[Federal Register Volume 85, Number 16 (Friday, January 24, 2020)]
[Rules and Regulations]
[Pages 4217-4219]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-00669]
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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: Final rule.
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SUMMARY: This final rule adopts without change an interim final rule
with request for comments published in the Federal Register on June 17,
2019. That interim final rule placed the substance brexanolone
(3[alpha]-hydroxy-5[alpha]-pregnan-20-one), 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
Controlled Substances Act. With the issuance of this final rule, the
Drug Enforcement Administration maintains brexanolone in schedule IV of
the Controlled Substances Act.
DATES: Effective January 24, 2020.
FOR FURTHER INFORMATION CONTACT: Scott Brinks, Diversion Control
Division, Drug Enforcement
[[Page 4218]]
Administration; Mailing Address: 8701 Morrissette Drive, Springfield,
Virginia 22152; Telephone: (571) 362-3261.
SUPPLEMENTARY INFORMATION:
Background
On June 17, 2019, the Drug Enforcement Administration (DEA)
published an interim final rule to make brexanolone (including its
salts, isomers, and salts of isomers whenever the existence of such
salts, isomers, and salts of isomers is possible) a schedule IV
controlled substance. 84 FR 27938. The interim final rule provided an
opportunity for interested persons to submit comments, as well as file
a request for hearing or waiver of hearing, on or before July 17, 2019.
Comments Received
The DEA received three comments in response to the interim final
rule to control brexanolone as a schedule IV substance of the
Controlled Substances Act (CSA). Two of the three commenters were in
support of the interim final rule to place brexanolone in schedule IV
of the CSA, and one commenter was opposed to the placement of
brexanolone in schedule IV of the CSA. The DEA did not receive any
requests for hearing or waiver of hearing.
Support of the Interim Final Rule
Two commenters supported controlling brexanolone as a schedule IV
controlled substance. These commenters indicated support for scheduling
brexanolone under the CSA due to its similarity to other schedule IV
sedatives including midazolam and alprazolam.
DEA Response. The DEA appreciates the support for this rulemaking.
Opposition to the Interim Final Rule
A commenter opposed the interim final rule to control brexanolone
as a schedule IV substance. Although the commenter did not state if or
where brexanolone should be scheduled, the commenter expressed concerns
about brexanolone's adverse health effects such as exposure of an
antidepressant to infants through breastmilk, potential for ``hidden
side effects,'' and drug-associated dizziness and somnolence affecting
the maternal care of the infant.
DEA Response. The commenter's concerns about adverse health effects
of brexanolone are related to the Food and Drug Administration's (FDA)
approval process (such as weighing the benefits versus risks) and
outside of the scope of this rulemaking. The FDA approved a new drug
application (NDA) for Zulresso (brexanolone)--a substance identified as
having abuse potential pursuant to 21 U.S.C. 811(f)--and provided the
DEA with a scheduling recommendation for control of brexanolone in
schedule IV of the CSA. As provided in 21 U.S.C. 811(j), the scheduling
recommendation by the Department of Health and Human Services (HHS) and
the FDA approval of the NDA necessitated the DEA review and scheduling
action. The DEA made the findings required under 21 U.S.C. 812(b)(4)
for the placement of brexanolone in schedule IV. The scheduling
determination was based on a comprehensive evaluation of all available
data as related to the eight-factor analysis pursuant to 21 U.S.C.
811(c), but not by a single metric such as adverse health effects as
expressed by this commenter. As stated in the interim final rule, after
careful consideration of data from preclinical and clinical studies,
the DEA concurred with the HHS recommendation that brexanolone has
abuse potential comparable to other schedule IV benzodiazepines such as
midazolam and alprazolam, and therefore, supported and continues to
support through the promulgation of this final rule placement of
brexanolone in schedule IV under the CSA. None of the commenter's
concerns about brexanolone's potential health effects undermine any
aspect of the interim final rule's analysis.
Based on the rationale set forth in the interim final rule, the DEA
adopts the interim final rule without change.
Requirements for Handling Brexanolone
As indicated above, brexanolone has been a schedule IV substance by
virtue of the interim final rule issued by DEA in June 2019. Therefore,
this final rule does not alter the regulatory requirements applicable
to handlers of brexanolone that have been in place since that time.
Nonetheless, for informational purposes, we restate here those
requirements. 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 intends to handle brexanolone and is not
registered with the DEA must submit an application for registration and
may not handle brexanolone, unless the DEA approves 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 obtains a schedule IV
registration to handle brexanolone, but who subsequently does not
desire or is not able to maintain such registration, must surrender all
quantities of 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.
5. Inventory. Every DEA registrant who possesses any quantity of
brexanolone was required to keep an inventory of all stocks of
brexanolone on hand, as of June 17, 2019, 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
[[Page 4219]]
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
This final rule, without change, affirms the amendment made by the
interim final rule that is already in effect. 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 new drug is (1) approved by the 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.
The DEA issued an interim final rule on June 17, 2019 and solicited
public comments on that rule. Section 811 further states that after
giving interested persons the opportunity to comment and to request a
hearing, ``the Attorney General shall issue a final rule in accordance
with the scheduling criteria of subsections (b), (c), and (d) of this
section and section 812 (b) of'' the CSA. 21 U.S.C. 811(j)(3). The DEA
is now responding to the comments submitted by the public and issuing
the final rule, in conformity with the APA and the procedure required
by 21 U.S.C. 811.
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 final rule is not an Executive Order 13771 regulatory action
pursuant to Executive Order 12866 and OMB guidance.\1\
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\1\ 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 final rulemaking does not have federalism implications
warranting the application of Executive Order 13132. The final 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 final 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), the DEA was not required to publish a
general notice of proposed rulemaking prior to this final rule.
Consequently, the RFA does not apply.
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 final 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, the DEA is submitting a copy of this 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.
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
Accordingly, the interim final rule amending 21 CFR part 1308, which
published on June 17, 2019 (84 FR 27938), is adopted as a final rule
without change.
Dated: January 3, 2020.
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-00669 Filed 1-23-20; 8:45 am]
BILLING CODE 4410-09-P