[Federal Register Volume 64, Number 127 (Friday, July 2, 1999)]
[Rules and Regulations]
[Pages 35928-35930]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-16833]


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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 
[(-)- 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: Final rule.

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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 [(-)- 9-(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  9-(trans)-tetrahydrocannabinol [(-)-
 9-(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

[[Page 35929]]

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 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 commercial containers of 
Marinol, which are packaged on or after January 3, 2000 
must have the appropriate Schedule III labeling as required by 
Secs. 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 Secs. 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 Secs. 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 
Secs. 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 Secs. 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.


Sec. 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:


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]

    (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:


Sec. 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