[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.
    <bullet> 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.
    <bullet> 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.
    <bullet> 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

[[Page 20314]]

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]
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