[Federal Register Volume 65, Number 49 (Monday, March 13, 2000)]
[Rules and Regulations]
[Pages 13235-13238]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-5925]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Parts 1301 and 1308

[DEA-200F]


Schedules of Controlled Substances: Addition of Gamma-
Hydroxybutyric Acid to Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final rule.

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SUMMARY: This is a final rule issued by the Deputy Administrator of the 
Drug Enforcement Administration (DEA) placing gamma-hydroxybutyric acid 
(GHB) and its salts, isomers, and salts of isomers into Schedule I of 
the Controlled Substances Act (CSA) pursuant to Public Law 106-172. 
Public

[[Page 13236]]

Law 106-172 also imposes Schedule III physical security requirements 
for storage on registered manufacturers and distributors of GHB when it 
is manufactured, distributed or possessed in accordance with Food and 
Drug Administration (FDA)-authorized Investigational New Drug (IND) 
exemptions under the Federal Food, Drug and Cosmetic Act (FFDCA). In 
addition, this final rule places FDA-approved products containing GHB 
into Schedule III, if or when they are approved.

EFFECTIVE DATE: March 13, 2000.

FOR FURTHER INFORMATION CONTACT: Frank Sapienza, Chief, Drug and 
Chemical Evaluation Section, Office of Diversion Control, Drug 
Enforcement Administration, Washington, DC 20537, (202) 307-7183.

SUPPLEMENTARY INFORMATION:  

What Is GHB and Why Is It Being Controlled?

    GHB is gamma-hydroxybutyric acid, including its salts, isomers and 
salts of isomers. In recent years, the abuse of GHB has increased 
substantially. GHB is a drug classified as a central nervous system 
depressant. It is not approved for marketing as a medicine in the 
United States, although FDA-authorized studies are in progress to 
examine its potential use in the treatment of cataplexy associated with 
narcolepsy. GHB is abused to produce euphoric and hallucinogenic 
states, and for its alleged role as growth hormone releasing agent to 
stimulate muscle growth. GHB can produce drowsiness, dizziness, nausea, 
visual disturbances, unconsciousness, seizures, severe respiratory 
depression and coma. Overdose usually requires emergency medical 
treatment, including intensive care for respiratory depression and 
coma. Several Poison Control Centers have characterized and reported 
cases of GHB-dependence and withdrawal to the DEA. To date, DEA has 
documented over 5,700 overdoses and law enforcement encounters with GHB 
in 45 states. DEA has also documented 65 GHB-related deaths.
    On November 8, 1990, the FDA issued an advisory declaring GHB 
unsafe and illicit, except under FDA-approved physician-supervised 
protocols. On February 18, 1997, FDA reissued its warning on GHB as an 
unapproved and potentially dangerous, illegal drug in the United 
States.
    GHB is produced in clandestine laboratories using a relatively 
simple synthesis with readily available and inexpensive starting 
materials. Gamma-butyrolactone (GBL) is an industrial solvent which is 
used in the clandestine manufacture of GHB. Once manufactured, GHB is a 
clear liquid and has been disguised by adding food coloring, 
flavorings, and/or storing it in different kinds of bottles and 
containers.
    The DEA has received reports that GBL, the solvent precursor for 
GHB, is being abused due to its rapid conversion to GHB soon after 
ingestion. On January 21, 1999, the FDA issued a request for a 
voluntary recall of all GBL-containing products sold in health food 
stores and warned the public of its danger to the public health. FDA 
has also declared 1,4-butanediol, a chemical related to both GHB and 
GBL, a Class I Health Hazard. On May 11, 1999, the FDA issued another 
warning on 1,4 butanediol, GHB, and GBL stating that these substances 
pose a significant health hazard. Public Law 106-172 also placed 
certain controls on GBL. These will be the subject of a separate 
Federal Register Notice.

Under What Authority Is GHB Being Controlled?

    ``The Samantha Reid and Hillory J. Farias Date-Rape Prevention Act 
of 1999'' (Pub. L. 106-172) declared that the abuse of GHB is an 
imminent hazard to the public safety. Section (3)(a)(1) of Public Law 
106-172 directs the Attorney General, notwithstanding sections 201(a), 
201(b), 201(c), and 202 of the CSA (21 U.S.C. 811(a), 811(b), 811(c) 
and 812), to issue a final order placing GHB in the same schedule as 
would apply to a scheduling of a substance under section 201(h)(1) of 
the CSA (21 U.S.C 811(h)(1)). All substances controlled under 201(h)(1) 
are placed in Schedule I. Therefore, this final rule will place GHB in 
Schedule I.
    With the issuance of this final order, GHB becomes subject to the 
regulatory controls and administrative, civil and criminal sanctions 
applicable to the manufacture, distribution, dispensing, importing and 
exporting of a Schedule I controlled substance with one exception. 
Section 3(a)(1)(A) of Public Law 106-172 provides that registered 
manufacturers and distributors of GHB that is subject to an 
investigational new drug (IND) application exemption under the FFDCA 
subject to Schedule III physical security requirements rather than the 
otherwise applicable Schedule I physical security requirements for 
storage.
    In Sections (3)(a)(1)(A) and (B) of Public Law 106-172, reference 
is made to certain scheduling recommendations contained in the May 19, 
1999, letter from the Department of Health and Human Services (DHHS) to 
the DEA. Pursuant to Public Law 106-172, the DEA is publishing a copy 
of the May 19, 1999 letter from David Satcher, M.D., Ph.D., Assistant 
Secretary for Health and Surgeon General. The letter follows:

Assistant Secretary for Health, Office of Public Health and Science, 
Washington, D.C. 20201

Mr. Donnie R. Marshall, Deputy Administrator, Drug Enforcement 
Administration, Washington, D.C. 20537

Dear Mr. Marshall:

In response to your request dated September 16, 1997, and pursuant 
to the Controlled Substances Act (CSA), 21 U.S.C. Sec. 811(b), (c), 
and (f), the Department of Health and Human Services (HHS) 
recommends that gamma-hydroxybutyric acid (GHB) should be subject to 
control under Schedule I of the CSA, except that GHB substances and 
products that are the subject of investigational new drug (IND) 
applications authorized by the Food and Drug Administration (FDA) 
should be subject to control under Schedule III.

GHB is a central nervous system depressant. As discussed in the 
attached analysis, GHB has a high potential for abuse relative to 
substances controlled in Schedules III, IV, and V. GHB has no 
accepted medical use, and when manufactured clandestinely, it is 
unsafe for use under medical supervision. Accordingly, and except as 
provided below, HHS recommends that GHB be controlled in Schedule I 
of the CSA.

Formulations of GHB currently are being studied under FDA-authorized 
INDs. At least one sponsor's formulation has been granted orphan 
drug status under Section 526 of the Food, Drug and Cosmetic Act, 
and is available under a treatment use protocol under 21 CFR 
Sec. 312.34. None of the reports of actual abuse of GHB that support 
the Schedule I recommendation have involved GHB that was diverted 
from an authorized study. Moreover, given the ease with which GHB 
can be synthesized from readily available materials, it is unlikely 
that authorized studies will become a source for abuse. Rather, the 
abuse potential of GHB, when used under an authorized research 
protocol, is consistent with substances typically controlled under 
Schedule IV. Information on the dependence-producing effects of GHB 
is limited, but available data suggest that its potential for 
physical and psychological dependence is also consistent with 
control under Schedule IV.

Authorized formulations of GHB, however, do not meet the ``accepted 
medical use'' criteria set forth in Schedule IV. An authorized 
formulation of GHB is far enough along in the development process to 
meet the standard under Schedule II of a drug or substance having a 
``currently accepted medical use with severe restrictions.'' Under 
these circumstances, HHS recommends placing authorized formulations 
of GHB in Schedule III.

You will find enclosed a document prepared by FDA's Drug Abuse 
Evaluation Staff that is the basis for the combined Schedule I/
Schedule III recommendation.

Should you have any questions regarding this recommendation, please 
contact Stuart L. Nightingale, M.D., FDA's Associate

[[Page 13237]]

Commissioner for Health Affairs, at (301) 443-6143.

Sincerely yours,

David Satcher, M.D., Ph.D., Assistant Secretary for Health and 
Surgeon General

Enclosure

    Specifically, as noted above, Section (3)(a)(1)(A) of Public Law 
106-172 directs that the physical security requirements for registered 
manufacturers and distributors of GHB that is subject to an IND 
application exemption under the FFDCA shall be those which apply to the 
schedule recommended in the first paragraph of the DHHS letter. The 
schedule referred to in this paragraph is Schedule III. This paragraph 
applies only to GHB which is the subject of an FDA-authorized exemption 
and does not affect the physical security requirements for GHB 
manufactured, distributed or possessed for any other purpose or for any 
other controlled substance handled by the registrant.
    Section (3)(a)(1)(B) of Public Law 106-172 directs that a drug 
product containing GHB for which an application is approved under 
section 505 of the FFDCA, shall be placed in the schedule recommended 
in the last sentence of the fourth paragraph of the DHHS May 19, 1999, 
letter. This sentence recommends Schedule III. Currently, there are no 
GHB drug products approved under section 505 of the FFDCA. However, if 
or when a drug product containing GHB is approved by the FDA under this 
section, it shall be a Schedule III controlled substance except that it 
will be subject to the criminal sanctions applicable to a Schedule I 
controlled substance, pursuant to Public Law 106-172. This paragraph 
applies only to drug products containing GHB which are approved under 
section 505 of the FFDCA and does not affect the schedule of any other 
form of GHB handled by the registrant.
    Therefore, pursuant to Public Law 106-172 and notwithstanding 
sections 201(a), 201(b), 201(c), and 202 of the CSA, the Deputy 
Administrator of the DEA orders that GHB and its salts, isomers, and 
salts of isomers be placed in Schedule I. With the issuance of this 
final order, GHB will be subject to the regulatory controls and 
administrative, civil and criminal sanctions applicable to the 
manufacture, distribution, dispensing, importing and exporting of a 
Schedule I controlled substance with the following one exception. 
Registered manufacturers and distributors of FDA-authorized IND 
exempted GHB shall be subject to Schedule III physical security 
requirements for storage purposes. In addition, an FDA-approved drug 
product containing GHB for which an application is approved under 
section 505 of the FFDCA shall be placed in Schedule III.

What Requirements Will GHB Be Subject To?

    Except as noted below, the Schedule I controls on GHB and, where 
applicable, the Schedule III physical security requirements on GHB will 
be effective on March 13, 2000. In the event that any of these 
requirements impose special hardships on the registrants, the DEA will 
entertain any justified request for an extension of time to comply with 
the Schedule I regulations regarding GHB. The applicable regulations 
are as follows:
    1. Registration. Any person who manufactures, distributes, 
dispenses, imports or exports GHB or who engages in research or 
conducts instructional activities with GHB, or who proposes to engage 
in such activities, must submit an application for Schedule I 
registration in accordance with part 1301 of Title 21 of the Code of 
Federal Regulations (CFR) by May 12, 2000.
    However, if and when there is an FDA-approved GHB-containing 
product for which an application is approved under section 505 of the 
FFDCA, any person who manufactures, distributes, dispenses, imports or 
exports that product or who engages in research or conducts 
instructional activities with such an FDA-approved GHB-containing 
product, or who proposes to engage in such activities, must submit an 
application for Schedule III registration in accordance with part 1301 
of Title 21 of the Code of Federal Regulations.
    2. Security. GHB is subject to Schedule I security requirements and 
must be manufactured, distributed and stored in accordance with 
Secs. 1301.71, 1301.72(a), (c), and (d), 1301.73, 1301.74, 1301.75(a) 
and (c) and 1301.76 of Title 21 of the Code of Federal Regulations.
    There is, however, an exception for registered manufacturers and 
distributors of GHB when manufactured, distributed or possessed in 
accordance with FDA-authorized IND exemptions under the FFDCA for 
storage. GHB used in FDA-authorized IND studies and FDA-approved GHB 
containing products are subject to Schedule III security requirements 
and must be manufactured, distributed and stored in accordance with 
Secs. 1301.71, 1301.72(b), (c), and (d), 1301.73, 1301.74, 1301.75(b) 
and (c) and 1301.76 of Title 21 of the Code of Federal Regulations.
    3. Labeling and packaging. All labels on commercial containers of, 
and all labeling of GHB, including FDA-authorized IND exempted 
formulations, which are distributed on or after May 12, 2000 shall 
comply with the requirements of Secs. 1302.03-1302.07 of Title 21 of 
the Code of Federal Regulations. Any commercial containers of GHB 
packaged on or before May 12, 2000 and not meeting the requirements 
specified in Secs. 1302.03-1302.07 of Title 21 of the Code of Federal 
Regulations shall not be distributed on or after June 12, 2000.
    Any labels on commercial containers of, and all labeling of, an 
FDA-approved GHB-containing drug product shall comply with the 
requirements of Secs. 1302.03-1302.7 of Title 21 of the Code of Federal 
Regulations.
    4. Quotas. Quotas for GHB are established pursuant to part 1303 of 
Title 21 of the Code of Federal Regulations. Any manufacturer who 
desires either a manufacturing or procurement quota for GHB shall apply 
for such quota to DEA on or before May 12, 2000.
    5. Inventory. Registrants possessing GHB are required to take 
inventories pursuant to Secs. 1304.03, 1304.04 and 1304.11 of Title 21 
of the Code of Federal Regulations. Every registrant who desires 
registration in Schedule I for GHB shall conduct an inventory of all 
stocks of GHB on or before May 12, 2000.
    6. Records. All registrants must keep records on GHB pursuant to 
Secs. 1304.03, 1304.04 and Secs. 1394,21-1394,23 if Title 21 of the 
Code of Federal Regulations.
    7. Reports. All registrants are required to submit reports on GHB 
to the DEA pursuant to Secs. 1304.33 of Title 21 of the Code of Federal 
Regulations.
    8. Order Forms. Each distribution of GHB, with the exception of an 
FDA-approved GHB-containing product for which an application is 
approved under section 505 of the FFDCA, shall utilize an order form 
pursuant to part 1305 of Title 21 of the Code of Federal Regulations.
    9. Prescriptions. If a drug product containing GHB is approved 
under section 505 of the FFDCA, all prescriptions for that product are 
to be issued pursuant to Secs. 1306.03-1306.06 and 1306.21-1306.26 of 
Title 21 of the Code of Federal Regulations.
    10. Important and Exportation. All importation and exportation of 
GHB shall be in compliance with part 1312 of Title 21 of the Code of 
Federal Regulations.
    11. Criminal Liability. Any activity with GHB not authorized by, or 
in violation of, the CSA or the Controlled Substances Import and Export 
Act shall be unlawful on or after March 13, 2000.

[[Page 13238]]

    Public Law 106-172 directs DEA to publish this final rule and DEA 
has no discretion in this matter. However, this action is structured in 
such a manner that limits its financial impact by reducing the physical 
security requirements for GHB under certain circumstances. 
Specifically, Congress directed DEA to apply Schedule III physical 
security requirements to registered manufacturers and registered 
distributors for the storage of GHB and GHB-containing formulations 
that are the subject of IND exemptions authorized by FDA.
    This regulation has been drafted and reviewed in accordance with 
Executive Order 12866, section 1(b), Principles of Regulation. DEA has 
determined that this rule is not a significant regulatory action under 
Executive Order 12866, section 3(f), Regulatory Planning and Review, 
and accordingly this rule has not been reviewed by the Office of 
Management and Budget. Further, this action will not have a significant 
economic impact on a substantial number of entities whose interests 
must be considered under the Regulatory Flexibility Act (5 U.S.C. 601, 
et seq.). This action places GHB in Schedule I of the GSA, but provides 
a reduction of the physical security requirements for GHB under certain 
circumstances. Specifically, Schedule III physical security 
requirements will apply to registered manufacturers and registered 
distributors for the storage of GHB and GHB-containing formulations 
that are the subject of IND exemptions authorized by FDA.

Unfunded Mandate Reform Act

    This rule will not result in the expenditure by State, local and 
tribal governments, in the aggregate, or by the private sector, of 
$100,000,000 or more in any one year, and it will not significantly or 
uniquely affect small governments. Therefore, no actions were deemed 
necessary under provisions of the Unfunded Mandates Reform Act of 1995.

Small Business Regulatory Enforcement Fairness Act of 1996

    This rule is not a major rule as defined by Sec. 804 of the Small 
Business Regulatory Enforcement Fairness Act of 1996. This rule will 
not result in an annual effect on the economy of $100,000,000 or more; 
a major increase in costs or prices; or significant adverse effects on 
competition, employment, investment, productivity, innovation, or on 
the ability of the United States-based companies to compete with 
foreign-based companies in domestic and export markets.

Executive Order 13132 Federalism

    This rule will not have substantial direct effects on the States, 
on the relationship between the national government and the States, or 
on the distribution of power and responsibilities among the various 
levels of government. Therefore, in accordance with E.O. 13132, it is 
determined that this rule will not have sufficient federalism 
implications to warrant the preparation of a Federalism Assessment.

Plain English

    The DEA makes every effort to write clearly. If you have 
suggestions as to how to improve the clarity of this regulation please 
contact Patricia M. Good, Chief, Policy and Liaison Section, Office of 
Diversion Control, Drug Enforcement Administration, Washington, DC 
20537, phone (202) 307-7297.

List of Subjects

21 CFR Part 1301

    Administrative practice and procedure, Drug traffic control, 
Security measures.

21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Narcotics, Prescription drugs.

    Under the authority vested in the Attorney General by section 
201(a) of the CSA (21 U.S.C. 811(a)), and delegated to the 
Administrator of the DEA by the Department of Justice regulations (28 
CFR 0.100) and redelegated to the Deputy Administrator pursuant to 28 
CFR 0.104, the Deputy Administrator hereby amends 21 CFR parts 1301 and 
1308 as follows:

PART 1301--[AMENDED]

    1. The authority citation for Part 1301 continues to read as 
follows:

    Authority: 21 U.S.C. 821, 822, 823, 824, 871(b), 875, 877.

    2. Section 1301.72 is amended by revising the introductory text of 
paragraphs (a) and (b) to read as follows:


1301.72  Physical Security controls for non-practitioners; narcotic 
treatment programs and compounders for narcotic treatment programs; 
storage areas.

    (a) Schedules I and II. Raw material, bulk materials awaiting 
further processing, and finished products which are controlled 
substances listed in Schedule I or II (except GHB that is manufactured 
or distributed in accordance with an exemption under section 505(i) of 
the FFDCA which shall be subject to the requirements of paragraph (b) 
of this section) shall be stored in one of the following secured areas:
* * * * *
    (b) Schedules III, IV and V. Raw material, bulk materials awaiting 
further processing, and finished products which are controlled 
substances listed in Schedules III, IV, and V, and GHB when it is 
manufactured or distributed in accordance with an exemption under 
section 505(i) of the FFDCA, shall be stored in the following secure 
storage areas:
* * * * *

PART 1308--[AMENDED]

    1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority:  21 U.S.C. 811, 812, 871(b) unless otherwise noted.


    2. Section 1308.11 is amended by redesignating the existing 
paragraphs (e)(1) through (e)(2) as (e)(2) through (e)(3) and by adding 
a new paragraph (e)(1) to read as follows:


Sec. 1308.11  Schedule I.

* * * * *
    (e) * * *

(1) gamma-hydroxybutyric acid (some other names include GHB;        2010
 gamma-hydroxybutyrate; 4-hydroxybutyrate; 4-hydroxybutanoic
 acid; sodium oxybate; sodium oxybutyrate)......................
 

* * * * *


    3. Section 1308.13 is amended by redesignating the existing 
paragraphs (c)(5) through (c)(11) as (c)(6) through (c)(12) and by 
adding a new paragraph (c)(5) to read as follows:


Sec. 1308.13  Scheduling III.

* * * * *
    (c) * * *

(5) Any drug product containing gamma hydroxybutyric acid,          2012
 including its salts, isomers, and salts of isomers, for which
 an application is approved under section 505 of the Federal
 Food, Drug, and Cosmetic Act...................................
 

* * * * *

    Dated: March 3, 2000.
Donnie R. Marshall,
Deputy Administrator.
[FR Doc. 00-5925 Filed 3-10-00; 8:45 am]
BILLING CODE 4410-09-M