[Federal Register Volume 78, Number 27 (Friday, February 8, 2013)]
[Notices]
[Pages 9397-9399]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-02859]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0448]


International Drug Scheduling; Convention on Psychotropic 
Substances; World Health Organization Scheduling Recommendations for 
Gamma-hydroxybutyric Acid

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is providing interested 
persons with the opportunity to submit written comments and to request 
an informal public meeting concerning recommendations by the World 
Health Organization (WHO) to impose international manufacturing and 
distributing restrictions, under international treaties, on certain 
drug substances. The comments received in response to this notice and/
or public meeting will be considered in preparing the U.S. position on 
these proposals for a meeting of the United Nations Commission on 
Narcotic Drugs (CND) in Vienna, Austria, in March 2013. This notice is 
issued under the Controlled Substances Act (the CSA).

DATES: Submit either electronic or written comments by February 25, 
2013. Submit requests for a public meeting on or before February 19, 
2013. (For additional information, see also section IV of this 
document).

ADDRESSES: Submit electronic comments to http://www.regulations.gov. 
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 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, Bldg. 51, rm. 5150, 10903 New Hampshire Ave., 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 (the Convention). Section 201(d)(2)(B) of the CSA (21 U.S.C. 
811(d)(2)(B)) provides that when the United States is notified under 
Article 2 of the Convention that CND proposes to decide whether to add 
a drug or other substance to one of the schedules of the Convention, 
transfer a drug or substance from one schedule to another, or delete it 
from the schedules, the Secretary of State must transmit notice of such 
information to the Secretary of Health and Human Services (Secretary of 
HHS). The Secretary of HHS must then publish a summary of such 
information in the Federal Register and provide opportunity for 
interested persons to submit comments. The Secretary of HHS must then 
evaluate the proposal and furnish a recommendation to the Secretary of 
State that shall be binding on the representative of the United States 
in discussions and negotiations relating to the proposal.
    As detailed in the following paragraphs, the Secretary of State has 
received one notification from the Secretary-General of the United 
Nations (the Secretary-General) regarding substances to be considered 
for control under the Convention. This notification reflects the 
recommendation from the 35th WHO Expert Committee for Drug Dependence 
(ECDD), which met in June 2012. In the Federal Register of September 
05, 2008 (73 FR 51823), FDA announced the WHO ECDD review and invited 
interested persons to submit information for WHO's consideration.
    The full text of the notification from the Secretary-General is 
provided in section II of this document. Section 201(d)(2)(B) of the 
CSA requires the Secretary of HHS, after receiving a notification 
proposing scheduling, to publish a notice in the Federal Register to 
provide the opportunity for interested persons to submit information 
and comments on the proposed scheduling action.

II. United Nations Notification

    The formal United Nations notification that identifies the drug 
substance and explains the basis for the recommendations is reproduced 
as follows:

Reference: NAR/CL.6/2012
WHO/ECDD35 1971C-Art.2
CU 2012/196/DTA/SGB

    The Secretary-General of the United Nations presents his 
compliments to the Secretary of State of the United States of America 
and has the honour to inform the Government that the Director-

[[Page 9398]]

General of the WHO, under article 2, paragraphs 1, 4, and 6, of the 
Convention on Psychotropic Substances of 1971 (1971 Convention), has 
notified the Secretary-General that it is of the opinion that Gamma-
hydroxybutyric acid (GHB) should be transferred from Schedule IV to 
Schedule II of the 1971 Convention.
    In accordance with the provisions of article 2, paragraph 2, of the 
1971 Convention, the Secretary-General hereby transmits the relevant 
excerpts of the notification as Annex I to the present note. Also in 
accordance with the same provisions, the notification from WHO will be 
brought to the attention of the CND at its next session in March 2013.
    In connection with the notification, WHO has also submitted 
excerpts from the report of the Thirty-fifth session of the WHO ECDD 
(4-8 June 2012) which reviewed the substance. The excerpts from that 
report concerning GHB are hereby transmitted as Annex II. The excerpts 
are currently available in English only, pending receipt of the 
official French translation from the WHO. The report of the Thirty-
fifth session of the WHO ECDD can be retrieved from the following Web 
site: http://www.who.int/medicines/areas/quality_safety/35thecddmeet/en/index.html. (FDA has verified the Web site address, but FDA is not 
responsible for any subsequent changes to the Web site after this 
document publishes in the Federal Register).
    Any action or decision taken by the Commission with respect to this 
notification, pursuant to article 2, paragraphs 5 and 6, of the 1971 
Convention, will be communicated to States Parties in due course. 
Article 2, paragraphs 5 and 6, reads as follows:

    5. The Commission, taking into account the communication from 
the WHO, whose assessments shall be determinative as to medical and 
scientific matters, and bearing in mind the economic, social, legal, 
administrative and other factors it may consider relevant, may add 
the substance to Schedule I, II, III or IV. The Commission may seek 
further information from the WHO or from other appropriate sources.
    6. If a notification under paragraph 1 relates to a substance 
already listed in one of the Schedules, the WHO shall communicate to 
the Commission its new findings, any new assessment of the substance 
it may make in accordance with paragraph 4 and any new 
recommendations on control measures it may find appropriate in the 
light of that assessment. The Commission, taking into account the 
communication from the WHO as under paragraph 5 and bearing in mind 
the factors referred to in that paragraph, may decide to transfer 
the substance from one Schedule to another or to delete it from the 
Schedules.

    To assist the Commission in reaching a decision, it would be 
appreciated if the Government could communicate any economic, social, 
legal, administrative, or other factors that it considers relevant to 
the possible rescheduling under the 1971 Convention, of GHB, at the 
latest by 28 December 2012 to the Executive Director of the United 
Nations Office on Drugs and Crime, c/o Secretary, Commission on 
Narcotic Drugs, P.O. Box 500, 1400 Vienna, Austria, FAX: +43-1-26060-
5885, email: [email protected].

9 November 2012, NAR/CL.6/201, Annex I, Page 1.

Annex I

Relevant excerpts of letter addressed to the Secretary-General of the 
United Nations by the Director-General of the World Health Organization
    ``With reference to article 2 of the Convention on Psychotropic 
Substances (1971), article 2, paragraphs 1, 4 and 6, I am pleased to 
submit the recommendations of the WHO, concerning the international 
control of y-hydroxybutyric acid (GHB). The recommendation is that GHB 
be rescheduled from Schedule IV to Schedule II of the 1971 Convention. 
The basis for this recommendation is set out in an extract from the 
Report of the ECDD, which advises on these issues, attached to this 
letter.''

Geneva, 22 October 2012, NAR/CL.6/2012, Annex II, Page 1.

Annex II

Extract From the 35th Report of the Expert Committee on Drug Dependence 
Recommendation on Gamma-Hydroxybutyric Acid (GHB)
    This section provides information in addition to the information 
presented in the report of the Thirty-fourth meeting. The Expert 
Committee discussed GHB in the context of Gamma-butyrolactone and 1,4-
butanediol (1,4-BD), precursors of GHB, see sections 4.4 and 4.5.
Substance Identification and Pharmacodynamics
    Gamma-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic 
acid and sodium oxybate, is a naturally occurring substance found in 
low concentrations in mammalian tissues. It is considered to act by 
binding to GHB-specific receptors and Gamma-aminobutyric acid B (GABAB) 
receptors. At pharmacological doses, it acts as a central nervous 
system depressant.
Previous Reviews
    GHB was pre-reviewed during the Thirty-first and Thirty-second 
meetings, held in 1998 and 2000, respectively. In 2001, GHB was placed 
in Schedule IV of the 1971 Convention by a decision of the CND. It was 
again pre-reviewed at the Thirty-fourth ECDD meeting in 2006 (1), at 
which time the Expert Committee recommended a new critical review to 
consider GHB's possible rescheduling.
Evidence on Dependence Potential
    The Expert Committee examined additional information from the 
updated critical review report and peer-review reports. The Expert 
Committee noted that there is compelling evidence that dependence on 
GHB exists in humans and noted withdrawal syndromes and withdrawal 
seizures.
Actual Abuse
    The Expert Committee noted that at present, GHB appears to be 
mainly used and abused in the United States of America, Europe and 
Australia. Most GHB used illicitly originates from clandestine 
manufacture.
    In their discussions, the Expert Committee and advisers agreed on 
the narrow margin of safety of GHB. There have been numerous reports 
from Europe and the United States of accidental fatal and non-fatal 
overdoses where GHB was implicated, both when used alone and with other 
substances.
    The Expert Committee also noted there have been reports of GHB 
being used to facilitate sexual assault.
Therapeutic Usefulness
    GHB is used as a medicine in some countries on a small scale for 
various indications. GHB is not included in the WHO Model List of 
Essential Medicines.
Need for the Substance for Other Purposes (e.g., Industrial)
    The Expert Committee acknowledged the use of GHB in the production 
of a wide variety of industrial polymers.

III. Discussion

    Although WHO has made specific scheduling recommendations for each 
of the drug substances, the CND is not obliged to follow the WHO 
recommendations. Options available to the CND for substances considered 
for control under the Psychotropic Convention include: (1) Acceptance 
of the WHO recommendations; (2) acceptance of the recommendations to 
control, but control the drug substance in a schedule other than that 
recommended; or (3) reject the recommendations entirely.

[[Page 9399]]

    GHB is classified as a central nervous system depressant. In 2002, 
FDA approved a GHB-containing product, Xyrem, for the treatment of 
excessive daytime sleepiness and cataplexy in patients with narcolepsy 
under the regulations in 21 CFR part 314, subpart H (21 CFR 314.520). 
Xyrem was included on the list of products deemed to have in effect an 
approved Risk Evaluation and Mitigation Strategy (REMS) under section 
505-1 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355-1) at 
the time of the passage of the Food and Drug Administration Amendments 
Act of 2007 (FDAAA). The REMS for Xyrem includes a medication guide and 
healthcare provider education brochure, mandatory patient and 
prescriber certification through enrollment, and restricted dispensing 
of the drug through a central pharmacy. Xyrem is controlled 
domestically in Schedule III of the CSA, while bulk GHB and all other 
material containing GHB are controlled in Schedule I. In addition, 
illicit use of Xyrem is subject to Schedule I penalties of the CSA. GHB 
is controlled internationally in Schedule IV of the Psychotropic 
Convention. The WHO ECDD pre-reviewed GHB at its Thirty-fourth meeting 
and recommended it for critical review at a future meeting. The WHO 
ECDD met in Hammamet, Tunisia, from 4-8 June 2012, critically reviewed 
GHB, and recommended that it be rescheduled from Schedule IV to 
Schedule II of the Convention on Psychotropic Substances.

IV. Submission of Comments and Opportunity for Public Meeting

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. 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 http://www.regulations.gov.
    FDA does not presently plan to hold a public meeting. If any person 
believes that, in addition to their written comments, a public meeting 
would contribute to the development of the U.S. position on the 
substances to be considered for control under the Psychotropic 
Convention, a request for a public meeting and the reasons for such a 
request should be sent to James R. Hunter (see FOR FURTHER INFORMATION 
CONTACT) on or before February 19, 2013.
    The short time period for the submission of comments and requests 
for a public meeting is needed to ensure that HHS may, in a timely 
fashion, carry out the required action and be responsive to the United 
Nations.

    Dated: February 1, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-02859 Filed 2-7-13; 8:45 am]
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