[Federal Register Volume 63, Number 71 (Tuesday, April 14, 1998)]
[Proposed Rules]
[Pages 18170-18172]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-9824]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[DEA-174P]
Schedules of Controlled Substances: Proposed Placement of
Modafinil Into Schedule IV
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 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
[[Page 18171]]
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:
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 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:
[[Page 18172]]
Sec. 1308.14 Schedule IV.
* * * * *
(e) * * *
(7) Modafinil......................................................1680
* * * * *
Dated: April 6, 1998.
Donnie R. Marshall,
Acting Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 98-9824 Filed 4-13-98; 8:45 am]
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