[Federal Register Volume 84, Number 116 (Monday, June 17, 2019)]
[Rules and Regulations]
[Pages 27938-27943]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-12721]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-503]
Schedules of Controlled Substances: Placement of Brexanolone in
Schedule IV
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Interim final rule, with request for comments.
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SUMMARY: On March 19, 2019, the U.S. Food and Drug Administration (FDA)
approved a new drug application for Zulresso (brexanolone). Brexanolone
is chemically known as 3[alpha]-hydroxy-5[alpha]-pregnan-20-one and is
also referred to as allopregnanolone. The Department of Health and
Human Services (HHS) provided the Drug Enforcement Administration (DEA)
with a recommendation that brexanolone be placed in schedule IV 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 brexanolone
(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 June 17, 2019.
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 July 17, 2019. 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 must be received on or before July 17, 2019.
ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-503'' 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: Lynnette M. Wingert, Diversion Control
Division, Drug Enforcement Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia 22152; Telephone: (202) 598-
6812.
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
[[Page 27939]]
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 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 and Drug
Enforcement Administration eight-factor analyses, to this interim final
rule are available at http://www.regulations.gov for easy reference.
Request for 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 the DEA using the address information provided above.
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, the Drug Enforcement Administration (DEA) is required to
commence an expedited scheduling action with respect to certain new
drugs approved by the 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 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, the 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 the 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 the 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).
Background
Brexanolone (3[alpha]-hydroxy-5[alpha]-pregnan-20-one), also known
as allopregnanolone, is a new molecular entity with central nervous
system (CNS) depressant properties. Brexanolone is an inhibitory
neurosteroidal substance structurally related to progesterone.
Brexanolone shares a pharmacological mechanism of action with schedule
IV substances such as diazepam and alprazolam and is a positive
allosteric modulator of the gamma-aminobutyric acid type A (GABA-A)
receptors.
On April 19, 2018, Sage Therapeutics (Sponsor) submitted an NDA for
brexanolone to the FDA. On March 19, 2019, the DEA received
notification that HHS/FDA approved, on that date, the NDA for Zulresso
(brexanolone) injection, for intravenous use, to treat postpartum
depression (PPD) in adult women. Zulresso is approved with a Risk
Evaluation and Mitigation Strategy (REMS) and is available to patients
through a restricted distribution program where a healthcare
professional can only administer the drug in a certified healthcare
facility.
Determination To Schedule Brexanolone
On March 19, 2019, the DEA received from the HHS a scientific and
medical evaluation document (dated March 08, 2019) prepared by the FDA
entitled ``Basis for the Recommendation to Control Brexanolone and its
Salts in schedule IV of the Controlled Substances Act.'' Pursuant to 21
U.S.C. 811(b), this document contained an eight-factor analysis of the
abuse potential of brexanolone, along with the HHS's recommendation to
control brexanolone under schedule IV of the CSA.
In response, the DEA reviewed the scientific and medical evaluation
and scheduling recommendation provided by the HHS, along with all other
relevant data, and completed its own eight-factor review document
pursuant to 21 U.S.C. 811(c). The DEA concluded that brexanolone met
the 21 U.S.C.
[[Page 27940]]
812(b)(4) criteria for placement in schedule IV of the CSA.
Pursuant to subsection 811(j), and based on the HHS recommendation,
NDA approvals by HHS/FDA, and the DEA's determination, the DEA is
issuing this interim final rule to schedule brexanolone as a schedule
IV controlled substance under the CSA.
Included below is a brief summary of each factor as analyzed by the
HHS and the DEA, and as considered by the DEA in its scheduling action.
Please note that both the DEA and the 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-503.'' 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: Brexanolone is a new
molecular entity and is not currently available or marketed in any
country; evidence regarding its diversion, illicit manufacturing, or
deliberate ingestion is lacking. However, as stated by the HHS,
brexanolone is related in action to schedule IV sedatives such as
midazolam and alprazolam. It is thus reasonable to assume that
brexanolone 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 sedatives.
Pre-clinical and clinical studies show that brexanolone produces
effects that are similar to schedule IV sedative-hypnotics, such as
midazolam and alprazolam. Data obtained from general behavioral studies
demonstrate that brexanolone produced a sedative effect. In a drug
discrimination study in rats, brexanolone mimicked stimulus effects of
midazolam at certain dosages. Brexanolone produced positive subjective
responses and euphoria-related adverse events (AEs) similar to that of
alprazolam (schedule IV) in nondependent and healthy humans with a
history of recreational use of CNS depressants. Thus, brexanolone
likely has abuse potential similar to that of schedule IV sedatives,
such as midazolam and alprazolam, and it is likely to be abused for its
sedative effects contrary to medical advice.
2. Scientific Evidence of Its Pharmacological Effects, if Known:
Brexanolone, an inhibitory neurosteroid, shares a similar
pharmacological profile to another inhibitory neurosteroid (alfaxalone,
a schedule IV controlled substance) and schedule IV benzodiazepines
such as alprazolam and midazolam. Brexanolone, a metabolite of
progesterone, acts on GABA-A receptors and enhances the effects of
GABA. GABA is the major inhibitory neurotransmitter in the CNS. The
GABA-A receptor is a ligand-gated chloride ion channel consisting of
five subunits and a central chloride channel. Benzodiazepines and other
GABAergic substances enhance the opening of the ligand-gated chloride
channel and the influx of chloride. Brexanolone's ability to bind to
GABA-related sites is consistent with the action of other related
neurosteroids, such as alfaxalone.
Brexanolone, like schedule IV benzodiazepines, has sedative
activity in animals. Acute and chronic administration of brexanolone to
male and female rats and dogs elicited dose-dependent behaviors
indicative of the sedative and muscle relaxation properties of the
drug. In a drug discrimination study using male rats previously trained
to discriminate midazolam, brexanolone produced interoceptive cues that
are similar to those of midazolam. In human abuse potential studies,
brexanolone produced subjective responses similar to that of alprazolam
and may have a reinforcing effect at a higher infusion rate. The abuse-
related neuropharmacology profile of brexanolone is similar to that of
schedule IV substances (alprazolam and midazolam) and consistent with
its mechanism of action as a positive allosteric modulator of the GABA-
A receptors.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: Brexanolone is a new molecular entity. It is the
established name for allopregnanolone, chemically known as 5[alpha]-
pregnan-3[alpha]-ol-20-one (also known as 3[alpha]-hydroxy-5[alpha]-
pregnan-20-one). It is insoluble in water, very slightly soluble in n-
heptane, sparingly soluble in ethyl acetate, slightly soluble in
methanol, soluble in 2-methyl-tetrahydrofuran, and freely soluble in
tetrahydrofuran. Brexanolone drug product is formulated as a sterile,
clear, colorless solution intended for dilution followed by intravenous
infusion; and it contains brexanolone, Betadex Sulfobutyl Ether Sodium
USP/NF (Captisol) as a solubilizer, citric acid and sodium citrate as
buffering agents, and water for injection. The pH of the final bulk
compounded solution is adjusted to 6.0 using either sodium hydroxide or
hydrochloric acid.
4. Its History and Current Pattern of Abuse: There is no
information on the history and current pattern of abuse for
brexanolone, since it has not been marketed, legally or illegally, in
any country. The DEA conducted a search on the National Forensic
Laboratory Information System (NFLIS) \2\ and STARLiMS \3\ databases
for brexanolone encounters. Consistent with the fact that brexanolone
is a new molecular entity, these databases had no records of encounters
by law enforcement.
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\2\ NFLIS is a national forensic laboratory reporting system
that systematically collects results from drug chemistry analyses
conducted by state and local forensic laboratories in the United
States.
\3\ STARLiMS is a web-based, commercial laboratory information
management system that systematically collects results from drug
chemistry analyses conducted by the DEA laboratories. On October 1,
2014, STARLiMS replaced the System to Retrieve Information from Drug
Evidence (STRIDE) as the DEA laboratory drug evidence data system of
record.
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HHS notes that brexanolone produces abuse-related signals and abuse
potential similar to that of schedule IV benzodiazepines. In
particular, the pharmacological mechanism of action of brexanolone
involving a positive allosteric modulation of the GABA-A receptors
suggests that its pattern of abuse would be similar to schedule IV
sedative-hypnotics with similar mechanisms of action, such as midazolam
and diazepam.
5. The Scope, Duration, and Significance of Abuse: As noted,
brexanolone is not marketed, legally or illegally, in any country.
Thus, information about the scope, duration, and significance of abuse
for brexanolone is lacking. However, because of brexanolone's
pharmacological similarities to certain schedule IV benzodiazepines,
brexanolone is likely to be abused when available in the market with a
scope, duration, and significance of abuse similar to those of schedule
IV benzodiazepines.
6. What, if any, Risk There Is to the Public Health: The extent of
abuse potential of a drug is an indication of its public health risk.
Data from preclinical and clinical studies showed that brexanolone has
abuse potential similar to that of certain schedule IV benzodiazepines.
Therefore, upon availability for marketing, it is likely to pose a
public health risk to a degree similar to schedule IV benzodiazepines.
Data from clinical trials showed that brexanolone caused excessive
sedation with occasional loss of consciousness and amnesia. In
addition, transient apnea occurred in one patient at a supratherapeutic
dose. The HHS states that these adverse effects would likely occur in
abusers of brexanolone.
[[Page 27941]]
The brexanolone prescription product label states that concomitant
use of opioids, antidepressants, or other CNS depressants such as
benzodiazepines or alcohol may increase the possibility or severity of
adverse reactions related to sedation. In addition, because of the risk
of excessive sedation or sudden loss of consciousness, brexanolone is
only available through a REMS program. A REMS is a drug safety program
required by the FDA for certain medications with serious safety
concerns to ensure the benefits of the medication outweighs its risks
and is designed to reinforce medication use behaviors and actions that
support the safe use of the medication.\4\
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\4\ More information may be found at https://www.fda.gov/Drugs/DrugSafety/REMS/default.htm.
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The abuse of brexanolone may present risks to the public health at
a level similar to those associated with the abuse of schedule IV
benzodiazepines, such as midazolam and alprazolam.
7. Its Psychic or Physiological Dependence Liability: The HHS
review states that there were no physical dependence studies conducted
in animals or humans using brexanolone. Brexanolone is
pharmacologically similar to benzodiazepines that are known to produce
physical dependence. Sleep disturbances, anxiety, and convulsions can
occur upon discontinuation of chronic administration of
benzodiazepines. Thus, it is likely brexanolone may have a physical
dependence potential similar to that of benzodiazepines. Data from a
dog toxicity study demonstrated that discontinuation of chronic
administration of brexanolone led to convulsions, similar to the effect
from discontinuing benzodiazepines. Because brexanolone produced
positive subjective responses and euphoria-related AEs, it is likely to
cause psychic dependence.
8. Whether the Substance Is an Immediate Precursor of a Substance
Already Controlled under the CSA: Brexanolone is not an immediate
precursor of any substance already controlled in the CSA.
Conclusion: After considering the scientific and medical evaluation
conducted by the HHS, the HHS's recommendation, and its own eight-
factor analysis, the DEA has determined that these facts and all
relevant data constitute substantial evidence of a potential for abuse
of brexanolone. As such, the DEA hereby schedules brexanolone 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 the HHS and review of all available
data, the Acting Administrator of the DEA, pursuant to 21 U.S.C.
812(b)(4), finds that:
(1) Brexanolone has a low potential for abuse relative to the drugs
or other substances in Schedule III.
Brexanolone, a neuroactive steroid, is a positive allosteric
modulator of GABA-A receptors and produces sedation in general
behavioral studies and locomotion study. In a drug discrimination study
in animals, brexanolone was generalized to midazolam (schedule IV) at
certain dosages, demonstrating it has GABA-A receptor agonist
properties. In a human abuse potential (HAP) study, brexanolone
produced positive subjective responses and euphoria-related AEs similar
to those of alprazolam (schedule IV) in an HAP study. Furthermore, data
from other clinical studies show that brexanolone produced abuse-
related AEs, namely somnolence and sedation. Because brexanolone is
similar to midazolam and alprazolam (both schedule IV controlled
substances) in its abuse potential, brexanolone has a low potential for
abuse relative to the drugs or other substances in schedule III.
(2) Brexanolone has a currently accepted medical use in the United
States.
The FDA recently approved the NDA for brexanolone as an intravenous
treatment of PPD in adult women. Thus, brexanolone has a currently
accepted medical use for treatment in the United States.
(3) Abuse of Brexanolone may lead to limited physical dependence or
psychological dependence relative to the drugs or other substances in
schedule III.
Brexanolone has a pharmacology profile similar to that of
benzodiazepine drugs. Because abrupt discontinuation of benzodiazepines
is associated with withdrawal symptoms, it is likely that brexanolone
may have the potential to produce physical dependence similar to that
produced by benzodiazepines. Data from a dog toxicity study
demonstrated that discontinuation of chronic administration of
brexanolone led to convulsions, similar to the effect from
discontinuing benzodiazepines. In addition, because brexanolone
produced positive subjective responses and euphoria-related AEs, it is
likely that brexanolone can produce psychic dependence. Thus, abuse of
brexanolone may lead to limited physical or psychological dependence
relative to the drugs or other substances in schedule III.
Based on these findings, the Acting Administrator of the DEA
concludes that brexanolone, including its salts, isomers, and salts of
isomers whenever the existence of such salts, isomers, and salts of
isomers is possible, warrants control in schedule IV of the CSA. 21
U.S.C. 812(b)(4).
Requirements for Handling Brexanolone
Brexanolone 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) brexanolone, or who desires to handle brexanolone, must be
registered with the DEA to conduct such activities pursuant to 21
U.S.C. 822, 823, 957, and 958 and in accordance with 21 CFR parts 1301
and 1312. Any person who currently handles or intends to handle
brexanolone, and is not registered with the DEA, must submit an
application for registration and may not continue to handle
brexanolone, unless the 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 brexanolone or may transfer all quantities
of brexanolone to a person registered with the DEA in accordance with
21 CFR part 1317, in addition to all other applicable federal, state,
local, and tribal laws.
3. Security. Brexanolone 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 brexanolone must comply with 21 U.S.C. 825 and
958(e), and be in accordance with 21 CFR part 1302.
[[Page 27942]]
5. Inventory. Every DEA registrant who possesses any quantity of
brexanolone must take an inventory of all stocks of brexanolone on
hand, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21
CFR 1304.03, 1304.04, and 1304.11.
Any person who becomes registered with the DEA to handle
brexanolone must take an initial inventory of all stocks of controlled
substances (including brexanolone) 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 an
inventory of all controlled substances (including brexanolone) 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 brexanolone, 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 brexanolone or products
containing brexanolone 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 brexanolone 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 and the CSA.
9. Importation and Exportation. All importation and exportation of
brexanolone 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 brexanolone 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
As explained above, under 21 U.S.C. 811(j), when a new drug is (1)
approved by the Department of Health and Human Services (HHS), and (2)
HHS recommends control in CSA schedule II-V, the 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 the DEA to
demonstrate good cause. Therefore, the DEA has determined that the
notice and comment requirements of section 553 of the APA, 5 U.S.C.
553, do not apply to this scheduling action.
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 Public Law 114-89, 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 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
In accordance with 5 U.S.C. 603(a), ``[w]henever an agency is
required by [5 U.S.C. 553], or any other law, to publish general notice
of proposed rulemaking for any proposed rule, or publishes a notice of
proposed rulemaking for an interpretive rule involving the internal
revenue laws of the United States, the agency shall prepare and make
available for public comment an initial regulatory flexibility
analysis.'' As noted in the above discussion regarding applicability of
the APA, the DEA has determined that the notice and comment
requirements of section 553 of the APA, 5 U.S.C. 553, do not apply to
this scheduling action. Consequently, the Regulatory Flexibility Act
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., the 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 for inflation) in any
one 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
[[Page 27943]]
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, the 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, the 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), unless otherwise noted.
0
2. Amend Sec. 1308.14 by:
0
a. Redesignating paragraphs (c)(4) through (c)(55) as (c)(5) through
(c)(56);
0
b. Adding new paragraph (c)(4).
The addition reads as follows:
Sec. 1308.14 Schedule IV.
* * * * *
(c) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
(4) Brexanolone................................................. 2400
------------------------------------------------------------------------
* * * * *
Dated: June 10, 2019.
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2019-12721 Filed 6-14-19; 8:45 am]
BILLING CODE 4410-09-P