[Federal Register Volume 85, Number 47 (Tuesday, March 10, 2020)]
[Rules and Regulations]
[Pages 13741-13746]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-04963]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-581]
Schedules of Controlled Substances: Placement of Cenobamate in
Schedule V
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Interim final rule, with request for comments.
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SUMMARY: On November 21, 2019, the U.S. Food and Drug Administration
(FDA) approved a new drug application for XCOPRI (cenobamate) tablets.
Cenobamate is chemically known as [(1R)-1-(2-chlorophenyl)-2-(tetrazol-
2-yl)ethyl] carbamate. Thereafter, the Department of Health and Human
Services provided the Drug Enforcement Administration (DEA) with a
scheduling recommendation to place cenobamate in schedule V of the
Controlled Substances Act (CSA). In accordance with the CSA, as revised
by the Improving Regulatory Transparency for New Medical Therapies Act,
DEA is hereby issuing an interim final rule placing cenobamate,
including its salts, in schedule V of the CSA.
DATES: The effective date of this rulemaking is March 10, 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 April 9, 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 pursuant to 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 must be received on or before April 9, 2020.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-581'' on all correspondence, including any
attachments.
Electronic comments: The Drug Enforcement Administration
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. 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 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 Brinks, 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 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 (FOIA) applies to all comments received. If you want to
[[Page 13742]]
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 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 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 http://www.regulations.gov for easy reference.
Request for Hearing, Notice of Appearance at Hearing, or Waiver of
Participation in Hearing
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,
concerning which the person desires to be heard. 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 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 (Pub. L. 114-89), which was signed into law on November
25, 2015, DEA is required to commence an expedited scheduling action
with respect to certain new drugs approved by the United States 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
(Secretary of HHS or the Secretary) has advised DEA that a New Drug
Application (NDA) has been approved 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 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/
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 therefor. 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) 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).
Cenobamate is a new molecular entity with CNS depressant
properties, and is chemically known as [(1R)-1-(2-chlorophenyl)-2-
(tetrazol-2-yl)ethyl] carbamate. Cenobamate is a voltage-gated sodium
channel (NaV) blocker that also has gamma-aminobutyric acid
(GABA)-A channel positive allosteric modulator (PAM) activity. On
November 21, 2018, SK Life Science (Sponsor) submitted an NDA to FDA
for XCOPRI (cenobamate) 12.5, 25, 50, 100, 150, and 200 mg oral
tablets. On November 22, 2019, DEA received notification from HHS that
FDA, on November 21, 2019, approved the NDA for XCOPRI (cenobamate)
under section 505(c) of the Federal Food, Drug, and Cosmetic Act
(FDCA), for the treatment of partial-onset seizures in adult patients.
Determination to Schedule Cenobamate
Pursuant to 21 U.S.C. 811(a)(1), proceedings to add a drug or
substance to those controlled under the CSA may be initiated by request
of the Secretary of HHS.\2\ On December 10, 2019, DEA received from HHS
a scientific and medical evaluation document (dated December 3, 2019)
prepared by FDA, titled ``Basis for the Recommendation to Control
Cenobamate and Its Salts in Schedule V of the Controlled Substances
Act.'' Pursuant to 21 U.S.C. 811(b) and (c), this document contained an
eight-factor analysis of the abuse potential of cenobamate, along with
HHS' recommendation to control cenobamate under schedule V of the CSA.
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\2\ As set forth in a memorandum of understanding entered into
by HHS, FDA, and the National Institute on Drug Abuse (NIDA), FDA
acts as the lead agency within HHS in carrying out the Secretary's
scheduling responsibilities under the CSA, with the concurrence of
NIDA. 50 FR 9518, Mar. 8, 1985. The Secretary of HHS has delegated
to the Assistant Secretary for Health of HHS the authority to make
domestic drug scheduling recommendations. 58 FR 35460, July 1, 1993.
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On January 15, 2020, DEA received from HHS a supplemental letter
(dated January 15, 2020) clarifying factors 6 and 7 listed in 21 U.S.C.
811(c), as well as the third finding under 21 U.S.C. 812(b)(5), to
control cenobamate in schedule V. This letter did not change HHS'
overall recommendation to place cenobamate in schedule V.
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 document
pursuant to 21 U.S.C. 811(c). DEA concluded that cenobamate
[[Page 13743]]
met the 21 U.S.C. 812(b)(5) criteria for placement in schedule V of the
CSA.
Pursuant to subsection 811(j), and based on HHS recommendation, NDA
approval by HHS/FDA, and DEA's determination, DEA is issuing this
interim final rule to schedule cenobamate as a schedule V 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-581.''
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: Cenobamate is a new
molecular entity and is not currently available or marketed in any
country. Evidence regarding its diversion, illicit manufacturing, or
deliberate ingestions is currently lacking. However, as reported by
HHS, preclinical studies show that cenobamate shares similar mechanisms
of action as substances in schedules IV or V. Cenobamate, like the
schedule V substance lacosamide, is a voltage-gated sodium channel
(Nav) blocker. In addition, cenobamate, like the schedule IV
substances alprazolam, chlordiazepoxide, and midazolam, has gamma-
aminobutyric acid (GABA)-A channel positive allosteric modulator (PAM)
activity and increases the effects of the inhibitory neurotransmitter,
GABA. Data obtained from general behavioral studies demonstrate that
cenobamate produces abuse-related CNS activity. In a preclinical drug
discrimination study in rats, cenobamate mimicked the discriminative
stimulus effects of the schedule IV substance chlordiazepoxide.
However, in a separate drug discrimination study, cenobamate only
partially mimicked the discriminative stimulus effects of the schedule
IV substance midazolam. In addition, cenobamate, like midazolam,
produced reinforcing effects in a rat self-administration assay by
significantly increasing the number of infusions compared to saline
infusions. In human abuse potential (HAP) studies, cenobamate produced
drug-liking visual analog scale scores that were significantly higher
compared to placebo but significantly lower than the schedule IV
substance alprazolam. Thus, these studies demonstrate that cenobamate
produced behavioral effects in rats comparable to that of schedule IV
substances (i.e., similar to chlordiazepoxide but less than midazolam);
whereas in humans, cenobamate produced drug-liking effects that were
significantly less than that of the schedule IV substance alprazolam.
Thus, cenobamate likely has abuse potential less than that of schedule
IV substances but similar to that of schedule V substances of the CSA.
Based on the totality of the available scientific data, HHS concluded
that cenobamate has an abuse potential similar to that of substances in
schedule V of the CSA.
2. Scientific Evidence of Its Pharmacological Effects, if Known:
Cenobamate shares similar mechanisms of action to substances in
schedule IV or V and has anti-epileptic activity in humans. Cenobamate,
like the schedule V substance lacosamide, is a voltage-gated sodium
channel blocker. In addition, cenobamate, like the schedule IV
benzodiazepines chlordiazepoxide, midazolam, and alprazolam, is a GABA-
A channel positive allosteric modulator. Cenobamate and other GABAergic
substances interact directly with the GABA-A receptor which is a
ligand-gated chloride ion channel consisting of five subunits and a
central chloride channel to enhance the opening of the ligand-gated
chloride channel and the influx of chloride. Cenobamate's ability to
bind to GABA-A receptors and sodium channel sites is consistent with
the action of anti-epileptic or sedative drugs, such as
chlordiazepoxide, midazolam, alprazolam, and lacosamide (schedule IV or
V substances).
As described in HHS' review document, studies evaluating
cenobamate's effect in these general behavioral studies showed that
cenobamate mimicked or partially mimicked substances such as
chlordiazepoxide, alprazolam, or midazolam (schedule IV substances) in
producing behaviors that are associated with abuse. In an in vivo drug
discrimination study in rats, cenobamate produced chlordiazepoxide-like
(schedule IV) discriminative stimulus effects. In a separate drug
discrimination study, cenobamate produced discriminative stimulus
effects that partially mimicked the effects of the schedule IV
substance midazolam. In self-administration studies, cenobamate was
self-administered by rodents, but the self-administration (i.e., number
of infusions) of cenobamate was lower than that of midazolam, a
schedule IV substance. In HAP studies, cenobamate produced drug-liking
scores higher than placebo but less than that of the schedule IV
substance alprazolam. Based on these studies, HHS concluded that
cenobamate has mechanisms of actions that are similar to that of
substances in schedule IV or V but the abuse potential of cenobamate is
less than that of alprazolam, a schedule IV substance.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: Cenobamate is a new molecular entity. It is chemically
known as [(1R)-1-(2-chlorophenyl)-2-(tetrazol-2-yl)ethyl] carbamate.
Other chemical names for cenobamate include: 2H-tetrazole-2-ethanol,
alpha-(2-chlorophenyl)-, carbamate (ester), (alphaR)-; and carbamic
acid (R)-(+)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl ester. It has
a molecular formula of
C10H10ClN5O2 and a
molecular weight of 267.67 g/mol. Cenobamate is a white to off-white
crystalline solid that has a melting point between 96.8-98.3 [deg]C. It
is partially soluble in water at a pH between 2 and 12. Pharmacokinetic
data indicate that cenobamate is rapidly absorbed, has good
bioavailability, and has a long half-life. Additional studies in humans
show that cenobamate is not extensively metabolized and does not
produce any major circulating metabolites. On November 21, 2019, FDA
approved an NDA for XCOPRI (cenobamate) for the treatment of partial-
onset seizures in adult patients. Thus, cenobamate 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 cenobamate,
since it has not been marketed, legally or illegally, in any country.
On December 19, 2019, DEA conducted a search on the National
Forensic Laboratory Information System (NFLIS) \3\ and the STARLiMS \4\
databases for cenobamate's encounters. Consistent with the fact that
cenobamate is a new molecular entity, these databases had no records of
encounters by law enforcement.
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\3\ NFLIS is a national forensic laboratory reporting system
that systematically collects results from drug chemistry analyses
conducted by Federal, State, and local forensic laboratories in the
United States.
\4\ STARLiMS is a laboratory information management system that
systematically collects results from drug chemistry analyses
conducted by DEA laboratories. On October 1, 2014, STARLiMS replaced
STRIDE as the DEA laboratory drug evidence data system of record.
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The pharmacological activity of cenobamate, like schedule IV or V
GABAergic or anti-epileptic substances, at sodium channels and GABA-A
receptors suggests that cenobamate's pattern of abuse would be less
than that
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of schedule IV substances but similar to that of schedule V anti-
epileptic drugs.
5. The Scope, Duration, and Significance of Abuse: Cenobamate is
not marketed, legally or illegally, in any country. However, HHS stated
that based on the preclinical and clinical study data of cenobamate,
the scope, duration, and significance of cenobamate abuse would likely
be similar to that of schedule V substances.
6. What, if any, Risk There is to the Public Health: According to
HHS, the public health risk associated with cenobamate is due to its
abuse potential. Thus, HHS concluded that the data from preclinical and
clinical studies (see Factor 2, above) showed that cenobamate has abuse
potential and physical or psychological dependence (Factor 7) similar
to that of substances in schedule V.
7. Its Psychic or Physiological Dependence Liability: The psychic
or physiological dependence liability of drugs can be demonstrated by
abuse-related animal and human studies (see Factor 2, above). In animal
studies, there were no significant alterations in the withdrawal phase
of the study in the measured parameters at either of the tested doses.
However, in human studies, cenobamate led to a mild withdrawal syndrome
characterized by insomnia, decreased appetite, depressed mood, tremor,
and amnesia. Based on these studies, HHS concluded that cenobamate has
a psychic or physiological dependence liability similar to that of
substances in schedule V.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled under the CSA: Cenobamate is not an immediate
precursor of any substance already controlled in the CSA.
Conclusion: After considering the scientific and medical evaluation
conducted by HHS, HHS' recommendation, and its own eight-factor
analysis, DEA has determined that these facts and all relevant data
constitute substantial evidence of a potential for abuse of cenobamate.
As such, DEA hereby schedules cenobamate 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)(5), finds
that:
(1) Cenobamate has a low potential for abuse relative to the drugs
or other substances in schedule IV.
Cenobamate, similar to the schedule IV substance lacosamide, is a
voltage-gated sodium channel blocker that also has GABA-A channel PAM
activity similar to schedule IV benzodiazepines. In drug discrimination
studies, cenobamate partially generalized to the discriminative
stimulus effects of midazolam (schedule IV) but fully generalized to
the discriminative stimulus effects of chlordiazepoxide (schedule IV)
in rats. In self-administration studies, cenobamate was self-
administered by rodents, but the self-administration (i.e., number of
infusions) of cenobamate was lower than that of midazolam. In the HAP
studies, cenobamate produced drug-liking scores higher than placebo but
less than that of alprazolam, a schedule IV substance. Based on all of
these studies, HHS concluded that cenobamate has an abuse potential
similar to that of substances in schedule V of the CSA. Thus, DEA finds
that the potential for abuse of cenobamate is less than that of
schedule IV benzodiazepines but similar to that of substances in
schedule V of the CSA.
(2) Cenobamate has a currently accepted medical use in the United
States.
FDA recently approved an NDA for cenobamate as a treatment for
partial-onset seizures in adult patients. Thus, cenobamate has a
currently accepted medical use in treatment in the United States.
(3) Abuse of Cenobamate may lead to limited physical dependence or
psychological dependence relative to the drugs or other substances in
schedule IV.
HHS reported in Factor 7 that cenobamate may lead to mild
withdrawal syndromes characterized by insomnia, decreased appetite, and
amnesia in humans. Thus, based on clinical study and preclinical data,
HHS concluded in Factor 6 that cenobamate has a physical or
psychological dependence liability similar to that of substances
controlled in schedule V. In a separate letter, dated January 15, 2020,
HHS further stated that based on the totality of available scientific
data, cenobamate may lead to physical or psychological dependence that
is low relative to substances in schedule IV of the CSA and similar to
that of substances in schedule V. Based on these data, DEA finds that
the abuse of cenobamate may lead to limited physical or psychological
dependence relative to the drugs or other substances in schedule IV.
Based on these findings, the Acting Administrator of DEA concludes
that cenobamate warrants control in schedule V of the CSA. 21 U.S.C.
812(b)(5).
Requirements for Handling Cenobamate
Cenobamate is subject to the CSA's schedule V 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 V 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) cenobamate, or who desires to handle cenobamate, 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 cenobamate,
and is not registered with DEA, must submit an application for
registration and may not continue to handle cenobamate, 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 V registration must surrender all
quantities of currently held cenobamate or may transfer all quantities
of cenobamate to a person registered with DEA in accordance with 21 CFR
part 1317, in addition to all other applicable federal, state, local,
and tribal laws.
3. Security. Cenobamate is subject to schedule III-V security
requirements and must be handled and stored in accordance with 21 CFR
1301.71-1301.93.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of cenobamate 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
cenobamate must take an inventory of cenobamate 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 cenobamate
must take an initial inventory of all stocks of controlled substances
(including
[[Page 13745]]
cenobamate) 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 cenobamate)
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.
6. Records and Reports. DEA registrants must maintain records and
submit reports for cenobamate, pursuant to 21 U.S.C. 827 and 958(e),
and in accordance with 21 CFR parts 1304, 1312, and 1317.
7. Prescriptions. All prescriptions for cenobamate, or products
containing cenobamate, 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 V controlled substances,
such registrants should be advised that (consistent with the foregoing
considerations) any manufacturing or distribution of cenobamate 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
cenobamate 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 cenobamate 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 Administrative Procedure Act (APA) (5 U.S.C.
553) generally requires notice and comment for rulemakings. However, 21
U.S.C. 811 provides that in cases where a certain new drug is (1)
approved by HHS and (2) HHS recommends control in CSA schedule II-V,
DEA shall issue an interim final rule scheduling the drug within 90
days. 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.\5\
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\5\ Office of Mgmt. & Budget, Exec. Office of The President,
Interim Guidance Implementing Section 2 of the Executive Order of
January 30, 2017 Titled ``Reducing Regulating 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 $100,000,000 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 U.S.-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:
[[Page 13746]]
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for part 1308 continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.
0
2. Amend Sec. 1308.15 by:
0
a. Redesignating paragraphs (e)(2) through (5) as (e)(3) through (6),
respectively;
0
b. Adding new paragraph (e)(2).
The addition reads as follows:
Sec. 1308.15 Schedule V.
* * * * *
(e) * * *
(2) Cenobamate ([(1R)-1-(2-chlorophenyl)-2-(tetrazol-2- 2720
yl)ethyl] carbamate; 2H-tetrazole-2-ethanol, alpha-(2-
chlorophenyl)-, carbamate (ester), (alphaR)-; carbamic
acid (R)-(+)-1-(2-chlorophenyl)-2-(2H-tetrazol-2-yl)ethyl
ester)....................................................
* * * * *
Dated: March 5, 2020.
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-04963 Filed 3-9-20; 8:45 am]
BILLING CODE 4410-09-P