[Federal Register Volume 86, Number 211 (Thursday, November 4, 2021)]
[Proposed Rules]
[Pages 60785-60790]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-23852]


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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: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration proposes to remove 
[\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 (CSA). This scheduling 
action is pursuant to the CSA which requires that such actions be made 
on the record after opportunity for a hearing through formal 
rulemaking. [\18\F]FP-CIT is currently 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 
would remove 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, conduct 
research, import, export, or

[[Page 60786]]

conduct chemical analysis) or propose to handle [\18\F]FP-CIT.

DATES: Interested persons may file written comments on this proposal in 
accordance with 21 CFR 1308.43(g). Electronic comments must be 
submitted, and written comments must be postmarked, on or before 
December 6, 2021. 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 
participation pursuant to 21 CFR 1308.44 and in accordance with 21 CFR 
1316.45, 1316.47, 1316.48, or 1316.49, as applicable. Requests for 
hearing, notices of appearance, and waivers of an opportunity for a 
hearing or to participate in a hearing must be received on or before 
December 6, 2021.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-837'' on all correspondence, including any 
attachments.
     Electronic comments: DEA encourages that all comments be 
submitted through the Federal eRulemaking Portal, which provides the 
ability to type short comments directly into the comment field on the 
web page or to 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 electronic 
submissions are not necessary and are discouraged. Should you wish to 
mail a paper comment in lieu of an electronic format, it should be sent 
via regular or express mail to: Drug Enforcement Administration, Attn: 
DEA Federal Register Representative/DPW, 8701 Morrissette Drive, 
Springfield, Virginia 22152.
     Hearing requests: All requests for a hearing and waivers 
of participation must be sent to: Drug Enforcement Administration, 
Attn: Administrator, 8701 Morrissette Drive, Springfield, Virginia 
22152.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug & Chemical 
Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Telephone: (571) 362-3261.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

    Please note that all comments received in response to this docket 
are considered part of the public record. They will, unless reasonable 
cause is given, be made available by the Drug Enforcement 
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 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 to 
this proposed rule are available at http://www.regulations.gov for easy 
reference. DEA specifically solicits written comments regarding DEA's 
economic analysis of the impact of these proposed changes. DEA requests 
that commenters provide detailed descriptions in their comments of any 
expected economic impacts, especially to small entities. Commenters 
should provide empirical data to illustrate the nature and scope of 
such impact.

Request for Hearing, Notice of Appearance at 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 (5 U.S.C. 551-559). 21 CFR 1308.41-1308.45, and 21 CFR part 1316 
subpart D. In accordance with 21 CFR 1308.44 (a)-(c), requests for 
hearing, notices of appearance, and waivers of an opportunity for a 
hearing or to participate in a hearing may be submitted by interested 
persons. Such requests or notices must conform to the requirements of 
21 CFR 1308.44(a) or (b), and 1316.47 or 1316.48, as applicable, and 
include a statement of the interest of the person in the proceeding and 
the objections or issues, if any, concerning which the person desires 
to be heard. Any waiver must conform to the requirements of 21 CFR 
1308.44(c) and 1316.49, including a written statement regarding the 
interested person's position on the matters of fact and law involved in 
any hearing.
    Please note that, pursuant to 21 U.S.C. 811(a)(2), the purpose of a 
hearing would be to determine whether [\18\F]FP-CIT should be removed 
from the list of controlled substances based on a finding that the drug 
does not meet the requirements for inclusion in any schedule. All 
requests for hearing and waivers of participation must be sent to DEA 
using the address information above, on or before the date specified 
above.

Legal Authority

    The Controlled Substances Act (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 (1) on his own 
motion, (2) at the request of the Secretary of the Department of Health 
and Human Services (HHS),\1\ or (3) on the petition

[[Page 60787]]

of any interested party. 21 U.S.C. 811(a). 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 HHS and an 
evaluation of all relevant data by DEA. If finalized, this action would 
remove 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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    \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.
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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 (80 FR 54715).
    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 [\18\F]FP-CIT is a schedule II controlled substance under 
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 on November 28, 2018.

Proposed Determination To Decontrol [\18\F]FP-CIT

    Pursuant to 21 U.S.C. 811(b), on May 2, 2019, DEA, having gathered 
the necessary data on [\18\F]FP-CIT, forwarded that data and the 
petition to HHS with a request for 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 
entitled ``Basis for the recommendation to remove [\18\F]FP-CIT from 
schedule II of the Controlled Substances Act'' and a scheduling 
recommendation. The National Institute on Drug Abuse (NIDA) concurred 
with the scientific and medical evaluation conducted by FDA. Based on 
the totality of the available scientific data, [\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.
    The CSA requires DEA, as delegated by the Attorney General,\2\ to 
determine whether HHS's scientific and medical evaluation, scheduling 
recommendation, and all other relevant data constitute substantial 
evidence that a substance should be scheduled. 21 U.S.C. 811(b). DEA 
reviewed the scientific and medical evaluation and scheduling 
recommendation provided by HHS, and all other relevant data, and 
completed its own eight-factor review document on [\18\F]FP-CIT 
pursuant to 21 U.S.C. 811(c). Included below is a brief summary of each 
factor as analyzed by HHS and DEA, and as considered by DEA in this 
proposal to remove [\18\F]FP-CIT from the schedules of the CSA. Both 
DEA and HHS analyses are available in their entirety under ``Supporting 
and Related Material'' of the public docket for this rule at http://www.regulations.gov under docket number DEA-837.
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    \2\ 28 CFR 0.100(b).
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1. The Drug's Actual or Relative Potential for Abuse

    The first factor that must be considered is the actual or relative 
potential for abuse of [\18\F]FP-CIT. The term ``abuse'' is not defined 
in the CSA. However, the legislative history of the CSA suggests the 
following points in determining whether a particular drug or substance 
has a potential for abuse: \3\
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    \3\ Comprehensive Drug Abuse Prevention and Control Act of 1970, 
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); 1970 U.S.C.C.A.N. 
4566, 4603.
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    a. Whether there is evidence that individuals are taking the drug 
or drugs containing such a substance in amounts sufficient to create a 
hazard to their health or to the safety of other individuals or to the 
community.
    According to HHS's scientific and medical evaluation, there are no 
data demonstrating that individuals are taking either [\18\F]FP-CIT or 
[\123\I]ioflupane in amounts sufficient to create a hazard to their 
health or to the safety of other individuals or to the community. 
Additionally, as reported in the [\123\I]ioflupane HHS review, no case 
reports or clinical trials were published in scientific or medical 
literature that describe any incidents of drug abuse, misuse, or 
diversion of [\123\I]ioflupane.
    HHS notes that in their assessment of the abuse potential of 
[\123\I]ioflupane from studies conducted in animals, it was estimated 
that doses of the radiolabeled FP-CIT in the milligram range would be 
needed to elicit stimulant effects. Since the active pharmaceutical 
ingredient (API) is the same, the same calculations apply to [\18\F]FP-
CIT. HHS further states that upon receiving prescriptions from 
physicians [\18\F]FP-CIT will be manufactured immediately prior to its 
shipment and its limited availability will make its abuse logistically 
not possible.
    b. Whether there is significant diversion of the drug or drugs 
containing such a substance from legitimate drug channels.
    There has been no demonstrated diversion of [\123\I]ioflupane or 
[\18\F]FP-CIT. According to DEA's forensic laboratory databases, the 
National Forensic Laboratory Information System (NFLIS),\4\ there are 
no cases of [\123\I]ioflupane or [\18\F]FP-CIT (queried May 27, 2021). 
Further, according to data assessed for [\123\I]ioflupane, it is highly 
unlikely that [\18\F]FP-CIT or [\18\F]FP-CIT-containing products will 
be diverted in the United States. In the

[[Page 60788]]

United States, the Nuclear Regulatory Commission (NRC), the 
Occupational Safety and Health Administration, the Environmental 
Protection Agency, the Department of Transportation, and state 
legislation regulate the production, handling, transportation, and 
disposal of radiopharmaceuticals, all of which limit the trade to 
licensed radiopharmacies with a valid prescription.\5\ [\18\F]FP-CIT 
and any [\18\F]FP-CIT-containing products will be subject to oversight 
by such agencies.
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    \4\ 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.
    \5\ For radioactive substances there are controls other than 
those imposed by the CSA and its implementing regulations, including 
regulations by the NRC under 10 CFR part 35 and/or by states, which 
limit the public's exposure to radioactivity in 
radiopharmaceuticals, thus limiting the potential for toxicity 
imposed on the public.
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    HHS notes that with the manufacturing limits and current 
restrictions regarding distribution, handling and disposal will limit 
the potential for diversion of [\18\F]FP-CIT from legitimate drug 
channels.
    c. Whether individuals are taking the drug or drugs containing such 
a substance on their own initiative rather than on the basis of medical 
advice from a practitioner licensed by law to administer such drugs in 
the course of his professional practice.
    There has been no demonstrated diversion of [\18\F]FP-CIT nor 
published case reports or epidemiological data indicating that 
individuals are using [\18\F]FP-CIT-containing products on their own 
initiative rather than on the basis of medical advice from a 
practitioner licensed by law to administer such substances. Due to the 
radioactive properties, [\18\F]FP-CIT will not be administered by the 
patient or be available for self-administration by patients.
    d. Whether the drug or drugs containing such a substance are new 
drugs so related in their action to a substance already listed as 
having a potential for abuse to make it likely that it will have the 
same potentiality for abuse as such drugs, thus making it reasonable to 
assume that there may be significant diversions from legitimate 
channels, significant use contrary to or without medical advice, or 
that they have a substantial capability of creating hazards to the 
health of the user or to the safety of the community.
    As noted above, [\18\F]FP-CIT is chemically and pharmacologically 
similar to [\123\I]ioflupane. A formulation containing [\18\F]FP-CIT, 
similar to [\123\I]ioflupane, that is intended for diagnostic purposes, 
would contain the API in amounts too low than what is feasible for 
eliciting a central nervous system (CNS) stimulant pharmacological 
effect. It is estimated that milligram quantities would have to be 
administered to elicit a stimulant effect. Due to the manufacturing 
limitations and expected low concentrations of [\18\F]FP-CIT in an 
approved product, the volume of [\18\F]FP-CIT-containing product that 
would need to be administered to achieve a psychoactive effect for 
abuse is not logistically possible.

2. Scientific Evidence of the Drug's Pharmacological Effects, if Known

Preclinical Studies
    According to HHS scientific review of [\123\I]ioflupane, non-
radiolabeled FP-CIT acts on the CNS by blocking monoamine transporters, 
including DAT and other monoamine transporters (e.g., serotonin) and is 
mechanistically similar to cocaine (a schedule II substance). FP-CIT's 
affinity for DAT is between 10- and 100-fold greater than cocaine's 
affinity for DAT and appears to be more potent than cocaine in some 
behavioral assessments. HHS states that this mechanism of action 
suggests, like [\123\I]ioflupane, [\18\F]FP-CIT may potentially have 
abuse potential if the dose taken is high enough and if the deterrent 
effect of the extremely low concentration of the available radioligand 
is not considered.
    Drug discrimination assays in animals can be used to predict if a 
test drug will have abuse potential in humans. According to HHS, in a 
drug discrimination study, administration of non-radiolabeled FP-CIT at 
doses >0.1 mg/kg (i.v.) resulted in cocaine-appropriate responses in 
rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline. 
Thus, non-radiolabeled FP-CIT may produce cocaine-like subjective 
effects.
    HHS's review also noted that the administration of non-radiolabeled 
FP-CIT resulted in an increase of locomotor activity in rodents 
relative to vehicle, but produced a lower maximum level and was less 
potent compared to cocaine (schedule II substance), however the 
locomotor effects induced by FP-CIT lasted longer than cocaine.
Human Studies
    HHS notes that when [\18\F]FP-CIT was administered at doses used in 
diagnostic tests there was no clinical evidence of stimulant effects.

3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance

    The international non-proprietary name of [\18\F]FP-CIT is methyl 
(1R,2S,3S,5S)-8-[3-(fluoro-\18\F)propyl]-3-(4-iodophenyl)-8-
azabicyclo[3.2.1]octane-2-carboxylate. The molecular formula of 
[\18\F]FP-CIT is C18H23[\18\F]INO2 and the molecular weight is 431.28 
g/mol.
    The petitioner states that their expected [\18\F]FP-CIT-containing 
product (Fluoroseek) exists only as a clear, colorless to slightly 
yellow liquid solution in ethanol and saline solution (sodium chloride 
0.9% in water) and contains antioxidants such as gentisic acid and 
sodium ascorbate, with sodium carbonate as a pH modifier. The general 
chemical properties of [\18\F]FP-CIT are inferred from the chemical 
properties of the non-radioactive FP-CIT substance. FP-CIT is a white 
solid with a melting point of 83 [deg]C to 87 [deg]C and soluble in 
water (less than 0.1 mg/ml), sodium acetate buffer (pH 7.4; 16 mg/ml), 
and ethanol (27 mg/ml).
    As noted by HHS, there are no currently marketed [\18\F]FP-CIT-
containing products available. However, in a letter dated January 8, 
2020, the Petitioner sent a response to DEA on a request for 
information regarding the composition of the product and the expected 
doses patients will receive. In this communication, the Petitioner 
states that the synthesized product ``. . . contains 40 micrograms 
([mu]g) of [18F] Fluoroseek per 29 milliliters (mL). Each patient will 
receive 0.3-3.0 mL of the solution.'' Thus, based on the concentration 
(40 [mu]g/29 mL) of the product, as indicated by the Petitioner, and 
the amount of the [\18\F]FP-CIT solution that the Petitioner estimates 
patients will receive (0.3-3.0 mL), the doses a patient may receive 
will be in the range of 0.41 [mu]g to 4.13 [mu]g.
    For [\123\I]ioflupane, HHS mentions that the meaningful extraction 
of [\123\I]ioflupane from the marketed drug product, DaTscan, would be 
impossible due to its limited production and availability and it is 
technically complex and would require advanced equipment not available 
to the general public.
Medical Use
    According to HHS, as of April 2021, the petitioner has yet to 
submit an NDA for the [\18\F]FP-CIT-containing drug product 
(Fluoroseek). It is expected that, similar to [\123\I]ioflupane, 
[18F]FP-CIT will be used as a diagnostic agent, potentially in 
conjunction with PET imaging, whereas [\123\I]ioflupane is used in 
SPECT imaging.

4. Its History and Current Pattern of Abuse

    There have been no reports of abuse of [\18\F]FP-CIT or 
[\123\I]ioflupane at the doses used for diagnostic purposes.

[[Page 60789]]

Similar to [\123\I]ioflupane, [\18\F]FP-CIT was developed for 
diagnostic purposes and contains a small amount of the API. The amount 
of [\18\F]FP-CIT in each vial of [\18\F]FP-CIT would be limited and it 
is produced based on demand. Additional regulations and control 
mechanisms by the NRC and other federal agencies exist for the 
production, handling and use of [\18\F]FP-CIT due to its radioactivity.

5. The Scope, Duration, and Significance of Abuse

    DEA has searched the scientific literature and the Federal, State, 
and local forensic laboratory databases such as NFLIS to assess the 
scope of [\18\F]FP-CIT abuse in the United States. There were no 
reports of [\18\F]FP-CIT seizures during the period of January 2010-
April 2021.

6. What, if Any, Risk There Is to the Public Health

    The risk to public health is unknown for [\18\F]FP-CIT. However, as 
stated by HHS the radioactive nature of the substance, limited amounts 
of substance needed for imaging purposes, and the existence of 
stringent regulatory controls on the manufacturing and handling, 
[\18\F]FP-CIT poses little or no practical risk to public health. 
Because the API for [\18\F]FP-CIT is the same as [\123\I]ioflupane, 
[\18\F]FP-CIT is expected to have the same product characteristics.

7. Its Psychic or Physiological Dependence Liability

    HHS reports that no systemic evaluation has been conducted to 
determine whether [\123\I]ioflupane or [\18\F]FP-CIT produces psychic 
or physiological dependence in animals or humans. It is expected that 
the use of the radiolabeled agents (i.e., [\123\I]ioflupane and 
[\18\F]FP-CIT) will not produce psychic or physiological dependence due 
to the low dose and short-term exposure.

8. Whether the Substance Is an Immediate Precursor of a Substance 
Already Controlled Under the CSA

    Similar to [\123\I]ioflupane, [\18\F]FP-CIT is not an immediate 
precursor of a substance already controlled under the CSA.

Conclusion

    Based on consideration of the scientific and medical evaluation and 
accompanying recommendation of HHS, and based on DEA's consideration of 
its own eight-factor analysis, DEA finds that these facts and all 
relevant data demonstrate that [\18\F]FP-CIT does not possess abuse or 
dependence potential. According to HHS, no NDA containing [\18\F]FP-CIT 
has been submitted. However, the finding that [\18\F]FP-CIT lacks abuse 
potential would, irrespective of other findings, permit decontrol of 
[\18\F]FP-CIT prior to or in the absence of an FDA action under 21 
U.S.C. 355(c). Accordingly, DEA finds that [\18\F]FP-CIT does not meet 
the requirements for inclusion in any schedule, and should be removed 
from 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 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 proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of E.O. 12988 Civil Justice Reform 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. The proposed 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 proposed rule does not have tribal implications warranting the 
application of E.O. 13175. This proposed 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 proposed 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 
proposed 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.
    If finalized, the proposed rule will affect all persons who would 
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 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 proposed 
rule, a qualitative analysis indicates that this rule is likely to 
result in some cost savings. As noted above, DEA is specifically 
soliciting comments on the economic impact of this proposed rule. DEA 
will revise this section if warranted after consideration of any 
comments received. 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.

[[Page 60790]]

    Because of these factors, DEA projects that this proposed rule will 
not result in a significant economic impact on a substantial number of 
small entities.

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. 44 U.S.C. 3501-
3521

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 proposed to be 
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) through (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.
* * * * *

Anne Milgram,
Administrator.
[FR Doc. 2021-23852 Filed 11-3-21; 8:45 am]
BILLING CODE 4410-09-P