Schedules of Controlled Substances: Placement of Lemborexant in Schedule IV, 19387-19391 [2020-07089]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 85, Number 67 (Tuesday, April 7, 2020)]
[Rules and Regulations]
[Pages 19387-19391]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-07089]



[[Page 19387]]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-600]


Schedules of Controlled Substances: Placement of Lemborexant in 
Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Interim final rule with request for comments.

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SUMMARY: On December 20, 2019, the U.S. Food and Drug Administration 
approved a new drug application for Dayvigo (lemborexant) tablets for 
oral use. Lemborexant is chemically known as (1R,2S)-2-[(2,4-
dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-N-(5-
fluoropyridin-2-yl)cyclopropane-1-carboxamide. The Department of Health 
and Human Services provided the Drug Enforcement Administration (DEA) 
with a scheduling recommendation to place lemborexant 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 
lemborexant, including its salts, isomers, and salts of isomers 
whenever the existence of such salts, isomers, and salts of isomers is 
possible, in schedule IV of the CSA.

DATES: The effective date of this rulemaking is April 7, 2020. 
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). Electronic 
comments must be submitted, and written comments must be postmarked, on 
or before May 7, 2020. 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.
    Interested persons may file a request for hearing or waiver of 
hearing in accordance with
    21 U.S.C. 811(j)(3) and 21 CFR 1308.44. Requests for hearing and 
waivers of an opportunity for a hearing or to participate in a hearing, 
together with a written statement of position on the matters of fact 
and law asserted in the hearing, must be received on or before May 7, 
2020.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-600'' 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 https://www.regulations.gov and follow the online instructions at the site for 
submitting comments. Upon completion of your submission, you will 
receive a Comment Tracking Number for your comment. Please be aware 
that 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 the 
electronic submission 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 regarding his position 
on the matter of fact and law involved in such hearing, must be sent 
to: Drug Enforcement Administration. Attn: Administrator, 8701 
Morrissette Drive, Springfield, Virginia 22152. All requests for 
hearing and waivers of participation should also be sent to: (1) Drug 
Enforcement Administration, Attn: Hearing Clerk/LJ. 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: Scott A. Brinks, Regulatory Drafting 
and Policy Support Section, Diversion Control Division, Drug 
Enforcement Administration; Mailing Address: 8701 Morrissette Drive, 
Springfield, Virginia 22152; Telephone: (571) 362-3261.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

    Please note that all comments received are considered part of the 
public record. They will, unless reasonable cause is given, be made 
available by the Drug Enforcement Administration (DEA) for public 
inspection online at https://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 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.
    Comments containing personal identifying information and 
confidential business information identified as directed above will 
generally be made publicly available in redacted form. If a comment has 
so much confidential business information or personal identifying 
information that it cannot be effectively redacted, all or part of that 
comment may not be made publicly available. Comments posted to https://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 directed above as 
confidential.
    An electronic copy of this document and supplemental information, 
including the complete Department of Health and Human Services (HHS) 
and DEA eight-factor analyses, to this interim final rule are available 
at https://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 include a statement of 
interest in the proceeding and the objections or issues, if any,

[[Page 19388]]

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 a hearing 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 Improving Regulatory Transparency for New Medical 
Therapies Act, Public Law 114-89, 2(b), 129 tat. 700 (2015), 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 HHS 
has advised DEA that a New Drug Application (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 of HHS 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 interim final rule controlling the drug within 90 days.
    The law further states that the 90-day timeframe starts the later 
of: (1) The date DEA receives HHS' scientific and medical evaluation 
and scheduling recommendation, or (2) the date DEA receives notice of 
the NDA approval by HHS. In addition, the law specifies that the 
rulemaking shall become immediately effective as an interim final rule 
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 parameter 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) further provides that the interim final rule 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 subsections 21 
U.S.C. 811(b), (c), and (d) and 21 U.S.C. 812(b).
    Lemborexant [(1R,2S)-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-2-
(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropane-1-carboxamide] is 
a new molecular entity with CNS depressant properties. Lemborexant acts 
as an antagonist at both orexin-1 and orexin-2 receptors (OX1R and 
OX2R, respectively). On December 27, 2018, Eisai, Inc., submitted an 
NDA for Dayvigo (lemborexant), 5 and 10 mg oral tablets, with the 
proposed dosage suggestion of 5 mg, not to exceed a maximum dose of 10 
mg once a day. On March 9, 2020, DEA received a letter from FDA, dated 
March 5, 2020, notifying DEA that FDA, on December 20, 2019, approved 
the NDA for Dayvigo (lemborexant), under section 505(c) of the Federal 
Food, Drug, and Cosmetic Act (FDCA), for the treatment of adult 
patients with insomnia, characterized by difficulties with sleep onset 
and/or sleep maintenance.\2\ Lemborexant has not been marketed in any 
other country for any medical indication.
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    \2\ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/212028Orig1s000ltr.pdf, accessed March 11, 2020.
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Determination To Schedule Lemborexant

    On January 9, 2020, DEA received from HHS a scientific and medical 
evaluation (dated December 19, 2019) entitled ``Basis for the 
Recommendation to Control Lemborexant 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 lemborexant, along with HHS's recommendation to 
control lemborexant 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 lemborexant 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's recommendation, 
the NDA approval by HHS/FDA, and DEA's determination, DEA is issuing 
this interim final rule to schedule lemborexant 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 https://www.regulations.gov, under Docket Number ``DEA-600.'' 
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

    As noted by HHS, lemborexant is a new molecular entity that has not 
been marketed in the United States or any other country. Thus, evidence 
regarding its diversion, illicit manufacture, or deliberate ingestion 
is currently lacking. DEA notes that there are no reports for 
lemborexant in the National Forensic Laboratory Information System 
(NFLIS),\3\ which collects drug identification results from drug cases 
submitted to and analyzed by state and local forensic laboratories. 
There were also no reports in STARLiMS,\4\ DEA's laboratory drug 
evidence data system of record.
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    \3\ NFLIS represents an important resource in monitoring illicit 
drug trafficking, including the diversion of legally manufactured 
pharmaceuticals into illegal markets. NFLIS is a comprehensive 
information system that includes data from forensic laboratories 
that handle more than 96% of an estimated 1.0 million distinct 
annual State and local drug analysis cases. NFLIS includes drug 
chemistry results from completed analyses only. While NFLIS data is 
not direct evidence of abuse, it can lead to an inference that a 
drug has been diverted and abused. See 76 FR 77330, 77332, Dec. 12, 
2011. NFLIS data were queried January 15, 2020.
    \4\ On October 1, 2014, DEA implemented STARLiMS (a web-based, 
commercial laboratory information management system) to replace the 
System to Retrieve Information from Drug Evidence (STRIDE) as its 
laboratory drug evidence data system of record. DEA laboratory data 
submitted after September 30, 2014, are reposited in STARLiMS. 
STARLiMS data were queried January 15, 2020.
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    As stated by HHS, lemborexant is a sedative that is highly 
selective for both the OX1R and OX2R receptors and has little to no 
affinity to other CNS receptor sites associated with abuse potential. 
In a clinical study investigating the abuse potential of lemborexant, 
HHS concluded that lemborexant produced subjective responses that were 
similar to those for the schedule IV sedative suvorexant.

[[Page 19389]]

2. Scientific Evidence of Its Pharmacological Effects, if Known

    According to HHS, lemborexant primarily acts as a dual orexin 
receptor antagonist and does not bind with any other CNS receptors that 
are typically associated with abuse, such as opioid or cannabinoid 
receptors, GABAergic, and other ion channels. According to HHS, general 
behavioral studies in animals indicate that acute oral administration 
of lemborexant using supratherapeutic doses (100, 300, and 1000 mg/kg), 
produced no overt behavioral changes in hindlimb foot splay, forelimb 
grip strength, hindlimb grip strength, and rectal temperature in cage-
side, hand-held, and open-field using functional observational methods. 
Additionally, lemborexant, even at supratherapeutic doses, does not 
significantly impair motor coordination. In drug discrimination 
studies, which are used to predict subjective effects in humans, 
lemborexant and suvorexant (a schedule IV substance which is another 
known dual orexin receptor antagonist) did not fully mimic stimulus 
effects of zolpidem, a schedule IV sedative. In a self-administration 
study in rhesus monkeys, the rewarding effects of lemborexant were 
insufficient to produce reinforcement.
    According to HHS, in a human abuse potential (HAP) study conducted 
by the Sponsor, lemborexant (at therapeutic and supratherapeutic doses) 
produced statistically significant increases on positive subjective 
measures in the bipolar visual analog scale (VAS) (i.e., Drug Liking, 
Overall Drug Liking, Good Effects, High, Stoned, and Take Drug Again) 
that were greater than placebo and statistically similar to suvorexant 
and/or zolpidem (schedule IV substances). With respect to two 
subjective measures, such as drowsiness and sedation, lemborexant, 
similar to zolpidem and suvorexant, produced statistically 
significantly greater scores than placebo. HHS concluded that 
lemborexant produces positive subjective effects and has an abuse 
potential similar to that of schedule IV sedatives, such as suvorexant 
and zolpidem, which were used as positive controls in the 
aforementioned study. According to HHS, in multiple-dose Phase I 
studies, lemborexant produced dose-dependent ``abnormal dreams.'' There 
were few incidents of abuse-related adverse events (AEs), such as 
``euphoric mood,'' ``disturbance in attention,'' and ``memory 
impairment.'' Furthermore, in Phase 2 clinical studies, lemborexant 
produced dose dependent somnolence. This response was considered 
appropriate given the proposed therapeutic use for lemborexant as a 
treatment for insomnia. No additional abuse-related AEs were reported 
by participants at an incidence greater than 1.0 percent. As per the 
adverse event data obtained from Phase 1 and Phase \2/3\ clinical 
safety and efficacy trials, there were no significant abuse-related 
signals.

3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance

    Lemborexant is a new molecular entity, chemically known as (1R,2S)-
2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-2-(3-fluorophenyl)-N-(5-
fluoropyridin-2-yl)cyclopropane-1-carboxamide. It is nearly insoluble 
in water and heptane; ``sparingly'' soluble in 1-octanol; very soluble 
in dimethyl sulfoxide; and freely soluble in methanol, acetone, ethyl 
acetate, and benzyl alcohol. Additionally, lemborexant is soluble in 
acetonitrile and ethanol. On December 20, 2019, FDA approved an NDA for 
lemborexant for medical use for the treatment of insomnia in adult 
patients with insomnia characterized by difficulties with sleep onset 
and/or sleep maintenance. Thus, lemborexant has an accepted medical use 
in the United States. Lemborexant will be marketed as a once daily 
tablet taken before bedtime, with at least 7 hours remaining before the 
planned time of awakening. The recommended dose for lemborexant is 5 
mg; however, the dosage may be increased to 10 mg based on clinical 
response and tolerability.\5\
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    \5\ https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212028s000lbl.pdf, accessed February 6, 2020.
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4. Its History and Current Pattern of Abuse

    There is no information available relating to the history and 
current pattern of abuse of lemborexant because this drug is not 
currently marketed in any country. As stated in Factor 1, DEA notes 
that there has been no diversion of lemborexant based on NFLIS and 
STARLiMS data. HHS notes that lemborexant produces abuse-related 
signals and abuse potential similar to that of the schedule IV 
controlled substance suvorexant.

5. The Scope, Duration, and Significance of Abuse

    Lemborexant as a single active ingredient in a drug product is 
currently not marketed in any country. Thus, information on the scope, 
duration, and significance of abuse for lemborexant is lacking. As 
described in Factor 4, NFLIS and STARLiMS databases have no evidence of 
law enforcement encounters of lemborexant. However, as HHS notes, data 
from preclinical and clinical studies summarized in Factor 2 indicate 
that the scope, duration, and significance of abuse for lemborexant 
would be similar to those of suvorexant, a schedule IV substance. As 
stated by HHS, data from animal and human studies indicate that 
lemborexant has an abuse potential similar to that of suvorexant.

6. What, if Any, Risk There Is to the Public Health

    As stated by HHS, the public health risk associated with 
lemborexant is largely a risk to the individual due to its abuse 
potential. The extent of abuse potential of a drug is an indication of 
its public health risk. Data from the preclinical and clinical studies 
suggest that the abuse potential of lemborexant is similar to schedule 
IV substances, such as suvorexant and zolpidem. Lemborexant, similar to 
schedule IV sedatives, is likely to pose a public health risk of abuse 
upon marketing in the United States.

7. Its Psychic or Physiological Dependence Liability

    Physical dependence for lemborexant was tested in a rat physical 
dependence study and during Phase \2/3\ clinical trials. Based on the 
data from these studies, HHS concluded that lemborexant lacked physical 
dependence potential. According to HHS, in the HAP study (presented in 
Factor 2), lemborexant administration was associated with positive 
subjective effects as assessed by participant responses to measures of 
Drug Liking, Overall Drug Liking, Good Drug Effects, High, Stoned, and 
Take Drug Again. The results indicated that the responses for 
lemborexant were similar to that of positive control drugs, such as 
zolpidem and suvorexant. Thus, it is likely that lemborexant can 
produce psychic dependence similar to that of schedule IV drugs, such 
as zolpidem and suvorexant.

8. Whether the Substance Is an Immediate Precursor of a Substance 
Already Controlled Under the CSA

    Lemborexant is not an immediate precursor of any controlled 
substance, as defined in 21 U.S.C. 802(23).

Conclusion

    After considering the scientific and medical evaluation conducted 
by HHS, HHS's recommendation, and its own eight-factor analysis, DEA 
has determined that these facts and all

[[Page 19390]]

relevant data constitute substantial evidence of a potential for abuse 
of lemborexant. As such, DEA hereby schedules lemborexant 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 Acting Administrator of DEA, pursuant to 21 U.S.C. 812(b)(4), finds 
that:
    1. Lemborexant has a low potential for abuse relative to the drugs 
or other substances in schedule III.
    Lemborexant is a dual orexin receptor antagonist, which produces 
sedation in human behavioral studies. In the HAP study, therapeutic and 
supratherapeutic doses of lemborexant produced positive subjective 
responses such as Drug Liking, Overall Drug Liking, Good Drug Effects, 
High, Stoned, and Take Drug Again that were statistically significantly 
greater than those produced by placebo. These responses of lemborexant 
are similar to those produced by schedule IV drugs suvorexant and 
zolpidem. Because lemborexant is similar to zolpidem and suvorexant in 
its abuse potential, lemborexant has a low potential for abuse relative 
to the drugs and other listed substances in schedule III of the CSA.
    2. Lemborexant has a currently accepted medical use in the United 
States.
    FDA recently approved lemborexant oral tablets for the treatment of 
adult patients with insomnia, characterized by difficulties with sleep 
onset and/or sleep maintenance. Thus, lemborexant has a currently 
accepted medical use in treatment in the United States.
    3. Lemborexant may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
schedule III.
    As stated by HHS, data from a rat physical dependence study, as 
well as a physical dependence assessment at the conclusion of the Phase 
\2/3\ clinical trials, showed that lemborexant did not produce 
withdrawal symptoms indicative of physical dependence. In the HAP 
study, lemborexant produced positive subjective responses to measures 
such as Drug Liking, Overall Drug Liking, Good Drug Effects, High, 
Stoned, and Take Drug Again that were greater than placebo and similar 
to that of the schedule IV drugs zolpidem and suvorexant. This data 
suggests that lemborexant can produce psychic dependence to a similar 
extent as zolpidem and suvorexant. Thus, abuse of lemborexant may lead 
to limited psychological dependence relative to the drugs or other 
substances in schedule III of the CSA.
    Based on these findings, the Acting Administrator of DEA concludes 
that lemborexant warrants control in schedule IV of the CSA. 21 U.S.C. 
812(b)(4).

Requirements for Handling Lemborexant

    Lemborexant 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) lemborexant, or who desires to handle lemborexant, 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 lemborexant 
and is not registered with DEA must submit an application for 
registration and may not continue to handle lemborexant, unless DEA has 
approved that application for registration, pursuant to 21 U.S.C. 822, 
823, 957, and 958, and in accordance with 21 CFR parts 1301 and 1312.
    2. Disposal of stocks. Any person who does not desire or is not 
able to maintain a schedule IV registration must surrender all 
quantities of currently held lemborexant or may transfer all quantities 
of lemborexant to a person registered with DEA in accordance with 21 
CFR part 1317, in additional to all other applicable Federal, State, 
local, and tribal laws.
    3. Security. Lemborexant is subject to schedule III-V security 
requirements and must be handled and stored in accordance with 21 CFR 
1301.71-1301.77. Non-practitioners handling lemborexant must also 
comply with the employee screening requirements of 1301.90-1301.93.
    4. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of lemborexant 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 
lemborexant must take an inventory of lemborexant on hand, pursuant to 
21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04, 
and 1304.11.
    Any person who becomes registered with DEA to handle lemborexant 
must take an initial inventory of all stocks of controlled substances 
(including lemborexant) 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.
    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including 
lemborexant) on hand at least 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.
    6. Records and Reports. DEA registrants must maintain records and 
submit reports for lemborexant, 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 lemborexant, or products 
containing lemborexant, 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 lemborexant may 
only be for the legitimate purposes consistent with the drug's 
labeling, or for research activities authorized by the FDCA and the 
CSA.
    9. Importation and Exportation. All importation and exportation of 
lemborexant must be in compliance with 21 U.S.C. 952, 953, 957, and 
958, and in accordance with 21 CFR part 1312.
    10. Liability. Any activity involving lemborexant 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

[[Page 19391]]

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 interim final rule 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, the law specifies that 
the rulemaking shall become immediately effective as an interim final 
rule without requiring DEA to demonstrate good cause.

Executive Orders 12866, 13563, and 13771, Regulatory Planning and 
Review, Improving Regulation and Regulatory Review, and Reducing 
Regulation and Controlling Regulatory Costs

    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 12866 and the principles 
reaffirmed in Executive Order 13563.
    This interim final rule is not an Executive Order 13771 regulatory 
action pursuant to Executive Order 12866 and OMB guidance.\6\
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    \6\ Office of Mgmt. & Budget, Exec. Office of The President, 
Interim Guidance Implementing Section 2 of the Executive Order of 
January 30, 2017 Titled ``Reducing Regulation and Controlling 
Regulatory Costs'' (Feb. 2, 2017).
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Executive Order 12988, Civil Justice Reform

    This 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 
burden reduction.

Executive Order 13132, Federalism

    This rulemaking does not have federalism implications warranting 
the application of Executive Order 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 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 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. Under 21 U.S.C. 811(j), DEA is not required to publish a 
general notice of proposed rulemaking. Consequently, the RFA does not 
apply to this interim final rule.

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. This rule will not result in: An annual 
effect on the economy of $100 million or more; a major increase in 
costs or prices for consumers, individual industries, Federal, State, 
or local government agencies, or geographic regions; or significant 
adverse effects on competition, employment, investment, productivity, 
innovation, or on the ability of United States-based companies to 
compete with foreign-based companies in domestic and export markets. 
However, pursuant to the CRA, DEA has submitted a copy of this interim 
final rule 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:

    Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise 
noted.


0
2. Amend Sec.  1308.14 by:
0
a. Redesignating paragraphs (c)(30) through (c)(56) as (c)(31) through 
(c)(57); and
0
b. Adding new paragraph (c)(30).
    The addition reads as follows:


Sec.  1308.14  Schedule IV.

* * * * *
    (c) * * *

 
 
 
(30) Lemborexant...............................................     2245
 

* * * * *

Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-07089 Filed 4-6-20; 8:45 am]
BILLING CODE 4410-09-P