[Federal Register Volume 63, Number 214 (Thursday, November 5, 1998)]
[Proposed Rules]
[Pages 59751-59753]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29571]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[DEA-180P]
21 CFR Parts 1308 and 1312
Schedules of Controlled Substances: Rescheduling of Synthetic
Dronabinol (Martinol; (-)-9-(trans)-
Tetrahydrocannabinol in Sesame oil and Encapsulated in Soft Gelatin
Capsules) From Schedule II to Schedule III.
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: This proposed rule is issued by the Acting Deputy
Administrator of the Drug Enforcement Administration (DEA) to remove
the Food and Drug Administration (FDA) approved drug product containing
dronabinol [Marinol; (-)-x-69-
(trans)-tetrahydrocannabinol in sesame oil and encapsulated in soft
gelatin capsules] from Schedule II and place it into Schedule III of
the Controlled Substances Act (CSA). This proposed action is based on
an evaluation of the relevant data by the DEA and a recommendation from
the Assistant Secretary for Health of the Department of Health and
Human Services (DHHS)
[[Page 59752]]
that the FDA-approved dronabinol product [Marinol; (-)-
9-(trans)-THC in sesame oil and encapsulated in
soft gelatin capsules] be rescheduled from Schedule II to Schedule III.
If finalized, this action will impose the regulatory controls and
criminal sanctions of Schedule III on those who handle dronabinol and
products containing dronabinol.
DATES: Comments, objections and requests for a hearing must be received
on or before December 7, 1998.
ADDRESSES: Comments, objections and requests for a hearing should be
submitted in quintuplicate to the Acting Deputy Administrator, Drug
Enforcement Administration, Washington, DC. 20537; Attention: DEA
Federal Register Representative/CCR.
FOR FURTHER INFORMATION CONTACT: Frank Sapienza, Chief, Drug and
Chemical Evaluation Section, Drug Enforcement Administration,
Washington, DC. 20537, 202-307-7183.
SUPPLEMENTARY INFORMATION: Dronabinol is the synthetic equivalent of
the (-)-isomer of 9-(trans)-tetrahydrocannabinol
[9-(trans)-THC], which is the major psychoactive
component of Cannabis sativa L. (Marijuana). Dronabinol, under the
trade name Marinol. was approved for marketing by the FDA
on May 31, 1985 for the treatment of nausea and vomiting associated
with cancer chemotherapy. Dronabinol [Marinol; (-)-
9-(trans)-THC in sesame oil and encapsulated in
soft gelatin capsules], but not THC itself, was transferred from
Schedule I to Schedule II of the CSA on May 13, 1986, in accordance
with 21 U.S.C. 811(a) and the FDA approval of a new drug application
for Marinol capsules. The rescheduling of
Marinol was based on a recommendation from the Assistant
Secretary for Health which also stated that THC should remain in
Schedule I. Marinol's indications were expanded on December
22, 1992 to include the treatment of anorexia associated with weight
loss in patients with AIDS.
On February 3, 1995, UNIMED Pharmaceuticals, Inc. petitioned the
Administrator of the DEA to reschedule dronabinol formulations from
Schedule II to Schedule III. This request involves only dronabinol
[synthetic (-)-9-(trans)-THC], specifically the
product Marinol (dronabinol in sesame oil in a soft gelatin
capsule). Prior to a review of the data in the petition, the DEA had to
determine whether the rescheduling of dronabinol formulations to
Schedule III was possible, in light of the control of THC in Schedule
II of the 1971 Convention on Psychotropic Substances. The DEA concluded
that control of dronabinol formulations in Schedule III of the CSA was
possible and would meet the requirements of Schedule II of the
convention provided that THC remained in Schedule I or II of the CSA
and that 21 CFR 1312.30 was amended to require import and export
permits for international transactions involving dronabinol.
On December 11, 1996, UNIMED Pharmaceuticals, Inc. submitted a
supplement to its petition to reschedule dronabinol formulations from
Schedule II to Schedule III. This supplement provided data regarding
the pharmacokinetics of Marinol, additional data about the
chemistry of the product and studies regarding the actual abuse of the
Marinol product. This information specifically addressed
the criteria required to be considered under the CSA.
On August 7, 1997, after gathering the necessary data, the DEA sent
its review document and a letter to the Acting Assistant Secretary for
Health, DHHS requesting a scientific and medical evaluation of the
available data and a scheduling recommendation on dronabinol, as
required by 21 U.S.C. 811(b).
On September 11, 1998, the Acting Assistant Secretary for Health
sent to the DEA a letter recommending that dronabinol
(Marinol; (-)-9-(trans)-THC in sesame
oil and encapsulated in soft gelatin capsules) be transferred from
Schedule II to Schedule III of the CSA. Enclosed with the September 11,
1998 letter was a document prepared by the FDA entitled ``Basis for the
Recommendation for Rescheduling Marinol Capsules from
Schedule II to Schedule III of the CSA.'' In this document, the FDA
defines the Marinol product as ``an FDA approved drug
product containing synthetically produced dranabinol dissolved in
sesame oil and encapsulated in soft gelatin capsules (2.5 mg, 5 mg, and
10 mg per dosage unit.'' The document contained a review of the factors
which the CSA requires the Secretary to consider [21 U.S.C. 811(c)].
The factors considered by the Acting Assistant Secretary for Health
and the DEA with respect to dranabinol were:
(1) Its actual or relative potential for abuse;
(2) Scientific evidence of its pharmacological effect, if known;
(3) The state of current scientific knowledge regarding the drug or
other substance;
(4) Its history and current pattern of abuse;
(5) The scope, duration, and significance of abuse;
(6) What, if any, risk there is to the public health;
(7) Its psychic or physiological dependence liability; and
(8) Whether the substance is an immediate precursor of a substance
already controlled under this subchapter.
The pharmacological and behavioral effects of dronabinol are
comparable to those of 9-THC, marijuana and other
active cannabinoids. There are few scientific studies that directly
evaluate the pharmacologeutical and behavioral effects of the product
Marinol to indicate that there are differences in its abuse
liability compared to oral THC. Nevertheless, there is little evidence
of actual abuse of Marinol, despite modest annual increases
in the total number of prescriptions written. Despite dronabinol's THC-
like abuse liability, there are several factors that deter its actual
abuse and trafficking. These factors include dronabinol's formulation
in sesame oil, the improbability that the THC would be extracted from
the product and abused by another route of administration, and its
delayed onset of effects. Although excessive use of Marinol
may result in the development of psychological dependence, there has
been no evidence of such use. The scientific data reviewed to date and
the minimal evidence of actual abuse and trafficking support the
transfer of dronabinol to Schedule III of the CSA.
Relying on the scientific and medical evaluation and the
recommendation of the Assistant Secretary for Health in accordance with
section 201(b) of the CSA (21 U.S.C. 811(b)), and the independent
review of the DEA, the Acting Deputy Administrator of the DEA, pursuant
to sections 201(a) and 201(b) of the CSA (21 U.S.C. 811(a) and 811(b)),
finds that:
(1) Based on information now available, dronabinol
(Marinol) has a potential for abuse less than the drugs or
other substances in Schedules I and II.
(2) Marinol [(-)-9-(trans)-THC in
sesame oil and encapsulated in soft gelatin capsules] is an FDA
approved drug product and has a currently accepted medical use in
treatment in the United States; and
(3) Abuse of dronabinol [Marinol; (-)-
9-(trans)-THC in seasame oil and encapsulated in
soft gelatin capsules] may lead to moderate or low physical dependence
or high psychological dependence.
Based on these findings, the Acting Deputy Administrator of the DEA
concludes that dronabinol [Marinol; (-)-
9-(trans)-THC in sesame oil and encapsulated in
soft gelatin capsules]
[[Page 59753]]
should be removed from Schedule II and placed into Schedule III of the
CSA.
Special Provisions Regarding Import/Export Authorization
Dronabinol is internationally controlled in Schedule II of the 1971
Convention on Psychotropic Substances, to which the United States is a
party. Under the special obligations of the Convention, Article 12
defines provisions relating to international trade relative to Schedule
II substances. Specifically, signatory countries are required to issue
import/export permits/authorizations to import or export a Schedule II
substance. Due to its international control status, import/export
permits for dronabinol still will be required despite the proposed
transfer of dronabinol to Schedule III of the CSA.
In accordance with 21 CFR 1312.13(b) ``[t]he Administrator may
require that such non-narcotic controlled substances in Schedule III as
he shall designate by regulation in Sec. 1312.30 of this part be
imported only pursuant to the issuance of an import permit'' (21 U.S.C.
952(b)(2)). Similarly, the DEA could require export permits for
Schedule III non-narcotic substances (21 CFR 1312.23(b) and 21 U.S.C.
953(e)(2)).
Currently, there are no Schedule III non-narcotic substances for
which the Administrator requires an import/export permit. However, in
accordance with 21 CFR 1312.30, this proposed designation of dronabinol
as a Schedule III non-narcotic substance requiring an import/export
permit is necessary for the United States to remain in compliance with
the Convention.
Interested persons are invited to submit their comments, objections
or requests for a hearing, in writing, with regard to this proposal.
Requests for a hearing should state, with particularity, the issues
concerning which the person desires to be heard. All correspondence
regarding this matter should be submitted to the Acting Deputy
Administrator, Drug Enforcement Administrator, Washington, DC 20537.
Attention: DEA Federal Register Representative/CCR. In the event that
comments, objections, or requests for a hearing raise one or more
issues which the Acting Deputy Administrator finds warrant a hearing,
the Acting Deputy Administrator shall order a public hearing by notice
in the Federal Register, summarizing the issues to be heard and setting
the time for the hearing.
In accordance with the provisions of the CSA (21 U.S.C. 811(a)),
this action is a formal rulemaking ``on the record after opportunity
for a hearing.'' such proceedings are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557 and, as such, are exempt from review
by the Office of Management and Budget pursuant to Executive Order
(E.O.) 12866, section 3(d)(1). The Acting Deputy Administrator, in
accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)), has
reviewed this proposed rule and by approving it certifies that it will
not have a significant economic impact on a substantial number of small
entities. Dronabinol products are prescription drugs used to treat
nausea due to cancer chemotherapy and AIDS wasting. Handlers of
dronabinol are likely to handle other controlled substances used to
treat cancer or AIDS, which are already subject to the regulatory
requirements of the CSA. Further, placement of dronabinol in Schedule
III of the CSA will mean a significant decrease in the regulatory
requirements for persons handling dronabinol products.
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.
This rule is not a major rule as defined by section 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 United States based companies to
compete with foreign based companies in domestic and export markets.
This rule will not have substantial direct effects on the United
States, on the relationship between the national government and the
United States, or on the distribution of power and responsibilities
among the various levels of government. Therefore, in accordance with
E.O. 12612, it is determined that this rule, if finalized, will not
have sufficient federalism implications to warrant the preparation of
Federalism Assessment.
List of Subjects
21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Narcotics, Prescription drugs.
21 CFR Part 1213
Administrative practice and procedure, Drug traffic control,
Exports, Imports, Narcotics, Reporting requirements.
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 Acting Deputy Administrator hereby proposes that 21 CFR
parts 1308 and 1312 be amended as follows:
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.
Sec. 1308.12 [Amended]
2. Section 1308.12 is proposed to be amended by removing paragraph
(f)(1) and redesignating the existing paragraph (f)(2) as (f)(1).
3. Section 1308.13 is proposed to be amended by adding a new
paragraph (g)(1) to read as follows:
Sec. 1308.13 Schedule III.
* * * * *
(g) Hallucinogenic substances.
(1) Dronabinol (synthetic) in sesame oil and encapsulated in a
soft gelatin capsule in a U.S. Food and Drug Administration
approved product................................................ 7369
[Some other names for dronabinol: (6aR-trans)-6a,7,8,10a-tetrahydro-
6,6,9-trimethyl-3-pentyl-[6H-dibenzo[b,d]pyran-1-ol] or (-)-delta-9-
(trans)-tetrahydrocannabinol]
PART 1312--[AMENDED]
1. Section 1312.30 is proposed to be amended by adding a new
paragraph (a) to read as follows:
Sec. 1313.30 Schedule III, IV and V non-narcotic controlled substances
requiring an import and export permit.
* * * * *
(a) Dronabinol (synthetic) in sesame oil and encapsulated in a soft
gelatin capsule in a U.S. Food and Drug Administration approved
product.
* * * * *
Dated: October 29, 1998.
Donnie R. Marshall,
Acting Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 98-29571 Filed 11-4-98; 8:45 am]
BILLING CODE 4410-09-M