Page 35928 Federal Register / Vol. 64, No. 127
/ Friday, July 2, 1999 / Rules and Regulations
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Parts 1308, 1312
[DEA-180F]
Schedules of Controlled Substances: Rescheduling of the Food and Drug Administration
Approved Product Containing Synthetic Dronabinol [(-)-Δ9-(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: Final rule.
SUMMARY: This is a final rule of the Deputy Administrator
of the Drug Enforcement Administration (DEA) transferring a drug between schedules
of the Controlled Substances Act (CSA) pursuant to 21 U.S.C. 811. With the issuance
of this final rule, the Deputy Administrator transfers from schedule II to schedule
III of the CSA the drug containing synthetic dronabinol [(-)-Δ9-(trans)-tetrahydrocannabinol]
in sesame oil and encapsulated in soft gelatin capsules in a product approved by
the Food and Drug Administration (FDA). This rule also designates this drug as a
schedule III non-narcotic substance requiring an import/export permit. As a result
of this rule, the regulatory controls and criminal sanctions of schedule III will
be applicable to the manufacture, distribution, importation and exportation of this
drug.
EFFECTIVE DATE: July 2, 1999.
FOR FURTHER INFORMATION CONTACT: Frank
Sapienza, Chief, Drug and Chemical Evaluation Section, Drug Enforcement Administration,
Washington, DC 20537, 202-307-7183.
SUPPLEMENTARY INFORMATION:
Background
Dronabinol is the United States Adopted Name (USAN)
for the (-)-isomer of Δ9-(trans)-tetrahydrocannabinol
[(-)-Δ9-(trans)-THC], which
is believed to be the major psychoactive component of Cannibas sativa L.
(marijuana). On May 31, 1985, FDA approved for marketing the product Marinol® which contains synthetic dronabinol in
sesame oil and encapsulated in soft gelatin capsules-for the treatment of nausea
and vomiting associated with cancer chemotherapy. Following this FDA approval, DEA
issued a final rule on May 13, 1986, transferring FDA-approved products of the same
formulation as Marinol® from schedule
I to schedule II of the CSA in accordance with 21 U.S.C. 811(a). (For simplicity
within this document, the term "Marinol®"
will be used hereafter to refer to Marinol®
and any other products, which may by approved by FDA in the future, that have the
same formulation as Marinol®.) The 1986
rescheduling of Marinol® was based on
a medical and scientific evaluation and scheduling recommendation from the Assistant
Secretary for Health in accordance with 21 U.S.C. 811(b). The transfer of Marinol® to schedule II did not affect the CSA
classification of pure dronabinol, which-as a tetrahydrocannabinol with no currently
accepted medical use in treatment in the United States-remains a schedule I controlled
substance. On December 22, 1992, FDA expanded Marinol®'s
indications to include the treatment of anorexia associated with weight loss in
patients with AIDS.
The Petition To Reschedule Marinol®
On February 3, 1995, UNIMED Pharmaceuticals, Inc.
petitioned the Administrator of DEA to transfer Marinol®
from schedule II to schedule III. In response to this petition, and in view of supplemental
information that UNIMED provided to DEA on December 11, 1996, DEA had to determine
whether this proposed rescheduling of Marinol®
would comport with United States obligations under the Convention on Psychotropic
Substances, 1971 (Psychotropic Convention). See 21 U.S.C. 811(d). Under the Psychotropic
Convention, dronabinol and all dronabinol-containing products, such as Marinol®, are listed in schedule II. As a result,
the United States is obligated under the Psychotropic Convention to impose certain
restrictions on the export and import of Marinol®.
DEA has concluded that, in order for the United States to continue to meet its obligations
under the Psychotropic Convention, DEA will continue to require import and export
permits for international transactions involving Marinol®,
even though Marinol® will be transferred
to schedule III of the CSA. (As set forth below, to accomplish this, DEA is hereby
amending 21 CFR 1312.30 to require import and export permits for international transactions
involving Marinol®.)
After determining that Marinol®
could be transferred to schedule III while maintaining the controls required by
the Psychotropic Convention, and after gathering the necessary data, on August 7,
1997, DEA requested from the Acting Assistant Secretary for Health, Department of
Health and Human Services (DHHS), a scientific and medical evaluation, and recommendation,
as to whether Marinol® should be rescheduled,
in accordance with 21 U.S.C. 811(b).
On September 11, 1998, the Acting Assistant Secretary
for Health sent to DEA a letter recommending that Marinol®
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 Controlled Substances Act (CSA)."
In this document, the FDA defines the Marinol®
product as "an FDA-approved drug product containing synthetically produced
dronabinol dissolved in sesame oil and encapsulated in soft
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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, which
are set forth in 21 U.S.C. 811(c).
The Proposed Rule
On November 7, 1998, the then-Acting Deputy Administrator
of DEA published a notice of proposed rule making in the Federal Register
(63 FR 59751), proposing to transfer Marinol®
from schedule II to schedule III of the CSA. The proposed rule was based on the
DHHS scientific and medical evaluation and scheduling recommendation and DEA's independent
evaluation. Also under the proposed rule, 21 CFR 1312.30 would be amended to include
Marinol® as a schedule III non-narcotic
controlled substance specifically designated as requiring import and export permits
pursuant to 21 U.S.C. 952(b)(2) and 953(e)(3). As discussed above, this proposed
amendment to 21 CFR 1312.30 is necessary for the United States to continue to meet
its obligations under the Psychotropic Convention. The notice of proposed rule provided
an opportunity for all interested persons to submit their comments, objections,
or requests for hearing in writing to DEA on or before December 7, 1998.
Comments From the Public
DEA received comments regarding the proposed rule
from ten persons. Nine of the commenters supported the proposed rule. One commenter
objected to the proposed rule and requested a hearing thereon. The comments are
briefly summarized below.
The nine commenters who supported the proposed rule
included organizations, physicians, and one individual. Eight of the nine commenters
who supported the proposed rule expressed the opinion that Marinol®
is a safe and effective alternative to smoking marijuana for treatment of nausea
and loss of appetite and has low abuse potential.
One commenter who supported the proposed rule expressed
the view that the rescheduling of Marinol®
should not serve as a substitute for making marijuana legally available for medical
use. This commenter stated that it supported the use of marijuana for medical purposes
and, therefore, wished to emphasize that the proposed rule affected the CSA status
of Marinol® -not that of marijuana, which
remains a schedule I controlled substance.
The one commenter who objected to the proposed rule,
and requested a hearing thereon, asserted that Marinol®
should not be transferred to schedule III unless and until marijuana and all other
THC-containing drugs are simultaneously and likewise rescheduled. This commenter
asserted that Marinol® has the same potential
for abuse as marijuana and all other THC-containing drugs. This commenter agreed
with the proposed rule that Marinol®
's potential for abuse is less than the "high potential for abuse" commensurate
with schedules I and II of the CSA. Accordingly, this commenter agreed that Marinol® should be transferred to a less restrictive
schedule than schedule II. However, this commenter disagreed with what would be
the resultant status of Marinol® vis-a-vis
marijuana and THC if the NPRM becomes final: Marinol®
would be in schedule III while marijuana and THC would remain in schedule I. This
commenter asserted that the CSA prohibited transferring Marinol®
to a less restrictive schedule unless marijuana and all THC-containing drugs are
simultaneously transferred to the same schedule. DEA has determined that this commenter's
objections are based on a misinterpretation of the CSA, which can be addressed,
as a matter of law, without conducting a fact-finding hearing. Accordingly, as this
commenter presented no material issues of fact, DEA denied this commenter's request
for a hearing.
Findings
Relying on the scientific and medical evaluation and
scheduling recommendations of the Assistant Secretary for Health, and based on DEA's
independent review thereof, the Deputy Administrator of the DEA, pursuant to 21
U.S.C. 811(a) and 811(b), finds that:
(1) Based on information now available, Marinol® has a potential for abuse less than the
drugs or other substances in schedules I and II.
(2) Marinol®
is a FDA-approved drug product and has a currently accepted medical use in treatment
in the United States; and
(3) Abuse of Marinol®
may lead to moderate of low physical dependence or high psychological dependence.
Rescheduling Action
Based on the above findings, the Deputy Administrator
of the DEA concludes that Marinol® should
be transferred from schedule II to schedule III. Schedule III regulations will,
among other things, allow five prescription refills in six months and lessen record
keeping requirements and distribution restrictions. The schedule III control of
Marinol® will become effective July 2,
1999, except that certain regulatory provisions governing registrants who handle
Marinol will take effect as indicated below. In the event that the regulations impose
special hardships on the registrants, the DEA will entertain any justified request
for an extension of time to comply with the schedule III regulations regarding Marinol®. The applicable regulations are as follows.
1. Registration. Any person who manufactures,
distributes, dispenses, imports or exports Marinol®
or who engages in research or conducts instructional activities with Marinol®, or who proposes to engage in such activities,
must be registered to conduct such activities in accordance with part 1301 of Title
21 of the Code of Federal Regulations.
2. Security. Marinol®
must be manufactured, distributed and stored in accordance with §§ 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 commercial
containers of Marinol®, which are packaged
on or after January 3, 2000 must have the appropriate Schedule III labeling as required
by §§ 1302.03-1302.07 of Title 21 of the Code of Federal Regulations.
Commercial containers of Marinol® packaged
before January 3, 2000. After April 3, 2000, all commercial containers of Marinol
must bear the CIII labels as specified in §§ 1302.03-1302.07 of Title
21 of the Code of Federal Regulations.
4. Inventory. Registrants possessing Marinol® are required to take inventories pursuant
to §§ 1304.03, 1304.04 and 1304.11 of Title 21 of the Code of Federal
Regulations.
5. Records. All registrants must keep records
pursuant to §§ 1304.03, 1304.04 and 1304.21-1304.23 of Title 21 of the
Code of Federal Regulations.
6. Prescriptions. All prescriptions for Marinol® are to be issued pursuant to §§
1306.03-1306.06 and 1306.21-1306.26 of Title 21 of the Code of Federal Regulations.
All prescriptions for Marinol® issued
on or after July 2, 1999, if authorized for refilling, shall as of that date be
limited to five refills and shall not be refilled after January 2, 2000.
7. Importation and Exportation. Due to its
international control status, import and export permits for Marinol®
will be required in accordance with 21 CFR 1312.30. All importation and exportation
of Marinol® shall be in compliance with
part 1312 of Title 21 of the CFR.
8. Criminal Liability. Any activity with
Marinol® not authorized by, or in violation
of, the CSA or the Controlled
Page 35930
Substances Import and Export Act shall continue to be unlawful.
In accordance with the provisions of the CSA (21 U.S.C.
811(a)), this action is a formal rule making "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 Deputy
Administrator, in accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)),
has reviewed this final rule and by approving it certifies that it will not have
a significant economic impact on a substantial number of small entities. Marinol® is a prescription drug used to treat
nausea due to cancer chemotherapy and AIDS wasting. Handlers of Marinol®
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 Marinol® in schedule III of the CSA
will mean a significant decrease in the regulatory requirements for persons handling
Marinol®.
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 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. 12612, it is determined that this
rule, if finalized, will not have sufficient federalism implications to warrant
the preparation of a Federalism Assessment.
List of Subjects
21 CFR Part 1308
Administrative practice and procedure, Drug traffic
control, Narcotics, Prescription drugs.
21 CFR Part 1312
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 Deputy Administrator hereby
amends 21 CFR parts 1308 and 1312 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.
§ 1308.12 -- [Amended]
2. Section 1308.12 is amended by removing paragraph
(f)(1) and redesignating the existing paragraph (f)(2) as (f)(1).
3. Section 1308.13 is amended by adding a new paragraph
(g) to read as follows:
§ 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: (6a R-trans)-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6
H -dibenzo [ b,d ]pyran-1-ol] or (-)-delta-9-(trans)-tetrahydrocannabinol]
(2) [Reserved]
PART 1312--[AMENDED]
1. The authority citation for part 1312 continues
to read as follows:
Authority: 21 U.S.C. 952, 953, 954,
957, 958.
2. Section 1312.30 is amended by adding a new paragraph
(a) and reserving paragraph (b) to read as follows:
§ 1312.30 -- 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.
(b) [Reserved]
Dated: June 28, 1999.
Donnie R. Marshall,
Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 99-16833 Filed 7-1-99; 8:45 am]
BILLING CODE 4410-09-M