Rules - 1998
[Federal Register Volume 63, Number 71 (Tuesday, April 14, 1998)]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 98-9824]
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
Schedules of Controlled Substances: Proposed Placement of Modafinil Into Schedule IV
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
SUMMARY: This proposed rule is issued by the Acting Deputy Administrator of the Drug Enforcement Administration (DEA) to place the substance modafinil, including its salts, isomers and salts of isomers, into Schedule IV of the Controlled Substances Act (CSA). This proposed action is based on a recommendation from the Acting Assistant Secretary for Health of the Department of Health and Human Services (DHHS) that modafinil be added to Schedule IV and on an evaluation of the relevant data by the DEA. The scheduling of modafinil in Schedule IV will not be finalized until the New Drug Application (NDA) for modafinil is approved by the Food and Drug Administration (FDA). If finalized, this action will impose the regulatory controls and criminal sanctions of Schedule IV on those who handle modafinil and products containing modafinil.
DATES: Comments, objections and requests for a hearing must be received on or before May 14, 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: Modafinil is a central nervous system (CNS) stimulant that is being considered for marketing approval by the FDA, under the trade name Provigil. If approved, modafinil will be marketed as a prescription drug product for the treatment of excessive daytime sleepiness associated with narcolepsy. Modafinil produces many of the same pharmacological effects and adverse reactions as, but is up to 50 to 100 times less potent than, classic psychomotor stimulants, such as amphetamine, methamphetamine and methylphenidate, all in Schedule II of the CSA.
Modafinil is a racemic mixture of levo- and dextro-isomers. Modafinil is structurally different from other CNS stimulants, such as cocaine, amphetamine, methamphetamine and methylphenidate. Modafinil binds at dopamine receptors and is active at central dopamine binding sites. It has a quick onset and short duration of action. Modafinil is reinforcing in animals, and produces euphoria, alterations in mood, perception, thinking and subjective effects typical of other classic Schedule II psychomotor stimulants. The levo-isomer, dextro-isomer and racemate are equipotent and produce similar behavioral effects.
Despite its classic CNS stimulant-like pharmacological profile, modafinil appears to have chemical properties that may limit its abuse (i.e., not water
soluble, decomposes in heat). In addition, relative potency differences between modafinil and other CNS stimulants in Schedule II are significant. These properties reduce the likelihood that modafinil could be abused by the parenteral, intranasal or inhalation route, as are cocaine, methylphenidate, and amphetamine. Thus, its abuse potential appears to be lower than that of Schedule II stimulants and similar to that of Schedule IV stimulants. The DEA is unaware of any reports of modafinil abuse.
On December 22, 1997, the Acting Assistant Secretary for Health sent the Acting Deputy Administrator of DEA a letter recommending that modafinil, and its salts, be placed in 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 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 correspondence from the FDA's Associate Commissioner for Health Affairs dated February 24, 1998, confirmed that FDA continues to evaluate the pending New Drug Application for modafinil. The FDA has determined that the NDA is "approvable" and has issued an approvable letter to the NDA sponsor on December 29, 1997. According to the February 24, 1998 letter from FDA, "upon full approval of the NDA, modafinil 'will have a currently accepted medical use in the United States.' "
The factors considered by the Acting Assistant Secretary for Health and the DEA with respect to modafinil were:
(1) Its actual or relative potential for abuse;
(2) Scientific evidence of its pharmacological effect;
(3) The state of current scientific knowledge regarding the drug;
(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.
Relying on the scientific and medical evaluation, the recommendation of the Acting Assistant Secretary for Health, the letter from the FDA Associate Commissioner for Health received in accordance with section 201(b) of the Act [21 U.S.C. 811(b)], and the independent review of the DEA, the Acting Deputy Administer of the DEA, pursuant to sections 201(a) and 201(b) of the Act [21 U.S.C. 811(a) and 811(b)], find 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 will, upon approval of a NDA by the FDA, have a currently accepted medical use in treatment in the United States; and
(3) Abuse of modafinil may be lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule III.
Based on these findings, the Acting Deputy Administrator of the DEA concludes that modafinil, including its salts, isomers, and salts of isomers, warrant control in Schedule IV of the CSA, if and when the modafinil NDA is approved by the FDA.
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 Administration, Washington, D.C. 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 warrants 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. Modafinil products will be prescription drugs used to treat narcolepsy. Handlers of modafinil also handle other controlled substances used to treat narcolepsy which are already subject to the regulatory requirements of the CSA.
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 the 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 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 Acting Deputy Administrator hereby proposes that 21 CFR part 1308 be amended as follows:
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 proposed to be 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) * * *
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Dated: April 6, 1998.
Donnie R. Marshall,
Acting Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 98-9824 Filed 4-13-98; 8:45 am]
BILLING CODE 4410-09-M
NOTICE: This is an unofficial version. An official version of this publication may be obtained directly from the Government Publishing Office (GPO).