98-29571. Schedules of Controlled Substances: Rescheduling of Synthetic Dronabinol (MartinolSUP/SUP; (-)-greek-DSUP9/SUP-(trans)- Tetrahydrocannabinol in Sesame oil and Encapsulated in Soft Gelatin Capsules) From Schedule II to Schedule III.  

  • [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
    
    
    

Document Information

Published:
11/05/1998
Department:
Drug Enforcement Administration
Entry Type:
Proposed Rule
Action:
Notice of proposed rulemaking.
Document Number:
98-29571
Dates:
Comments, objections and requests for a hearing must be received on or before December 7, 1998.
Pages:
59751-59753 (3 pages)
Docket Numbers:
DEA-180P
PDF File:
98-29571.pdf
CFR: (3)
21 CFR 1308.12
21 CFR 1308.13
21 CFR 1313.30