[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