Schedules of Controlled Substances: Removal of [18, 70715-70717 [2022-25212]
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Federal Register / Vol. 87, No. 223 / Monday, November 21, 2022 / Rules and Regulations
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA–837]
Schedules of Controlled Substances:
Removal of [18F]FP–CIT From Control
Drug Enforcement
Administration, Department of Justice.
ACTION: Final rule.
AGENCY:
With the issuance of this final
rule, the Drug Enforcement
Administration removes [18F]FP–CIT
(chemical names: [18F]N-wfluoropropyl-b-CIT; fluorine-18-N-3fluoropropyl-2-beta-carbomethoxy-3beta-(4-iodophenyl)tropane;
[18F]fluoropropylcarbomethoxy
nortropane) from the schedules of the
Controlled Substances Act. Prior to the
effective date of this rule, [18F]FP–CIT
was a schedule II controlled substance
because it can be derived from cocaine,
a schedule II substance, via ecgonine,
also a schedule II substance. This action
removes the regulatory controls and
administrative, civil, and criminal
sanctions applicable to controlled
substances, including those specific to
schedule II 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 [18F]FP–CIT.
DATES: Effective December 21, 2022.
FOR FURTHER INFORMATION CONTACT:
Terrence L. Boos, Drug & Chemical
Evaluation Section, Diversion Control
Division, Drug Enforcement
Administration; Telephone: (571) 362–
3249.
SUMMARY:
SUPPLEMENTARY INFORMATION:
lotter on DSK11XQN23PROD with RULES1
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.
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
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
[18F]FP–CIT 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 II controlled
substances, on persons who handle or
propose to handle [18F]FP–CIT.
Background
[18F]FP–CIT (chemical names: [18F]Nw-fluoropropyl-b-CIT; fluorine-18-N-3fluoropropyl-2-beta-carbomethoxy-3beta-(4-iodophenyl)tropane;
[18F]fluoropropylcarbomethoxy
nortropane) is described as a diagnostic
substance that is used in assisting the
evaluation of adult patients with
suspected Parkinsonian syndromes. It is
an entity used in the visualization of
striatal dopamine transporters (DAT)
using positron emission tomography
(PET) imaging. [18F]FP–CIT is not yet
approved by the United States Food and
Drug Administration (FDA) and no New
Drug Application (NDA) for [18F]FP–CIT
or any [18F]FP–CIT-containing drug has
been submitted to FDA.
[18F]FP–CIT is structurally similar to
[123I]ioflupane, known as DaTscan or
[123I]FP–CIT. Both [18F]FP–CIT and
[123I]ioflupane were developed as
clinical diagnostic substances to
visualize DAT and contain the same
tracer amount of the precursor,
ecgonine. The only difference between
these two compounds is the radiotracer
(123I versus 18F). On January 14, 2011,
FDA approved the NDA for
[123I]ioflupane-containing drug product,
DaTscan, for use to visualize striatal
DAT in the brains of adult patients with
suspected Parkinsonian syndromes
using single photon emission computed
tomography (SPECT) imaging. DEA
2 28
1 21
U.S.C. 812.
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U.S.C. 811(a).
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70715
removed [123I]ioflupane from schedule
II of the CSA on September 11, 2015.4
The starting material for the synthesis
of [18F]FP–CIT and [123I]ioflupane is Nnor-b-CIT (2b-carbomethoxy-3b -(4iodophenyl) nortropane), which is
derived from cocaine, a schedule II
substance, via ecgonine (a schedule II
substance). Thus, by definition 5
[18F]FP–CIT is currently controlled in
schedule II of the CSA. On June 28,
2018, DEA received a petition from
Advanced Imaging Projects to initiate
proceedings to amend 21 CFR
1308.12(b)(4) so as to decontrol [18F]FP–
CIT (proposed tradename Fluoroseek)
from schedule II of the CSA. On October
6, 2018 and November 6, 2018, DEA
received supplemental information from
the Petitioner; DEA accepted the
petition for filing on November 28,
2018.
DEA and HHS Eight-Factor Analyses
Pursuant to 21 U.S.C. 811(b), on May
2, 2019, DEA provided the necessary
data on [18F]FP–CIT, along with the
petition, to HHS with a request for a
scientific and medical evaluation and
scheduling recommendation for
[18F]FP–CIT. On April 16, 2021, DEA
received from HHS a scientific and
medical evaluation, conducted by
FDA 6, and a recommendation to remove
[18F]FP–CIT from all schedules of the
CSA. Following consideration of the
eight factors and findings related to the
substance’s abuse potential, legitimate
medical use, and dependence liability,
HHS recommended that [18F]FP–CIT be
removed from all schedules of control of
the CSA. In response, DEA conducted
its own eight-factor analysis of [18F]FP–
CIT pursuant to 21 U.S.C. 811(c). Both
DEA and HHS analyses are available in
their entirety in the public docket for
this rule (Docket Number DEA–837) at
https://www.regulations.gov under
‘‘Supporting and Related Material’’.
Determination To Decontrol [18F]FP–
CIT
On November 4, 2021, DEA published
a notice of proposed rulemaking
(NPRM) to remove [18F]FP–CIT from the
schedules of the CSA. 86 FR 60785. The
NPRM provided an opportunity for
interested persons to file a request for a
4 80
FR 54715.
CFR 1308.12(b)(4).
6 As discussed in a memorandum of
understanding entered into by 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.
5 21
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70716
Federal Register / Vol. 87, No. 223 / Monday, November 21, 2022 / Rules and Regulations
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hearing in accordance with DEA
regulations by December 6, 2021. 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 December 6, 2021.
Comments Received
DEA received six comments on the
NPRM to remove [18F]FP–CIT from
control.
Support for rulemaking: Five
commenters supported decontrol of
[18F]FP–CIT. Four of these commenters
noted the potential therapeutic benefit
of this radiolabeled substance related to
diagnosing Parkinson’s disease.
DEA Response: DEA appreciates these
comments in support of this
rulemaking.
Opposition to rulemaking: One
commenter opposed decontrol of
[18F]FP–CIT, suggesting rescheduling
cocaine, or any cocaine derivative, is a
safety concern and such rescheduling
would wrongly signal that cocaine is
less harmful than cannabis.
DEA Response: DEA does not agree
with the commenter’s concern about
harm. [18F]FP–CIT is derived from
cocaine, a schedule II substance, via
ecgonine, a schedule II substance. As
described below [18F]FP–CIT is
manufactured as a radiopharmaceutical
containing minute amounts of this
radiolabeled substance in limited and
specified places (e.g., nuclear
pharmacies) and distributed and
handled under a highly regulatory
environment.
As stated by FDA in its scientific and
medical evaluation, radioligands in
general are used in very dilute, or low
dose formulations, and are unlikely to
produce pharmacological effect and be
abused, which is the case for the
[123I]ioflupane-containing drug product,
DaTscan. Similar to [123I]ioflupane,
[18F]FP–CIT is expected to be present in
low concentration in the final drug
product, thus it is unlikely that [18F]FP–
CIT will produce stimulant effects or be
abused. Further, due to its radioactive
nature and similar to the handling of
[123I]ioflupane, [18F]FP–CIT will be
restricted to nuclear medicine
departments and radiopharmacies
authorized to handle radioactive
substances. Both nuclear medicine
departments and radiopharmacies are
highly regulated by multiple federal,
state and local regulating agencies.
Based on the totality of the available
scientific data, FDA stated that [18F]FP–
CIT does not conform with the findings
for schedule II in 21 U.S.C. 812(b)(2) or
in any other schedule as set forth in 21
U.S.C. 812(b). Based on FDA’s scientific
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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 [18F]FP–CIT 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’s scientific and medical evaluation
and scheduling recommendation, DEA
concurred with HHS’s assessment that
there is no evidence that [18F]FP–CIT
has a comparable potential for abuse
relative to schedule V substances. DEA
is therefore promulgating this final rule
to remove [18F]FP–CIT from control
under the CSA and notes that nonradiolabeled FP–CIT remains a schedule
II substance.
Scheduling Conclusion
Based on consideration of all
comments, the scientific and medical
evaluation and accompanying
recommendation of HHS, and based on
DEA’s consideration of its own eightfactor analysis, the Administrator finds
that these facts and all relevant data
demonstrate that [18F]FP–CIT does not
meet the requirements for inclusion in
any schedule. As such, DEA is removing
[18F]FP–CIT form control under the
CSA.
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
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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 [18F]FP–CIT 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 [18F]FP–CIT. Accordingly, it
has the potential for some economic
impact in the form of cost savings.
This rule will affect all persons who
handle, or propose to handle, [18F]FP–
CIT. [18F]FP–CIT is not currently
available or marketed in any country.
Due to the wide variety of unidentifiable
and unquantifiable variables that
potentially could influence the
distribution and dispensing rates, if any,
of [18F]FP–CIT, DEA is unable to
determine the number of entities and
small entities which might handle
[18F]FP–CIT. In some instances where a
controlled pharmaceutical drug is
removed from the schedules of the CSA,
DEA is able to quantify the estimated
number of affected entities and small
entities because the handling of the drug
is expected to be limited to DEA
registrants even after removal from the
schedules. In such instances, DEA’s
knowledge of its registrant population
forms the basis for estimating the
number of affected entities and small
entities. However, DEA does not have a
basis to estimate whether [18F]FP–CIT is
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Federal Register / Vol. 87, No. 223 / Monday, November 21, 2022 / Rules and Regulations
expected to be handled by persons who
hold DEA registrations, by persons who
are not currently registered with DEA to
handle controlled substances, or both.
Therefore, DEA is unable to estimate the
number of entities and small entities
who plan to handle [18F]FP–CIT.
Although DEA does not have a
reliable basis to estimate the number of
affected entities and quantify the
economic impact of this final rule, a
qualitative analysis indicates that this
rule is likely to result in some cost
savings. Any person planning to handle
[18F]FP–CIT 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.
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.
Administrative Procedure Act
■
DEA finds that good cause exists for
adopting this rule as a final rule with an
immediate effective date under 5 U.S.C.
553(d) because this final rule relieves a
restriction.
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
1995.7
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
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.
2. In § 1308.12, revise paragraphs
(b)(4)(i) and (ii) and add paragraph
(b)(4)(iii) to read as follows:
■
§ 1308.12
Schedule II.
*
*
*
*
*
(b) * * *
(4) * * *
(i) Decocainized coca leaves or
extraction of coca leaves, which
extractions do not contain cocaine or
ecgonine;
(ii) [123I]ioflupane; or
(iii) [18F]FP–CIT.
*
*
*
*
*
Scott Brinks,
Federal Register Liaison Officer, Drug
Enforcement Administration.
[FR Doc. 2022–25212 Filed 11–18–22; 8:45 am]
BILLING CODE 4410–09–P
Congressional Review Act
DEPARTMENT OF JUSTICE
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.
Drug Enforcement Administration
Signing Authority
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List of Subjects in 21 CFR part 1308
U.S.C. 3501–3521.
VerDate Sep<11>2014
15:56 Nov 18, 2022
[Docket No. DEA–477]
Schedules of Controlled Substances:
Placement of Zipeprol in Schedule I
Drug Enforcement
Administration, Department of Justice.
ACTION: Final rule.
AGENCY:
This document of the Drug
Enforcement Administration was signed
on November 14, 2022, by
Administrator Anne Milgram. That
document with the original signature
7 44
21 CFR Part 1308
Jkt 259001
With the issuance of this final
rule, the Drug Enforcement
Administration places zipeprol
(chemical name: 1-methoxy-3-[4-(2-
SUMMARY:
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Sfmt 4700
70717
methoxy-2-phenylethyl)piperazin-1-yl]1-phenylpropan-2-ol), including its
isomers, esters, ethers, salts, and salts of
isomers, esters and ethers, whenever the
existence of such isomers, esters, ethers
and salts is possible within the specific
chemical designation, in schedule I of
the Controlled Substances Act. This
action is being taken to enable the
United States to meet its obligations
under the 1971 Convention on
Psychotropic Substances. This action
imposes the regulatory controls and
administrative, civil, and criminal
sanctions applicable to schedule I
controlled substances on persons who
handle (manufacture, distribute, import,
export, engage in research, conduct
instructional activities or chemical
analysis with, or possess), or propose to
handle zipeprol.
DATES: Effective December 21, 2022.
FOR FURTHER INFORMATION CONTACT: Dr.
Terrence L. Boos, Drug and Chemical
Evaluation Section, Diversion Control
Division, Drug Enforcement
Administration; Telephone: (571) 362–
3249.
SUPPLEMENTARY INFORMATION:
Legal Authority
The United States is a party to the
1971 United Nations Convention on
Psychotropic Substances (1971
Convention), February 21, 1971, 32
U.S.T. 543, 1019 U.N.T.S. 175, as
amended. Procedures respecting
changes in drug schedules under the
1971 Convention are governed
domestically by 21 U.S.C. 811(d)(2)–(4).
When the United States receives
notification of a scheduling decision
pursuant to Article 2 of the 1971
Convention adding a drug or other
substance to a specific schedule, the
Secretary of the Department of Health
and Human Services (HHS),1 after
consultation with the Attorney General,
shall first determine whether existing
legal controls under subchapter I of the
Controlled Substances Act (CSA) and
the Federal Food, Drug, and Cosmetic
Act meet the requirements of the
schedule specified in the notification
with respect to the specific drug or
substance.2 Based on those
1 As discussed in a memorandum of
understanding entered into by the Food and Drug
Administration (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 (March 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).
2 21 U.S.C. 811(d)(3).
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Agencies
[Federal Register Volume 87, Number 223 (Monday, November 21, 2022)]
[Rules and Regulations]
[Pages 70715-70717]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-25212]
[[Page 70715]]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-837]
Schedules of Controlled Substances: Removal of [\18\F]FP-CIT From
Control
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: With the issuance of this final rule, the Drug Enforcement
Administration removes [\18\F]FP-CIT (chemical names: [\18\F]N-[omega]-
fluoropropyl-[beta]-CIT; fluorine-18-N-3-fluoropropyl-2-beta-
carbomethoxy-3-beta-(4-iodophenyl)tropane;
[\18\F]fluoropropylcarbomethoxy nortropane) from the schedules of the
Controlled Substances Act. Prior to the effective date of this rule,
[\18\F]FP-CIT was a schedule II controlled substance because it can be
derived from cocaine, a schedule II substance, via ecgonine, also a
schedule II substance. This action removes the regulatory controls and
administrative, civil, and criminal sanctions applicable to controlled
substances, including those specific to schedule II 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 [\18\F]FP-CIT.
DATES: Effective December 21, 2022.
FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug & 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.
---------------------------------------------------------------------------
\1\ 21 U.S.C. 812.
---------------------------------------------------------------------------
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 [\18\F]FP-
CIT 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 II controlled substances, on persons who handle or propose to
handle [\18\F]FP-CIT.
---------------------------------------------------------------------------
\3\ 21 U.S.C. 811(a).
---------------------------------------------------------------------------
Background
[\18\F]FP-CIT (chemical names: [\18\F]N-[omega]-fluoropropyl-
[beta]-CIT; fluorine-18-N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-
iodophenyl)tropane; [\18\F]fluoropropylcarbomethoxy nortropane) is
described as a diagnostic substance that is used in assisting the
evaluation of adult patients with suspected Parkinsonian syndromes. It
is an entity used in the visualization of striatal dopamine
transporters (DAT) using positron emission tomography (PET) imaging.
[\18\F]FP-CIT is not yet approved by the United States Food and Drug
Administration (FDA) and no New Drug Application (NDA) for [\18\F]FP-
CIT or any [\18\F]FP-CIT-containing drug has been submitted to FDA.
[\18\F]FP-CIT is structurally similar to [\123\I]ioflupane, known
as DaTscan or [\123\I]FP-CIT. Both [\18\F]FP-CIT and [\123\I]ioflupane
were developed as clinical diagnostic substances to visualize DAT and
contain the same tracer amount of the precursor, ecgonine. The only
difference between these two compounds is the radiotracer (\123\I
versus \18\F). On January 14, 2011, FDA approved the NDA for
[\123\I]ioflupane-containing drug product, DaTscan, for use to
visualize striatal DAT in the brains of adult patients with suspected
Parkinsonian syndromes using single photon emission computed tomography
(SPECT) imaging. DEA removed [\123\I]ioflupane from schedule II of the
CSA on September 11, 2015.\4\
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\4\ 80 FR 54715.
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The starting material for the synthesis of [\18\F]FP-CIT and
[\123\I]ioflupane is N-nor-[beta]-CIT (2[beta]-carbomethoxy-3[beta] -
(4-iodophenyl) nortropane), which is derived from cocaine, a schedule
II substance, via ecgonine (a schedule II substance). Thus, by
definition \5\ [\18\F]FP-CIT is currently controlled in schedule II of
the CSA. On June 28, 2018, DEA received a petition from Advanced
Imaging Projects to initiate proceedings to amend 21 CFR 1308.12(b)(4)
so as to decontrol [\18\F]FP-CIT (proposed tradename Fluoroseek) from
schedule II of the CSA. On October 6, 2018 and November 6, 2018, DEA
received supplemental information from the Petitioner; DEA accepted the
petition for filing on November 28, 2018.
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\5\ 21 CFR 1308.12(b)(4).
---------------------------------------------------------------------------
DEA and HHS Eight-Factor Analyses
Pursuant to 21 U.S.C. 811(b), on May 2, 2019, DEA provided the
necessary data on [\18\F]FP-CIT, along with the petition, to HHS with a
request for a scientific and medical evaluation and scheduling
recommendation for [\18\F]FP-CIT. On April 16, 2021, DEA received from
HHS a scientific and medical evaluation, conducted by FDA \6\, and a
recommendation to remove [\18\F]FP-CIT from all schedules of the CSA.
Following consideration of the eight factors and findings related to
the substance's abuse potential, legitimate medical use, and dependence
liability, HHS recommended that [\18\F]FP-CIT be removed from all
schedules of control of the CSA. In response, DEA conducted its own
eight-factor analysis of [\18\F]FP-CIT pursuant to 21 U.S.C. 811(c).
Both DEA and HHS analyses are available in their entirety in the public
docket for this rule (Docket Number DEA-837) at https://www.regulations.gov under ``Supporting and Related Material''.
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\6\ As discussed in a memorandum of understanding entered into
by 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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Determination To Decontrol [\18\F]FP-CIT
On November 4, 2021, DEA published a notice of proposed rulemaking
(NPRM) to remove [\18\F]FP-CIT from the schedules of the CSA. 86 FR
60785. The NPRM provided an opportunity for interested persons to file
a request for a
[[Page 70716]]
hearing in accordance with DEA regulations by December 6, 2021. 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 December 6, 2021.
Comments Received
DEA received six comments on the NPRM to remove [\18\F]FP-CIT from
control.
Support for rulemaking: Five commenters supported decontrol of
[\18\F]FP-CIT. Four of these commenters noted the potential therapeutic
benefit of this radiolabeled substance related to diagnosing
Parkinson's disease.
DEA Response: DEA appreciates these comments in support of this
rulemaking.
Opposition to rulemaking: One commenter opposed decontrol of
[\18\F]FP-CIT, suggesting rescheduling cocaine, or any cocaine
derivative, is a safety concern and such rescheduling would wrongly
signal that cocaine is less harmful than cannabis.
DEA Response: DEA does not agree with the commenter's concern about
harm. [\18\F]FP-CIT is derived from cocaine, a schedule II substance,
via ecgonine, a schedule II substance. As described below [\18\F]FP-CIT
is manufactured as a radiopharmaceutical containing minute amounts of
this radiolabeled substance in limited and specified places (e.g.,
nuclear pharmacies) and distributed and handled under a highly
regulatory environment.
As stated by FDA in its scientific and medical evaluation,
radioligands in general are used in very dilute, or low dose
formulations, and are unlikely to produce pharmacological effect and be
abused, which is the case for the [\123\I]ioflupane-containing drug
product, DaTscan. Similar to [\123\I]ioflupane, [\18\F]FP-CIT is
expected to be present in low concentration in the final drug product,
thus it is unlikely that [\18\F]FP-CIT will produce stimulant effects
or be abused. Further, due to its radioactive nature and similar to the
handling of [\123\I]ioflupane, [\18\F]FP-CIT will be restricted to
nuclear medicine departments and radiopharmacies authorized to handle
radioactive substances. Both nuclear medicine departments and
radiopharmacies are highly regulated by multiple federal, state and
local regulating agencies.
Based on the totality of the available scientific data, FDA stated
that [\18\F]FP-CIT does not conform with the findings for schedule II
in 21 U.S.C. 812(b)(2) or in any other schedule as set forth in 21
U.S.C. 812(b). 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
[\18\F]FP-CIT 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's scientific and medical
evaluation and scheduling recommendation, DEA concurred with HHS's
assessment that there is no evidence that [\18\F]FP-CIT has a
comparable potential for abuse relative to schedule V substances. DEA
is therefore promulgating this final rule to remove [\18\F]FP-CIT from
control under the CSA and notes that non-radiolabeled FP-CIT remains a
schedule II substance.
Scheduling Conclusion
Based on consideration of all comments, the scientific and medical
evaluation and accompanying recommendation of HHS, and based on DEA's
consideration of its own eight-factor analysis, the Administrator finds
that these facts and all relevant data demonstrate that [\18\F]FP-CIT
does not meet the requirements for inclusion in any schedule. As such,
DEA is removing [\18\F]FP-CIT form control under the CSA.
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 [\18\F]FP-CIT 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 [\18\F]FP-CIT. Accordingly, it has the potential for some
economic impact in the form of cost savings.
This rule will affect all persons who handle, or propose to handle,
[\18\F]FP-CIT. [\18\F]FP-CIT is not currently available or marketed in
any country. Due to the wide variety of unidentifiable and
unquantifiable variables that potentially could influence the
distribution and dispensing rates, if any, of [\18\F]FP-CIT, DEA is
unable to determine the number of entities and small entities which
might handle [\18\F]FP-CIT. In some instances where a controlled
pharmaceutical drug is removed from the schedules of the CSA, DEA is
able to quantify the estimated number of affected entities and small
entities because the handling of the drug is expected to be limited to
DEA registrants even after removal from the schedules. In such
instances, DEA's knowledge of its registrant population forms the basis
for estimating the number of affected entities and small entities.
However, DEA does not have a basis to estimate whether [\18\F]FP-CIT is
[[Page 70717]]
expected to be handled by persons who hold DEA registrations, by
persons who are not currently registered with DEA to handle controlled
substances, or both. Therefore, DEA is unable to estimate the number of
entities and small entities who plan to handle [\18\F]FP-CIT.
Although DEA does not have a reliable basis to estimate the number
of affected entities and quantify the economic impact of this final
rule, a qualitative analysis indicates that this rule is likely to
result in some cost savings. Any person planning to handle [\18\F]FP-
CIT 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
DEA finds that good cause exists for adopting this rule as a final
rule with an immediate effective date under 5 U.S.C. 553(d) because
this final rule relieves a restriction.
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.\7\
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\7\ 44 U.S.C. 3501-3521.
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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.
Signing Authority
This document of the Drug Enforcement Administration was signed on
November 14, 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.
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.
0
2. In Sec. 1308.12, revise paragraphs (b)(4)(i) and (ii) and add
paragraph (b)(4)(iii) to read as follows:
Sec. 1308.12 Schedule II.
* * * * *
(b) * * *
(4) * * *
(i) Decocainized coca leaves or extraction of coca leaves, which
extractions do not contain cocaine or ecgonine;
(ii) [\123\I]ioflupane; or
(iii) [\18\F]FP-CIT.
* * * * *
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2022-25212 Filed 11-18-22; 8:45 am]
BILLING CODE 4410-09-P