[Federal Register Volume 65, Number 83 (Friday, April 28, 2000)]
[Notices]
[Pages 24969-24970]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-10631]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1257]


International Drug Scheduling; Convention on Psychotropic 
Substances; 4-Bromo-2,5-dimethoxyphenethylamine (2C-B); Gamma-
hydroxybutyric acid (GHB); 4-Methylthioamphetamine (4-MTA); N-Methyl-1-
(3,4-methylenedioxyphenyl)-2-butanamine (MBDB); Diazepam (INN); 
Zolpidem (INN)

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is requesting 
interested persons to submit comments concerning abuse potential, 
actual abuse, medical usefulness, and trafficking of six 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 comments by May 15, 2000.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Corinne P. Moody, Center for Drug 
Evaluation and Research (HFD-009), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-1999, e-mail: 
[email protected].

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.
    The CSA (21 U.S.C. 811 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. The 
Secretary of HHS received the following notices from WHO:

I. WHO Notification

    Ref.: C.L.1.2000
    WHO questionnaire for collection of information for review of 
dependence-producing psychoactive substances.
    The Director-General of the World Health Organization presents 
her compliments and has the pleasure of informing Member States that 
the Thirty-second Expert Committee on Drug Dependence (ECDD) will 
meet from 11 to 14 September 2000 to review the following 
substances:
    1. 4-Bromo-2,5-dimethoxyphenethylamine (2C-B)
    2. Gamma-hydroxybutyric acid (GHB)
    3. 4-Methylthioamphetamine (4-MTA)\1\
---------------------------------------------------------------------------

    \1\ If the reply to the questionnaire confirms a medical use of 
4-MTA recognized by any Member State, the substance will be 
subjected to a prereview instead of a critical review.
---------------------------------------------------------------------------

    4. N-Methyl-l-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB)
    5. Diazepam (INN)
    6. Zolpidem (INN)
    One of the essential elements of the established review 
procedure is for the Secretariat to collect relevant information 
from Member States to prepare a Critical Review document for 
submission to the Expert Committee on Drug Dependence. The World 
Health Organization invites Member States to collaborate, as in the 
past, in this process by providing pertinent information mentioned 
in the attached questionnaire\2\ concerning the substances listed 
above.
---------------------------------------------------------------------------

    \2\ For Ministries of Health only.
---------------------------------------------------------------------------

    Further clarification on any of the above items can be obtained 
from Quality Assurance and Safety: Medicines (QSM), Essential Drugs 
and Medicines Policy (EDM), WHO, Geneva, to which replies should be 
sent not later than 1 May 2000.

[[Page 24970]]

    GENEVA, 12 January 2000

WHO Questionnaire for review of dependence-producing psychoactive 
substances by the Thirty-second Expert Committee on Drug Dependence. 
Substance reported on:
    1. Availability of the substance (registered, marketed, 
dispensed, etc.);
    2. Extent of the abuse or misuse\3\ of the substance;
---------------------------------------------------------------------------

    \3\ In this questionnaire, ``abuse or misuse'' refers to use of 
the substance other than for medical or scientific purposes.
---------------------------------------------------------------------------

    3. Degree of seriousness of the public health and social 
problems associated with the abuse of the substance (statistics on 
cases of overdose deaths, dependence, etc.); and
    4. Any information on the nature and extent of illicit 
activities involving the substance (clandestine manufacture, 
smuggling, diversion, seizure, etc.).
    In addition to the above, with regard to Diazepam (INN) report 
on:
    5. The impact of transferring diazepam from Schedule IV to 
Schedule III of the Convention on Psychotropic Substances, 1971, and 
its effect on availability for medical use.
    In addition to items 1 to 4 above, with regard to Zolpidem (INN) 
report on:
    6. The impact of placing zolpidem in Schedule IV of the 
Convention on Psychotropic Substances, 1971, and its effect on 
availability for medical use.

II. Background

    The substance 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a 
structural analogue of the phenethylamine hallucinogens. In various 
preclinical and clinical studies, it has been described as a stimulant, 
depressant, and hallucinogen, but appears to more closely fit the 
profile of the latter. It is not marketed in the United States, 
however, it is controlled domestically in Schedule I of the CSA.
    Gamma-hydroxybutyric acid (GHB) is a substance classified as a 
central nervous system depressant. It is not marketed in the United 
States. The Drug Enforcement Administration published a final rule on 
March 13, 2000 (65 FR 13235), placing gamma-hydroxybutyric acid and its 
salts, isomers, and salts of isomers into Schedule I of the CSA under 
Public Law 106-172. The final rule imposes Schedule III security 
requirements for registered manufacturers and distributors of GHB when 
it is manufactured, distributed, or possessed in accordance with FDA 
authorized investigational new drug exemptions under section 505(i) of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)). If drug 
products containing GHB are approved by FDA, the final rule places FDA 
approved products containing GHB into Schedule III of the CSA under 
Public Law 106-172.
    The substance 4-Methylthioamphetamine (4-MTA) is a compound 
structurally similar to amphetamine. 4-MTA is reported to have 
physiological effects similar to that of 3,4-methylenedioxyamphetamine 
(MDA) and 3,4-methylenedioxymethamphetamine (MDMA/ecstasy). The 
substance is not marketed in the United States. It is not specifically 
listed as a controlled substance in the United States. However, it is 
considered a Schedule I controlled substance as an analogue of either 
MDA or MDMA under the analogue provisions of the CSA.
    N-Methyl-l-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) is a 
positional isomer of MDE (3,4-methylenedioxy-N-ethylamphetamine) which 
is controlled domestically in Schedule I. The psychoactive effects of 
MBDB have been described as hallucinogenic. It is not marketed in the 
United States. As an isomer of MDE, MBDB is a Schedule I substance in 
the United States.
    Diazepam (INN) is a benzodiazepine derivative. It is marketed in 
the United States for the management of anxiety disorders or for the 
short-term relief of the symptoms of anxiety; in acute alcohol 
withdrawal, it is used in the symptomatic relief of acute agitation, 
tremor, impending or acute delirium tremens, and hallucinosis; as an 
adjunct for the relief of skeletal muscle spasm; spasticity caused by 
upper motor neuron disorders; athetosis; stiff-man syndrome; tetanus; 
as an adjunct in convulsive disorders; and as a premedication for 
relief of anxiety and tension in patients who are to undergo surgical 
procedures. Domestically, it is controlled in Schedule IV of the CSA. 
Diazepam is controlled internationally in Schedule IV of the 
Psychotropic Convention.
    Zolpidem (INN) is a hypnotic agent with a chemical structure 
unrelated to benzodiazepines, barbiturates, or other drugs with known 
hypnotic properties. It interacts with a GABA-BZ receptor complex and 
shares some of the pharmacological properties of the benzodiazepines. 
It is marketed in the United States for the short-term treatment of 
insomnia. Domestically, it is controlled in Schedule IV of the CSA.

III. 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 (DHHS), invites interested persons to submit comments 
regarding the six named drugs. Any comments received will be considered 
by DHHS when it prepares a scientific and medical evaluation of these 
drugs. DHHS 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.
    DHHS will not now make any recommendations to WHO regarding whether 
any of these drugs should be subjected to international controls. 
Instead, DHHS will defer such consideration until WHO has made official 
recommendations to the Commission on Narcotic Drugs, which are expected 
to be made in late 2000. Any DHHS position regarding international 
control of these drugs will be preceded by another Federal Register 
notice soliciting public comments as required by 201(d)(2)(B) of the 
CSA.

IV. Comments

    Interested persons may submit to the Dockets Management Branch 
(address above) written comments regarding the drugs by May 15, 2000. 
This abbreviated comment period is necessary to allow sufficient time 
to prepare and submit the domestic information package by the deadline 
imposed by WHO. Two copies of any comments are to be submitted, except 
that individuals may submit one copy. Comments are to be identified 
with the docket number found in brackets in the heading of this 
document. Received comments may be seen in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: April 24, 2000.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 00-10631 Filed 4-27-00; 8:45 am]
BILLING CODE 4160-01-F