[Federal Register Volume 64, Number 17 (Wednesday, January 27, 1999)]
[Rules and Regulations]
[Pages 4050-4052]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-1791]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

21 CFR Part 1308

[DEA-17F]


Schedules of Controlled Substances: Placement of Modafinil Into 
Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: With the issuance of this final rule, the Deputy Administrator 
of the Drug Enforcement Administration (DEA) places the substance, 
modafinil, including its salts, isomers and salts of isomers, into 
Schedule IV of the Controlled Substances Act (CSA). As a result of this 
rule, the regulatory controls and criminal sanctions of Schedule IV 
will be applicable to the manufacture, distribution, importation and 
exportation of modafinil and products containing modafinil.

EFFECTIVE DATE: January 27, 1999.

FOR FURTHER INFORMATION CONTACT:
Frank Sapienza, Chief, Drug and Chemical Evaluation Section, Drug 
Enforcement Administration,

[[Page 4051]]

Washington, DC 20537, Telephone: (202) 307-7183.

SUPPLEMENTARY INFORMATION: Modafinil is a central nervous system (CNS) 
stimulant that produces many of the same pharmacological effects and 
adverse reactions as classic psychomotor stimulants, but at higher 
doses. Modafinil will be marketed as a prescription drug product for 
the treatment of excessive daytime sleepiness associated with 
narcolepsy under the trade name Provigil.
    On December 22, 1997, the Acting Assistant Secretary for Health, 
Department of Health and Human Services (DHHS), sent the Acting Deputy 
Administrator of DEA a letter recommending that modafinil, and its 
salts, be placed into Schedule IV of the CSA (21 U.S.C. 801 et seq.). 
Enclosed with the December 22, 1997 letter was a document prepared by 
the Food and Drug Administration (FDA) entitled ``Basis for the 
Recommendation for Control of Modafinil in Schedule IV of the 
Controlled Substances Act (CSA).'' The document contained a review of 
the factors which the CSA requires the Secretary to consider (21 U.S.C. 
811(b)).
    Subsequent correspondent from the FDA's Associate Commissioner for 
Health Affairs dated February 24, 1998, confirmed that the FDA had 
determined that the New Drug Application (NDA) for modafinil was 
``approvable'' and had issued an approvable letter to the NDA sponsor 
on December 29, 1997. According to the February 24, 1998 letter from 
the FDA, ``upon full approval of the NDA, modafinil will have a 
currently accepted medical use in treatment in the United States.''
    After a review of the available data, including the DHHS 
recommendation, the Acting Deputy Administrator of the DEA, in an April 
14, 1998 Federal Register notice (63 FR 18170), proposed placement of 
modafinil into Schedule IV of the CSA, if and when the modafinil NDA is 
approved by the FDA. The notice provided an opportunity for all 
interested persons to submit their comments, objections, or requests 
for hearing in writing to be received by the DEA on or before May 14, 
1998.
    The DEA received one comment regarding the proposal. The comment 
was received from Cephalon, Inc., the company sponsoring the modafinil 
NDA. The comment did not object to the placement of modafinil in 
Schedule IV, but requested clarification of some of the descriptions of 
the pharmacological effects of modafinil. Cephalon, Inc. commented that 
modafinil did not produce significant dopaminergic activity nor did it 
produce classic dopaminergic-like pharmacological effects. Cephalon 
also stated that the time to peak pharmacological activity of modafinil 
is one to three hours and the effects last six to eight hours after 
oral administration. It did not characterize such pharmacodynamic 
effects of modafinil as ``quick onset and short duration of action,'' 
as they were described in the Federal Register proposal.
    The DEA's review of the DHHS scheduling recommendation and review 
document and the available scientific literature indicates that the 
precise biochemical mechanism of action of modafinil is not clearly 
defined. Data indicate that modafinil does not act directly on any 
single neurotransmitter system, but appears to act indirectly on 
dopamineric, serotonergic, and GABA systems. Although its mechanism of 
action may not be medicated primarily through the dopaminergic system, 
the behavioral and pharmacological effects and adverse reactions 
produced by modafinil are similar to those of other psychomotor or 
stimulants which produce significant dopaminergic activity. The data 
reviewed by the DHHS and the DEA show that modafinil is well-absorbed 
after oral administration. Peak plasma concentration for modafinil 
occurs at one to four hours. Elimination half-life was nine to fourteen 
hours after oral administration of 200 to 400 mg of modafinil. These 
pharmacodynamic actions of modafinil were characterized at ``fast onset 
and short duration'' by the DHHS. Thus, the modafinil data presented in 
the Federal Register proposal and the comments by Cephalon regarding 
these statements are not substantive scientific discrepancies, but are 
differences in describing the same data.
    On December 30, 1998, the FDA notified the DEA that the modafinil 
NDA was approved by the FDA on December 24, 1998. Relying on the 
scientific and medical evaluation and the recommendation of the DHHS 
Acting Assistant Secretary for Health received in accordance with 
section 201(b) of the Act (21 U.S.C. 811(b)), communication with the 
FDA Associate Commissioner for Health and the independent review of the 
DEA, the Deputy Administrator of the DEA, pursuant to sections 201(a) 
and 201(b) of the Act (21 U.S.C. 811(a) and 811(b)), finds that:
    (1) Based on information now available, modafinil has a low 
potential for abuse relative to the drugs or other substances in 
Schedule III;
    (2) Modafinil has a currently accepted medical use in treatment in 
the United States; and
    (3) Abuse of modafinil may lead to limited physical dependence and 
psychological dependence relative to the drugs or other substances in 
Schedule III.
    Based on these findings, the Deputy Administrator of the DEA 
concludes that modafinil, including its salts, isomers and salts of 
isomers, warrants control in Schedule IV of the CSA. In order to make 
modafinil pharmaceutical products available for medical use as soon as 
possible, the Schedule IV controls of modafinil will be effective 
January 27, 1999. 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 IV 
regulations regarding modafinil. The applicable regulations are as 
follows:
    1. Registration. Any person who manufactures, distributes, 
dispenses, imports or exports modafinil or who engages in research or 
conducts instructional activities with modafinil, 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. Modafinil 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, modafinil which is distributed shall comply with 
the requirements of Secs. 1302.03-1302.07 of Title 21 of the Code of 
Federal Regulations.
    4. Inventory. Registrants possessing modafinil 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 modafinil 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.
    7. Importation and Exportation. All importation and exportation of 
modafinil shall be in compliance with Part 1312 of Title 21 of the 
Federal Code of Regulations.
    8. Criminal Liability. Any activity with modafinil not authorized 
by, or in violation of, the CAS or the Controlled

[[Page 4052]]

Substances Import and Export Act shall be unlawful.
    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 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. Modafinil is a new 
drug in the United States; recent approval of the product and its 
labeling by the FDA will allow it to be marketed once it is placed into 
Schedule IV of the CAS. This final rule will allow these entities to 
have access to a new pharmaceutical product.
    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 does not have sufficient federalism 
implications to warrant the preparation of a Federalism Assessment.

List of Subjects in 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 part 1308 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.

    2. Section 1308.14 is amended by redesignating the existing 
paragraphs (e)(7) through (e)(11) as (e)(8) through (e)(12) and by 
adding a new paragraph (e)(7) to read as follows: Sec. 1308.14 Schedule 
IV.
* * * * *
    (e) * * *

(7) Modafinil................................................       1680
 
*                  *                  *                  *
                                     *
 

    Dated: January 20, 1999.
Donnie R. Marshall,
Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 99-1791 Filed 1-26-99; 8:45 am]
BILLING CODE 4410-09-M