulness, trafficking,                  posted on https://www.regulations.gov.
                                                  Additional Information: Copies of the                         and impact of scheduling changes on                        • If you want to submit a comment
                                                proposed collection may be obtained by                          availability for medical use of 17 drug                  with confidential information that you
                                                writing to the Administration for                               substances. These comments will be                       do not wish to be made available to the
                                                Children and Families, Office of                                considered in preparing a response from                  public, submit the comment as a
                                                Planning, Research and Evaluation, 330                          the United States to the World Health                    written/paper submission and in the
                                                C Street SW., Washington, DC 20201.                             Organization (WHO) regarding the abuse                   manner detailed (see ‘‘Written/Paper
                                                Attention Reports Clearance Officer. All                        liability and diversion of these drugs.                  Submissions’’ and ‘‘Instructions’’).
                                                requests should be identified by the title                      WHO will use this information to                         Written/Paper Submissions
                                                of the information collection. Email                            consider whether to recommend that
                                                address: infocollection@acf.hhs.gov.                            certain international restrictions be                      Submit written/paper submissions as
                                                  OMB Comment: OMB is required to                               placed on these drugs. This notice                       follows:
                                                make a decision concerning the                                  requesting comments is required by the                     • Mail/Hand Delivery/Courier (for
                                                collection of information between 30                            Controlled Substances Act (the CSA).                     Written/Paper Submissions): Dockets
                                                and 60 days after publication of this                           DATES: Submit either electronic or
                                                                                                                                                                         Management Staff (HFA–305), Food and
                                                document in the Federal Register.                               written comments by September 13,                        Drug Administration, 5630 Fishers
                                                Therefore, a comment is best assured of                         2017.                                                    Lane, Rm. 1061, Rockville, MD 20852.
                                                                                                                                                                           • For written/paper comments
                                                having its full effect if OMB receives it                       ADDRESSES: You may submit comments                       submitted to the Dockets Management
                                                within 30 days of publication. Written                          as follows. Please note that late,                       Staff, FDA will post your comment, as
                                                comments and recommendations for the                            untimely filed comments will not be                      well as any attachments, except for
                                                proposed information collection should                          considered. Electronic comments must                     information submitted, marked and
                                                be sent directly to the following: Office                       be submitted on or before September 13,                  identified, as confidential, if submitted
                                                of Management and Budget, Paperwork                             2017. The https://www.regulations.gov                    as detailed in ‘‘Instructions.’’
                                                Reduction Project, Email: OIRA_                                 electronic filing system will accept                       Instructions: All submissions received
                                                SUBMISSION@OMB.EOP.GOV, Attn:                                   comments until midnight Eastern Time                     must include the Docket No. FDA–
                                                Desk Officer for the Administration for                         at the end of September 13, 2017.                        2017–N–4515 for ‘‘International Drug
                                                Children and Families.                                          Comments received by mail/hand                           Scheduling; Convention on
                                                Robert Sargis,                                                  delivery/courier (for written/paper                      Psychotropic Substances; Single
                                                Reports Clearance Officer.                                      submissions) will be considered timely                   Convention on Narcotic Drugs;
                                                [FR Doc. 2017–17098 Filed 8–11–17; 8:45 am]                     if they are postmarked or the delivery                   Ocfentanil; Furanyl fentanyl (Fu-F);
                                                                                                                service acceptance receipt is on or                      Acryloylfentanyl (Acrylfentanyl);
                                                BILLING CODE 4184–24–P
                                                                                                                before that date.                                        Carfentanil; 4-fluoroisobutyrfentanyl (4–
                                                                                                                                                                         FIBF); Tetrahydrofuranylfentanyl (THF–
                                                                                                                Electronic Submissions
                                                DEPARTMENT OF HEALTH AND                                                                                                 F); 4-fluoroamphetamine (4–FA); AB–
                                                                                                                  Submit electronic comments in the                      PINACA; AB–CHMINACA; 5F–PB–22;
                                                HUMAN SERVICES
                                                                                                                following way:                                           UR–144; 5F–ADB; Etizolam; Pregabalin;
                                                Food and Drug Administration                                      • Federal eRulemaking Portal:                          Tramadol; Cannabidiol; Ketamine;
                                                                                                                https://www.regulations.gov. Follow the                  Request for Comments.’’ Received
                                                [Docket No. FDA–2017–N–4515]                                    instructions for submitting comments.                    comments, those filed in a timely
                                                                                                                Comments submitted electronically,                       manner (see ADDRESSES), will be placed
                                                International Drug Scheduling;                                  including attachments, to https://
                                                Convention on Psychotropic                                                                                               in the docket and, except for those
                                                                                                                www.regulations.gov will be posted to                    submitted as ‘‘Confidential
                                                Substances; Single Convention on                                the docket unchanged. Because your                       Submissions,’’ publicly viewable at
                                                Narcotic Drugs; Ocfentanil,                                     comment will be made public, you are                     https://www.regulations.gov or at the
                                                Carfentanil, Pregabalin, Tramadol,                              solely responsible for ensuring that your                Dockets Management Staff between
                                                Cannabidiol, Ketamine, and Eleven                               comment does not include any                             9 a.m. and 4 p.m., Monday through
                                                Other Substances; Request for                                   confidential information that you or a                   Friday.
                                                Comments                                                        third party may not wish to be posted,                     • Confidential Submissions—To
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                                                AGENCY:      Food and Drug Administration,                      such as medical information, your or                     submit a comment with confidential
                                                HHS.                                                            anyone else’s Social Security number, or                 information that you do not wish to be
                                                ACTION:    Notice.                                              confidential business information, such                  made publicly available, submit your
                                                                                                                as a manufacturing process. Please note                  comments only as a written/paper
                                                SUMMARY:   The Food and Drug                                    that if you include your name, contact                   submission. You should submit two
                                                Administration (FDA) is requesting                              information, or other information that                   copies total. One copy will include the
                                                interested persons to submit comments                           identifies you in the body of your                       information you claim to be confidential


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                                                                             Federal Register / Vol. 82, No. 155 / Monday, August 14, 2017 / Notices                                               37867

                                                with a heading or cover note that states                the United States under Article 2 of the              11. UR–144
                                                ‘‘THIS DOCUMENT CONTAINS                                Psychotropic Convention that it has                   12. 5F–ADB
                                                CONFIDENTIAL INFORMATION.’’ The                         information that may justify adding a                 13. Etizolam
                                                                                                                                                              14. Pregabalin
                                                Agency will review this copy, including                 drug or other substances to one of the                15. Tramadol
                                                the claimed confidential information, in                schedules of the Psychotropic                         16. Cannabidiol
                                                its consideration of comments. The                      Convention, transferring a drug or                    17. Ketamine
                                                second copy, which will have the                        substance from one schedule to another,                 PDF versions of the questionnaire in
                                                claimed confidential information                        or deleting it from the schedules, the                English, French and Spanish may be
                                                redacted/blacked out, will be available                 Secretary of State must transmit the                  downloaded from the link http://
                                                for public viewing and posted on                        notice to the Secretary of Health and                 www.who.int/medicines/access/controlled-
                                                https://www.regulations.gov. Submit                     Human Services (Secretary of HHS). The                substances/ecdd/en/. Please note that these
                                                both copies to the Dockets Management                   Secretary of HHS must then publish the                versions are for reference only and all
                                                Staff. If you do not wish your name and                 notice in the Federal Register and                    questionnaires must be answered through the
                                                                                                                                                              online system. Further clarification regarding
                                                contact information to be made publicly                 provide opportunity for interested                    the questionnaire may be obtained from the
                                                available, you can provide this                         persons to submit comments that will be               Secretariat by emailing: ecddsecretariat@
                                                information on the cover sheet and not                  considered by HHS in its preparation of               who.int.
                                                in the body of your comments and you                    the scientific and medical evaluations of               Replies to the questionnaire must reach the
                                                must identify this information as                       the drug or substance.                                Secretariat by 30 September 2017 in order to
                                                ‘‘confidential.’’ Any information marked                                                                      facilitate analyses and preparation of the
                                                                                                        II. WHO Notification                                  report before the planned meeting. Where
                                                as ‘‘confidential’’ will not be disclosed
                                                except in accordance with 21 CFR 10.20                     The Secretary of HHS received the                  there is a competent National Authority
                                                                                                        following notice from WHO (non-                       under the International Drug Control
                                                and other applicable disclosure law. For                                                                      Treaties, it is kindly requested that the
                                                more information about FDA’s posting                    relevant text removed):
                                                                                                                                                              questionnaire be completed in collaboration
                                                of comments to public dockets, see 80                   Ref.: C.L.xx.2017                                     with such body.
                                                FR 56469, September 18, 2015, or access                    The World Health Organization (WHO)                  The summary information from the
                                                the information at: https://www.gpo.gov/                presents its compliments to Member States             questionnaire will be published online as
                                                fdsys/pkg/FR-2015-09-18/pdf/2015-                       and Associate Members and has the pleasure            part of the report on the Web site for the
                                                23389.pdf.                                              of informing that the Thirty-ninth Expert             Thirty-ninth ECDD linked to the Department
                                                   Docket: For access to the docket to                  Committee on Drug Dependence (ECDD) will              of Essential Medicines and Health Products
                                                read background documents or the                        meet in Geneva from 6 to 10 November 2017             (EMP). The provisional agenda of the Thirty-
                                                                                                        to review a number of substances with                 ninth ECDD and the list of psychoactive
                                                electronic and written/paper comments                   potential for dependence, abuse and harm to           substances under review are also published
                                                received, go to https://                                health, and will make recommendations to              on Thirty-ninth ECDD Web page: http://
                                                www.regulations.gov and insert the                      the U.N. Secretary-General, on the need for           www.who.int/medicines/access/controlled-
                                                docket number, found in brackets in the                 and level of international control of these           substances/ecdd/en/.
                                                heading of this document, into the                      substances.                                             Member States are also encouraged to
                                                ‘‘Search’’ box and follow the prompts                      At its 126th session in January 2010, the          provide any additional relevant information
                                                and/or go to the Dockets Management                     Executive Board approved the publication              (unpublished or published) that is available
                                                Staff, 5630 Fishers Lane, Rm. 1061,                     ‘‘Guidance on the WHO review of                       on these substances to: ecddsecretariat@
                                                                                                        psychoactive substances for international             who.int. This information will be an
                                                Rockville, MD 20852.                                    control’’ (EB126/2010/REC1, Annex 6) which            invaluable contribution to the ECDD and all
                                                FOR FURTHER INFORMATION CONTACT:                        requires the Secretariat to request relevant          submissions will be treated as confidential.
                                                James R. Hunter, Center for Drug                        information from Ministers of Health in                 The World Health Organization takes this
                                                Evaluation and Research, Controlled                     Member States to prepare a report for                 opportunity to renew to Member States and
                                                Substance Staff, Food and Drug                          submission to the ECDD. For this purpose, a           Associate Members the assurance of its
                                                Administration, 10903 New Hampshire                     questionnaire was designed to gather                  highest consideration.
                                                Ave., Bldg. 51, Rm. 5150, Silver Spring,                information on the legitimate use, harmful            GENEVA, 7 July 2017
                                                                                                        use, status of national control and potential
                                                MD 20993–0002, 301–796–3156, email:                     impact of international control for each                FDA has verified the Web site
                                                james.hunter@fda.hhs.gov.                               substance under evaluation. Member States             addresses contained in the WHO notice,
                                                SUPPLEMENTARY INFORMATION:                              are invited to collaborate, as in the past, in        as of the date this document publishes
                                                                                                        this process by providing pertinent                   in the Federal Register, but Web sites
                                                I. Background                                           information as requested in the questionnaire         are subject to change over time.
                                                  The United States is a party to the                   and concerning substances under review.
                                                1971 Convention on Psychotropic                            It would be appreciated if a person from           III. Substances Under WHO Review
                                                                                                        the Ministry of Health could be designated as
                                                Substances (Psychotropic Convention).                   the focal point responsible for coordinating             Ocfentanil is a synthetically produced
                                                Article 2 of the Psychotropic                           and answering the questionnaire. (non                 opioid that is structurally related to
                                                Convention provides that if a party to                  relevant information from letter not shown,           fentanyl and approximately equipotent
                                                the convention or WHO has information                   see letter for text not shown here) The               in effect. Reported risks associated with
                                                about a substance, which in its opinion                 designated focal point, and only this person,         use of ocfentanil include development
                                                may require international control or                    should access and complete the                        of opioid use disorder, overdose, and
                                                change in such control, it shall so notify              questionnaires:                                       fatal overdose. It has no approved
                                                the Secretary-General of the United                     1. Ocfentanil                                         medical use in the United States and is
                                                Nations (the U.N. Secretary-General)                    2. Furanyl fentanyl (Fu-F)
sradovich on DSK3GMQ082PROD with NOTICES




                                                                                                                                                              not a controlled substance in the United
                                                and provide the U.N. Secretary-General                  3. Acryloylfentanyl (Acrylfentanyl)                   States under the CSA.
                                                                                                        4. Carfentanil
                                                with information in support of its                                                                               Furanyl fentanyl (Fu-F) is a potent
                                                                                                        5. 4-fluoroisobutyrfentanyl (4–FIBF)
                                                opinion.                                                6. Tetrahydrofuranylfentanyl (THF–F)                  clandestinely produced synthetic opioid
                                                  Section 201 of the CSA (21 U.S.C.                     7. 4-fluoroamphetamine (4–FA)                         that is an analog of fentanyl. Evidence
                                                811) (Title II of the Comprehensive Drug                8. AB–PINACA                                          suggests that the pattern of abuse of
                                                Abuse Prevention and Control Act of                     9. AB–CHMINACA                                        fentanyl analogues, including furanyl
                                                1970) provides that when WHO notifies                   10. 5F–PB–22                                          fentanyl, parallels that of heroin and


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                                                37868                        Federal Register / Vol. 82, No. 155 / Monday, August 14, 2017 / Notices

                                                prescription opioid analgesics. Fu-F                       4-fluoroisobutyrfentanyl is a                         AB–CHMINACA is a clandestinely
                                                produces the typical opioid effects that                clandestinely produced synthetic opioid               produced synthetic cannabinoid agonist
                                                include respiratory depression and loss                 that is an analog of fentanyl. It has m-              that is approximately 16 times more
                                                of consciousness. Seizures of Fu-F have                 receptor agonist activity similar to that             potent than delta-9-
                                                been encountered in powder form. Fu-                    of fentanyl. This would result in effects             tetrahydrocannabinol. Adverse effects
                                                F has been connected to fatal overdoses,                associated with opioid agonists such as               produced by cannabinoid agonists
                                                in which intravenous routes of                          analgesia, respiratory depression,                    include tachycardia, agitation,
                                                administration are documented. It has                   anxiety, constipation, tiredness,                     hallucination, chest pain, seizure,
                                                no approved medical use in the United                   hallucinations, withdrawal, the                       anxiety, acute psychosis, and death.
                                                States. On November 29, 2016, the Drug                  development of opioid use disorder,                   AB–CHMINACA has been detected in
                                                Enforcement Administration (DEA)                        overdose, and fatal overdose. The use of              illicit synthetic cannabinoid substances
                                                issued a final order to temporarily                     4-fluoroisobutyrfentanyl has been                     and found in cases of overdose and
                                                schedule Fu-F and its isomers, esters,                  implicated in several cases of overdose               hospitalizations. AB–CHMINACA has
                                                ethers, salts and salts of isomers, esters              and fatal overdoses. 4-                               not been pre-reviewed or critically
                                                and ethers, into Schedule I pursuant to                 fluoroisobutyrfentanyl has not been                   reviewed by the WHO. On January 27,
                                                the temporary scheduling provisions of                  approved for medical use in the U.S. On               2017, the DEA published a Notice of
                                                the CSA.                                                May 3, 2017, the DEA issued a                         Proposed Rulemaking to permanently
                                                   Acryloylfentanyl (Acrylfentanyl)                     temporary order to temporarily schedule               control AB–CHMINACA as a Schedule
                                                belongs to the 4-anilidopiperidine class                4-fluoroisobutyrfentanyl, its isomers,                I substance under the CSA.
                                                of synthetic opioids and is similar in                  esters, ethers, salts and salts of isomers,              5F–PB–22 is a synthetic cannabinoid
                                                structure to fentanyl. Acryloylfentanyl                 esters and ethers, into Schedule I                    agonist with similar effects to delta-9-
                                                is a clandestinely produced analog of                   pursuant to the temporary scheduling                  tetrahydrocannabinol, one of the main
                                                fentanyl and sold illegally as a research               provisions of the CSA.                                psychoactive components of cannabis.
                                                chemical on several Web sites.                             Tetrahydrofuranylfentanyl (THF–F) is               Adverse effects produced by
                                                Acryloylfentanyl has also been                          a synthetic opioid that is an analog of               cannabinoid agonists include
                                                associated with adverse events typically                fentanyl. It has m-receptor agonist                   tachycardia, agitation, hallucination,
                                                associated with opioid use such as                      activity similar to that of fentanyl,                 chest pain, seizure, anxiety, acute
                                                respiratory depression, anxiety,                        resulting in effects associated with                  psychosis, and death. 5F–PB–22 is
                                                constipation, tiredness, hallucinations,                opioid agonists such as analgesia,                    clandestinely produced. It has been
                                                and withdrawal. The use of                              respiratory depression, anxiety,                      found laced on plant material and
                                                acryloylfentanyl has also been linked to                constipation, tiredness, hallucinations,              marketed as herbal products, and is
                                                the development of opioid use disorder,                 withdrawal, the development of opioid                 smoked for its psychoactive effects.
                                                overdose, and fatal overdose.                           use disorder, overdose, and fatal                     According to the WHO, 5F–PB–22 has
                                                Acryloylfentanyl has no commercial or                   overdose. THF–F is not approved for                   been associated with fatal intoxications.
                                                medical uses. On July 14, 2017, the DEA                 medical use or controlled in the United               On September 6, 2016, the DEA issued
                                                issued a temporary order to temporarily                 States under the CSA.                                 a final rule to permanently place 5F–
                                                schedule acryloylfentanyl, its isomers,                    4-Fluoroamphetamine (4–FA) is a                    PB–22 into Schedule I of the CSA.
                                                esters, ethers, salts and salts of isomers,             psychoactive substance of the                            UR–144 is a clandestinely produced
                                                esters, and ethers, into Schedule I                     phenethylamine and substituted                        synthetic cannabinoid agonist. In
                                                pursuant to the temporary scheduling                    amphetamine chemical classes and                      general, adverse effects produced by
                                                provisions of the CSA.                                  produces stimulant effects. WHO                       cannabinoid agonists include
                                                   Carfentanil, also known as 4-                        reports that 4–FA is clandestinely                    tachycardia, agitation, hallucination,
                                                carbomethoxyfentanyl, is an extremely                   produced, and its use is associated with              chest pain, seizure, anxiety, and acute
                                                potent synthetic opioid that is similar in              fatal and non-fatal intoxications. 4–FA               psychosis. UR–144 has been detected in
                                                structure to and approximately 100                      was reviewed at the 37th ECDD (2015)                  herbal smoking blends that are sold as
                                                times more potent than fentanyl as an                   and, while not placed under                           herbal incense. In June 2014, the 36th
                                                analgesic. At one time legitimately                     international control due to insufficient             (2014) ECDD reviewed UR–144 and
                                                produced, carfentanil is no longer                      data, was kept under surveillance. 4–FA               recommended that it be placed under
                                                manufactured, marketed, or used in the                  is not approved for medical use in the                surveillance. On May 11, 2016, the DEA
                                                United States; it is approved by FDA for                United States and it is not controlled                issued a final rule to permanently
                                                use under restricted conditions by                      under the CSA.                                        schedule UR–144 into Schedule I of the
                                                veterinarians as a immobilizing agent                      AB–PINACA is a clandestinely                       CSA.
                                                for certain large animals. Illicitly                    produced synthetic cannabinoid agonist                   5F–ADB is a clandestinely produced
                                                produced carfentanil is a particularly                  approximately 1.5 times as potent as                  synthetic cannabinoid agonist. In
                                                harmful fentanyl analogue that is also                  delta-9-tetrahydrocannabinol. Adverse                 general, adverse effects produced by
                                                being laced into heroin or sold by itself               effects produced by cannabinoid                       cannabinoid agonists include
                                                and trafficked in the United States. It is              agonists include tachycardia, agitation,              tachycardia, agitation, hallucination,
                                                not approved for human use. Drug                        hallucination, chest pain, seizure,                   chest pain, seizure, anxiety, and acute
                                                seizure data indicate that carfentanil is               anxiety, acute psychosis, and death.                  psychosis. 5F–ADB has been identified
                                                typically used in small doses to cut                    AB–PINACA has been detected in illicit                in overdose and/or cases involving
                                                heroin and other illicitly abused drugs.                synthetic cannabinoid substances, and                 death attributed to their abuse. Adverse
                                                                                                        reported in cases of overdose and                     health effects reported from incidents
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                                                The significant risk to public health
                                                associated with carfentanil use stems                   hospitalizations. It has not been                     involving 5F–ADB and other synthetic
                                                from its respiratory depressive effects                 approved for medical use in the United                cannabinoids have included: Nausea,
                                                with very small amounts. Several                        States. On January 27, 2017, the DEA                  persistent vomiting, agitation, altered
                                                fatalities have been reported as the                    published a Notice of Proposed                        mental status, seizures, convulsions,
                                                result of carfentanil overdoses. On                     Rulemaking to permanently control AB–                 loss of consciousness, and/or cardio
                                                October 28, 1988, the DEA placed                        PINACA as a Schedule I substance                      toxicity. On April 10, 2017, the DEA
                                                carfentanil in Schedule II of the CSA.                  under the CSA.                                        issued a temporary scheduling order to


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                                                                             Federal Register / Vol. 82, No. 155 / Monday, August 14, 2017 / Notices                                                  37869

                                                temporarily schedule 5F–ADB, its                        treatment of moderate to moderately                   IV. Opportunity To Submit Domestic
                                                isomers, esters, ethers, salts and salts of             severe pain. On July 2, 2014, the DEA                 Information
                                                isomers, esters, and ethers into                        published a final rule in the Federal                   As required by section 201(d)(2)(A) of
                                                Schedule I pursuant to the temporary                    Register controlling tramadol as a                    the CSA, FDA, on behalf of HHS, invites
                                                scheduling provisions of the CSA.                       Schedule IV substance of the CSA                      interested persons to submit comments
                                                   Etizolam belongs to a class of                       effective from August 18, 2014.                       regarding the 17 named drug
                                                substances known as benzodiazepines.                    Tramadol was pre-reviewed by the                      substances. Any comments received
                                                Benzodiazepines produce central                         ECDD at its 28th (1992) and 32nd (2000)               will be considered by HHS when it
                                                nervous system depression and are                       meetings, and critically reviewed at the              prepares a scientific and medical
                                                commonly used to treat insomnia,                        33rd (2002) meeting and not                           evaluation of these drug substances.
                                                anxiety, and seizure disorders. Etizolam                recommended for international control                 HHS will forward a scientific and
                                                is currently prescribed in some                         but placed on surveillance. Tramadol                  medical evaluation of these drug
                                                countries to treat generalized anxiety                  was pre-reviewed again by the ECDD at                 substances to WHO, through the
                                                disorder with depressive symptoms, but                  its 34th (2006) meeting; however, the                 Secretary of State, for WHO’s
                                                is not approved for medical use or                      ECDD concluded that there was not                     consideration in deciding whether to
                                                controlled in the United States under                   sufficient evidence to justify a critical             recommend international control/
                                                the CSA. WHO reported that non-fatal                    review. At the 36th (2014) meeting, the               decontrol of any of these drug
                                                intoxications that include cases of                     ECDD considered updated information                   substances. Such control could limit,
                                                driving under the influence of drugs                    on tramadol, but again concluded that                 among other things, the manufacture
                                                have been linked to etizolam. The ECDD                  there was insufficient evidence to                    and distribution (import/export) of these
                                                at its 37th (2015 meeting reviewed                      warrant a critical review.                            drug substances and could impose
                                                etizolam and recommended that a                            Cannabidiol (CBD) is one of the active             certain recordkeeping requirements on
                                                critical review of etizolam is warranted.               cannabinoids identified in cannabis.                  them.
                                                   Pregabalin is an anticonvulsant-type                                                                         Although FDA is, through this notice,
                                                                                                        CBD has been shown to be beneficial in
                                                drug used to treat pain generated from                                                                        requesting comments from interested
                                                                                                        experimental models of several
                                                the nervous system. It is available as an                                                                     persons, which will be considered by
                                                                                                        neurological disorders, including those
                                                oral capsule and oral solution and                                                                            HHS when it prepares an evaluation of
                                                                                                        of seizure and epilepsy. In the United
                                                approved for medical use in the United                                                                        these drug substances, HHS will not
                                                                                                        States, CBD-containing products are in
                                                States for the management of                                                                                  now make any recommendations to
                                                                                                        human clinical testing in three
                                                neuropathic pain associated with                                                                              WHO regarding whether any of these
                                                                                                        therapeutic areas, but no such products
                                                diabetic peripheral neuropathy, post-                                                                         drugs should be subjected to
                                                                                                        are approved by FDA for marketing for
                                                herpetic neuralgia, and adjunctive                                                                            international controls. Instead, HHS will
                                                therapy for partial onset seizures,                     medical purposes in the United States.
                                                                                                        CBD is a Schedule I controlled                        defer such consideration until WHO has
                                                fibromyalgia, and neuropathic pain
                                                                                                        substance under the CSA. At the 37th                  made official recommendations to the
                                                associated with spinal cord injury.
                                                                                                        (2015) meeting of the ECDD, the                       Commission on Narcotic Drugs, which
                                                Although the mechanism of action of
                                                                                                        committee requested that the Secretariat              are expected to be made in early 2018.
                                                pregabalin is unknown, studies in
                                                                                                        prepare relevant documentation to                     Any HHS position regarding
                                                animals suggest that binding to the
                                                                                                        conduct pre-reviews for several                       international control of these drug
                                                nervous system tissues may be involved
                                                                                                        substances, including CBD.                            substances will be preceded by another
                                                in its pain-relieving and anti-seizure
                                                                                                           Ketamine is classified as a rapid-                 Federal Register notice soliciting public
                                                effects. Pregabalin binds with high
                                                                                                        acting general anesthetic agent used for              comments, as required by section
                                                affinity to the alpha 2-delta receptor site
                                                                                                        short diagnostic and surgical procedures              201(d)(2)(B) of the CSA.
                                                (a subunit of voltage-gated calcium
                                                channels) in the central nervous system.                that do not require skeletal muscle                   V. Electronic Access
                                                The binding of pregabalin at this site is               relaxation. It is marketed in the United
                                                                                                        States as a solution for injection.                     Persons with access to the Internet
                                                thought to be responsible for its                                                                             may obtain the document at either
                                                therapeutic effect on neuropathic pain.                 Ketamine is controlled in Schedule III of
                                                                                                        the CSA in the United States. It is not               https://www.fda.gov/Drugs/Guidance
                                                Reports indicate that patients are self-                                                                      ComplianceRegulatoryInformation/
                                                administering higher than                               controlled internationally under the
                                                                                                        Convention on Psychotropic Substances                 Guidances/default.htm or https://www.
                                                recommended doses to achieve                                                                                  regulations.gov.
                                                euphoria, especially patients who have                  or the Single Convention on Narcotic
                                                a history of substance abuse,                           Drugs. The ECDD reviewed ketamine at                    Dated: August 9, 2017.
                                                particularly opioids, and psychiatric                   its 34th (2006), 35th (2012), and 36th                Anna K. Abram,
                                                illness. While effects of excessively high              (2014) meetings. On March 13, 2015, the               Deputy Commissioner for Policy, Planning,
                                                doses are generally non-lethal,                         Commission on Narcotic Drugs (CND)                    Legislation, and Analysis.
                                                gabapentinoids such as pregabalin are                   decided by consensus to postpone the                  [FR Doc. 2017–17119 Filed 8–11–17; 8:45 am]
                                                increasingly being identified in post-                  consideration of a proposal concerning                BILLING CODE 4164–01–P
                                                mortem toxicology analyses. Pregabalin                  the recommendation to place ketamine
                                                is a Schedule V controlled substance in                 in Schedule IV of the Psychotropic
                                                the United States under the CSA.                        Convention. The CND requested                         DEPARTMENT OF HEALTH AND
                                                   Tramadol is an opioid analgesic that                 additional information from the WHO.                  HUMAN SERVICES
                                                produces its primary opioid-like action                 The ECDD reviewed updated
sradovich on DSK3GMQ082PROD with NOTICES




                                                through an active metabolite referred to                information at its 37th (2015) meeting                Indian Health Service
                                                as the M1 metabolite (O-                                and found no reason to recommend a
                                                                                                                                                              Division of Behavioral Health; Office of
                                                desmethyltramadol). Tramadol was first                  new pre-review or critical review of
                                                                                                                                                              Clinical and Preventive Services;
                                                approved for marketing in the United                    ketamine that could potentially change
                                                                                                                                                              Behavioral Health Integration Initiative
                                                States in 1995 and is available as                      its standing 2014 recommendation that
                                                                                                                                                              (BH2I)
                                                immediate-release, extended-release,                    ketamine should not be placed under
                                                and combination products for the                        international control.                                  Announcement Type: New.


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Document Created: 2018-10-24 11:50:17
Document Modified: 2018-10-24 11:50:17
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice.
DatesSubmit either electronic or written comments by September 13, 2017.
ContactJames 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]
FR Citation82 FR 37866 

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