International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; Tapentadol; Tramadol; Ketamine; gamma-Butyrolactone; 22 Additional Substances; Request for Comments, 79465-79469 [2013-31212]
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79465
Federal Register / Vol. 78, No. 250 / Monday, December 30, 2013 / Notices
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1—Continued
Number of
recordkeepers
21 CFR section
Number of
records per
recordkeeper
100
1
101.105(t); recordkeeping pertaining to disclosure requirements for food not accurately labeled for quantity
of contents ....................................................................
Total ..........................................................................
1 There
Average
burden per
recordkeeping
Total annual
records
100
Total hours
1
100
676,150
are no capital costs or operating and maintenance costs associated with this collection of information.
TABLE 3—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
responses per
respondent
Number of
respondents
21 CFR Section/Form No.
101.9(j)(18) and 101.36(h)(2); procedure for small business nutrition labeling exemption notice using Form
FDA 3570 .........................................................................
101.12(h); petitions to establish or amend a RACC ...........
101.69; petitions for nutrient content claims ........................
101.70; petitions for health claims .......................................
101.108; written proposal for requesting temporary exemptions from certain regulations for the purpose of conducting food labeling experiments ...................................
Average
burden per
response
Total annual
responses
Total hours
10,000
5
3
5
1
1
1
1
10,000
5
3
5
8
80
25
80
80,000
400
75
400
1
1
1
40
40
Total ..............................................................................
maindgalligan on DSK5TPTVN1PROD with NOTICES
1 There
80,915
are no capital costs or operating and maintenance costs associated with this collection of information.
The estimated annual third-party
disclosure, recordkeeping, and reporting
burdens are based on our
communications with industry and our
knowledge of and experience with food
labeling and the submission of petitions
and requests to us.
As noted, we are revising this
collection to include previously
approved third-party disclosure burdens
associated with the requirement to
declare the amount of trans fatty acids
present in a food, including dietary
supplements. The third-party disclosure
burden hours formerly associated with
OMB control number 0910–0515
(collection entitled, ‘‘Food Labeling:
Trans Fatty Acids in Nutrition
Labeling’’) are represented by the
citation to § 101.9 on line 4 of table 1
and the citation to § 101.36 on line 17
of table 1. For this revision, we have not
added burden hours to line 4 or line 17
of table 1 because, based on our
experience with food labeling, the 4
hours estimated for meeting the labeling
requirements of § 101.9 and the 4 hours
estimated for meeting the labeling
requirements of § 101.36 are appropriate
estimates of the total time it takes a
respondent to meet our requirements for
nutrition labeling in §§ 101.9 and
101.36.
We are also revising this collection to
include previously approved third-party
disclosure burdens associated with the
voluntary declaration of the quantitative
amount and the percent of Daily Value
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Jkt 232001
of a dietary ingredient on a ‘‘per day’’
basis in addition to the required ‘‘per
serving’’ basis. The third-party
disclosure burden hours formerly
associated with OMB control number
0910–0395 (collection entitled, ‘‘Food
Labeling: Nutrition Labeling of Dietary
Supplements on a ‘Per Day’ Basis’’) are
represented by the citation to § 101.36
on line 17 of Table 1 and the addition
of 300 hours to our previous estimate of
48,000 hours. For this revision, we
added 300 burden hours to line 17 of
table 1 because voluntary labeling on a
‘‘per day’’ basis is in addition to the
required ‘‘per serving’’ basis. We
estimate that ‘‘per day’’ information
would generally be placed on, at most,
10 percent of the estimated 12,000
disclosures, for a total of 1,200 annual
disclosures, and that a respondent will
spend 15 minutes (0.25 hours) per
disclosure, for a total of 300 hours.
Thus, the total estimated burden on line
17 of table 1 is 48,300 hours and average
burden per disclosure on line 17 of table
1 has been increased from 4.0 to 4.025
hours, to represent an averaging of the
burden hours across all of the estimated
12,000 disclosures.
We expect that the burden hours for
submissions under § 101.108 will be
insignificant. Section 101.108 was
originally issued to provide a procedure
whereby we could grant exemptions
from certain food labeling requirements.
Exemption petitions have infrequently
been submitted in the recent past; none
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Frm 00076
Fmt 4703
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have been submitted since publication
on January 6, 1993, of the final
regulations implementing section 403(q)
and (r) of the FD&C Act. Thus, in order
to maintain OMB approval of § 101.108
to accommodate the possibility that a
food producer may propose to conduct
a labeling experiment on its own
initiative, we estimate that we will
receive one or fewer submissions under
§ 101.108 in the next 3 years.
Dated: December 23, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013–31215 Filed 12–27–13; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–1676]
International Drug Scheduling;
Convention on Psychotropic
Substances; Single Convention on
Narcotic Drugs; Tapentadol; Tramadol;
Ketamine; gamma-Butyrolactone; 22
Additional Substances; Request for
Comments
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is requesting
SUMMARY:
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interested persons to submit comments
concerning abuse potential, actual
abuse, medical usefulness, trafficking,
and impact of scheduling changes on
availability for medical use of 26 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 (CSA).
DATES: Submit written or electronic
comments by January 29, 2014.
ADDRESSES: Submit written comments
to the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. Submit
electronic comments to https://
www.regulations.gov.
maindgalligan on DSK5TPTVN1PROD with NOTICES
FOR FURTHER INFORMATION CONTACT:
James R. Hunter, Center for Drug
Evaluation and Research, Controlled
Substance Staff, Food and Drug
Administration, Bldg. 51, Rm. 5150,
10903 New Hampshire Ave., Silver
Spring, MD 20993–0002, 301–796–3156,
email: james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: The
United States is a party to the 1971
Convention on Psychotropic
Substances. Article 2 of the Convention
on Psychotropic Substances 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 and
provide the Secretary General of the
United Nations with information in
support of its opinion.
Section 201 of the CSA (21 U.S.C. 801
et seq.) (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 Convention on Psychotropic
Substances that it has information that
may justify adding a drug or other
substances to one of the schedules of the
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 (the 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
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the scientific and medical evaluations of
the drug or substance.
I. WHO Notification
Substances Identified for Evaluation During
the 36th Expert Committee on Drug
Dependence
Tapentadol
N-benzylpiperazine (BZP)
Gamma-Butyrolactone (GBL)
1,4-Butanediol (I,4BD)
Synthetic cannabinoids
JWH–018
JWH–073
AM–2201
UR–144
APINACA (AKB 48)
RCS–4
JWH–250
Synthetic Cathinones
Mephedrone 4-methylmethcathinone (4–
MMC)
3,4-Methylenedioxypyrovalerone (MDPV)
Methylone (bk-MDMA)
4-Methylethcathinone (4–MEC)
4-Fluoromethcathinone (flephedrone;
4–FMC)
Miscellaneous
25 B NBOMe
25 C NBOMe
25 I NBOMe
Alpha-methyltryptamine (AMT)
AH–7921
Methoxetamine (MXE)
Methiopropamine (MPA)
Lisdexamphetamine
Tramadol
Ketamine
The Secretary of HHS received the
following notices from WHO:
Ref.: C.L.29.2013
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 June 2014 to review a number of
substances with potential for misuse in order
to make recommendations to the DirectorGeneral, 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 mentioned in the questionnaire
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 email address of the focal
point be shared with the Secretariat * * *.
Upon receipt of the email of the designated
person, the focal point will receive a unique
user name, password and link for accessing
the questionnaire and responding to
questions. Further instructions on answering
the questionnaire will be provided, along
with the questionnaire, online. Further
clarification on the above items can be
obtained from the Secretariat by emailing:
ecdd_secretariat@who.int. Replies to the
questionnaire must reach the Secretariat by 1
February 2014 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 at the
Web site for the Thirty-sixth ECDD linked to
the Department of Essential Medicines and
Health Products (EMP): https://www.who.int/
medicines/areas/quality_safety/ECDD/en/
index.html.
The World Health Organization takes this
opportunity to renew to Member States and
Associate Members the assurance of its
highest consideration.
GENEVA, 11 November 2013
*
*
*
*
*
ENCL.: (1)
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*
*
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WHO Questionnaire for the 36th Meeting of
Expert Committee on Drug Dependence:
Substance
Definitions:
(Def. 1) Legitimate use is use of a substance
for legally valid purposes such as medical
scientific and industrial.
(Def. 2) Harmful use is defined as a pattern
of psychoactive substance use that increases
the risk of harmful physical, mental, and
social consequences for the user or to others.
Harmful use of drugs by an individual has
potential for adverse effects on the substance
user’s family, the community and society in
general.
Substance* (Insert name of substance)
—Do you have any information on this
substance on legitimate use, recreational/
harmful use or control status in your
country? * (Yes/No)
A. LEGITIMATE MEDICAL OR OTHER
SCIENTIFIC USE OF THE SUBSTANCE (Def.
1)
—Is the substance currently authorized or in
the process of being authorized/registered
as a medical product in your country?
(Yes/No)
If ‘‘yes,’’ since when has it been on the
market? (input year)
—Please state registered indications for this
medicine:
—Please mention other, if any, medical use
not included in the approved indications
(off label use):
—Please indicate dosage form(s) and
strength(s) available in your country; also
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indicate special properties such as slow
release, etc.:
Dosage
form
Strength
Remarks
1.
2.
3.
—Please list alphabetically the brand names
available in your country (there is no need
for dosage forms, strengths, etc.):
—Are there any other uses for the substance
in health care (such as for diagnostic tests)
in your country? (Yes/No)
If ‘‘yes,’’ what is the use?
—Is the chemical used for medical or
scientific research in your country? (Yes/
No)
If ‘‘yes,’’ please specify:
—Is the substance used for animal care
(veterinary use)? (Yes/No)
—Is there any other legitimate (Def. 1) use of
the substance (e.g. industry uses)? (Yes/No)
If ‘‘yes,’’ please state the purpose:
—If there is any legitimate (Def. 1) use of the
substance, how is the substance sourced?
(Manufactured in country/Imported)
—What is the estimated approximate amount
needed for its legitimate use in your
country per year?
—Is the substance used for cultural or
ceremonial purposes? (Yes/No)
If ‘‘yes,’’ specify why it is used:
Who uses it (the group using)?
How is it used? (route of administration):
What is its source?
79467
B. HARMFUL USE OF THE SUBSTANCE
(Def. 2)
—Is there recreational/harmful use of this
substance in your country? (Def. 2) (Yes/
No/Unknown)
If ‘‘yes,’’ please specify how the substance
is used and the extent of use by answering
the following questions:
Common route(s) of administration (Oral/
Injection/Inhaling or sniffing)
How is it obtained? (Diversion/Trafficking/
Clandestine manufacturing)
Common formulation(s) available:
(Powder/Tablet/Liquid)
—Any other information on recreational/
harmful use:
—Quantity of substance used by an average
misuse per sitting (average dose used):
—Is it used by special population(s)? (Club
use/General population)
Club use
(percent)
General
population
(percent)
Emergency room
visits resulting
from the use of
this substance
Dependence to
this substance
Estimated proportion of the population using the substance ......................................................................
—Please provide any information on the
extent/magnitude of public health or social
harm from the use of the substance (Def.
2) in your country:
Overdose deaths
reported
Addiction
programme
enrolment from
the use of this
substance
Numbers in 2012 .....................................................................
—Are there reports of withdrawal, tolerance,
other adverse effects or medical illnesses
caused by this substance in your country?
(Yes/No)
If ‘‘yes,’’ please provide details:
—Any other relevant information on harm to
individuals or the society:
—Please indicate the sources of information
on harm:
—If actual data are not available, please
provide a short description on harm caused
by this substance:
C. CONTROL OF THE SUBSTANCE
—Is the substance controlled under
legislation that is intended to regulate its
availability in the country? (Yes/No)
Number of
seizures
Year
If ‘‘yes,’’ please select which one:
(Controlled substances act/Medicines law/
Poisons acts/Consumer protection acts/
Generic legislation/Analogue legislation/
Temporary ban/Other legislation (name))
—How is this law enforced? Please provide
a short description:
—Are there challenges to implementation?
(Yes/No)
If ‘‘yes,’’ please specify (e.g. laboratory
capacity, resources to implement and/or
enforce, expertise):
—Are there illicit activities involving the
substance? (Yes/No)
Clandestine manufacture? (Yes/No)
Kilograms
Litres
The manufacture (synthesis) of the
chemical itself (Yes/No)
The processing into the consumer product,
i.e. adding it to herbal material,
packaging (Yes/No)
Trafficking (Yes/No)
Diversion (Yes/No)
Internet market (Yes/No)
Other (please specify):
—Please provide any other relevant
information on illicit activities:
—Data on seizures
Number of
ampoules
Number of
tablets/pills
Other type
(quantity)
maindgalligan on DSK5TPTVN1PROD with NOTICES
2011 .....................
2012 .....................
D. IMPACT OF SCHEDULING
—If this substance is placed under
international control, does your country
have the lab capacity to identify the
substance? (Yes/No/Unknown)
—If this substance is placed under
international control, do you think its
availability for medical use will be
affected? (Yes/No)
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If ‘‘yes,’’ please explain (consider both
human and veterinary needs): How could
control impact its medical availability?
Please identify specific population groups
that may be affected, and describe the
implications of increased control.
—Any additional information on impact of
scheduling:
*
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*
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II. Background
Tapentadol is a central nervous
system active analgesic agent that has
mu (m) opioid agonist properties and
inhibits the reuptake of norepinephrine.
Tapentadol is approved for marketing in
the United States for the treatment of
moderate to severe acute pain.
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Tapentadol is controlled in Schedule II
under the CSA in the United States.
Tapentadol was pre-reviewed by the
WHO Expert Committee on Drug
Dependence at its 35th meeting and
recommended for critical review at its
36th meeting.
N-benzylpiperazine (BZP) is used as
an intermediate in chemical synthesis
but has been taken orally as either
powder or tablets and by other routes,
including smoking or snorting. It has no
medical use in the United States. BZP
is controlled in Schedule I under the
CSA in the United States. BZP is not
controlled internationally under the
Convention on Psychotropic Substances
or the Single Convention on Narcotic
Drugs. BZP was pre-reviewed by the
WHO Expert Committee on Drug
Dependence at its 35th meeting and
recommended for critical review at its
36th meeting.
Gamma-Butyrolactone (GBL) is used
as an industrial solvent. GBL can be
converted in the body to the central
nervous system depressant drug gammahydroxybutyric acid (GHB). GBL is
controlled as a List I chemical in the
United States under the CSA. It is not
controlled internationally under the
Convention on Psychotropic Substances
or the Single Convention on Narcotic
Drugs. GBL was pre-reviewed by the
WHO Expert Committee on Drug
Dependence at its 35th meeting and
recommended for critical review at its
36th meeting.
1,4-Butanediol is used as an industrial
solvent for manufacturing and also used
for the synthesis of GBL. 1,4-Butanediol
can also be converted to the central
nervous depressant drug GHB. It has no
medical use in the United States. 1,4Butanediol is not controlled under the
CSA in the United States, but it is
subject to controls in several states
under state law. 1,4-Butanediol was prereviewed by the WHO Expert
Committee on Drug Dependence at its
35th meeting and recommended for
critical review at its 36th meeting.
The following substances are
classified as synthetic cannabinoids
with pharmacological properties like
tetrahydrocannabinol: (1-pentyl-1Hindol-3-yl)-1-naphthalenyl-methanone
(JWH–018), (1-butyl-1H-indol-3-yl)-1naphthalenyl-methanone (JWH–073), 1(1-pentyl-1H-indol-3-yl)-2-(2methoxyphenyl)-ethanone (JWH–250),
[1-(5-fluoropentyl)-1H-indol-3-yl]-1naphthalenyl-methanone (AM–2201),
(1-pentyl-1H-indol-3-yl)(2,2,3,3tetramethylcyclopropyl)-methanone
(UR–144), 1-pentyl-Ntricyclo[3.3.1.13,7]dec-l-yl-1H-indazole3-carboxamide (APINACA; AKB48), and
(4-methoxyphenyl)(1-pentyl-1H-indol-3-
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yl)methanone (RCS–4). JWH–018, JWH–
073, JWH–250, AM–2201, and RCS–4
are controlled in Schedule I under the
CSA in the United States. On May 16,
2013, UR–144 and AKB 48 were
temporarily placed in Schedule I under
the CSA pursuant to the temporary
scheduling provisions of section 201(h)
of the CSA (21 U.S.C. 811(h)).
4-Methylmethcathinone (4–MMC;
mephedrone), 3,4methylenedioxypyrovalerone (MDPV),
3,4-methylenedioxy-N-methylcathinone
(bk-MDMA; Methylone), 4methylethcathinone (4–MEC), and 4fluoromethcathinone (flephedrone; 4–
FMC) are classified as synthetic
cathinones in the phenethylamine class
and are structurally and
pharmacologically similar to
amphetamine, 3,4methylenedioxymethamphetamine
(MDMA), cathinone and other related
substances. 4–MMC, MDPV, and
Methylone are controlled in Schedule I
under the CSA in the United States. 4–
MEC and 4–FMC are not controlled
under the CSA in the United States.
2-(4-bromo-2,5-dimethoxyphenyl)-N[(2-methoxyphenyl)methyl]ethanamine
(25B–NBOMe), 2-(4-chloro-2,5dimethoxyphenyl)-N-(2methoxybenzyl)ethanamine (25C–
NBOMe), and 2-(4-iodo-2,5dimethoxyphenyl)-N-[(2methoxyphenyl)methyl]ethanamine
(25I–NBOMe) are synthetic 2C
phenethylamine substances and were
developed for use in mapping and
investigating the serotonin receptors in
the mammalian brain. On November 15,
2013, 25B–NBOMe, 25C–NBOMe, and
25I–NBOMe were temporarily placed in
Schedule I of the CSA pursuant to the
temporary scheduling provision of
section 201(h) of the CSA.
Alpha-Methyltryptamine (AMT) is a
tryptamine (indoleethylamine)
derivative and shares several
similarities with the Schedule I
tryptamine hallucinogens, such as
alpha-ethyltryptamine (AET) and N,Ndimethyltryptamine (DMT). AMT is
controlled in Schedule I under the CSA
in the United States.
AH–7921, or 1-(3,4dichlorobenzamidomethyl)
cyclohexyldimethylamine, is an opioid
analgesic drug selective for the m-opioid
receptor and is not controlled under the
CSA in the United States.
Methoxetamine (MXE), or 2(ethylamino)-2-(3-methoxyphenyl)cyclohexanone, is an arylcyclohexamine
and is not controlled under the CSA in
the United States. MXE can be
considered as a controlled substance
analogue of eticyclidine (PCE) under the
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CSA if intended for human
consumption.
Methiopropamine (MPA) is a
thiophene analog of methamphetamine
and is not controlled under the CSA in
the United States.
Lisdexamphetamine is an amide ester
conjugate comprised of the amino acid
L-lysine covalently bound to the amino
group of d-amphetamine.
Lisdexamphetamine was approved for
marketing in the United States in 2007
and is used for the treatment of
Attention Deficit Hyperactivity
Disorder. Lisdexamphetamine was
placed in Schedule II of the CSA in June
2007.
Tramadol is an opioid analgesic that
produces its primary opioid-like action
through an active metabolite referred to
as the M1 metabolite·(Odesmethyltramadol). Tramadol was first
approved for marketing in the United
States in 1995 and is available in
immediate-release, extended-release,
and combination product for the
treatment of moderate to moderatelysevere pain. In November 2013,
Tramadol was proposed to be placed in
Schedule IV of the CSA. The Secretariat
indicates that additional safety
information on this substance is
available, thus an updated review for
Tramadol is necessary for presentation
at the 36th meeting of the WHO Expert
Committee on Drug Dependence.
Ketamine is classified as a rapidacting 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. 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
WHO Expert Committee on Drug
Dependence reviewed ketamine at its
34th and 35th meetings. The Secretariat
indicates that additional safety
information on this substance is
available, thus an updated review for
ketamine is necessary for presentation at
the 36th meeting of the WHO Expert
Committee on Drug Dependence.
III. Opportunity To Submit Domestic
Information
As required by section 201(d)(2)(A) of
the CSA, FDA, on behalf of the
Department of Health and Human
Services (HHS), invites interested
persons to submit comments regarding
the 26 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
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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.
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 2015.
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.
IV. Comments
Interested persons may submit either
electronic comments regarding the
drugs to https://www.regulations.gov or
written comments to the Division of
Dockets Management (see ADDRESSES)
by January 29, 2014. It is only necessary
to send one set of comments. Identify
comments with the docket number
found in brackets in the heading of this
notice. Received comments may be seen
in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday
through Friday, and will be posted to
the docket at https://
www.regulations.gov.
Dated: December 24, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013–31212 Filed 12–27–13; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–0001]
Strategies To Address Hemolytic
Complications of Immune Globulin
Infusions; Public Workshop
maindgalligan on DSK5TPTVN1PROD with NOTICES
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of public workshop.
The Food and Drug Administration
(FDA) is announcing a public workshop
entitled ‘‘Strategies to Address
Hemolytic Complications of Immune
Globulin Infusions.’’ The purpose of the
public workshop is to identify and
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17:15 Dec 27, 2013
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discuss potential risk mitigation
strategies for Immune Globulin (Ig)associated hemolysis and to identify
and discuss important research
questions related to patient risk and
product characteristics. The workshop
has been planned in partnership with
the National Heart, Lung, and Blood
Institute, National Institutes of Health,
and the Plasma Protein Therapeutics
Association. The workshop will include
presentations and panel discussions by
experts from academic institutions,
industry, and government agencies.
Dates and Times: The public
workshop will be held on January 28,
2014, 8:30 a.m. to 5 p.m. and January
29, 2014, 8:30 a.m. to 12 noon.
Location: The public workshop will
be held at Lister Hill Center
Auditorium, National Institutes of
Health Campus, Building 38A, 8600
Rockville Pike, Bethesda, MD 20894.
Contact Person: Chris Nguyen, Center
for Biologics Evaluation and Research
(HFM–49), Food and Drug
Administration, 1401 Rockville Pike,
suite 200N, Rockville, MD 20852–1448,
301–827–2000, FAX: 301–827–3079,
email: CBERPublicEvents@fda.hhs.gov.
Registration: Mail or fax your
registration information (including
name, title, firm name, address,
telephone, and fax numbers) to Chris
Nguyen (see Contact Person) or email to
CBERPublicEvents@fda.hhs.gov (subject
line: IG Hemolysis Workshop
Registration) by January 10, 2014. There
is no registration fee for the public
workshop. Early registration is
recommended because seating is
limited. Registration on the day of the
public workshop will be provided on a
space available basis beginning at 7:30
a.m. Pre-registered participants will
receive additional information on
security procedures, parking, and public
transportation with their email
registration confirmation.
If you need special accommodations
due to a disability, please contact Chris
Nguyen (see Contact Person) at least 7
days in advance.
SUPPLEMENTARY INFORMATION: Clinically
significant hemolysis is a longrecognized complication of Immune
Globulin Intravenous (IGIV) (Human)
infusion. Complications of hemolysis
include severe anemia requiring
transfusion, renal failure, and
disseminated intravascular coagulation.
Ig-associated hemolysis has been
generally thought to be caused by the
presence of Immunoglobulin G (IgG)
antibodies against major red blood cell
antigens. All FDA-licensed Ig products
are tested and have upper limit release
specifications for antibodies against
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79469
blood group antigens A, B, and Rho(D).
However, IGIV-associated hemolysis
occurs despite adherence to these
specifications. In addition, there are
factors that may increase a patient’s risk
for hemolysis. Known patient risk
factors for hemolysis include: (1) High
doses of IGIV; (2) recipient blood type
A, AB, or B; and (3) other factors, such
as history of hemolysis and possibly
underlying inflammatory disease.
The goals of the workshop are to
identify and discuss potential risk
mitigation strategies for Ig-associated
hemolysis, including improved
identification of patients at high risk for
hemolysis; changes in product
specifications, tests, or test methods;
and modifications to manufacturing to
lower product risk. In addition, this
workshop is intended to identify and
discuss important outstanding research
questions related to patient risk and
product characteristics.
The first day of this workshop will
include presentations and panel
discussions on the following topics: (1)
Pathogenesis and epidemiology of IGIVassociated hemolysis; (2) patient risk
factors; and (3) possible product risk
factors, including the presence of AntiA and Anti-B hemagglutinins.
The second day of the workshop will
include presentations and panel
discussions on the following topics: (1)
Immune globulin manufacturing and
risk mitigation strategies and (2)
workshop summary and conclusions.
Transcripts: Please be advised that as
soon as possible after a transcript of the
public workshop is available, it will be
accessible at: https://www.fda.gov/
BiologicsBloodVaccines/NewsEvents/
WorkshopsMeetingsConferences/
TranscriptsMinutes/default.htm.
Transcripts of the public workshop may
also be requested in writing from the
Division of Freedom of Information
(ELEM–1029), Food and Drug
Administration, 12420 Parklawn Dr.,
Rockville, MD 20857.
Dated: December 23, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013–31213 Filed 12–27–13; 8:45 am]
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E:\FR\FM\30DEN1.SGM
30DEN1
Agencies
[Federal Register Volume 78, Number 250 (Monday, December 30, 2013)]
[Notices]
[Pages 79465-79469]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-31212]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2013-N-1676]
International Drug Scheduling; Convention on Psychotropic
Substances; Single Convention on Narcotic Drugs; Tapentadol; Tramadol;
Ketamine; gamma-Butyrolactone; 22 Additional Substances; Request for
Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is requesting
[[Page 79466]]
interested persons to submit comments concerning abuse potential,
actual abuse, medical usefulness, trafficking, and impact of scheduling
changes on availability for medical use of 26 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 (CSA).
DATES: Submit written or electronic comments by January 29, 2014.
ADDRESSES: Submit written comments to the Division of Dockets
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov.
FOR FURTHER INFORMATION CONTACT: James R. Hunter, Center for Drug
Evaluation and Research, Controlled Substance Staff, Food and Drug
Administration, Bldg. 51, Rm. 5150, 10903 New Hampshire Ave., Silver
Spring, MD 20993-0002, 301-796-3156, email: james.hunter@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: The United States is a party to the 1971
Convention on Psychotropic Substances. Article 2 of the Convention on
Psychotropic Substances 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 and provide the Secretary
General of the United Nations with information in support of its
opinion.
Section 201 of the CSA (21 U.S.C. 801 et seq.) (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
Convention on Psychotropic Substances that it has information that may
justify adding a drug or other substances to one of the schedules of
the 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 (the
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.
I. WHO Notification
The Secretary of HHS received the following notices from WHO:
Ref.: C.L.29.2013
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 June 2014 to review a number of substances with
potential for misuse in order to make recommendations to the
Director-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 mentioned in the questionnaire
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 email
address of the focal point be shared with the Secretariat * * *.
Upon receipt of the email of the designated person, the focal point
will receive a unique user name, password and link for accessing the
questionnaire and responding to questions. Further instructions on
answering the questionnaire will be provided, along with the
questionnaire, online. Further clarification on the above items can
be obtained from the Secretariat by emailing: ecdd_secretariat@who.int. Replies to the questionnaire must reach the
Secretariat by 1 February 2014 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 at the
Web site for the Thirty-sixth ECDD linked to the Department of
Essential Medicines and Health Products (EMP): https://www.who.int/medicines/areas/quality_safety/ECDD/en/.
The World Health Organization takes this opportunity to renew to
Member States and Associate Members the assurance of its highest
consideration.
GENEVA, 11 November 2013
* * * * *
ENCL.: (1)
Substances Identified for Evaluation During the 36th Expert Committee
on Drug Dependence
Tapentadol
N-benzylpiperazine (BZP)
Gamma-Butyrolactone (GBL)
1,4-Butanediol (I,4BD)
Synthetic cannabinoids
JWH-018
JWH-073
AM-2201
UR-144
APINACA (AKB 48)
RCS-4
JWH-250
Synthetic Cathinones
Mephedrone 4-methylmethcathinone (4-MMC)
3,4-Methylenedioxypyrovalerone (MDPV)
Methylone (bk-MDMA)
4-Methylethcathinone (4-MEC)
4-Fluoromethcathinone (flephedrone; 4-FMC)
Miscellaneous
25 B NBOMe
25 C NBOMe
25 I NBOMe
Alpha-methyltryptamine (AMT)
AH-7921
Methoxetamine (MXE)
Methiopropamine (MPA)
Lisdexamphetamine
Tramadol
Ketamine
* * * * *
WHO Questionnaire for the 36th Meeting of Expert Committee on Drug
Dependence: Substance
Definitions:
(Def. 1) Legitimate use is use of a substance for legally valid
purposes such as medical scientific and industrial.
(Def. 2) Harmful use is defined as a pattern of psychoactive
substance use that increases the risk of harmful physical, mental,
and social consequences for the user or to others. Harmful use of
drugs by an individual has potential for adverse effects on the
substance user's family, the community and society in general.
Substance* (Insert name of substance)
--Do you have any information on this substance on legitimate use,
recreational/harmful use or control status in your country? \*\
(Yes/No)
A. LEGITIMATE MEDICAL OR OTHER SCIENTIFIC USE OF THE SUBSTANCE (Def. 1)
--Is the substance currently authorized or in the process of being
authorized/registered as a medical product in your country? (Yes/No)
If ``yes,'' since when has it been on the market? (input year)
--Please state registered indications for this medicine:
--Please mention other, if any, medical use not included in the
approved indications (off label use):
--Please indicate dosage form(s) and strength(s) available in your
country; also
[[Page 79467]]
indicate special properties such as slow release, etc.:
------------------------------------------------------------------------
Dosage form Strength Remarks
------------------------------------------------------------------------
1. ................. ................ ................
2. ................. ................ ................
3. ................. ................ ................
------------------------------------------------------------------------
--Please list alphabetically the brand names available in your
country (there is no need for dosage forms, strengths, etc.):
--Are there any other uses for the substance in health care (such as
for diagnostic tests) in your country? (Yes/No)
If ``yes,'' what is the use?
--Is the chemical used for medical or scientific research in your
country? (Yes/No)
If ``yes,'' please specify:
--Is the substance used for animal care (veterinary use)? (Yes/No)
--Is there any other legitimate (Def. 1) use of the substance (e.g.
industry uses)? (Yes/No)
If ``yes,'' please state the purpose:
--If there is any legitimate (Def. 1) use of the substance, how is
the substance sourced? (Manufactured in country/Imported)
--What is the estimated approximate amount needed for its legitimate
use in your country per year?
--Is the substance used for cultural or ceremonial purposes? (Yes/
No)
If ``yes,'' specify why it is used:
Who uses it (the group using)?
How is it used? (route of administration):
What is its source?
B. HARMFUL USE OF THE SUBSTANCE (Def. 2)
--Is there recreational/harmful use of this substance in your
country? (Def. 2) (Yes/No/Unknown)
If ``yes,'' please specify how the substance is used and the
extent of use by answering the following questions:
Common route(s) of administration (Oral/Injection/Inhaling or
sniffing)
How is it obtained? (Diversion/Trafficking/Clandestine
manufacturing)
Common formulation(s) available: (Powder/Tablet/Liquid)
--Any other information on recreational/harmful use:
--Quantity of substance used by an average misuse per sitting
(average dose used):
--Is it used by special population(s)? (Club use/General population)
------------------------------------------------------------------------
General
Club use population
(percent) (percent)
------------------------------------------------------------------------
Estimated proportion of the
population using the substance...
------------------------------------------------------------------------
--Please provide any information on the extent/magnitude of public
health or social harm from the use of the substance (Def. 2) in your
country:
----------------------------------------------------------------------------------------------------------------
Addiction
programme Emergency room
Overdose deaths enrolment from visits resulting Dependence to
reported the use of this from the use of this substance
substance this substance
----------------------------------------------------------------------------------------------------------------
Numbers in 2012.....................
----------------------------------------------------------------------------------------------------------------
--Are there reports of withdrawal, tolerance, other adverse effects
or medical illnesses caused by this substance in your country? (Yes/
No)
If ``yes,'' please provide details:
--Any other relevant information on harm to individuals or the
society:
--Please indicate the sources of information on harm:
--If actual data are not available, please provide a short
description on harm caused by this substance:
C. CONTROL OF THE SUBSTANCE
--Is the substance controlled under legislation that is intended to
regulate its availability in the country? (Yes/No)
If ``yes,'' please select which one: (Controlled substances act/
Medicines law/Poisons acts/Consumer protection acts/Generic
legislation/Analogue legislation/Temporary ban/Other legislation
(name))
--How is this law enforced? Please provide a short description:
--Are there challenges to implementation? (Yes/No)
If ``yes,'' please specify (e.g. laboratory capacity, resources
to implement and/or enforce, expertise):
--Are there illicit activities involving the substance? (Yes/No)
Clandestine manufacture? (Yes/No)
The manufacture (synthesis) of the chemical itself (Yes/No)
The processing into the consumer product, i.e. adding it to
herbal material, packaging (Yes/No)
Trafficking (Yes/No)
Diversion (Yes/No)
Internet market (Yes/No)
Other (please specify):
--Please provide any other relevant information on illicit
activities:
--Data on seizures
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of Number of tablets/ Other type
Year seizures Kilograms Litres ampoules pills (quantity)
--------------------------------------------------------------------------------------------------------------------------------------------------------
2011..................................
2012..................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
D. IMPACT OF SCHEDULING
--If this substance is placed under international control, does your
country have the lab capacity to identify the substance? (Yes/No/
Unknown)
--If this substance is placed under international control, do you
think its availability for medical use will be affected? (Yes/No)
If ``yes,'' please explain (consider both human and veterinary
needs): How could control impact its medical availability? Please
identify specific population groups that may be affected, and
describe the implications of increased control.
--Any additional information on impact of scheduling:
* * * * *
II. Background
Tapentadol is a central nervous system active analgesic agent that
has mu ([micro]) opioid agonist properties and inhibits the reuptake of
norepinephrine. Tapentadol is approved for marketing in the United
States for the treatment of moderate to severe acute pain.
[[Page 79468]]
Tapentadol is controlled in Schedule II under the CSA in the United
States. Tapentadol was pre-reviewed by the WHO Expert Committee on Drug
Dependence at its 35th meeting and recommended for critical review at
its 36th meeting.
N-benzylpiperazine (BZP) is used as an intermediate in chemical
synthesis but has been taken orally as either powder or tablets and by
other routes, including smoking or snorting. It has no medical use in
the United States. BZP is controlled in Schedule I under the CSA in the
United States. BZP is not controlled internationally under the
Convention on Psychotropic Substances or the Single Convention on
Narcotic Drugs. BZP was pre-reviewed by the WHO Expert Committee on
Drug Dependence at its 35th meeting and recommended for critical review
at its 36th meeting.
Gamma-Butyrolactone (GBL) is used as an industrial solvent. GBL can
be converted in the body to the central nervous system depressant drug
gamma-hydroxybutyric acid (GHB). GBL is controlled as a List I chemical
in the United States under the CSA. It is not controlled
internationally under the Convention on Psychotropic Substances or the
Single Convention on Narcotic Drugs. GBL was pre-reviewed by the WHO
Expert Committee on Drug Dependence at its 35th meeting and recommended
for critical review at its 36th meeting.
1,4-Butanediol is used as an industrial solvent for manufacturing
and also used for the synthesis of GBL. 1,4-Butanediol can also be
converted to the central nervous depressant drug GHB. It has no medical
use in the United States. 1,4-Butanediol is not controlled under the
CSA in the United States, but it is subject to controls in several
states under state law. 1,4-Butanediol was pre-reviewed by the WHO
Expert Committee on Drug Dependence at its 35th meeting and recommended
for critical review at its 36th meeting.
The following substances are classified as synthetic cannabinoids
with pharmacological properties like tetrahydrocannabinol: (1-pentyl-
1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-018), (1-butyl-1H-indol-3-
yl)-1-naphthalenyl-methanone (JWH-073), 1-(1-pentyl-1H-indol-3-yl)-2-
(2-methoxyphenyl)-ethanone (JWH-250), [1-(5-fluoropentyl)-1H-indol-3-
yl]-1-naphthalenyl-methanone (AM-2201), (1-pentyl-1H-indol-3-
yl)(2,2,3,3-tetramethylcyclopropyl)-methanone (UR-144), 1-pentyl-N-
tricyclo[3.3.1.13,7]dec-l-yl-1H-indazole-3-carboxamide (APINACA;
AKB48), and (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone (RCS-4).
JWH-018, JWH-073, JWH-250, AM-2201, and RCS-4 are controlled in
Schedule I under the CSA in the United States. On May 16, 2013, UR-144
and AKB 48 were temporarily placed in Schedule I under the CSA pursuant
to the temporary scheduling provisions of section 201(h) of the CSA (21
U.S.C. 811(h)).
4-Methylmethcathinone (4-MMC; mephedrone), 3,4-
methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone
(bk-MDMA; Methylone), 4-methylethcathinone (4-MEC), and 4-
fluoromethcathinone (flephedrone; 4-FMC) are classified as synthetic
cathinones in the phenethylamine class and are structurally and
pharmacologically similar to amphetamine, 3,4-
methylenedioxymethamphetamine (MDMA), cathinone and other related
substances. 4-MMC, MDPV, and Methylone are controlled in Schedule I
under the CSA in the United States. 4-MEC and 4-FMC are not controlled
under the CSA in the United States.
2-(4-bromo-2,5-dimethoxyphenyl)-N-[(2-
methoxyphenyl)methyl]ethanamine (25B-NBOMe), 2-(4-chloro-2,5-
dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25C-NBOMe), and 2-(4-
iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-
NBOMe) are synthetic 2C phenethylamine substances and were developed
for use in mapping and investigating the serotonin receptors in the
mammalian brain. On November 15, 2013, 25B-NBOMe, 25C-NBOMe, and 25I-
NBOMe were temporarily placed in Schedule I of the CSA pursuant to the
temporary scheduling provision of section 201(h) of the CSA.
Alpha-Methyltryptamine (AMT) is a tryptamine (indoleethylamine)
derivative and shares several similarities with the Schedule I
tryptamine hallucinogens, such as alpha-ethyltryptamine (AET) and N,N-
dimethyltryptamine (DMT). AMT is controlled in Schedule I under the CSA
in the United States.
AH-7921, or 1-(3,4-dichlorobenzamidomethyl)cyclohexyldimethylamine,
is an opioid analgesic drug selective for the [micro]-opioid receptor
and is not controlled under the CSA in the United States.
Methoxetamine (MXE), or 2-(ethylamino)-2-(3-methoxyphenyl)-
cyclohexanone, is an arylcyclohexamine and is not controlled under the
CSA in the United States. MXE can be considered as a controlled
substance analogue of eticyclidine (PCE) under the CSA if intended for
human consumption.
Methiopropamine (MPA) is a thiophene analog of methamphetamine and
is not controlled under the CSA in the United States.
Lisdexamphetamine is an amide ester conjugate comprised of the
amino acid L-lysine covalently bound to the amino group of d-
amphetamine. Lisdexamphetamine was approved for marketing in the United
States in 2007 and is used for the treatment of Attention Deficit
Hyperactivity Disorder. Lisdexamphetamine was placed in Schedule II of
the CSA in June 2007.
Tramadol is an opioid analgesic that produces its primary opioid-
like action through an active metabolite referred to as the M1
metabolite[middot](O-desmethyltramadol). Tramadol was first approved
for marketing in the United States in 1995 and is available in
immediate-release, extended-release, and combination product for the
treatment of moderate to moderately-severe pain. In November 2013,
Tramadol was proposed to be placed in Schedule IV of the CSA. The
Secretariat indicates that additional safety information on this
substance is available, thus an updated review for Tramadol is
necessary for presentation at the 36th meeting of the WHO Expert
Committee on Drug Dependence.
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. 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 WHO Expert Committee on Drug Dependence reviewed
ketamine at its 34th and 35th meetings. The Secretariat indicates that
additional safety information on this substance is available, thus an
updated review for ketamine is necessary for presentation at the 36th
meeting of the WHO Expert Committee on Drug Dependence.
III. Opportunity To Submit Domestic Information
As required by section 201(d)(2)(A) of the CSA, FDA, on behalf of
the Department of Health and Human Services (HHS), invites interested
persons to submit comments regarding the 26 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
[[Page 79469]]
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.
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 2015. 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.
IV. Comments
Interested persons may submit either electronic comments regarding
the drugs to https://www.regulations.gov or written comments to the
Division of Dockets Management (see ADDRESSES) by January 29, 2014. It
is only necessary to send one set of comments. Identify comments with
the docket number found in brackets in the heading of this notice.
Received comments may be seen in the Division of Dockets Management
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to
the docket at https://www.regulations.gov.
Dated: December 24, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-31212 Filed 12-27-13; 8:45 am]
BILLING CODE 4160-01-P