International Drug Scheduling; Convention on Psychotropic Substances; Dihydroetorphine; Ephedrine; Remifentanil; Isomers of Psychotropic Substances

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N-0148]

International Drug Scheduling; Convention on Psychotropic

Substances; Dihydroetorphine; Ephedrine; Remifentanil; Isomers of

Psychotropic Substances

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is requesting

interested persons to submit data or comments concerning abuse

potential, actual abuse, medical usefulness, and trafficking of three

drug substances. This information will be considered in preparing a

response from the United States to the World Health Organization (WHO)

regarding abuse liability, actual abuse, and trafficking 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 information is required by the Controlled Substances

Act (CSA).

DATES: Submit written comments by April 17, 1998.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Nicholas P. Reuter, Office of Health

Affairs (HFY-20), Food and Drug Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301-827-1696, 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 that 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 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 substance to one of the schedules of that 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 to assist HHS in preparing scientific and medical

evaluations about the drug or substance. The Secretary of HHS received

the following notices from WHO:

I. WHO Notification

Ref. : C. L.23 .1997

WHO questionnaire for collection of information for review of

dependence-producing psychoactive substances

The Director-General of the World Health Organization presents

his compliments and has the pleasure of informing Member States that

the Thirty-first Expert Committee on Drug Dependence will meet from

23 to 26 June 1998 to review the following substances:

1. Dihydroetorphine

2. Ephedrine

3. Remifentanil

4. With regard to all substances in Schedules I and II of the

Convention on Psychotropic Substances, 1971:

(a) their isomers, except where expressly excluded, whenever the

existence of such isomers is possible;

(b) their esters and ethers, except where included in another

schedule, whenever the existence of such esters and ethers is

possible;

(c) salts of those esters, ethers and isomers, under the

conditions stated above, whenever the formation of such salts is

possible;

(d) a substance resulting from modification of the chemical

structure of a substance already in these schedules and which

produces pharmacological effects similar to those produced by the

original substance.

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 Director-

General invites Member States to collaborate, as in the past, in

this process by providing all pertinent information mentioned in the

attached questionnaire\1\ concerning the substances mentioned in

items 1 to 3 above. The questionnaire does not include any questions

about the groups of substances specified under item 4, since the

required information is already being sought by the Secretary-

General of the United Nations in his Circular Letter NAR/CL.4/1997.

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\1\ For Ministries of Health only.

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Further clarification on any of the above items can be obtained

from Psychotropic and Narcotic Drugs (PND), Division of Drug

Management and Policies, WHO, Geneva, to which replies should be

sent not later than 1 March 1998.

GENEVA, 30 December 1997

Questionnaire for data collection for use by the World Health

Organization and the Commission on Narcotic Drugs of the Economic and

Social Council

Substance reported on:

1. Availability of the substance (registered, marketed,

dispensed, etc.).

2. Extent of abuse of the substance.

3. Degree of seriousness of the public health and social

problems\2\ associated with abuse of the substance.

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\2\ Examples of public health and social problems are acute

intoxication, accidents, work absenteeism, mortality, behaviour

problems, criminality, etc.

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4. Number of seizures of the substance in the illicit traffic

during the previous three years and the quantities involved.

5. Identification of the seized substance as of local or foreign

manufacture and indication of any commercial markings.

6. Existence of clandestine laboratories manufacturing the

substance.

II. United Nations Notifications

The U.S. Government has received two notifications from the

Secretary General of the United Nations. The first notification (NAR/

CL./1997, signed May 28, 1997), transmits under to Article 2, paragraph

1 of the Convention on Psychotropic Substances, 1971, a request from

the Government of Spain to amend Schedules I and II of the Convention

to include:

``(a) isomers, except where expressly excluded, of substances

listed in those Schedules, whenever the existence of such isomers is

possible;

``(b) esters and ethers of substances in those Schedules, except

where included in another Schedule, whenever the existence of such

esters or ethers is possible;

``(c) salts of those esters, ethers and isomers, under the

conditions stated above, whenever the formation of such salts is

possible;

``(d) a substance resulting from modification of the chemical

structure of a substance already in Schedule I or Schedule II and which

produces pharmacological effects similar to those produced by the

original substance.''

The May 28, 1997, notification included as annexes, the original

request from the Government of Spain, along with a questionnaire. A

subsequent notification from the United

[[Page 13259]]

Nations Secretary General dated February 23, 1998 (NAR/CL.2/1998),

identified additional issues to be considered within the context of the

Government of Spain's request.

These notifications appear to relate to the amendment of the

Convention and not to the addition of specific substances to the

schedules of the Convention (See 21 U.S.C. 811 (d)). Therefore, they

are not published in this notice. The notifications are on display and

copies may be obtained by contacting Nicholas Reuter (address above).

Comments submitted in response to the United Nations notifications will

be forwarded to the WHO through the United Nations Secretariat.

III. Background

None of the three substances under consideration by WHO are

controlled internationally. Dihydroetorphine is a hydrogenated

derivative of etorphine and a potent -opioid-receptor agonist

used as a short-acting analgesic in China. It is neither marketed nor

controlled in the United States.

Ephedrine is available in the United States as an over-the-counter

bronchodilator. Further, ephedrine has been designated as a listed

chemical and is subject to chemical diversion regulations under 21 CFR

part 1310 which are enforced by the Drug Enforcement Administration.

According to WHO, information is now available to indicate that illicit

trafficking in ephedrine has increased significantly in recent years.

Further, although the substance is illicitly used primarily in the

manufacture of stimulants, WHO has evidence to indicate the increasing

abuse of ephedrine preparations in some countries.

Remifentanil is a selective -opioid-receptor agonist of

the fentanyl group. Remifentanil is approved in the United States as an

anesthetic for use in animals and is controlled domestically as a

narcotic in schedule II of the CSA.

IV. Opportunity to Submit Domestic Information

As required by section 201(d)(2)(A) of the Controlled Substances

Act (21 U.S.C. 811(c)(2)(A)). FDA on behalf of the Department of Health

and Human Services (DHHS) invites interested persons to submit data or

comments regarding the eight named drugs. Data and information received

in response to this notice will be used to prepare scientific and

medical information on these drugs, with a particular focus on each

drug's abuse liability. DHHS will forward that information to WHO,

through the Secretary of State, for WHO's consideration in deciding

whether to recommend international control 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 1998 or early 1999. Any DHHS position regarding

international control of these drugs will be preceded by another

Federal Register notice soliciting public comment as required by 21

U.S.C. 811(d)(2)(B).

V. Comments

Interested persons may, on or before April 17, 1998, submit to the

Docket Management Branch (address above) written comments regarding

this action. This abbreviated acceptance period is necessary to allow

sufficient time to prepare and submit the domestic information package

by the deadline imposed by WHO. Although WHO has requested comments and

information by March 1, 1998, WHO will accept and consider material

transmitted after the March date. Respondents should submit material in

the format set forth by the WHO Questionnaire reprinted previously.

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 office above between 9 a.m. and 4

p.m, Monday through Friday.

This notice contains information collection requirements that were

submitted for review and approval to the Director of the Office of

Management and Budget (OMB). The requirements were approved and

assigned OMB control number 0910-0226.

Dated: March 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-6910 Filed 3-17-98; 8:45 am]

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