Schedules of Controlled Substances: Removal of [18

CourtDrug Enforcement Administration,Justice Department
Citation86 FR 60785
Publication Date04 November 2021
Record Number2021-23852
60785
Federal Register / Vol. 86, No. 211 / Thursday, November 4, 2021 / Proposed Rules
All communications received before
the specified closing date for comments
will be considered before taking action
on the proposed rule. The proposal
contained in this document may be
changed in light of the comments
received. All comments submitted will
be available for examination in the
public docket both before and after the
comment closing date. A report
summarizing each substantive public
contact with FAA personnel concerned
with this rulemaking will be filed in the
docket.
Availability of NPRMs
An electronic copy of this document
may be downloaded through the
internet at https://www.regulations.gov.
Recently published rulemaking
documents can also be accessed through
the FAA’s web page at https://
www.faa.gov/air_traffic/publications/
airspace_amendments/.
You may review the public docket
containing the proposal, any comments
received and any final disposition in
person in the Dockets Office (see the
ADDRESSES
section for address and
phone number) between 9:00 a.m. and
5:00 p.m., Monday through Friday,
except federal holidays. An informal
docket may also be examined between
8:00 a.m. and 4:30 p.m., Monday
through Friday, except federal holidays,
at the office of the Eastern Service
Center, Federal Aviation
Administration, Room 350, 1701
Columbia Avenue, College Park, GA
30337.
Availability and Summary of
Documents for Incorporation by
Reference
This document proposes to amend
FAA Order JO 7400.11F, Airspace
Designations and Reporting Points,
dated August 10, 2021, and effective
September 15, 2021. FAA Order JO
7400.11F is publicly available as listed
in the
ADDRESSES
section of this
document. FAA Order JO 7400.11F lists
Class A, B, C, D, and E airspace areas,
air traffic service routes, and reporting
points.
The Proposal
The FAA proposes an amendment to
14 CFR part 71 to establish Class E
airspace extending upward from 700
feet above the surface within a 6.4-mile
radius of Dewitt Municipal Airport/
Whitcomb Field, Dewitt, AR. This
proposed amendment provides the
controlled airspace required to support
RNAV (GPS) standard instrument
approach procedures for IFR operations
at this airport.
Class E airspace designations are
published in Paragraph 6005 of FAA
Order JO 7400.11F, dated August 10,
2021, and effective September 15, 2021,
which is incorporated by reference in 14
CFR 71.1. The Class E airspace
designations listed in this document
will be published subsequently in the
FAA Order JO 7400.11.
FAA Order JO 7400.11, Airspace
Designations and Reporting Points, is
published yearly and effective on
September 15.
Regulatory Notices and Analyses
The FAA has determined that this
proposed regulation only involves an
established body of technical
regulations for which frequent and
routine amendments are necessary to
keep them operationally current. It,
therefore: (1) Is not a ‘‘significant
regulatory action’’ under Executive
Order 12866; (2) is not a ‘‘significant
rule’’ under DOT Regulatory Policies
and Procedures (44 FR 11034; February
26, 1979); and (3) does not warrant
preparation of a Regulatory Evaluation
as the anticipated impact is so minimal.
Since this is a routine matter that will
only affect air traffic procedures and air
navigation, it is certified that this
proposed rule, when promulgated, will
not have a significant economic impact
on a substantial number of small entities
under the criteria of the Regulatory
Flexibility Act.
Environmental Review
This proposal will be subject to an
environmental analysis in accordance
with FAA Order 1050.1F,
‘‘Environmental Impacts: Policies and
Procedures’’ prior to any FAA final
regulatory action.
Lists of Subjects in 14 CFR Part 71
Airspace, Incorporation by reference,
Navigation (air).
The Proposed Amendment
In consideration of the foregoing, the
Federal Aviation Administration
proposes to amend 14 CFR part 71 as
follows:
PART 71—DESIGNATION OF CLASS A,
B, C, D, AND E AIRSPACE AREAS; AIR
TRAFFIC SERVICE ROUTES; AND
REPORTING POINTS
1. The authority citation for part 71
continues to read as follows:
Authority: 49 U.S.C. 106(f), 106(g); 40103,
40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR,
1959–1963 Comp., p. 389.
§ 71.1 [Amended]
2. The incorporation by reference in
14 CFR 71.1 of Federal Aviation
Administration Order JO 7400.11F,
Airspace Designations and Reporting
Points, dated August 10, 2021, and
effective September 15, 2021, is
amended as follows:
Paragraph 6005 Class E Airspace Areas
Extending Upward From 700 Feet or More
Above the Surface of the Earth.
* * * * *
ASW AR E5 Dewitt, AR [Established]
Dewitt Municipal Airport/Whitcomb Field,
AR
(Lat. 34°1544WN, long. 91°1827W)
That airspace extending upward from 700
feet above the surface within a 6.4-mile
radius of Dewitt Municipal Airport/
Whitcomb Field.
Issued in College Park, Georgia, on October
27, 2021.
Andreese C. Davis,
Manager, Airspace & Procedures Team South,
Eastern Service Center, Air Traffic
Organization.
[FR Doc. 2021–23966 Filed 11–3–21; 8:45 am]
BILLING CODE 4910–13–P
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-w-
fluoropropyl-b-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
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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
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
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domestic drug scheduling recommendations. 58 FR
35460, July 1, 1993.
2
28 CFR 0.100(b).
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.
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.
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.
Background
[
18
F]FP-CIT (chemical names: [
18
F]N-
w-fluoropropyl-b-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-b-CIT (2b-carbomethoxy-3b -(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.
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
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
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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.
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.
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 °C to 87°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 (mg) 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 mg/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 mg to 4.13 mg.
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.
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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.
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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
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) through (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) [
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
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