[Federal Register Volume 87, Number 67 (Thursday, April 7, 2022)]
[Rules and Regulations]
[Pages 20313-20318]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-07322]
[[Page 20313]]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-949]
Schedules of Controlled Substances: Placement of Daridorexant in
Schedule IV
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Interim final rule with request for comments.
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SUMMARY: On January 7, 2022, the United States Food and Drug
Administration approved a new drug application for QUIVIVIQ
(daridorexant) tablets for the treatment of adult patients with
insomnia characterized by difficulties with sleep onset and/or sleep
maintenance. The Department of Health and Human Services provided the
Drug Enforcement Administration (DEA) with a scheduling recommendation
to place daridorexant and its salts in schedule IV of the Controlled
Substances Act (CSA). In accordance with the CSA, as amended by the
Improving Regulatory Transparency for New Medical Therapies Act, DEA is
hereby issuing an interim final rule placing daridorexant in schedule
IV, including its salts, isomers, and salts of isomers whenever the
existence of such salts, isomers, and salts of such isomers is possible
within the specific chemical designation, thereby facilitating the
commercial distribution of QUIVIVIQ as a lawful controlled substance.
DATES: The effective date of this rule is April 7, 2022. Comments must
be submitted electronically or postmarked on or before May 9, 2022.
Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after 11:59 p.m. Eastern
Time on the last day of the comment period.
Requests for hearing and waivers of an opportunity for a hearing or
to participate in a hearing must be received on or before May 9, 2022.
ADDRESSES: Interested persons may file written comments on this
rulemaking in accordance with 21 U.S.C. 811(j)(3) and 21 CFR
1308.43(g). To ensure proper handling of comments, please reference
``Docket No. DEA-949'' on all correspondence, including any
attachments.
Electronic comments: The Drug Enforcement Administration
(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. Please go to http://www.regulations.gov and follow the online instructions at that site for
submitting comments. Upon completion of your submission, you will
receive a Comment Tracking Number for your comment. Submitted comments
are not instantaneously available for public view on Regulations.gov.
If you have received a Comment Tracking Number, your comment has been
successfully submitted and there is no need to resubmit the same
comment.
Paper comments: Paper comments that duplicate electronic
submissions are not necessary and are discouraged. Should you wish to
mail a paper comment in lieu of an electronic comment, it should be
sent via regular or express mail to: Drug Enforcement Administration,
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, VA 22152.
Hearing requests: All requests for hearing and waivers of
participation, together with a written statement of position on the
matters of fact and law asserted in the hearing, must be sent to: Drug
Enforcement Administration, Attn: Hearing Clerk/OALJ, 8701 Morrissette
Drive, Springfield, Virginia 22152. All requests for hearing and
waivers of participation should also be sent to: (1) Drug Enforcement
Administration, Attn: Administrator, 8701 Morrissette Drive,
Springfield, Virginia 22152; and (2) Drug Enforcement Administration,
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug & Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. The Drug Enforcement Administration (DEA)
will make comments available, unless reasonable cause is given, for
public inspection online at http://www.regulations.gov. Such
information includes personal identifying information (such as your
name, address, etc.) voluntarily submitted by the commenter. The
Freedom of Information Act applies to all comments received. If you
want to submit personal identifying information (such as your name,
address, etc.) as part of your comment, but do not want DEA to make it
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 DEA to make it 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.
DEA will generally make available in publicly redacted form
comments containing personal identifying information and confidential
business information identified, as directed above. If a comment has so
much confidential business information or personal identifying
information that DEA cannot effectively redact it, DEA may not make
available publicly all or part of that comment. Comments posted to
http://www.regulations.gov may include any personal identifying
information (such as name, address, and phone number) included in the
text of your electronic submission that is not identified as
confidential as directed above.
An electronic copy of this document and supplemental information to
this interim final rule (IFR) are available at http://www.regulations.gov for easy reference.
Request for Hearing or Appearance; Waiver
Pursuant to 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. Interested persons may file requests for a hearing or
notices of intent to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(a) or (b), and such requests must
include a statement of the person's interests in the proceeding and the
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objections or issues, if any, concerning which the person desires to be
heard. 21 CFR 1316.47(a). Any interested person may file a waiver of an
opportunity for a hearing or to participate in a hearing together with
a written statement regarding the interested person's position on the
matters of fact and law involved in any hearing as set forth in 21 CFR
1308.44(c).
All requests for hearings and waivers of participation, together
with a written statement of position on the matters of fact and law
involved in such hearing, must be sent to DEA using the address
information provided above.
Background and Legal Authority
Under the Controlled Substances Act (CSA), as amended in 2015 by
the Improving Regulatory Transparency for New Medical Therapies Act
(section 2(b) of Pub. L. 114-89), DEA is required to commence an
expedited scheduling action with respect to certain new drugs approved
by the Food and Drug Administration (FDA). As provided in 21 U.S.C.
811(j), this expedited scheduling is required where both of the
following conditions apply: (1) The Secretary of the Department of
Health and Human Services (HHS) has advised DEA that an NDA has been
submitted for a drug that has a stimulant, depressant, or
hallucinogenic effect on the central nervous system (CNS), and that it
appears that such drug has an abuse potential; and (2) the Secretary
recommends that DEA control the drug in schedule II, III, IV, or V
pursuant to 21 U.S.C. 811(a) and (b). In these circumstances, DEA is
required to issue an IFR controlling the drug within 90 days.
Subsection (j)(2) states that the 90-day timeframe starts the later
of (1) the date DEA receives HHS' scientific and medical evaluation/
scheduling recommendation, or (2) the date DEA receives notice of the
NDA approval by HHS. Subsection (j)(3) specifies that the rulemaking
shall become immediately effective as an IFR without requiring DEA to
demonstrate good cause therefore. Thus, the purpose of subsection (j)
is to speed the process by which DEA schedules newly approved drugs
that are currently either in schedule I or not controlled (but which
have sufficient abuse potential to warrant control) so that such drugs
may be marketed without undue delay following FDA approval.\1\
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\1\ Given the parameters of subsection (j), in DEA's view, it
would not apply to a reformulation of a drug containing a substance
currently in schedules II through V for which an NDA has recently
been approved.
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Subsection (j)(3) further provides that the IFR shall give
interested persons the opportunity to comment and to request a hearing.
After the conclusion of such proceedings, DEA must issue a final rule
in accordance with the scheduling criteria of 21 U.S.C. 811(b) through
(d) and 812(b).
Daridorexant, chemically known as [(S)-2-(5-chloro-4-methyl-1H-
benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl](5-methoxy-2-(2H-1,2,3-
triazol-2-yl)phenyl)methanone, is a new molecular entity (NME) with CNS
activity. Daridorexant is a dual orexin receptor antagonist that
inhibits the orexin neuropeptide-induced activation of the orexin
receptor type 1 (OX1R) and orexin receptor type 2 (OX2R) subtypes.
Daridorexant shares chemical structure and pharmacological mechanism of
action with certain schedule IV CNS depressants such as suvorexant and
lemborexant.
On January 8, 2021, Idorsia Pharmaceuticals, Ltd (Sponsor)
submitted an NDA to FDA for QUIVIVIQ (daridorexant) tablets for use as
a treatment of adult patients with insomnia, characterized by
difficulties with sleep onset and/or sleep maintenance. On January 7,
2022, DEA received notification that FDA, on the same date, approved
this NDA. The recommended dosage is 25-50 mg once per night, taken
orally within 30 minutes before going to bed, with at least seven hours
remaining prior to planned awakening.
Determination To Schedule Daridorexant
On December 22, 2021, DEA received from HHS a scientific and
medical evaluation entitled ``Basis for the Recommendation to Control
Daridorexant and its Salts in schedule IV of the Controlled Substances
Act'' and a scheduling recommendation. Pursuant to 21 U.S.C. 811(b) and
(c), this document contained an eight-factor analysis of the abuse
potential, legitimate medical use, and dependence liability of
daridorexant, along with HHS's recommendation to control daridorexant
and its salts under schedule IV of the CSA.
In response, DEA reviewed the scientific and medical evaluation and
scheduling recommendation provided by HHS, along with all other
relevant data, and completed its own eight-factor review pursuant to 21
U.S.C. 811(c). DEA concluded that daridorexant meets the 21 U.S.C.
812(b)(4) criteria for placement in schedule IV of the CSA.
Pursuant to subsection 811(j), and based on HHS' scheduling
recommendation, the approval of the NDA by HHS/FDA, and DEA's
determination, DEA is issuing this IFR to schedule daridorexant as a
schedule IV controlled substance under the CSA.
Included below is a brief summary of each factor as analyzed by HHS
and DEA, and as considered by DEA in its scheduling action. Please note
that both DEA and HHS analyses are available in their entirety under
``Supporting Documents'' in the public docket for this interim final
rule at http://www.regulations.gov, under Docket Number ``DEA-949.''
Full analysis of, and citations to, the information referenced in the
summary may also be found in the supporting and related material.
1. Its Actual or Relative Potential for Abuse
Daridorexant is an NME that has not been marketed in the United
States or any country; evidence regarding its diversion, illicit
manufacturing, or deliberate ingestion is lacking. There are no reports
of law enforcement encounters of daridorexant in the National Forensic
Laboratory Information System (NFLIS) database.\2\ However,
daridorexant is related in action to schedule IV depressants such as
suvorexant and lemborexant. It is thus reasonable to assume that
daridorexant may be diverted from legitimate channels, used contrary to
or without medical advice, and otherwise abused so as to create hazards
to the users and to the safety of the community to an extent similar to
that of schedule IV CNS depressants. In clinical studies, daridorexant
produced abuse-related effects in humans similar to suvorexant and
zolpidem (schedule IV sedatives) and shares pharmacological mechanism
of action similar to suvorexant and lemborexant; thus, it is likely to
be abused for its sedative effects contrary to medical advice.
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\2\ NFLIS represents an important resource in monitoring illicit
drug trafficking, including the diversion of legally manufactured
pharmaceuticals into illegal markets. It systematically collects
results from drug chemistry analyses conducted by State and local
forensic laboratories. NFLIS data were queried on January 18, 2022.
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2. Scientific Evidence of Its Pharmacological Effects, if Known
Daridorexant shares pharmacological profiles with other dual orexin
receptor antagonists such as suvorexant and lemborexant, schedule IV
CNS depressants. Data from the orexin binding studies demonstrated that
daridorexant behaved as an insurmountable antagonist at the dual orexin
receptors (OXIR and OX2R).
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Daridorexant is similar to suvorexant in its potency and duration of
action at OX1R; however, it is more potent and has double the occupancy
time as suvorexant at OX2R.
In animal studies, oral doses of daridorexant (100, 300, and 1000
mg/kg) produced transient decrease in rectally measured body
temperature and increased incidence of whole-body tremors. Dose-
dependent decline in activity was observed in unstimulated rats. In a
study conducted to measure locomotor activity following daridorexant
administration, rats given single oral dose of 300 mg/kg showed decline
in locomotor activity when compared to the vehicle control group.
Daridorexant's reinforcing properties were assessed by determining
whether self-administration behavior was maintained when the drug was
substituted for cocaine. Data from this study showed that rats self-
administered cocaine (0.8 mg/kg/infusion), but doses of 0.1, 0.3, and 1
mg/kg/infusion of daridorexant produced a significantly lower mean
number of active lever presses.
A randomized, double-blind, double-dummy, active-and placebo-
controlled, 6-way cross-over study was conducted to determine the abuse
potential of single oral doses of daridorexant. Suvorexant (150 mg) and
Zolpidem (30 mg) served as the positive controls. Subjects received
daridorexant at therapeutic (50 mg) and supratherapeutic (100 and 150
mg) doses. Bipolar visual analog scale (VAS) for Drug-Liking (0-100)
served as the primary end. A score of 0 described a drug-disliking
response; a score of 50 represented a neutral response, while a score
of 100 described a strong drug liking. Drug liking scores following
supratherapeutic doses (100 and 150 mg) of daridorexant showed
statistically significant increases as compared to placebo on positive
subjective measures (VAS measures for Drug Liking, Take Drug Again,
Overall Drug Liking, High, and Good Drug Effects) and were
statistically similar to those following suvorexant and zolpidem.
Further, using a Drowsiness/Alertness VAS and an observer assessment of
alertness/sedation, daridorexant's sedative properties were assessed.
Both measures demonstrate that similar to suvorexant and zolpidem,
daridorexant elicits drowsiness and sedation.
Data from Phase 1 clinical safety studies showed that daridorexant
(5-200 mg) administered to 478 subjects produced somnolence in 52.7
percent (252), fatigue in 10.9 percent (52), and disturbances in
attention in 3.8 percent (18) of subjects, respectively. Daridorexant
at every dose produced somnolence at a rate that is 2- to 3-fold higher
than that reported in the placebo-treated group. In two Phase 2 studies
conducted to evaluate the efficacy and safety of daridorexant in
subjects with insomnia disorder (one with adults (aged 18-64 years) at
doses of 5-50 mg and the other with the elderly (>=65 years) at doses
of 10-50 mg), daridorexant treatment led to reports of somnolence that
exceeded reports of other effects that may be associated with abuse
potential, including fatigue (5 (2.1 percent)) and dizziness (3 (1.3
percent). In three Phase 3 studies, which were conducted as
confirmatory studies in adults and elderly subjects with insomnia
disorder and were similarly designed to the two Phase 2 studies, the
treatment-emergent adverse effects with the highest number of reports
were somnolence (38 (2.14 percent)), fatigue (34 (1.91 percent)), and
dizziness (26 (1.46 percent)). These types of reports were similar to
those reported in the Phase 1 and 2 studies. The reported adverse
events from the Phase 1, 2, and 3 studies demonstrate there were no
significant abuse-related signals in these studies.
Daridorexant, similar to schedule IV drugs such as suvorexant and
zolpidem, has sedative effects. In a human abuse potential (HAP) study,
daridorexant produced abuse-related effects in humans similar to those
of suvorexant and zolpidem. The abuse-related neuropharmacology profile
of daridorexant is similar to that of schedule IV CNS depressants, such
as suvorexant and lemborexant, and is consistent with its mechanism of
action as a dual orexin receptors antagonist.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance
Daridorexant, chemically known as [(S)-2-(5-chloro-4-methyl-1H-
benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl](5-methoxy-2-(2H-1,2,3-
triazol-2-yl)phenyl)methanone, is an NME. It is soluble in acidic water
and slightly soluble in ethanol. It has one stereoisomer with one
chiral center. The drug product is manufactured in tablet dose
strengths that contain 25 mg and 50 mg of the active ingredient (i.e.,
daridorexant) and a series of excipients to aid in taste and tablet
disintegration. The excipients in the tablet have no known abuse
liability. Daridorexant plasma exposure is dose proportional from 25 mg
to 50 mg with an absolute bioavailability of 62 percent, and has
consistent pharmacokinetic profile following multiple-dose and single-
dose administration with no accumulation.
As discussed in the background section, daridorexant has an
accepted medical use in the United States.
4. Its History and Current Pattern of Abuse
There is no information on the history and current pattern of abuse
for daridorexant, since it has not been marketed, legally or illegally,
in the United States or any country. There is no evidence of diversion
of daridorexant that has been distributed for research, such as for
clinical trials. Data from preclinical and clinical studies indicate
that the abuse potential of daridorexant is similar to that of schedule
IV CNS depressants such as suvorexant and lemborexant. Consistent with
the fact that daridorexant is an NME; NFLIS database had no records of
encounters by the law enforcement.
The pharmacological mechanism of action of daridorexant as a dual
orexin receptor antagonist suggests that its pattern of abuse would be
similar to schedule IV depressants with a similar mechanism of action,
such as suvorexant and lemborexant.
5. The Scope, Duration, and Significance of Abuse
Data from preclinical and clinical studies showed that daridorexant
has an abuse potential similar to that of the schedule IV depressants
such as suvorexant and zolpidem. Thus, daridorexant, similar to these
schedule IV substances, will have low potential for abuse relative to
drugs and substances in schedule III. A search by DEA of the NFLIS
database found no evidence of law enforcement encounters of
daridorexant in the United States. Because daridorexant has a mechanism
of action similar to schedule IV drugs suvorexant and lemborexant, it
is likely that upon availability of daridorexant in the market, it will
be abused similar to these schedule IV depressants.
6. What, if any, Risk There Is to the Public Health
The public health risk associated with daridorexant is largely due
to its abuse potential. Data from preclinical and clinical studies
showed that daridorexant has abuse potential similar to that of
schedule IV depressants zolpidem and suvorexant. Therefore, upon
availability for marketing, it is likely to pose a public health risk
to a degree similar to these schedule IV depressants. Data from
clinical trials showed that daridorexant has rewarding and depressant
effects. The abuse of daridorexant may present risks to the
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public health at a level similar to those associated with the abuse of
schedule IV CNS depressants.
7. Its Psychic or Physiological Dependence Liability
Data obtained from a HAP study demonstrate that similar to
suvorexant and zolpidem, daridorexant produced subjective responses to
measures such as Drug Liking, Overall Drug Liking, Good Drug Effects,
High, and Take Drug Again; indicative of psychological effects. HHS
states that the data suggest daridorexant can produce psychic
dependence similar to zolpidem and suvorexant, schedule IV depressants.
Results from a physiologic dependence study conducted in rats
demonstrate that oral doses (0, 20, or 200 mg/kg/day) of daridorexant
administered for 28-days followed by a 14-days discontinuation period
did not produce alterations in physiological, neurobehavioral, or
locomotor parameters during the discontinuation Phase of the study.
Physical dependence signs were not observed in clinical studies after
discontinuation of treatment in Phase 3 studies.
Data from animal studies and clinical trials demonstrate that
chronic administration of daridorexant did not produce withdrawal signs
or symptoms upon discontinuation. Daridorexant does not produce
physical dependence.
8. Whether the Substance Is an Immediate Precursor of a Substance
Already Controlled Under the CSA
Daridorexant is not an immediate precursor of any controlled
substance, as defined by 21 U.S.C. 802(23).
Conclusion: After considering the scientific and medical evaluation
and scheduling recommendation provided by HHS, and its own eight-factor
analysis, DEA has determined that these facts and all relevant data
constitute substantial evidence of potential for abuse of daridorexant.
As such, DEA hereby schedules daridorexant as a controlled substance
under the CSA.
Determination of Appropriate Schedule
The CSA lists 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 HHS and review of all available data,
the Administrator of DEA (Administrator), pursuant to 21 U.S.C.
812(b)(4), finds that:
(1) Daridorexant has a low potential for abuse relative to the
drugs or other substances in Schedule III.
Daridorexant, similar to schedule IV depressants such as suvorexant
and lemborexant, is an orexin receptor antagonist. It produced sedation
in general behavioral and locomotor studies. In a HAP study, oral
administration of therapeutic (50 mg) and supratherapeutic doses (100
and 150 mg) of daridorexant produced increases in positive subjective
measures such as Drug Liking, Overall Drug Liking, Good Drug Effects,
High, and Take Drug Again that were statistically greater than those
produced by placebo. These subjective responses following daridorexant
were statistically similar to those produced by the positive control
drugs that are schedule IV depressant such as zolpidem and suvorexant.
These data show that daridorexant has an abuse potential that is
similar to the schedule IV drugs zolpidem and suvorexant. Because
daridorexant is similar to suvorexant and zolpidem in its abuse
potential, daridorexant has a low potential for abuse relative to the
drugs or other substances in schedule III.
(2) Daridorexant has a currently accepted medical use in treatment
in the United States.
FDA recently approved the NDA for daridorexant as an oral treatment
for adult patients with insomnia characterized by difficulties with
sleep onset and/or sleep maintenance. Thus, daridorexant has a
currently accepted medical use in treatment in the United States.
(3) Abuse of daridorexant may lead to limited physical dependence
or psychological dependence relative to the drugs or other substances
in schedule III.
Data from both preclinical and clinical studies demonstrate that
discontinuation of daridorexant was not associated with withdrawal
symptoms indicative of physical dependence. Because daridorexant
produced positive subjective responses in a HAP study similar to those
of zolpidem and suvorexant (both schedule IV drugs), it is likely that
daridorexant can produce psychic dependence to an extent that is
similar to these schedule IV substances. Thus, abuse of daridorexant
may lead to limited physical or psychological dependence relative to
the drugs or other substances in schedule III.
Based on these findings, the Administrator concludes that
daridorexant warrants control in schedule IV of the CSA. 21 U.S.C.
812(b)(4).
Requirements for Handling Daridorexant
Daridorexant is subject to the CSA's schedule IV regulatory
controls and administrative, civil, and criminal sanctions applicable
to the manufacture, distribution, reverse distribution, dispensing,
importing, exporting, research, and conduct of instructional activities
and chemical analysis with, and possession involving schedule IV
substances, including the following:
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, dispenses, imports, exports, engages in research,
or conducts instructional activities or chemical analysis with, or
possesses), or who desires to handle, daridorexant must be registered
with 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 or intends to handle daridorexant and is
not registered with DEA must submit an application for registration and
may not continue to handle daridorexant unless DEA has approved that
application, pursuant to 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312. These registration
requirements, however, are not applicable to patients (end users) who
possess daridorexant pursuant to a lawful prescription.
2. Disposal of stocks. Any person unwilling or unable to obtain a
schedule IV registration must surrender all quantities of currently
held daridorexant, or may transfer all quantities of currently held
daridorexant to a person registered with DEA. Daridorexant is required
to be disposed of in accordance with 21 CFR part 1317, in addition to
all other applicable Federal, state, local, and tribal laws.
3. Security. Daridorexant is subject to schedule III-V security
requirements for DEA registrants and it must be handled and stored in
accordance with 21 CFR 1301.71-1301.77. Non-practitioners handling
daridorexant must also comply with the employee screening requirements
of 21 CFR 1301.90-1301.93. These requirements, however, are not
applicable to patients (end users) who possess daridorexant pursuant to
a lawful prescription.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of daridorexant must comply with 21 U.S.C. 825
and 958(e), and be in accordance with 21 CFR part 1302.
5. Inventory. Every DEA registrant who possesses any quantity of
[[Page 20317]]
daridorexant must take an inventory of daridorexant on hand, pursuant
to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03,
1304.04, and 1304.11(a) and (d).
Any person who registers with DEA to handle daridorexant must take
an initial inventory of all stocks of controlled substances (including
daridorexant) on hand on the date the registrant first engages in the
handling of controlled substances, pursuant to 21 U.S.C. 827 and
958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a)
and (b).
After the initial inventory, every DEA registrant must take an
inventory of all stocks of controlled substances (including
daridorexant) on hand every two years, pursuant to 21 U.S.C. 827 and
958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
These requirements, however, are not applicable to patients (end users)
who possess daridorexant pursuant to a lawful prescription.
6. Records and Reports. DEA registrants must maintain records and
submit reports for daridorexant, pursuant to 21 U.S.C. 827, 832(a), and
958(e), and in accordance with 21 CFR 1301.74(b) and (c) and parts
1304, 1312, and 1317.
7. Prescriptions. All prescriptions for daridorexant, or products
containing daridorexant, must comply with 21 U.S.C. 829, and be issued
in accordance with 21 CFR parts 1306 and 1311, subpart C.
8. Manufacturing and Distributing. In addition to the general
requirements of the CSA and DEA regulations that are applicable to
manufacturers and distributors of schedule IV controlled substances,
such registrants should be advised that (consistent with the foregoing
considerations) any manufacturing or distribution of daridorexant may
only be for the legitimate purposes consistent with the drug's
labeling, or for research activities authorized by the Federal Food,
Drug, and Cosmetic Act (FDCA), as applicable, and the CSA.
9. Importation and Exportation. All importation and exportation of
daridorexant must comply with 21 U.S.C. 952, 953, 957, and 958, and in
accordance with 21 CFR part 1312.
10. Liability. Any activity involving daridorexant not authorized
by, or in violation of, the CSA or its implementing regulations, is
unlawful, and may subject the person to administrative, civil, and/or
criminal sanctions.
Regulatory Analyses
Administrative Procedure Act
Section 553 of the APA (5 U.S.C. 553) generally requires notice and
comment for rulemakings. However, 21 U.S.C. 811(j) provides that in
cases where a certain new drug is (1) approved by HHS, under section
505(c) of the FDCA and (2) HHS recommends control in CSA schedule II-V,
DEA shall issue an IFR scheduling the drug within 90 days. As stated in
the legal authority section, the 90-day time frame is the later of: (1)
The date DEA receives HHS's scientific and medical evaluation/
scheduling recommendation, or (2) the date DEA receives notice of the
NDA approval by HHS. Additionally, subsection (j) specifies that the
rulemaking shall become immediately effective as an IFR without
requiring DEA to demonstrate good cause.
Executive Orders 12866 (Regulatory Planning and Review) and 13563
(Improving Regulation and Regulatory Review)
In accordance with 21 U.S.C. 811(a) and (j), this 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 (E.O.) 12866 and the
principles reaffirmed in E.O. 13563.
Executive Order 12988, Civil Justice Reform
This regulation meets the applicable standards set forth in
sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors
and ambiguity, minimize litigation, provide a clear legal standard for
affected conduct, and promote simplification and burden reduction.
Executive Order 13132, Federalism
This rulemaking does not have federalism implications warranting
the application of E.O. 13132. The rule does 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.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This rule does not have tribal implications warranting the
application of E.O. 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 Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to
rules that are subject to notice and comment under section 553(b) of
the APA. As noted in the above discussion regarding the applicability
of the APA, DEA is not required to publish a general notice of proposed
rulemaking. Consequently, the RFA does not apply to this IFR.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., DEA has determined 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 annually for
inflation) in any 1 year.'' Therefore, neither a Small Government
Agency Plan nor any other action is required under UMRA of 1995.
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.
Congressional Review Act
This rule is not a major rule as defined by the Congressional
Review Act (CRA), 5 U.S.C. 804. However, pursuant to the CRA, DEA is
submitting a copy of this IFR to both Houses of Congress and to the
Comptroller General.
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, DEA amends 21 CFR part 1308 as
follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for 21 CFR part 1308 continues to read as
follows:
[[Page 20318]]
Authority: 21 U.S.C. 811, 812, 871(b), 956(b) unless otherwise
noted.
0
2. In Sec. 1308.14:
0
a. Redesignate paragraphs (c)(16) through (58) as (c)(17) through (59);
and
0
b. Add new paragraph (c)(16).
0
The addition reads as follows:
Sec. 1308.14 Schedule IV.
* * * * *
(c) * * *
(16) Daridorexant............................................... 2410
* * * * *
Anne Milgram,
Administrator.
[FR Doc. 2022-07322 Filed 4-6-22; 8:45 am]
BILLING CODE 4410-09-P