[Federal Register Volume 79, Number 30 (Thursday, February 13, 2014)]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-03124]
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-381]
Schedules of Controlled Substances: Placement of Suvorexant into
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
SUMMARY: The Drug Enforcement Administration (DEA) proposes to place
the substance suvorexant ([(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-
yl)phenyl]methanone), including its salts, isomers, and salts of
isomers, into schedule IV of the Controlled Substances Act (CSA). This
proposed scheduling action is pursuant to the CSA which requires that
such actions be made on the record after opportunity for a hearing
through formal rulemaking. If finalized, this action would impose the
regulatory controls and administrative, civil, and criminal sanctions
applicable to schedule IV controlled substances on persons who handle
(manufacture, distribute, dispense, import, export, engage in research,
conduct instructional activities, or possess), or propose to handle
DATES: Interested persons may file written comments on this proposal in
accordance with 21 CFR 1308.43(g). Comments must be submitted
electronically or postmarked on or before March 17, 2014. Commenters
should be aware that the electronic Federal Docket Management System
will not accept comments after midnight Eastern Time on the last day of
the comment period.
Interested persons, defined as those ``adversely affected or
aggrieved by any rule or proposed rule issuable pursuant to section 201
of the Act (21 U.S.C. 811),'' 21 CFR 1300.01, may file a request for
hearing or waiver of participation pursuant to 21 CFR 1308.44 and in
accordance with 21 CFR 1316.45, 1316.47, 1316.48, or 1316.49, as
applicable. Requests for hearing, notices of appearance, and waivers of
an opportunity for a hearing or to participate in a hearing must be
received on or before March 17, 2014.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-381'' on all electronic and written correspondence.
The DEA encourages that all comments be submitted electronically
through the Federal eRulemaking Portal which provides the ability to
type short comments directly into the comment field on the Web page or
attach a file for lengthier comments. Go to www.regulations.gov and
follow the on-line instructions at that site for submitting comments.
An electronic copy of this document and supplemental information to
this proposed rule are also available at www.regulations.gov for easy
reference. Paper comments that duplicate electronic submissions are not
necessary. All comments submitted to www.regulations.gov will be posted
for public review and are part of the official docket record. Should
you, however, wish to submit written comments, in lieu of electronic
comments, they should be sent via regular or express mail to: Drug
Enforcement Administration, Attention: DEA Federal Register
Representative/ODW, 8701 Morrissette Drive, Springfield, VA 22152. All
requests for a hearing and waivers of participation must be sent to:
Drug Enforcement Administration, Attention: Hearing Clerk/LJ, 8701
Morrissette Drive, Springfield, VA 22152.
FOR FURTHER INFORMATION CONTACT: Ruth A. Carter, Office of Diversion
Control, Drug Enforcement Administration; Mailing Address: 8701
Morrissette Drive, Springfield, VA 22152, Telephone: (202) 598-6812.
Posting of Public Comments
Please note that all comments received in response to this docket
are considered part of the public record and will be made available for
public inspection online at www.regulations.gov. Such information
includes personal identifying information (such as your name, address,
etc.) voluntarily submitted by the commenter.
If you want to submit personal identifying information (such as
your name, address, etc.) as part of your comment, but do not want it
to be made publicly available, you must include the phrase ``PERSONAL
IDENTIFYING INFORMATION'' in the first paragraph of your comment. You
must also place all of the personal identifying information you do not
want made publicly available in the first paragraph of your comment and
identify what information you want redacted.
If you want to submit confidential business information as part of
your comment, but do not want it to be made publicly available, you
must include the
phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the first paragraph of
your comment. You must also prominently identify the confidential
business information to be redacted within the comment. If a comment
has so much confidential business information that it cannot be
effectively redacted, all or part of that comment may not be made
publicly available. Comments containing personal identifying
information or confidential business information identified as directed
above will be made publicly available in redacted form.
The Freedom of Information Act (FOIA) applies to all comments
received. If you wish to personally inspect the comments and materials
received or the supporting documentation the DEA used in preparing the
proposed action, these materials will be available for public
inspection by appointment. To arrange a viewing, please see the For
Further Information Contact paragraph above.
Request for Hearing, Notice of Appearance at Hearing, or Waiver of
Participation in Hearing
Pursuant to 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
the Administrative Procedure Act (APA), 5 U.S.C. 551-559. 21 CFR
1308.41-1308.45; 21 CFR part 1316 subpart D. In accordance with 21 CFR
1308.44(a)-(c), requests for a hearing, notices of appearance, and
waivers of an opportunity for a hearing or to participate in a hearing
may be submitted only by interested persons, defined as those
``adversely affected or aggrieved by any rule or proposed rule issuable
pursuant to section 201 of the Act (21 U.S.C. 811).'' 21 CFR 1300.01.
Requests for hearing and notices of appearance must conform to the
requirements of 21 CFR 1308.44(a) or (b), and 1316.47 or 1316.48 as
applicable, and include a statement of the interest of the person in
the proceeding and the objections or issues, if any, concerning which
the person desires to be heard. Any waiver must conform to the
requirements of 21 CFR 1308.44(c) and 1316.49, including a written
statement regarding the interested person's position on the matters of
fact and law involved in any hearing.
Please note that pursuant to 21 U.S.C. 811(a), the purpose and
subject matter of a hearing held in relation to this rulemaking is
restricted to: ``(A) find[ing] that such drug or other substance has a
potential for abuse, and (B) mak[ing] with respect to such drug or
other substance the findings prescribed by subsection (b) of section
812 of [Title 21] for the schedule in which such drug is to be placed.
. . .'' Requests for a hearing, notices of appearance at a hearing, and
waivers of an opportunity for a hearing or to participate in a hearing
must be submitted to the DEA using the address information provided
The DEA implements and enforces titles II and III of the
Comprehensive Drug Abuse Prevention and Control Act of 1970, as
amended. Titles II and III are referred to as the ``Controlled
Substances Act'' and the ``Controlled Substances Import and Export
Act,'' respectively, and are collectively referred to as the
``Controlled Substances Act'' or the ``CSA'' for the purpose of this
action. 21 U.S.C. 801-971. The DEA publishes the implementing
regulations for these statutes in title 21 of the Code of Federal
Regulations (CFR), parts 1300 to 1321. The CSA and its implementing
regulations are designed to prevent, detect, and eliminate the
diversion of controlled substances and listed chemicals into the
illicit market while providing for the legitimate medical, scientific,
research, and industrial needs of the United States. Controlled
substances have the potential for abuse and dependence and are
controlled to protect the public health and safety.
Under the CSA, controlled substances are classified into one of
five schedules based upon their potential for abuse, their currently
accepted medical use, and the degree of dependence the substance may
cause. 21 U.S.C. 812. The initial schedules of controlled substances
established by Congress are found at 21 U.S.C. 812(c), and the current
list of all scheduled substances is published at 21 CFR part 1308.
Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule,
``add to such a schedule or transfer between such schedules any drug or
other substance if he (A) finds that such drug or other substance has a
potential for abuse, and (B) makes with respect to such drug or other
substance the findings prescribed by [21 U.S.C. 812(b)] for the
schedule in which such drug is to be placed. . . .'' Pursuant to 28 CFR
0.100(b), the Attorney General has delegated this scheduling authority
to the Administrator of the DEA who has further delegated this
authority to the Deputy Administrator of the DEA under 28 CFR 0.104.
The CSA provides that scheduling of any drug or other substance may
be initiated by the Attorney General (1) on his own motion; (2) at the
request of the Secretary of Health and Human Services (HHS); or (3) on
the petition of any interested party. 21 U.S.C. 811(a). If finalized,
this action would impose the regulatory controls and administrative,
civil, and criminal sanctions of schedule IV controlled substances for
any person who handles suvorexant.
also known as MK-4305, is a new chemical entity developed for the
treatment of insomnia. Suvorexant is a novel, first in class, orexin
receptor antagonist with a mechanism of action distinct from any
marketed drug. It acts via inhibition of the orexin 1 (OX1) and orexin
2 (OX2) receptors. In pharmacological activity studies, suvorexant
functioned as an antagonist as demonstrated by its ability to block
agonist-induced calcium (Ca\2+\) release.
Proposed Determination to Schedule Suvorexant
Pursuant to 21 U.S.C. 811(a), proceedings to add a drug or
substance to those controlled under the CSA may be initiated by request
of the Secretary of the HHS.\1\ On June 27, 2013, the HHS provided the
DEA with a scientific and medical evaluation document prepared by the
FDA entitled ``Basis for the Recommendation to Place Suvorexant in
Schedule IV of the Controlled Substances Act.'' Pursuant to 21 U.S.C.
811(b), this document contained an eight-factor analysis of the abuse
potential of suvorexant as a new drug, along with the HHS'
recommendation to control suvorexant under schedule IV of the CSA.
\1\ As set forth in a memorandum of understanding entered into
by the HHS, the Food and Drug Administration, (FDA), and the
National Institute on Drug Abuse (NIDA), the FDA acts as the lead
agency within the HHS in carrying out the Secretary's scheduling
responsibilities under the CSA, with the concurrence of the NIDA. 50
FR 9518, Mar. 8, 1985. In addition, because the Secretary of the HHS
has delegated to the Assistant Secretary for Health of the HHS the
authority to make domestic drug scheduling recommendations, for
purposes of this document, all subsequent references to
``Secretary'' have been replaced with ``Assistant Secretary.''
In response, the DEA reviewed the scientific and medical evaluation
and scheduling recommendation provided by the HHS, and all other
relevant data, and completed its own eight-factor review document
pursuant to 21 U.S.C. 811(c). Included below is a brief summary of each
factor as analyzed by the HHS and the DEA, and as
considered by the DEA in its proposed scheduling action. Please note
that both the DEA and HHS analyses are available in their entirety
under ``Supporting and Related Material'' in the public docket for this
proposed rule at www.regulations.gov, under Docket Number ``DEA-381.''
Full analysis of, and citations to, the information referenced in the
summary may also be found in the supporting and related material.
1. The Drug's Actual or Relative Potential for Abuse: Suvorexant is
a new chemical entity that has not been marketed in the United States
or any other country. As such, there is no information available
detailing actual abuse of suvorexant. However, the legislative history
of the CSA offers the following criterion for assessing a new drug or
substance's potential for abuse:
The drug or drugs containing such a substance are new drugs so
related in their action to a drug or drugs already listed as having
a potential for abuse to make it likely that the drug will have the
same potentiality for abuse as such drugs, thus making it reasonable
to assume that there may be significant diversions from legitimate
channels, significant use contrary to or without medical advice, or
that it has a substantial capability of creating hazards to the
health of the user or to the safety of the community.\2\
\2\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); as reprinted in
1970 U.S.C.C.A.N. 4566, 4601.
As described further below, there is strong evidence that
suvorexant produces behavioral effects in humans and in animals that
are similar to those produced by zolpidem (schedule IV).
With a mechanism of action that is distinct from any other marketed
drug, including those marketed for insomnia (i.e., schedule IV
benzodiazepines, and non-benzodiazepine hypnotics such as zolpidem
(schedule IV), eszopiclone \3\ (schedule IV), and zaleplon (schedule
IV)), suvorexant acts as an antagonist at the OX1 and OX2 receptors and
produces sedative and sleep promoting effects in humans.
\3\ Eszopiclone is the dextrarotory stereoisomer, i.e., an
isomer, of zopiclone (schedule IV).
In a human abuse potential study in subjects with histories of
recreational sedative use, suvorexant produced reinforcing subjective
effects similar to zolpidem (schedule IV). Doses of 40, 80, and 150 mg
of suvorexant were compared to 15 and 30 mg doses of zolpidem (schedule
IV). On the visual analog scale (VAS), suvorexant produced `` `at the
moment' Drug Liking'' and ``High and Good,'' effects statistically
indistinguishable from zolpidem (schedule IV). Suvorexant also produced
effects similar to zolpidem (schedule IV) in ``Overall Drug Liking,''
``Take Drug Again,'' ``Any Drug Effect,'' assessments of subjective
drug value, and overall familiarity measures. Additionally, on the
Bowdle VAS (a measure of perceptual and hallucinogenic effects)
suvorexant produced effects statistically similar to zolpidem (schedule
IV). Suvorexant produced less dysphoria and adverse effects than
zolpidem (schedule IV), suggesting that suvorexant may have an
increased abuse potential relative to zolpidem (schedule IV). Measures
to evaluate cognitive and psychomotor impairment (e.g., reaction time,
attention, and vigilance) showed that suvorexant produced levels of
impairment that were similar to the low dose (15 mg) of zolpidem
(schedule IV). These data suggest that zolpidem (schedule IV) and
suvorexant present a similar risk to the public health, and that
suvorexant impairs cognition at both therapeutic (e.g., 40 mg) and
supratherapeutic doses. As the dose of suvorexant increased, there was
no increase in drug effects. This fact is especially important because
the lowest dose of suvorexant examined in the human abuse potential
study (40 mg) is the maximum planned therapeutic dose--suggesting that
therapeutic doses of suvorexant (e.g., 40 mg) will have significant
abuse liability and produce cognitive and psychomotor impairment.
These data suggest that suvorexant and zolpidem (schedule IV) have
a similar abuse potential. The similarities between suvorexant and
zolpidem (schedule IV) indicate that there will be significant
diversion of these substances from legitimate channels, and significant
use contrary to or without medical advice. In addition, as discussed in
Factor 3, the long half-life of suvorexant may be a critical factor in
the drug's safety profile as suvorexant's duration of action may create
significant hazards to the health of the user or to the safety of the
community, and result in ``next day'' effects in patients.
2. Scientific Evidence of the Drug's Pharmacological Effects, if
Known: The orexin signaling system was discovered in 1998 and has been
implicated in numerous physiological functions involving the central
nervous system (CNS) such as sleep and wakefulness, appetite/
metabolism, stress response, reward/addiction, and analgesia. Orexin A
and orexin B are peptide neurotransmitters produced through cleavage of
a preprohormone. These neurotransmitters bind with a high degree of
selectivity to two different G-protein coupled receptors (GPCR's),
namely OX1 and OX2. These orexin receptors are broadly expressed in
cortical, thalamic, and hypothalamic neuronal circuits. Suvorexant
blocks the wakefulness promoting effects of the orexins, facilitating
the sleep process. In pharmacological studies, suvorexant functioned as
an antagonist as demonstrated by its ability to block agonist-induced
calcium (Ca\2+\) release.
In receptor binding studies to determine the binding affinity as
assessed by the ability of suvorexant to displace a reference compound
(expressed as Ki value), suvorexant produced Ki
values of 0.55 nM and 0.35 nM for the OX1 and OX2 receptors, indicating
a high affinity for these receptor subtypes. In in vitro functional
studies, suvorexant blocked the effects of orexin receptor agonist in
cells expressing OX1 and OX2 receptors. The concentrations of
suvorexant inhibiting 50 percent of response (known as IC50)
were 49.9 nM at the OX1 receptors and 54.8 nM at OX2 receptors.
Like zolpidem, suvorexant (10, 20, 30 and 60 mg/kg) dose
dependently reduced locomotor activity in rats, an expected
characteristic of a sedative drug. Although rhesus monkeys trained to
self-administer methohexital (schedule IV) did not self-administer
suvorexant, the predictive validity of self-administration studies in
evaluating the abuse potential of drugs acting via orexin receptors is
A human abuse potential study was performed to assess the abuse
potential of suvorexant in human participants. The study demonstrated
that suvorexant and zolpidem (schedule IV) produce similar reinforcing
effects and have a similar potential for abuse in recreational drug
users. Results showed that suvorexant produced effects statistically
indistinguishable from zolpidem (schedule IV) in primary and secondary
outcome measures. There was no increase in drug effects as the dose of
suvorexant increased. This is an important observation, as the low dose
of suvorexant (40 mg) in the human abuse potential study is the maximum
proposed therapeutic dose. These data suggest that the maximum
therapeutic dose of suvorexant (40 mg) was shown to produce cognitive
and psychomotor impairment and will have a significant liability for
Results from another study measuring the effects of suvorexant (10,
50, and 100 mg) on sleep parameters and next-day residual effects
demonstrated that the mid and high doses of suvorexant (50 and 100 mg)
produced effects on next-day assessments of psychomotor performance and
subjective effects. These results may be clinically relevant
as the residual effects may be present in the morning following an
evening administration (10 hours post-dose).
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: The chemical name for suvorexant is [(7R)-4-(5-chloro-
triazol-2-yl)phenyl]methanone. It is a white to off-white powder. Other
chemical names include: 1) Methanone, [(7R)-4-(5-chloro-2-
1,2,3-triazol-2-yl)phenyl]-; 2) [(7R)-4-(5-chlorobenzoxazol-2-yl)-7-
yl)phenyl]methanone; 3) MK-4305; and 4) DORA-22. The Chemical Abstract
Services number (CAS ) of suvorexant is: 1030377-33-3. At 25
[deg]C, suvorexant is insoluble in water, soluble in methanol, very
slightly soluble in heptane, and soluble in isopropyl acetate. The pH
of a saturated aqueous solution of suvorexant was 8.6. Suvorexant has a
molecular formula of
C23H23ClN6O2 and a
molecular weight of 450.921 g. Suvorexant has a distinct chemical
structure that is different from that of other sedative hypnotics such
as the benzodiazepines (schedule IV).
There are several metabolites of suvorexant, although none appear
to contribute significantly to its pharmacodynamic effects or abuse
potential. Eight metabolites were detected in the plasma of healthy
males administered radiolabeled suvorexant, with two of the metabolites
present at concentrations great than 10 percent (M9 and M12). After
oral administration of 15-40-mg, peak plasma concentrations (i.e.,
Tmax) of suvorexant occurred at approximately 1-2 hours
(range 0.5-6.0 hours), although the study authors noted slight
variability based on the time of day. The terminal half-life of
suvorexant is approximately 8-11 hours after a 40-mg dose. The
pharmacokinetics of suvorexant following multiple dose administrations
were similar to those following single dose administrations, with
slightly less than dose proportional pharmacokinetics over 10-80 mg as
assessed by AUC0-[infin] and Cmax. Steady state
exposure was reached after 2-3 days of consecutive dosing.
4. Its History and Current Pattern of Abuse: Suvorexant is not
currently marketed or available for sale in any country, therefore
there is no known history or pattern of abuse. However, results from
the human abuse potential study suggest that suvorexant produces
effects that are similar to zolpidem (schedule IV) and would have a
similar pattern of abuse.
5. The Scope, Duration, and Significance of Abuse: While the
current scope, duration, and significance of abuse of suvorexant are
unknown due to its non-marketed status, the results of the human abuse
potential study previously described suggest that, upon marketing, the
scope, duration, and significance of suvorexant abuse may be similar to
zolpidem (schedule IV). Data from the Drug Abuse Warning Network (DAWN)
and the Adverse Event Reporting System (AERS) demonstrate the scope,
duration, and significance of abuse of zolpidem (schedule IV) and
related sedative-like drugs. In general, emergency department (ED)
visits reported for zolpidem (schedule IV) along with those
specifically categorized as ``misuse/abuse'' have increased every year
from 2004 to 2010, with a modest decrease reported for 2011. ED visits
related to benzodiazepine sedatives including diazepam (schedule IV)
and lorazepam (schedule IV) demonstrated a similar trend. Suvorexant
would be expected to have a similar scope, duration, and significance
6. What, If Any, Risk There Is to the Public Health: Suvorexant has
a long terminal half-life of approximately 8-11 hours, which may
increase the duration of its sedative effects and psychomotor
impairment. Suvorexant's extended duration of action increases its risk
to the public health relative to zolpidem (schedule IV) and other short
acting sedatives. Results of the human abuse potential study showed
that suvorexant produces behavioral impairment, as evidenced by its
effects on psychomotor performance and cognitive function. On these
assessments, suvorexant generally produced deficits that were
statistically indistinguishable from 15 mg of zolpidem (schedule IV),
demonstrating the behavioral impairing effects of suvorexant, and
suggesting that even at therapeutic doses, suvorexant will present a
risk to the public health that is at least equivalent to that of
zolpidem (schedule IV).
7. Its Psychic or Physiological Dependence Liability: Results of
the human abuse potential study demonstrate that suvorexant has a
psychic dependence liability similar to zolpidem (schedule IV). Self-
administration in laboratory animals, epidemiological data documenting
its use and abuse, and the ability to produce ``Drug Liking'' in human
drug users demonstrate the psychic dependence liability of zolpidem
(schedule IV). Similar data was collected for suvorexant and compared
Discontinuation studies suggest that suvorexant does not produce
physical dependence or withdrawal syndrome. Observed effects following
suvorexant discontinuation include the return of insomnia symptoms.
Furthermore, a lack of tolerance in humans from suvorexant was
demonstrated by the sustained efficacy of suvorexant in Phase 3 trials
where subjects reported improvement in sleep-related assessments that
were still present one month after the start of treatment.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled under the CSA: Suvorexant is not an immediate
precursor of a substance already controlled under the CSA.
Conclusion: After considering the scientific and medical evaluation
conducted by the HHS, the HHS' recommendation, and its own eight-factor
analysis, the DEA has determined that these facts and all relevant data
constitute substantial evidence of a potential for abuse of suvorexant.
As such, the DEA hereby proposes to schedule suvorexant as a controlled
substance under the CSA.
Proposed Determination of Appropriate Schedule
The CSA outlines the findings required to place a drug or other
substance in any particular schedule (I, II, III, IV, or V). 21 U.S.C.
812(b). After consideration of the analysis and recommendation of the
Assistant Secretary for Health of the HHS and review of all available
data, the Deputy Administrator of the DEA, pursuant to 21 U.S.C.
812(b)(4), finds that:
1. Suvorexant has a low potential for abuse relative to the drugs
or other substances in schedule III. The overall abuse potential of
suvorexant is comparable to schedule IV controlled substances such as
2. Upon approval of the pending new drug application, suvorexant
will have a currently accepted medical use in the treatment of insomnia
in the United States; and
3. The available evidence indicates that abuse of suvorexant may
lead to limited psychological dependence relative to the drugs or other
substances in schedule III. The potential for psychological dependence
is similar to that of zolpidem (schedule IV).
Based on these findings, the Deputy Administrator of the DEA
concludes that suvorexant ([(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-
yl)phenyl]methanone), including its salts, isomers, and salts of
warrants control in schedule IV of the CSA. 21 U.S.C. 812(b)(4).
Requirements for Handling Suvorexant
If this rule is finalized as proposed, suvorexant would be subject
to the CSA's schedule IV regulatory controls and administrative, civil,
and criminal sanctions applicable to the manufacture, distribution,
dispensing, importing, exporting, research, and conduct of
instructional activities, including the following:
Registration. Any person who handles (manufactures, distributes,
dispenses, imports, exports, engages in research, or conducts
instructional activities with) suvorexant, or who desires to handle
suvorexant, would be required to be registered with the DEA to conduct
such activities pursuant to 21 U.S.C. 822, 823, 957, and 958 and in
accordance with 21 CFR parts 1301 and 1312. Any person who currently
handles suvorexant, and is not registered with the DEA, would need to
be registered with the DEA by the effective date of the final rule to
conduct such activities pursuant to 21 U.S.C. 822, 823, 957, and 958,
and in accordance with 21 CFR parts 1301 and 1312.
Security. Suvorexant would be subject to schedule III-V security
requirements and would need to be handled and stored pursuant to 21
U.S.C. 821, 823, 871(b) and in accordance with 21 CFR 1301.71-1301.93.
Labeling and Packaging. All labels and labeling for commercial
containers of suvorexant on or after finalization of this rule would
need to comply with 21 U.S.C. 825, 958(e), and be in accordance with 21
CFR part 1302.
Inventory. Every DEA registrant who possesses any quantity of
suvorexant on the effective date of the final rule would be required to
take an inventory of all stocks of suvorexant on hand as of the
effective date of the rule, pursuant to 21 U.S.C. 827, 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a) and (d).
Any person who becomes registered with the DEA after the effective
date of the final rule would be required to take an initial inventory
of all stocks of controlled substances (including suvorexant) on hand
at the time of registration pursuant to 21 U.S.C. 827, 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a) and (b). After
the initial inventory, every DEA registrant would be required to take a
biennial inventory of all controlled substances (including suvorexant)
on hand, on a biennial basis, pursuant to 21 U.S.C. 827, 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
Records. All DEA registrants would be required to maintain records
with respect to suvorexant pursuant to 21 U.S.C. 827, 958, and in
accordance with 21 CFR parts 1304, 1307, and 1312.
Prescriptions. All prescriptions for suvorexant or products
containing suvorexant would need to comply with 21 U.S.C. 829, and be
issued in accordance with 21 CFR part 1306, and part 1311 subpart C.
Importation and Exportation. All importation and exportation of
suvorexant would need to be in compliance with 21 U.S.C. 952, 953, 957,
and 958, and in accordance with 21 CFR part 1312.
Criminal Liability. Any activity involving suvorexant not
authorized by, or in violation of, the CSA, occurring on or after
finalization of this proposed rule, would be unlawful, and may subject
the person to administrative, civil, and/or criminal sanctions.
Executive Orders 12866 and 13563
In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures performed ``on the
record after opportunity for a hearing,'' which are conducted pursuant
to the provisions of 5 U.S.C. 556 and 557. The CSA sets forth the
procedures and criteria for scheduling a drug or other substance. Such
actions are exempt from review by the Office of Management and Budget
(OMB) pursuant to section 3(d)(1) of Executive Order 12866 and the
principles reaffirmed in Executive Order 13563.
Executive Order 12988
This proposed regulation meets the applicable standards set forth
in Sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate
drafting errors and ambiguity, minimize litigation, provide a clear
legal standard for affected conduct, and promote simplification and
Executive Order 13132
This proposed rulemaking does not have federalism implications
warranting the application of Executive Order 13132. The proposed rule
does not have substantial direct effects on the States, on the
relationship between the national government and the States, or the
distribution of power and responsibilities among the various levels of
Executive Order 13175
This proposed rule will not have tribal implications warranting the
application of Executive Order 13175. It does not have substantial
direct effects on one or more Indian tribes, on the relationship
between the Federal government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
government and Indian tribes.
Regulatory Flexibility Act
The Deputy Administrator, in accordance with the Regulatory
Flexibility Act (RFA), 5 U.S.C. 601-612, 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. The purpose
of this proposed rule is to place suvorexant, including its salts,
isomers, and salts of isomers, into schedule IV of the CSA. No less
restrictive measures (i.e., non-control, or control in schedule V)
enable the DEA to meet its statutory obligations under the CSA. In
preparing this certification, the DEA has assessed economic impact by
size category and has considered costs with respect to the various DEA
registrant business activity classes.
Suvorexant is a new molecular entity which has not yet been
marketed in the United States or any other country. Accordingly, the
number of currently identifiable manufacturers, importers, and
distributors for suvorexant is extremely small. The publicly available
materials also specify the readily identifiable persons subject to
direct regulation by this proposed rule. Based on guidelines utilized
by the Small Business Administration (SBA), the suvorexant
manufacturer/distributor/importer was determined not to be a small
entity. Once generic equivalents are developed and approved for
manufacturing and marketing, there may be additional manufacturers,
importers, and distributors of suvorexant, but whether they may qualify
as small entities cannot be determined at this time.
There are approximately 1.5 million controlled substance
registrants, who represent approximately 381,000 entities (which
include businesses, organizations, and governmental jurisdictions). The
DEA estimates that 371,000 (97 percent) of these entities are
considered ``small entities'' in accordance with the RFA and SBA
standards. 5 U.S.C. 601(6); 15 U.S.C. 632. Due to the wide variety of
unidentifiable and unquantifiable variables that potentially could
influence the dispensing rates of new molecular entities, the DEA is
unable to determine what number of these 371,000 small entities might
Despite the fact that the number of small entities possibly
impacted by this proposed rule could not be determined, the DEA
concludes that they would not experience a significant economic impact
as a result of this proposed rule. The DEA estimates all anticipated
suvorexant handlers to be DEA registrants and currently 98 percent of
DEA registrants (most of which are small entities) are authorized to
handle schedule IV controlled substances. Even assuming that all of
these registrants were to handle suvorexant the costs that they would
incur as a result of suvorexant scheduling would be nominal as they
have already established and implemented the required security,
inventory, recordkeeping, and labeling systems and processes to handle
schedule IV controlled substances.
Because of these facts, this proposed rule will not result in a
significant economic impact on a substantial number of small entities.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., the DEA has determined and certifies that this
action would not result in any Federal mandate that may result ``in the
expenditure by State, local, and tribal governments, in the aggregate,
or by the private sector, of $100,000,000 or more (adjusted for
inflation) in any one year. . . .'' Therefore, neither a Small
Government Agency Plan nor any other action is required under UMRA of
Paperwork Reduction Act of 1995
This action does not impose a new collection of information
requirement under the Paperwork Reduction Act of 1995, 44 U.S.C. 3501-
3521. This action would not impose recordkeeping or reporting
requirements on State or local governments, individuals, businesses, or
organizations. An agency may not conduct or sponsor, and a person is
not required to respond to, a collection of information unless it
displays a currently valid OMB control number.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, the DEA proposes to amend 21 CFR
part 1308 as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
1. The authority citation for 21 CFR part 1308 continues to read as
Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.
2. Amend Sec. 1308.14 by redesignating paragraphs (c)(50) through
(c)(55) as paragraphs (c)(51) through (c)(56) and adding new paragraph
(c)(50) to read as follows:
Sec. 1308.14 Schedule IV.
* * * * *
(c) * * *
(50) Suvorexant............................................ 2223
* * * * *
Dated: February 7, 2014.
Thomas M. Harrigan,
[FR Doc. 2014-03124 Filed 2-12-14; 8:45 am]
BILLING CODE 4410-09-P