[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.

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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.
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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 [\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.
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    \3\ 21 U.S.C. 811(a).
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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).
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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