[Federal Register Volume 87, Number 246 (Friday, December 23, 2022)]
[Rules and Regulations]
[Pages 78857-78859]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-27400]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-945]


Schedules of Controlled Substances: Removal of Fenfluramine From 
Control

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final rule.

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SUMMARY: With the issuance of this final rule, the Drug Enforcement 
Administration removes fenfluramine (chemical name: N-ethyl-[alpha]-
methyl-3-(trifluoromethyl)phenethylamine), including its salts, 
isomers, and salts of isomers whenever the existence of such salts, 
isomers, and salts is possible, from the schedules of the Controlled 
Substances Act. Prior to the effective date of this rule, fenfluramine 
was a

[[Page 78858]]

schedule IV controlled substance. This action removes the regulatory 
controls and administrative, civil, and criminal sanctions applicable 
to controlled substances, including those specific to schedule IV 
controlled substances, on persons who handle (manufacture, distribute, 
reverse distribute, dispense, engage in research, import, export, 
conduct instructional activities or chemical analysis with, or possess) 
or propose to handle fenfluramine.

DATES: Effective December 23, 2022.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., Chief, Drug 
and Chemical Evaluation Section, Diversion Control Division, Drug 
Enforcement Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION: 

Legal Authority

    Under the Controlled Substances Act (CSA), each controlled 
substance is classified into one of five schedules based upon its 
potential for abuse, its currently accepted medical use in treatment in 
the United States, and the degree of dependence the drug or other 
substance may cause.\1\ The initial schedules of controlled substances 
established by Congress are found at 21 U.S.C. 812(c) and the current 
list of scheduled substances is published at 21 CFR part 1308.
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    \1\ 21 U.S.C. 812.
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    Pursuant to 21 U.S.C. 811(a)(2), the Attorney General may, by rule, 
``remove any drug or other substance from the schedules if he finds 
that the drug or other substance does not meet the requirements for 
inclusion in any schedule.'' The Attorney General has delegated 
scheduling authority under 21 U.S.C. 811 to the Administrator of the 
Drug Enforcement Administration (DEA).\2\
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    \2\ 28 CFR 0.100.
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    The CSA provides that proceedings for the issuance, amendment, or 
repeal of the scheduling of any drug or other substance may be 
initiated by the Attorney General on the petition of any interested 
party.\3\ This action was initiated by a petition to remove 
fenfluramine from the list of scheduled controlled substances of the 
CSA, and is supported by, inter alia, a recommendation from the 
Assistant Secretary for Health of the Department of Health and Human 
Services (HHS) and an evaluation of all relevant data by DEA. This 
action removes the regulatory controls and administrative, civil, and 
criminal sanctions applicable to controlled substances, including those 
specific to schedule IV controlled substances, on persons who handle or 
propose to handle fenfluramine.
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    \3\ 21 U.S.C. 811(a).
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Background

    Fenfluramine (chemical name: N-ethyl-[alpha]-methyl-3-
(trifluoromethyl)phenethylamine), including its salts, isomers, and 
salts of such isomers, has been controlled under 21 CFR 1308.14(d) as a 
schedule IV substance of the CSA since June 15, 1973.\4\ On September 
25, 2019, Zogenix, Inc. (Zogenix; the Sponsor) submitted to the Food 
and Drug Administration (FDA) a New Drug Application (NDA) for Fintepla 
(fenfluramine), for the treatment of seizures associated with Dravet 
syndrome (DS) in patients two years of age and older. FDA approved the 
NDA on June 25, 2020, with the labelling listing fenfluramine as a 
schedule IV controlled substance.
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    \4\ 38 FR 15719, May 9, 1973.
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    On October 18, 2018, Zogenix submitted to DEA a petition requesting 
that fenfluramine be removed from schedule IV of the CSA. The petition 
complied with the requirements of 21 CFR 1308.43(b) and DEA accepted 
the petition for filing on November 13, 2018.

Notice of Proposed Rulemaking To Decontrol Fenfluramine

    On July 19, 2022, DEA published a notice of proposed rulemaking 
(NPRM) to remove fenfluramine from the schedules of the CSA.\5\ The 
NPRM provided an opportunity for interested persons to file a request 
for a hearing in accordance with DEA regulations by August 18, 2022. No 
requests for such a hearing were received by DEA. The NPRM also 
provided an opportunity for interested persons to submit comments on 
the proposal on or before August 18, 2022.
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    \5\ 87 FR 42979.
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Comment Received

    DEA received one comment on the NPRM to remove fenfluramine from 
control.
    Opposition to rulemaking: One commenter opposed decontrol of 
fenfluramine, however the comment was at times ambiguous. The commenter 
seemed to be concerned about children using fenfluramine illicitly and 
the potential harm related to the combined use with a stimulant, 
specifically noting the fenfluramine-phentermine (``fen-phen'') 
combination and noting ``Stimulants+Psychedelics=Psychosis.''
    DEA Response: DEA acknowledges the commenter's concerns about 
relative harm, especially related to children. DEA notes FDA approved 
Fintepla (fenfluramine) on June 25, 2020, for the treatment of DS in 
patients two years of age and older. Currently Fintepla is the only 
FDA-approved drug product with fenfluramine. HHS considered the harms 
the fenfluramine-phentermine combination produced in their April 2021 
scientific and medical evaluation, which was provided to DEA as part of 
this rulemaking process, pursuant to 21 U.S.C. 811(b).
    DEA notes that the combination historically produced serious 
cardiac effects, not psychological effects. The FDA-approved labeling 
for Fintepla indicates that patients must be enrolled in the Fintepla 
risk evaluation and mitigation strategy (REMS) program and undergo 
cardiac monitoring before, during, and after treatment with Fintepla to 
monitor for serious heart valve changes or high blood pressure in the 
arteries of the lungs. The FDA-required REMS program for Fintepla, 
including ongoing cardiac monitoring, would still be applicable under 
the FDA rules even after fenfluramine is decontrolled by DEA.
    Based on FDA's scientific and medical review of the eight factors 
and findings related to the substance's abuse potential, legitimate 
medical use, and dependence liability, HHS recommended that 
fenfluramine and its salts be removed from all schedules of the CSA. 
Pursuant to 21 U.S.C. 811(b), the recommendations of HHS shall be 
binding on DEA as to such scientific and medical matters and if the 
Secretary recommends that a drug or other substance not be controlled, 
DEA shall not control the drug or other substances. As stated in the 
NPRM, after careful review of all relevant data including HHS' 
scientific and medical evaluation and scheduling recommendation, DEA is 
therefore promulgating this final rule to remove fenfluramine, 
including its salts, isomers, and salts of such isomers whenever the 
existence of such salts, isomers, and salts of isomers is possible, 
from control under the CSA.

Determination To Decontrol Fenfluramine

    Based on consideration of the comment, and the rationale set forth 
in the NPRM, the Administrator finds that fenfluramine does not meet 
the requirements for inclusion in any schedule. As such, DEA is 
removing fenfluramine, including its salts, isomers, and salts of such 
isomers whenever the existence of such salts, isomers, and salts of 
isomers is possible, from control under the CSA.

[[Page 78859]]

Regulatory Analyses

Executive Orders 12866 (Regulatory Planning and Review) and 13563 
(Improving Regulation and Regulatory Review)

    In accordance with 21 U.S.C. 811(a), this scheduling action is 
subject to formal rulemaking procedures done ``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 criteria for 
removing a drug or other substance from the list of controlled 
substances. Such actions are exempt from review by the Office of 
Management and Budget pursuant to section 3(d)(1) of Executive Order 
(E.O.) 12866 and the principles reaffirmed in E.O. 13563.

Executive Order 12988, Civil Justice Reform

    This regulation meets the applicable standards set forth in 
sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors 
and ambiguity, minimize litigation, provide a clear legal standard for 
affected conduct, and promote simplification and burden reduction.

Executive Order 13132, Federalism

    This rulemaking does not have federalism implications warranting 
the application of E.O. 13132. This rule does not have substantial 
direct effects on the States, on the relationship between the Federal 
government and the States, or the distribution of power and 
responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This rule does not have tribal implications warranting the 
application of E.O. 13175. This rule 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 Administrator, in accordance with the Regulatory Flexibility 
Act (5 U.S.C. 601-612), has reviewed this rule and by approving it 
certifies that it will not have a significant economic impact on a 
substantial number of small entities. The purpose of this rule is to 
remove fenfluramine from the list of schedules of the CSA. This action 
will remove regulatory controls and administrative, civil, and criminal 
sanctions applicable to controlled substances for handlers and proposed 
handlers of fenfluramine. Accordingly, it has the potential for some 
economic impact in the form of cost savings.
    Fenfluramine as a pharmaceutical product (Fintepla) is currently 
available and marketed in the U.S. Because fenfluramine is currently a 
schedule IV drug, all legal handling of fenfluramine is currently done 
under appropriate DEA license. In such instances, DEA's knowledge of 
its registrant population forms the basis for estimating the number of 
affected entities and small entities that are affected by this 
rulemaking. There are currently 40 unique registrations authorized to 
handle fenfluramine specifically, as well as a number of registered 
analytical labs that are authorized to handle schedule IV controlled 
substances generally. From review of entity names, DEA estimates these 
40 registrations represent 27 entities. Some of these entities are 
likely to be small entities. However, since DEA does not have 
information of registrant size and the majority of DEA registrants are 
small entities or are employed by small entities, DEA estimates a 
maximum of 27 entities are small entities. Therefore, DEA 
conservatively estimates as many as 27 small entities are affected by 
this final rule. However, because this rule would remove fenfluramine 
from regulatory controls of the CSA, it is likely to result in some 
cost savings. Any person planning to handle fenfluramine will realize 
cost savings in the form of saved DEA registration fees, and the 
elimination of physical security, recordkeeping, and reporting 
requirements. Because of these factors, DEA projects that this rule 
will not result in a significant economic impact on a substantial 
number of small entities.

Administrative Procedure Act

    The Administrative Procedure Act requires the publication of a 
substantive rule to be made not less than 30 days before its effective 
date.\6\ However, this requirement need not apply for ``a substantive 
rule which . . . relieves a restriction.'' \7\ Therefore, DEA makes 
this rule effective immediately upon publication.
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    \6\ 5 U.S.C. 553(d).
    \7\ 5 U.S.C. 553(d)(1).
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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.

Congressional Review Act

    This rule is not a major rule as defined by the Congressional 
Review Act (CRA), 5 U.S.C. 804. However, pursuant to the CRA, DEA is 
submitting a copy of the 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, 21 CFR part 1308 is amended to read 
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.


Sec.  1308.14   [Amended]

0
2. In Sec.  1308.14, remove and reserve paragraph (d).

Signing Authority

    This document of the Drug Enforcement Administration was signed on 
December 12, 2022, by Administrator Anne Milgram. That document with 
the original signature and date is maintained by DEA. For 
administrative purposes only, and in compliance with requirements of 
the Office of the Federal Register, the undersigned DEA Federal 
Register Liaison Officer has been authorized to sign and submit the 
document in electronic format for publication, as an official document 
of DEA. This administrative process in no way alters the legal effect 
of this document upon publication in the Federal Register.

Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2022-27400 Filed 12-22-22; 8:45 am]
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