Proposed Rule2021-23852
Schedules of Controlled Substances: Removal of [18F]FP-CIT From Control
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
November 4, 2021
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
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 conduct chemical analysis) or propose to handle [\18\F]FP-CIT.
Full Text
<html>
<head>
<title>Federal Register, Volume 86 Issue 211 (Thursday, November 4, 2021)</title>
</head>
<body><pre>
[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 [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-23852]
=======================================================================
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
<bullet> 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
<a href="http://www.regulations.gov">http://www.regulations.gov</a> 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 <a href="http://Regulations.gov">Regulations.gov</a>. If you have received a Comment Tracking
Number, your comment has been successfully submitted and there is no
need to resubmit the same comment.
<bullet> 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.
<bullet> 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 <a href="http://www.regulations.gov">http://www.regulations.gov</a>. 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 <a href="http://www.regulations.gov">http://www.regulations.gov</a> 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 <a href="http://www.regulations.gov">http://www.regulations.gov</a> 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.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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 <a href="http://www.regulations.gov">http://www.regulations.gov</a> under docket number DEA-837.
---------------------------------------------------------------------------
\2\ 28 CFR 0.100(b).
---------------------------------------------------------------------------
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\
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
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
</pre></body>
</html>Indexed from Federal Register on November 4, 2021.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.