
[Federal Register: September 5, 2008 (Volume 73, Number 173)]
[Notices]               
[Page 51823-51829]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05se08-57]                         

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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; Single Convention on Narcotic Drugs; Gamma-hydroxybutyric 
acid; Ketamine; Dextromethorphan; N-benzylpiperazine; 1-(3-
trifluoromethylphenyl)piperazine; 1-(3-chlorophenyl)piperazine; 1-(4-
Methoxyphenyl)piperazine; 1-(3,4-methylenedioxybenzyl)piperazine; 
Gamma-butyrolactone; 1,4-Butanediol

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is requesting 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 the United States' response 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 October 6, 2008.

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 http://
www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: James R. Hunter, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, rm. 5146, Silver Spring, MD 20993-0002, 301 
796-3156, e-mail: james.hunter@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: The United States is a party to the 1971 
Convention on Psychotropic Substances (the 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 
should notify the Secretary General of the United Nations (the 
Secretary-General) and provide the Secretary-General 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 Psychotropic 
Convention that it has information that may justify: (1) Adding a drug 
or other substances to one of the schedules of the convention, (2) 
transferring a drug or substance from one schedule to another, or (3) 
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 HHS will consider 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.16.2008

WHO Questionnaire for Collection of Information for Review of 
Dependence-Producing Psychoactive Substances

    The World Health Organization presents its compliments and has 
the pleasure of informing Member States and Associate Members that 
the Thirty-fifth Expert Committee on Drug Dependence will meet from 
20 to 23 April 2009 to review the following substances:
    1. Gamma-hydroxybutyric acid (GHB)
    2. Ketamine INN
    3. Dextromethorphan pINN
    4. N-benzylpiperazine (BZP)
    5. 1-(3-trifluoromethylphenyl)piperazine (TFMPP)
    6. 1-(3-chlorophenyl)piperazine (mCPP)
    7. 1-(4-Methoxyphenyl)piperazine (MeOPP)
    8. 1-(3,4-methylenedioxybenzyl)piperazine (MDBP)
    9. Gamma-butyrolactone
    10. 1,4-Butanediol
    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 Report 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 concerning substances listed above.
    Further clarification on any of the above items can be obtained 
from Quality Assurance and Safety: Medicines, Department of 
Medicines Policy and Standards, WHO, Geneva, to which replies should 
be sent not later than 20 September 2008.
    The World Health Organization takes this opportunity to renew to 
Member States and Associate Members the assurance of its highest 
consideration.
    GENEVA, 28 May 2008
* * * * *
    If statistical information requested is not readily available, a 
brief descriptive answer would be appreciated.
    Please attach copies of relevant study reports and other 
background information as appropriate.
* * * * *

1. GAMMA-HYDROXYBUTYRIC ACID (GHB)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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[[Page 51824]]

    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country?
    If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance?
    If ``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? \1\ 
(Yes/No/Unknown)
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    \1\ Harmful use is defined as a pattern of psychoactive drug use 
that causes damage to health, either mental or physical. Harmful use 
of drugs by an individual often has adverse effects on the drug 
user's family, the community, and society in general.
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    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/liter/number of ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.
4. IMPACT OF SCHEDULING
    (Gamma-hydroxybutyrate is in Schedule IV of the Convention on 
Psychotropic Substances of 1971 currently.)
    4.1 If gamma-hydroxybutyric acid (GHB) is placed under more 
strict international control, do you think that its availability for 
medical use will be affected? (Yes/No)
    4.2 If ``yes,'' how do you think that a transfer will impact its 
medical availability?

2. KETAMINE INN

1.LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country?
    If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If ``yes,'' are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.
4. IMPACT OF SCHEDULING
    (Ketamine is not scheduled in one of the drug conventions 
currently.)
    4.1 If ketamine is placed under international control, do you 
think that its availability for medical use will be affected? (Yes/
No)
    4.2 If ``yes,'' how do you think that scheduling will impact its 
medical availability?

3. DEXTROMETHORPHAN pINN

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).

[[Page 51825]]

    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No /Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If ``yes,'' are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.
4. IMPACT OF SCHEDULING
    (Dextromethorphan is not scheduled in one of the drug 
conventions currently.)
    4.1 If dextromethorphan is placed under international control, 
do you think that its availability for medical use will be affected? 
(Yes/No)
    4.2 If ``yes,'' how do you think that scheduling will impact its 
medical availability?

4. N-BENZYLPIPERAZINE (BZP)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country?
    If ``yes,'' please specify(Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If ``yes,'' are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

5. 1-(3-TRIFLUOROMETHYL PHENYL)PIPERAZINE (TFMPP)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify(Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules)

[[Page 51826]]

    3.4 Any additional information with regard to questions 3.2 and 
3.3.

6. 1-(3-CHLOROPHENYL)PIPERAZINE (MCCP)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country?
    If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify(Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

7. 1-(4-METHOXYPHENYL)PIPERAZINE (MeOPP)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

----------------------------------------------------------------------------------------------------------------
               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If ``yes,'' are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

8. 1-(3,4-METHYLENEDIOXYBENZYL)PIPERAZINE (MDBP)

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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[[Page 51827]]


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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/number of tablets/number of 
ampoules).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

9. GAMMA-BUTYROLACTONE

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

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               Dosage Form                             Strength                             Remark
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify. (Yes/No)
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?
    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/liter).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

10. 1,4-BUTANEDIOL

1. LEGITIMATE USE OF THE SUBSTANCE
    1.1 Is the substance currently authorized as a medical or 
veterinary product? (Yes/No)
    1.2 If ``yes,'' since when has it been on the market?
    1.3 Please indicate registered indications alphabetically.
    1.4 Please indicate known off-label medical indications for 
which the substance is also used in your country.
    1.5 Please indicate dosage form(s) and strength(s); also 
indicate special properties like slow release, etc.

----------------------------------------------------------------------------------------------------------------
               Dosage Form                             Strength                             Remark
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----------------------------------------------------------------------------------------------------------------
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    1.6 Please indicate brand names alphabetically (no dosage forms, 
strengths, etc.).
    1.7 Are there any technical uses for the substance in your 
country? If ``yes,'' please specify (Yes/No).
    1.8 Is there any other legitimate use of the substance? If 
``yes,'' please specify (Yes/No).
    1.9 If there is a legitimate use of the substance, how is the 
substance supplied? (Manufactured in the country/Imported/Both)
2. ABUSE OF THE SUBSTANCE
    2.1 Is the substance used in a harmful way in your country? 
(Yes/No/Unknown)
    2.2 If ``yes,'' any information on how this is used (including 
route of administration)?
    2.3 If ``yes,'' any information on the extent of harmful use?

[[Page 51828]]

    2.4 If ``yes,'' any information on the extent of public health 
or social problems associated with the harmful use of the substance 
(statistics on overdose deaths, dependence, etc.)?
3. CONTROL OF THE SUBSTANCE
    3.1 Is the substance controlled under legislation that is 
intended to regulate availability of substances of abuse (Controlled 
Substances Act or similar)? (Yes/No)
    3.2 If yes, are there illicit activities involving the 
substance:
    a. clandestine manufacture (Yes/No)
    b. smuggling (Yes/No)
    c. diversion (Yes/No)
    d. other (please specify) (Yes/No)
    3.3 Total quantity of seizures (kg/liter).
    3.4 Any additional information with regard to questions 3.2 and 
3.3.

II. Background

    Gamma-hydroxybutyric acid (GHB) is classified as a central nervous 
system depressant. In 2002, FDA approved a GHB-containing product, 
Xyrem, for the treatment of cataplexy associated with narcolepsy. Xyrem 
was approved under the regulations in 21 CFR 314.520, and the product 
labeling contained a comprehensive risk management program, which 
includes restricted distribution 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 is 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 Expert Committee on Drug 
Dependence pre-reviewed GHB at its thirty-fourth meeting and 
recommended it for critical review at a future meeting.
    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 domestically in Schedule III of the 
CSA. It is not controlled internationally under the Psychotropic 
Convention or the Single Convention on Narcotic Drugs. The WHO Expert 
Committee on Drug Dependence reviewed ketamine at its thirty-fourth 
meeting, and recommended that the Secretariat produce an updated 
version of the critical review for ketamine and present it to the next 
meeting of the WHO Expert Committee on Drug Dependence.
    Dextromethorphan is classified as an oral antitussive agent for 
treating uncomplicated, nonproductive coughs. It is marketed in the 
United States without a prescription in mixtures such as syrups, 
lozenges, or in combination with antihistamines. Dextromethorphan is 
not controlled domestically or controlled internationally under the 
Psychotropic Convention or the Single Convention on Narcotic Drugs.
    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 domestically in Schedule I of the 
CSA. BZP is not controlled internationally under the Psychotropic 
Convention or the Single Convention on Narcotic Drugs.
    1-(3-trifluoromethylphenyl)piperazine (TFMPP) is a piperazine-based 
serotonin receptor agonist. It has no medical use in the United States. 
TFMPP is not controlled domestically or controlled internationally 
under the Psychotropic Convention or the Single Convention on Narcotic 
Drugs.
    1-(3-chlorophenyl)piperazine (mCPP) is a piperazine-based serotonin 
receptor agonist. It has no medical use in the United States. mCPP is 
not controlled domestically or controlled internationally under the 
Psychotropic Convention or the Single Convention on Narcotic Drugs.
    1-(4-Methoxyphenyl)piperazine (MeOPP) is a piperazine-based 
derivative. It has no medical use in the United States. MeOPP is not 
controlled domestically or controlled internationally under the 
Psychotropic Convention or the Single Convention on Narcotic Drugs.
    1-(3,4-methylenedioxybenzyl)piperazine (MDBP) is a piperazine 
derivative with no medical use in the United States. It is not 
controlled domestically or controlled internationally under the 
Psychotropic Convention or the Single Convention on Narcotic Drugs.
    Gamma-butyrolactone (GBL) is used as a solvent and reagent in 
chemistry. GBL can be used in the synthesis of GHB, and can be 
converted to the central nervous system depressant drug Gamma-
hydroxybutyric acid (GHB) in the body after ingestion. As a precursor 
in the manufacture of GHB, GBL is controlled domestically as a List I 
chemical in the United States under the CSA. It is not controlled 
internationally under the Psychotropic Convention or the Single 
Convention on Narcotic Drugs.
    1,4-Butanediol is used as an industrial solvent for manufacturing 
and also used for the synthesis of GBL. After ingestion, 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 domestically under the CSA in the United States, but is 
subject to controls in several states under State law.

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 HHS, invites interested persons to 
submit comments regarding the 10 named drugs. HHS will consider any 
received comments 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.
    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 2010. 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 to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding the drugs by 
(see DATES). 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 paper copies of any comments are to 
be submitted, except that individuals may submit one paper 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 
Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
    Please note that on January 15, 2008, the FDA Division of Dockets 
Management Web site transitioned to the Federal Dockets Management 
System (FDMS). FDMS is a Government-wide, electronic docket management 
system. Electronic comments or submissions will be

[[Page 51829]]

accepted by FDA only through FDMS at http://www.regulations.gov.

    Dated: August 22, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-20564 Filed 9-4-08; 8:45 am]

BILLING CODE 4160-01-S
