Document ID: FDA-2015-N-0045-0062
Agency: fda
Document Type: Notice
Title: International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Ketamine and Nine
Other Substances; Request for Comments
Posted Date: 2015-10-05T04:00Z

[Federal Register Volume 80, Number 192 (Monday, October 5, 2015)]
[Notices]
[Pages 60151-60153]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-25201]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-0045]

International Drug Scheduling; Convention on Psychotropic 
Substances; Single Convention on Narcotic Drugs; Ketamine and Nine 
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 10 drug substances. These 
comments will be considered in preparing a response from the United 
States to the World Health Organization (WHO) regarding the abuse 
liability and diversion of these drugs. WHO will use this information 
to consider whether to recommend that certain international 
restrictions be placed on these drugs. This notice requesting comments 
is required by the Controlled Substances Act (the CSA).

DATES: Submit either electronic or written comments by October 15, 
2015.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2015-N-0045 for International Drug Scheduling; Convention on 
Psychotropic Substances; Single Convention on Narcotic Drugs; Ketamine; 
Phenazepam; Etizolam; 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine 
(MT-45); N-(1-Phenethylpiperidin-4-yl)-N-phenylacetamide 
(Acetylfentanyl); [alpha]-Pyrrolidinovalerophenone ([alpha]-PVP); 4-
Fluoroamphetamine (4-FA); para-Methyl-4-methylaminorex (4,4'-DMAR); 
para-Methoxymethylamphetamine (PMMA); 2-(ethylamino)-2-(3-
methoxyphenyl)-cyclohexanone (Methoxetamine or MXE); Request for 
Comments. Received comments will be placed in the docket and, except 
for those submitted as ``Confidential Submissions,'' publicly viewable 
at http://www.regulations.gov or at the Division of Dockets Management 
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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852.

[[Page 60152]]

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.
    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 
(emphasis removed):

    Ref.: C.L.28.2015

    The World Health Organization (WHO) presents its compliments to 
Member States and Associate Members and has the pleasure of 
informing that the Thirty-sixth Expert Committee on Drug Dependence 
(ECDD) will meet in Geneva from 16 to 20 November 2015 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. It is requested that the focal 
point's contact details (including email address) be emailed to: 
ecddsecretariat@who.int. The designated focal point, and only this 
person, should access and complete the questionnaires via these 
links:

1. Ketamine INN--https://extranet.who.int/dataform/961512/lang-en
2. Phenazepam--https://extranet.who.int/dataform/482684/lang-en
3. Etizolam--https://extranet.who.int/dataform/278963/lang-en
4. MT-45--https://extranet.who.int/dataform/465468/lang-en
5. Acetylfentanyl--https://extranet.who.int/dataform/495475/lang-en
6. [alpha]-Pyrrolidinovalerophenone ([alpha]-PVP)--https://extranet.who.int/dataform/758275/lang-en
7. 4-Fluoroamphetamine (4-FA)--https://extranet.who.int/dataform/538126/lang-en
8. para-Methyl-4-methylaminorex (4,4'-DMAR)--https://extranet.who.int/dataform/422472/lang-en
9. para-Methoxymethylamphetamine (PMMA)--https://extranet.who.int/dataform/665818/lang-en
10. Methoxetamine (MXE)--https://extranet.who.int/dataform/266376/lang-en

    Upon accessing the links the focal point will be prompted for a 
token (password) which is the country name in English, non-case 
sensitive and without spaces.
    For ease of reference a PDF version of the questionnaire in 
English, French and Spanish may be downloaded from the link http://www.who.int/medicines/access/controlled-substances/ecdd/en/. Further 
clarification regarding the questionnaire may be obtained from the 
Secretariat by emailing: ecddsecretariat@who.int.
    Replies to the questionnaire must reach the Secretariat by 15 
October 2015 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 37th ECDD 
linked to the Department of Essential Medicines and Health Products 
(EMP).
    The World Health Organization takes this opportunity to renew to 
Member States and Associate Members the assurance of its highest 
consideration.

GENEVA, 11 September 2015

    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

    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 an 
injectable product for medical and veterinary use. Ketamine is 
controlled in Schedule III of the CSA in the United States. It is not 
controlled internationally under either the Psychotropic Convention or 
the Single Convention on Narcotic Drugs. The WHO Expert Committee on 
Drug Dependence reviewed ketamine at its 34th, 35th, and 36th meetings. 
On March 13, 2015, the Commission on Narcotic Drugs decided by 
consensus to postpone the consideration of a proposal concerning the 
recommendation to place ketamine in Schedule IV of the Psychotropic 
Convention and to request additional information from the WHO.
    Phenazepam and Etizolam belong to a class of substances known as 
benzodiazepines. Benzodiazepines produce central nervous system 
depression and are commonly used to treat insomnia, anxiety, and 
seizure disorders. Phenazepam and Etizolam are currently prescribed in 
some countries, but neither drug substance is approved for medical use 
or controlled in the United States under the CSA.
    1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine (MT-45) is a 
synthetic opioid with potent analgesic activity comparable to morphine 
despite being structurally unrelated to most other opioids. MT-45 use 
has been associated with deaths in the United States and in other 
countries. MT-45 is not currently controlled in the United States under 
the CSA.
    Acetylfentanyl (N-(1-phenethylpiperidin-4-yl)-N-phenylacetamide) is 
a potent opioid analgesic in the phenylpiperidine class of synthetic 
opioids. With the exception of its analgesic effects, this fentanyl-
like substance is similar to other opioid analgesics that produce a 
variety of pharmacological effects, including alteration in mood, 
euphoria, drowsiness, respiratory depression, constriction of pupils 
(miosis), and impaired gastrointestinal motility. Acetylfentanyl has 
been associated with

[[Page 60153]]

several confirmed deaths in the United States. On July 17, 2015, 
Acetylfentanyl was temporarily placed into Schedule I of the CSA for 2 
years upon finding that it posed an imminent hazard to the public 
safety. The Attorney General, though, may extend this temporary 
scheduling for up to 1 year.
    [alpha]-Pyrrolidinovalerophenone ([alpha]-PVP or alpha-PVP) is a 
synthetic cathinone structurally and pharmacologically similar to 
amphetamine, 3,4-methylenedioxymethamphetamine (MDMA); cathinone; and 
other related substances. Effects reported by abusers of synthetic 
cathinone substances include euphoria; sense of well-being; and 
increased sociability, energy, empathy, alertness, and concentration 
and focus. Abusers also report experiencing unwanted effects such as 
tremor, vomiting, agitation, sweating, fever, and chest pain. Other 
adverse or toxic effects that have been reported with the abuse of 
synthetic cathinones include tachycardia, hypertension, hyperthermia, 
mydriasis, rhabdomyolysis, hyponatremia, seizures, altered mental 
status (e.g., paranoia, hallucinations, or delusions), and even death. 
On March 7, 2014, alpha-PVP was temporarily placed into Schedule I of 
the CSA for 2 years upon finding that it posed an imminent hazard to 
the public safety. The Attorney General, though, may extend this 
temporary scheduling for up to 1 year.
    4-Fluoroamphetamine (4-FA) is a psychoactive substance of the 
phenethylamine and substituted amphetamine chemical classes and 
produces stimulant effects. 4-FA is not currently controlled in the 
United States under the CSA.
    Para-Methyl-4-methylaminorex (4,4'-DMAR) is a derivative of the 
stimulant drug 4-methylaminorex and has been involved in several deaths 
in the United States. 4,4'-DMAR is not currently controlled in the 
United States under the CSA.
    Para-Methoxymethylamphetamine (PMMA) is a substituted amphetamine 
of the phenethylamine class, as well as a structural analog of para-
methoxyamphetamine (PMA) which produces effects similar but not 
identical to that of MDMA. PMMA is not currently controlled in the 
United States under the CSA.
    2-(ethylamino)-2-(3-methoxyphenyl)-cyclohexanone (Methoxetamine or 
MXE) is an arylcyclohexamine and is not currently controlled under the 
CSA in the United States. At its 36th meeting, the WHO Expert Committee 
on Drug Dependence noted the insufficiency of data regarding 
dependence, abuse, and risks to the public health, thereby recommending 
that Methoxetamine not be placed under international control but be 
kept under international surveillance.

IV. Opportunity To Submit Domestic Information

    As required by section 201(d)(2)(A) of the CSA (21 U.S.C. 
811(d)(2)(A)), FDA, on behalf of the Department of Health and Human 
Services (HHS), invites interested persons to submit comments regarding 
the 10 named drugs. Any comments received will be considered by HHS 
when it prepares a scientific and medical evaluation of these drugs. 
HHS will forward a scientific and medical evaluation of these drugs to 
WHO, through the Secretary of State, for WHO's consideration in 
deciding whether to recommend international control/decontrol of any of 
these drugs. Such control could limit, among other things, the 
manufacture and distribution (import/export) of these drugs 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 drugs, 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 2016. Any HHS 
position regarding international control of these drugs 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 http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: September 29, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-25201 Filed 10-2-15; 8:45 am]
 BILLING CODE 4164-01-P