80 FR 31521 - Schedules of Controlled Substances: Removal of [123

DEPARTMENT OF JUSTICE
Drug Enforcement Administration

Federal Register Volume 80, Issue 106 (June 3, 2015)

Page Range		31521-31525
FR Document		2015-13455

The Drug Enforcement Administration proposes to remove [\123\I]ioflupane from the schedules of the Controlled Substances Act. This action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after an opportunity for a hearing through formal rulemaking. [\123\I]Ioflupane is, by definition, a schedule II controlled substance because it is derived from cocaine via ecgonine, both of which are schedule II controlled substances. 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 [\123\I]ioflupane.

Federal Register, Volume 80 Issue 106 (Wednesday, June 3, 2015)

[Federal Register Volume 80, Number 106 (Wednesday, June 3, 2015)]
[Proposed Rules]
[Pages 31521-31525]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2015-13455]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-415]

Schedules of Controlled Substances: Removal of [\123\I]Ioflupane
From Schedule II of the Controlled Substances Act

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration proposes to remove
[\123\I]ioflupane from the schedules of the Controlled Substances Act.
This action is pursuant to the Controlled Substances Act which requires
that such actions be made on the record after an opportunity for a
hearing through formal rulemaking. [\123\I]Ioflupane is, by definition,
a schedule II controlled substance because it is derived from cocaine
via ecgonine, both of which are schedule II controlled substances. 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 [\123\I]ioflupane.

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 July
6, 2015. 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, defined at 21 CFR 1300.01 as those ``adversely
affected or aggrieved by any rule or proposed rule issuable pursuant to
section 201 of the Act (21 U.S.C. 811)'', 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 July 6, 2015.

ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-415'' on all correspondence, including any
attachments.
Electronic comments: The 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 an
electronic submission are not necessary and are discouraged. Should you
wish to mail a comment in lieu of submitting a comment online, it
should be sent via regular or express mail to: Drug Enforcement
Administration, Attention: DEA Federal Register Representative/ODXL,
8701 Morrissette Drive, Springfield, Virginia 22152.
Hearing requests: All requests for hearing must be sent
to: DEA Federal Register Representative/ODL, 8701 Morrissette Drive,
Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: John R. Scherbenske, Office of
Diversion

[[Page 31522]]

Control, Drug Enforcement Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia 22152; Telephone: (202) 598-
6812.

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 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
(FOIA) 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 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
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
online 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.

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 (APA) (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 only by
interested persons, defined as those ``adversely affected or aggrieved
by any rule or proposed rule issuable pursuant to section 201 of the
Act (21 U.S.C. 811).'' 21 CFR 1300.01. 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.

Legal Authority

The Drug Enforcement Administration (DEA) implements and enforces
titles II and III of the Comprehensive Drug Abuse Prevention and
Control Act of 1970, as amended. 21 U.S.C. 801-971. Titles II and III
are referred to as the ``Controlled Substances Act'' and the
``Controlled Substances Import and Export Act,'' respectively, but they
are collectively referred to as the ``Controlled Substances Act'' or
the ``CSA'' for the purposes of this action. The DEA publishes the
implementing regulations for these statutes in title 21 of the Code of
Federal Regulations (CFR), chapter II. The CSA and its implementing
regulations are designed to prevent, detect, and eliminate the
diversion of controlled substances and listed chemicals into the
illicit market while ensuring an adequate supply is available for the
legitimate medical, scientific, research, and industrial needs of the
United States. Controlled substances have the potential for abuse and
dependence and are controlled to protect the public health and safety.
Under the CSA, each controlled substance is classified into one of
five schedules based upon its potential for abuse, its currently
accepted medical use in treatment in the United States, and the degree
of dependence the drug or other substance may cause. 21 U.S.C. 812. The
initial schedules of controlled substances established by Congress are
found at 21 U.S.C. 812(c) and the current list of scheduled substances
is published at 21 CFR part 1308.
Pursuant to 21 U.S.C. 811(a)(2), the Attorney General may, by rule,
``remove any drug or other substance from the schedules if he [or she]
finds that the drug or other substance does not meet the requirements
for inclusion in any schedule.'' The Attorney General has delegated
scheduling authority under 21 U.S.C. 811 to the Administrator of the
DEA, 28 CFR 0.100.
The CSA provides that proceedings for the issuance, amendment, or
repeal of the scheduling of any drug or other substance may be
initiated by the Attorney General (1) on his or her own motion, (2) at
the request of the Secretary of the Department of Health and Human
Services,\1\ or (3) on the petition of any interested party. 21 U.S.C.
811(a). This action was initiated at the request of the Assistant
Secretary for Health of the HHS, and is supported by an evaluation of
all relevant data by the HHS and the DEA. 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 [\123\I]ioflupane.
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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), the FDA acts as the lead agency within the HHS
in carrying out the Secretary's scheduling responsibilities under
the CSA, with the concurrence of NIDA. 50 FR 9518, Mar. 8, 1985. The
Secretary of the HHS has delegated to the Assistant Secretary for
Health of the HHS the authority to make domestic drug scheduling
recommendations. 58 FR 35460, July 1, 1993.
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Background

DaTscan is a single-dose, injectable diagnostic radiopharmaceutical
for use in hospital settings with specialized gamma cameras. It was
developed as a diagnostic tool for visualization of dopamine
transporters (DAT) by using single photon emission computed tomography
(SPECT) brain imaging. The Food and Drug Administration (FDA) approved
the New Drug Application (NDA) for DaTscan on January 14, 2011, for the
indication of visualizing striatal DATs in the brains of adult patients
with suspected Parkinsonian syndromes (PS). [\123\I]Ioflupane is the
active pharmaceutical ingredient (API) in DaTscan and it is a new
molecular entity. However, [\123\I]Ioflupane is, by definition, a
schedule II controlled substance because it is derived from cocaine, a
schedule II substance, via ecgonine (a schedule II substance). See 21
U.S.C. 812(c), Schedule II, (a)(4).

[[Page 31523]]

Each vial of DaTscan contains 0.325 micrograms ([mu]g) of
[\123\I]ioflupane per 2.5 milliliters (ml). The average and maximum
amounts of non-radioactive ioflupane in each DaTscan vial are estimated
to be between 0.21 [mu]g and 0.31 [mu]g. Although ioflupane, the non-
radiolabeled API of the drug product DaTscan, binds to DAT and elicits
behavioral effects similar to that of cocaine, based upon the available
information and DaTscan's unique formulation-specific properties,
DaTscan itself presents no practical possibility of abuse, misuse,
diversion or clandestine production.

Proposed Determination To Decontrol [\123\I]Ioflupane

Pursuant to 21 U.S.C. 811(b), (c), and (f), the HHS recommended to
the DEA on November 2, 2010, that FDA-approved products containing
[\123\I]ioflupane be removed from schedule II of the CSA. HHS provided
to DEA a scientific and medical evaluation document entitled ``Basis
for the Recommendation to Remove FDA Approved Products Containing
[\123\I]Ioflupane from Schedule II of the Controlled Substances Act
(CSA).'' Pursuant to 21 U.S.C. 811(b), this document contained an
eight-factor analysis of FDA-approved products containing
[\123\I]ioflupane, along with the HHS's recommendation to remove FDA-
approved products containing [\123\I]ioflupane from the schedules of
the CSA.
In response, the DEA reviewed the scientific and medical evaluation
and scheduling recommendation provided by the HHS, and all other
relevant data. The DEA and HHS collaborated further regarding the
available information. By letter dated February 2, 2015, the HHS
provided detailed responses to specific inquiries from the DEA
(submitted by letter dated September 16, 2014). Upon further review of
all of the available information, the DEA completed its own eight-
factor review document on FDA-approved diagnostic products containing
[\123\I]ioflupane (currently, only DaTscan) pursuant to 21 U.S.C.
811(c). The FDA-approved diagnostic product, DaTscan, was used as the
basis for the scientific and medical evaluation of FDA-approved
diagnostic products containing [\123\I]ioflupane for both the HHS and
DEA eight-factor analysis. Included below is a brief summary of each
factor as analyzed by the HHS and the DEA, and as considered by the DEA
in this proposed rule to remove [\123\I]ioflupane from the schedules of
the CSA. Please note that both the DEA and HHS analyses and other
relevant documents 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-415.

1. The Drug's Actual or Relative Potential for Abuse

According to HHS and the DEA, there are no data demonstrating that
individuals are administering quantities of DaTscan sufficient to
create a hazard to their health or to the safety of other individuals
or to the community. In clinical studies, DaTscan, due to its low
concentrations of [\123\I]ioflupane lacked, central nervous activity
(CNS) in humans.
According to HHS review of Sponsor's calculation regarding
psychoactive doses of DaTscan, approximately 6,000 vials of DaTscan
would be required to produce a subjective ``high'' in humans from
exposure to [\123\I]ioflupane in this product. The volume of 6,000
vials is about 15 liters (L) of fluid, an amount that would be lethal
if administered intravenously (i.v.). The short half-life of DaTscan
(due to its radioactive decay) will prevent its extended storage for
future use at the manufacturing, distributing, or radiopharmacy site;
thereby limiting the amount available for diversion. It is highly
unlikely that individuals will administer DaTscan on their own
initiative since DaTscan has a very dilute and small dose of
[\123\I]ioflupane, and possesses radioactivity. As a result, DaTscan
will not have significant capability of creating hazards to the health
of the user or to the safety of the community.

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

DaTscan blocks monoamine transporters, such as DAT and other
monoamine transporters such as serotonin transporters. Ioflupane, the
active pharmaceutical ingredient in DaTscan, was demonstrated to have
an affinity to DAT that was approximately 10- and 100-fold greater than
cocaine in rodent brain homogenates or in cells transfected with rat
DAT (Neumeyer et al., 1996; Okada et al., 1998; Scheffel et al., 1997).
As reported by HHS, non-radiolabeled ioflupane at doses >0.1 mg/kg,
i.v. was able to substitute for cocaine in cocaine-trained rats (10 mg/
kg, intraperitoneal administration) using a drug discrimination
protocol which is predictive of subjective behavioral effects in
humans.
HHS reviewed data from eight human clinical trials involving 942
subjects and nine years of post-approval use in Europe and found that
there was not any clinical evidence of pharmacological effects
resulting from DaTscan administration. The maximum dose of
[\123\I]ioflupane in DaTscan that is administered to the patient prior
to undergoing an imaging procedure is 0.325 [mu]g (0.13 [mu]g/ml). HHS
extrapolated from the locomotor study and drug discrimination study on
non-radiolabeled ioflupane and estimated that the lowest active dose of
DaTscan for a 60 kg (132.2 lb) human to achieve a pharmacologic effect
would be 288 [mu]g or 886 vials of DaTscan. In addition, the
recreational dose of DaTscan is estimated as 1921 [micro]g or 5,910
vials.
Although [\123\I]ioflupane would be expected to have a
pharmacological profile nearly identical to its non-radioactive form,
its unique properties (i.e., manufacturing limits and radioactive
properties) pose practical barriers to its abuse. Furthermore,
according to HHS, the amount of [\123\I]ioflupane in DaTscan is
significantly less than the amounts of ioflupane used to elicit the
pharmacological response in preclinical studies with this compound.

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

The international non-proprietary name of [\123\I]ioflupane is
methyl(1R, 2S, 3S, 5S)-8-(3-fluoropropyl)-3-(4-[\123\I]iodophenyl)-8-
azabicyclo[3,2,1] octane-2-carboxylate. The molecular formula of
[\123\I]ioflupane is
C18H23F[\123\I]NO2 and the molecular
weight is 427.28 g/mol. [\123\I]Ioflupane is a clear, colorless
solution and is only present in a solution of ethanol and sodium
acetate buffer. Non-radioactive ioflupane 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).
HHS states that meaningful extraction of [\123\I]ioflupane from
DaTscan would be impossible due to its limited production and
availability and because extraction is technically complex and would
require advanced equipment not available to the general public.
Importantly, if extraction of ioflupane from [\123\I]ioflupane is
accomplished, the ioflupane would be subject to schedule II controls
under the CSA. According to HHS, the retrosynthesis of DaTscan to
cocaine and ecgonine would be difficult. Production of DaTscan is
technically complex as it requires specialized equipment, facilities,
scientific training and expertise, making clandestine manufacturing
particularly difficult. HHS indicated that the non-radiolabeled
precursors needed for the synthesis of [\123\I]ioflupane (and

[[Page 31524]]

DaTscan) are abusable. In addition, the non-radiolabeled precursors
derived from cocaine or ecgonine are also schedule II controlled
substances. However, even if an individual obtained the precursors, it
is impractical and highly unlikely that they would synthesize the
abusable compound into a radiolabeled formulation with a limited
storage life that is not desired by drug users.
On January 14, 2011, FDA approved the NDA for DaTscan with the
indication of visualizing striatal dopamine transporters in the brains
of adult patients with suspected Parkinsonian syndromes using SPECT
imaging. As such, any FDA-approved diagnostic product containing
[\123\I]ioflupane has a currently accepted medical use in the United
States.

4. Its History and Current Pattern of Abuse

According to HHS, there have been no reports of abuse of
[\123\I]ioflupane. Over 168,000 doses of DaTscan have been administered
to patients worldwide, and no pharmacological effects have been noted.
Further, according to HHS, no single user has received more than 10
vials of DaTscan in a single day.

5. The Scope, Duration, and Significance of Abuse

There have been no reports of abuse of [\123\I]ioflupane. According
to the National Forensic Laboratory Information System (NFLIS) \2\ and
the System to Retrieve Information from Drug Evidence (STRIDE) \3\,
there have been no reports of [\123\I]ioflupane seizures during the
time period January 2010 to February 2015.
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\2\ NFLIS is a program of the DEA that collects drug
identification results from drug cases analyzed by other Federal,
State, and local forensic laboratories. NFLIS was queried on April
16, 2015.
\3\ STRIDE collected the results of drug evidence analyzed at
DEA laboratories and reflects evidence submitted by the DEA, other
Federal law enforcement agencies, and some local law enforcement
agencies. STRIDE data was queried by date submitted to Federal
forensic laboratories. On October 1, 2014, STARLiMS replaced STRIDE
as the DEA laboratory drug evidence data system of record.
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6. What, If Any, Risk There Is to the Public Health

According to the HHS, because of the limited amounts of
manufactured DaTscan, the low concentration of [\123\I]ioflupane per
vial, and the existence of stringent regulatory controls (controls
other than those imposed by the CSA and its implementing regulations,
including regulation by the United States Nuclear Regulatory Commission
under 10 CFR part 35 and/or by states) \4\ on the manufacturing and
handling of DaTscan, abuse of DaTscan is not possible as a practical
matter. Thus, there is little to no practical risk to public health
from DaTscan abuse.
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\4\ There are Federal and state laws and regulations which limit
the public's exposure to radioactivity in radiopharmaceuticals, thus
limiting the potential for toxicity imposed on the public.
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7. Its Psychic or Physiological Dependence Liability

As reviewed by HHS, non-radiolabeled ioflupane has cocaine-like
properties. In a drug discrimination study in cocaine-trained rats,
non-radiolabeled ioflupane produced cocaine-appropriate responding,
which suggests that non-radiolabeled ioflupane may produce cocaine-like
subjective effects in humans (HHS, 2010).
However, the available evidence suggests that there is no psychic
or physiological dependence potential of FDA-approved diagnostic
products containing [\123\I]ioflupane. The psychic or physiological
dependence potential of FDA-approved diagnostic products is currently
expected to be very limited due to the low exposure concentration of
[\123\I]ioflupane, the aforementioned low potential for abuse (see
Factor 1) and the extremely high and lethal quantities needed to
achieve a subjective ``high.''

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

[\123\I]Ioflupane 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 the HHS and based on the DEA's
consideration of its own eight-factor analysis, the DEA finds that the
facts and all available and relevant data demonstrate that
[\123\I]ioflupane does not possess abuse or dependence potential.
Accordingly, the DEA finds that [\123\I]ioflupane does not meet the
requirements for inclusion in any schedule and should be removed from
control under the CSA.

Findings for Schedule Placement Pursuant to 21 U.S.C. 812(b)

The CSA outlines the findings required to place a drug or other
substance in any particular schedule (I, II, III, IV, or V). 21 U.S.C.
812(b). The Assistant Secretary for Health of the HHS recommended
removal of ``FDA approved products containing [\123\I]ioflupane from
schedule II of the'' CSA. However, because the DEA finds no basis to
remove only FDA approved products containing [\123\I]ioflupane from the
schedules, this action proposes to remove the substance
[\123\I]ioflupane from the CSA schedules. Historically, when new
molecular entities are removed from control, the substance itself is
removed from control rather than the specific FDA-approved drug product
(e.g., naloxegol, 80 FR 3468; naloxone, 39 FR 44392). As summarized
above, the data currently support removal of substances that contain
[\123\I]ioflupane, primarily because [\123\I]ioflupane itself has a
lethal radioactive barrier, and its manufacturing process is highly
regulated and technically complex, thus making abuse highly unlikely.
After consideration of the analyses and recommendation of the
Assistant Secretary for Health of the HHS and review of all relevant
and available data, the Administrator of the DEA, pursuant to 21 U.S.C.
812(b)(5), finds that:
(1) [\123\I]Ioflupane has no comparable potential for abuse
relative to substances in Schedule V.
(2) [\123\I]Ioflupane has a currently accepted medical use in
treatment in the United States. FDA approved the New Drug Application
for DaTscan on January 14, 2011, with the indication of visualizing
striatal dopamine transporters in the brains of adult patients with
suspected Parkinsonian syndromes using SPECT imaging.
(3) [\123\I]Ioflupane is not abusable, therefore, its use is not
likely to lead to physical or psychological dependence.
Based on these findings, the Administrator of the DEA concludes
that [\123\I]ioflupane does not warrant control under the CSA.

Effect on Other Rulemakings

On November 25, 2014, DEA published an interim final rule waiving
the requirement of DEA registration for certain entities that are
authorized under other federal or state authorities to administer
DaTscan. 79 FR 70085. If finalized, this proposal to remove
[\123\I]ioflupane from the schedules of controlled substances would
make such waivers unnecessary. Therefore, if this action is finalized,
DEA intends to withdraw the regulations established through that
interim final rule.

Regulatory Analyses

Executive Orders 12866 and 15363

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

[[Page 31525]]

hearing,'' which are conducted pursuant to the provisions of 5 U.S.C.
556 and 557. The CSA sets forth the criteria for scheduling a drug or
other substance and for removing a drug or substance from the schedules
of controlled substances. Such actions are exempt from review by the
Office of Management and Budget (OMB) pursuant to section 3(d)(1) of
Executive Order 12866 and the principles reaffirmed in Executive Order
13563.

Executive Order 12988

This regulation meets the applicable standards set forth in
sections 3(a) and 3(b)(2) of Executive Order 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

This rulemaking does not have federalism implications warranting
the application of Executive Order 13132. The 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

This rule does not have tribal implications warranting the
application of Executive Order 13175. This rule does not have
substantial direct effects on one or more Indian tribes, on the
relationship between the Federal Government and Indian tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian tribes.

Regulatory Flexibility Act

The Administrator, in accordance with the Regulatory Flexibility
Act (5 U.S.C. 601-612) (RFA), 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
rule is to remove [\123\I]ioflupane 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 [\123\I]ioflupane. 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, [\123\I]ioflupane. Due to the wide
variety of unidentifiable and unquantifiable variables that potentially
could influence the distribution and administration rates of new
molecular entities, the DEA is unable to determine the number of
entities and small entities which might handle [\123\I]ioflupane.
Although the 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, if finalized,
this rule is likely to result in some cost savings for the healthcare
industry. The affected entities will continue to meet existing Federal
and/or state requirements applicable to those who handle
radiopharmaceutical substances, including licensure, security,
recordkeeping, and reporting requirements, which in many cases are more
stringent than the DEA's requirements. However, the DEA estimates cost
savings will be realized from the removal of the administrative, civil,
and criminal sanctions for those entities handling or proposing to
handle [\123\I]ioflupane, in the form of saved registration fees, and
the elimination of additional physical security, recordkeeping, and
reporting requirements.
Because of these facts, this rule will not result in a significant
economic impact on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, the DEA has determined and certifies
pursuant to the Unfunded Mandates Reform Act of 1995 (UMRA), 2 U.S.C.
1501 et seq., 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 for inflation) in any one year * * * .''
Therefore, neither a Small Government Agency Plan nor any other action
is required under provisions of UMRA.

Paperwork Reduction Act

This action does not impose a new collection of information
requirement under the Paperwork Reduction Act, 44 U.S.C. 3501-3521.
This action would not impose recordkeeping or reporting requirements on
State or local governments, individuals, businesses, or organizations.
An agency may not conduct or sponsor, and a person is not required to
respond to, a collection of information unless it displays a currently
valid OMB control number.

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), unless otherwise noted.

0
2. In Sec. 1308.12, revise paragraph (b)(4) to read as follows:

Sec. 1308.12 Schedule II.

* * * * *
(b) * * *
(4) Coca leaves (9040) and any salt, compound, derivative or
preparation of coca leaves (including cocaine (9041) and ecgonine
(9180) and their salts, isomers, derivatives and salts of isomers and
derivatives), and any salt, compound, derivative, or preparation
thereof which is chemically equivalent or identical with any of these
substances, except that the substances shall not include:
(i) Decocainized coca leaves or extraction of coca leaves, which
extractions do not contain cocaine or ecgonine; or
(ii) [\123\I]ioflupane.
* * * * *

Dated: May 6, 2015.
Michele M. Leonhart,
Administrator.
[FR Doc. 2015-13455 Filed 6-2-15; 8:45 am]
BILLING CODE 4410-09-P

31522 Federal Register / Vol. 80, No. 106 / Wednesday, June 3, 2015 / Proposed Rules

Control, Drug Enforcement record after opportunity for a hearing.’’ found at 21 U.S.C. 812(c) and the
Administration; Mailing Address: 8701 Such proceedings are conducted current list of scheduled substances is
Morrissette Drive, Springfield, Virginia pursuant to the provisions of the published at 21 CFR part 1308.
22152; Telephone: (202) 598–6812. Administrative Procedure Act (APA) (5 Pursuant to 21 U.S.C. 811(a)(2), the
SUPPLEMENTARY INFORMATION: U.S.C. 551–559). 21 CFR 1308.41– Attorney General may, by rule, ‘‘remove
1308.45, and 21 CFR part 1316 subpart any drug or other substance from the
Posting of Public Comments D. In accordance with 21 CFR 1308.44 schedules if he [or she] finds that the
Please note that all comments (a)–(c), requests for hearing, notices of drug or other substance does not meet
received in response to this docket are appearance, and waivers of an the requirements for inclusion in any
considered part of the public record. opportunity for a hearing or to schedule.’’ The Attorney General has
They will, unless reasonable cause is participate in a hearing may be delegated scheduling authority under 21
given, be made available by the DEA for submitted only by interested persons, U.S.C. 811 to the Administrator of the
public inspection online at http:// defined as those ‘‘adversely affected or DEA, 28 CFR 0.100.
www.regulations.gov. Such information aggrieved by any rule or proposed rule The CSA provides that proceedings
includes personal identifying issuable pursuant to section 201 of the for the issuance, amendment, or repeal
information (such as your name, Act (21 U.S.C. 811).’’ 21 CFR 1300.01. of the scheduling of any drug or other
address, etc.) voluntarily submitted by Such requests or notices must conform substance may be initiated by the
the commenter. The Freedom of to the requirements of 21 CFR 1308.44 Attorney General (1) on his or her own
Information Act (FOIA) applies to all (a) or (b), and 1316.47 or 1316.48, as motion, (2) at the request of the
comments received. If you want to applicable, and include a statement of Secretary of the Department of Health
submit personal identifying information the interest of the person in the and Human Services,1 or (3) on the
(such as your name, address, etc.) as proceeding and the objections or issues, petition of any interested party. 21
part of your comment, but do not want if any, concerning which the person U.S.C. 811(a). This action was initiated
it to be made publicly available, you desires to be heard. Any waiver must at the request of the Assistant Secretary
must include the phrase ‘‘PERSONAL conform to the requirements of 21 CFR for Health of the HHS, and is supported
IDENTIFYING INFORMATION’’ in the 1308.44(c) and 1316.49, including a by an evaluation of all relevant data by
first paragraph of your comment. You written statement regarding the the HHS and the DEA. This action
must also place the personal identifying interested person’s position on the would remove the regulatory controls
information you do not want made matters of fact and law involved in any and administrative, civil, and criminal
publicly available in the first paragraph hearing. sanctions applicable to controlled
of your comment and identify what substances, including those specific to
Legal Authority schedule II controlled substances, on
information you want redacted.
If you want to submit confidential The Drug Enforcement persons who handle or propose to
business information as part of your Administration (DEA) implements and handle [123I]ioflupane.
comment, but do not want it to be made enforces titles II and III of the
Background
publicly available, you must include the Comprehensive Drug Abuse Prevention
phrase ‘‘CONFIDENTIAL BUSINESS and Control Act of 1970, as amended. 21 DaTscan is a single-dose, injectable
INFORMATION’’ in the first paragraph U.S.C. 801–971. Titles II and III are diagnostic radiopharmaceutical for use
of your comment. You must also referred to as the ‘‘Controlled in hospital settings with specialized
prominently identify confidential Substances Act’’ and the ‘‘Controlled gamma cameras. It was developed as a
business information to be redacted Substances Import and Export Act,’’ diagnostic tool for visualization of
within the comment. respectively, but they are collectively dopamine transporters (DAT) by using
Comments containing personal referred to as the ‘‘Controlled single photon emission computed
identifying information and confidential Substances Act’’ or the ‘‘CSA’’ for the tomography (SPECT) brain imaging. The
business information identified as purposes of this action. The DEA Food and Drug Administration (FDA)
directed above will generally be made publishes the implementing regulations approved the New Drug Application
publicly available in redacted form. If a for these statutes in title 21 of the Code (NDA) for DaTscan on January 14, 2011,
comment has so much confidential of Federal Regulations (CFR), chapter II. for the indication of visualizing striatal
business information or personal The CSA and its implementing DATs in the brains of adult patients
identifying information that it cannot be regulations are designed to prevent, with suspected Parkinsonian syndromes
effectively redacted, all or part of that detect, and eliminate the diversion of (PS). [123I]Ioflupane is the active
comment may not be made publicly controlled substances and listed pharmaceutical ingredient (API) in
available. Comments posted to http:// chemicals into the illicit market while DaTscan and it is a new molecular
www.regulations.gov may include any ensuring an adequate supply is available entity. However, [123I]Ioflupane is, by
personal identifying information (such for the legitimate medical, scientific, definition, a schedule II controlled
as name, address, and phone number) research, and industrial needs of the substance because it is derived from
included in the text of your online United States. Controlled substances cocaine, a schedule II substance, via
submission that is not identified as have the potential for abuse and ecgonine (a schedule II substance). See
directed above as confidential. dependence and are controlled to 21 U.S.C. 812(c), Schedule II, (a)(4).
An electronic copy of this document protect the public health and safety.
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS

and supplemental information to this Under the CSA, each controlled 1 As discussed in a memorandum of

substance is classified into one of five understanding entered into by the Food and Drug
proposed rule are available at http:// Administration (FDA) and the National Institute on
www.regulations.gov for easy reference. schedules based upon its potential for Drug Abuse (NIDA), the FDA acts as the lead agency
abuse, its currently accepted medical within the HHS in carrying out the Secretary’s
Request for Hearing, Notice of use in treatment in the United States, scheduling responsibilities under the CSA, with the
Appearance at or Waiver of and the degree of dependence the drug concurrence of NIDA. 50 FR 9518, Mar. 8, 1985.
Participation in Hearing or other substance may cause. 21 U.S.C. The Secretary of the HHS has delegated to the
Assistant Secretary for Health of the HHS the
Pursuant to 21 U.S.C. 811(a), this 812. The initial schedules of controlled authority to make domestic drug scheduling
action is a formal rulemaking ‘‘on the substances established by Congress are recommendations. 58 FR 35460, July 1, 1993.

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31524 Federal Register / Vol. 80, No. 106 / Wednesday, June 3, 2015 / Proposed Rules

DaTscan) are abusable. In addition, the part 35 and/or by states) 4 on the [123I]ioflupane from schedule II of the’’
non-radiolabeled precursors derived manufacturing and handling of CSA. However, because the DEA finds
from cocaine or ecgonine are also DaTscan, abuse of DaTscan is not no basis to remove only FDA approved
schedule II controlled substances. possible as a practical matter. Thus, products containing [123I]ioflupane from
However, even if an individual obtained there is little to no practical risk to the schedules, this action proposes to
the precursors, it is impractical and public health from DaTscan abuse. remove the substance [123I]ioflupane
highly unlikely that they would 7. Its Psychic or Physiological from the CSA schedules. Historically,
synthesize the abusable compound into Dependence Liability when new molecular entities are
a radiolabeled formulation with a removed from control, the substance
limited storage life that is not desired by As reviewed by HHS, non- itself is removed from control rather
drug users. radiolabeled ioflupane has cocaine-like than the specific FDA-approved drug
On January 14, 2011, FDA approved properties. In a drug discrimination product (e.g., naloxegol, 80 FR 3468;
the NDA for DaTscan with the study in cocaine-trained rats, non- naloxone, 39 FR 44392). As summarized
indication of visualizing striatal radiolabeled ioflupane produced above, the data currently support
dopamine transporters in the brains of cocaine-appropriate responding, which removal of substances that contain
adult patients with suspected suggests that non-radiolabeled ioflupane [123I]ioflupane, primarily because
Parkinsonian syndromes using SPECT may produce cocaine-like subjective [123I]ioflupane itself has a lethal
imaging. As such, any FDA-approved effects in humans (HHS, 2010). radioactive barrier, and its
diagnostic product containing However, the available evidence manufacturing process is highly
[123I]ioflupane has a currently accepted suggests that there is no psychic or regulated and technically complex, thus
medical use in the United States. physiological dependence potential of making abuse highly unlikely.
FDA-approved diagnostic products After consideration of the analyses
4. Its History and Current Pattern of containing [123I]ioflupane. The psychic and recommendation of the Assistant
Abuse or physiological dependence potential Secretary for Health of the HHS and
According to HHS, there have been no of FDA-approved diagnostic products is
review of all relevant and available data,
reports of abuse of [123I]ioflupane. Over currently expected to be very limited
the Administrator of the DEA, pursuant
168,000 doses of DaTscan have been due to the low exposure concentration
to 21 U.S.C. 812(b)(5), finds that:
administered to patients worldwide, of [123I]ioflupane, the aforementioned
(1) [123I]Ioflupane has no comparable
and no pharmacological effects have low potential for abuse (see Factor 1)
potential for abuse relative to substances
been noted. Further, according to HHS, and the extremely high and lethal
in Schedule V.
no single user has received more than quantities needed to achieve a
(2) [123I]Ioflupane has a currently
10 vials of DaTscan in a single day. subjective ‘‘high.’’
accepted medical use in treatment in the
5. The Scope, Duration, and 8. Whether the Substance Is an United States. FDA approved the New
Significance of Abuse Immediate Precursor of a Substance Drug Application for DaTscan on
Already Controlled Under the CSA January 14, 2011, with the indication of
There have been no reports of abuse visualizing striatal dopamine
of [123I]ioflupane. According to the [123I]Ioflupane is not an immediate
precursor of a substance already transporters in the brains of adult
National Forensic Laboratory patients with suspected Parkinsonian
Information System (NFLIS) 2 and the controlled under the CSA.
syndromes using SPECT imaging.
System to Retrieve Information from Conclusion (3) [123I]Ioflupane is not abusable,
Drug Evidence (STRIDE) 3, there have Based on consideration of the therefore, its use is not likely to lead to
been no reports of [123I]ioflupane scientific and medical evaluation and physical or psychological dependence.
seizures during the time period January accompanying recommendation of the Based on these findings, the
2010 to February 2015. HHS and based on the DEA’s Administrator of the DEA concludes
6. What, If Any, Risk There Is to the consideration of its own eight-factor that [123I]ioflupane does not warrant
Public Health analysis, the DEA finds that the facts control under the CSA.
and all available and relevant data Effect on Other Rulemakings
According to the HHS, because of the
demonstrate that [123I]ioflupane does
limited amounts of manufactured On November 25, 2014, DEA
not possess abuse or dependence
DaTscan, the low concentration of published an interim final rule waiving
potential. Accordingly, the DEA finds
[123I]ioflupane per vial, and the the requirement of DEA registration for
that [123I]ioflupane does not meet the
existence of stringent regulatory certain entities that are authorized
requirements for inclusion in any
controls (controls other than those under other federal or state authorities
schedule and should be removed from
imposed by the CSA and its to administer DaTscan. 79 FR 70085. If
control under the CSA.
implementing regulations, including finalized, this proposal to remove
regulation by the United States Nuclear Findings for Schedule Placement [123I]ioflupane from the schedules of
Regulatory Commission under 10 CFR Pursuant to 21 U.S.C. 812(b) controlled substances would make such
The CSA outlines the findings waivers unnecessary. Therefore, if this
2 NFLIS is a program of the DEA that collects drug
required to place a drug or other action is finalized, DEA intends to
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS

identification results from drug cases analyzed by
other Federal, State, and local forensic laboratories. substance in any particular schedule (I, withdraw the regulations established
NFLIS was queried on April 16, 2015. II, III, IV, or V). 21 U.S.C. 812(b). The through that interim final rule.
3 STRIDE collected the results of drug evidence
Assistant Secretary for Health of the
analyzed at DEA laboratories and reflects evidence Regulatory Analyses
HHS recommended removal of ‘‘FDA
submitted by the DEA, other Federal law
enforcement agencies, and some local law approved products containing Executive Orders 12866 and 15363
enforcement agencies. STRIDE data was queried by In accordance with 21 U.S.C. 811(a),
date submitted to Federal forensic laboratories. On 4 There are Federal and state laws and regulations

October 1, 2014, STARLiMS replaced STRIDE as which limit the public’s exposure to radioactivity
this scheduling action is subject to
the DEA laboratory drug evidence data system of in radiopharmaceuticals, thus limiting the potential formal rulemaking procedures done ‘‘on
record. for toxicity imposed on the public. the record after opportunity for a

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Federal Register / Vol. 80, No. 106 / Wednesday, June 3, 2015 / Proposed Rules 31525

hearing,’’ which are conducted pursuant unquantifiable variables that potentially List of Subjects in 21 CFR part 1308
to the provisions of 5 U.S.C. 556 and could influence the distribution and Administrative practice and
557. The CSA sets forth the criteria for administration rates of new molecular procedure, Drug traffic control,
scheduling a drug or other substance entities, the DEA is unable to determine Reporting and recordkeeping
and for removing a drug or substance the number of entities and small entities requirements.
from the schedules of controlled which might handle [123I]ioflupane. For the reasons set out above, 21 CFR
substances. Such actions are exempt Although the DEA does not have a part 1308 is proposed to be amended to
from review by the Office of reliable basis to estimate the number of read as follows:
Management and Budget (OMB)
affected entities and quantify the
pursuant to section 3(d)(1) of Executive PART 1308—SCHEDULES OF
economic impact of this proposed rule,
Order 12866 and the principles CONTROLLED SUBSTANCES
a qualitative analysis indicates that, if
reaffirmed in Executive Order 13563.
finalized, this rule is likely to result in
Executive Order 12988 ■ 1. The authority citation for 21 CFR
some cost savings for the healthcare
part 1308 continues to read as follows:
This regulation meets the applicable industry. The affected entities will
continue to meet existing Federal and/ Authority: 21 U.S.C. 811, 812, 871(b),
standards set forth in sections 3(a) and
or state requirements applicable to those unless otherwise noted.
3(b)(2) of Executive Order 12988 Civil
Justice Reform to eliminate drafting who handle radiopharmaceutical ■ 2. In § 1308.12, revise paragraph (b)(4)
errors and ambiguity, minimize substances, including licensure, to read as follows:
litigation, provide a clear legal standard security, recordkeeping, and reporting
§ 1308.12 Schedule II.
for affected conduct, and promote requirements, which in many cases are
simplification and burden reduction. more stringent than the DEA’s * * * * *
requirements. However, the DEA (b) * * *
Executive Order 13132 estimates cost savings will be realized (4) Coca leaves (9040) and any salt,
This rulemaking does not have from the removal of the administrative, compound, derivative or preparation of
federalism implications warranting the civil, and criminal sanctions for those coca leaves (including cocaine (9041)
application of Executive Order 13132. entities handling or proposing to handle and ecgonine (9180) and their salts,
The rule does not have substantial isomers, derivatives and salts of isomers
[123I]ioflupane, in the form of saved
direct effects on the States, on the and derivatives), and any salt,
registration fees, and the elimination of
relationship between the Federal compound, derivative, or preparation
additional physical security,
Government and the States, or the thereof which is chemically equivalent
recordkeeping, and reporting
distribution of power and or identical with any of these
requirements.
responsibilities among the various substances, except that the substances
levels of government. Because of these facts, this rule will shall not include:
not result in a significant economic (i) Decocainized coca leaves or
Executive Order 13175 impact on a substantial number of small extraction of coca leaves, which
This rule does not have tribal entities. extractions do not contain cocaine or
implications warranting the application ecgonine; or
Unfunded Mandates Reform Act of 1995 (ii) [123I]ioflupane.
of Executive Order 13175. This rule
does not have substantial direct effects On the basis of information contained * * * * *
on one or more Indian tribes, on the in the ‘‘Regulatory Flexibility Act’’ Dated: May 6, 2015.
relationship between the Federal section above, the DEA has determined Michele M. Leonhart,
Government and Indian tribes, or on the and certifies pursuant to the Unfunded Administrator.
distribution of power and Mandates Reform Act of 1995 (UMRA), [FR Doc. 2015–13455 Filed 6–2–15; 8:45 am]
responsibilities between the Federal 2 U.S.C. 1501 et seq., that this action
Government and Indian tribes. BILLING CODE 4410–09–P
would not result in any federal mandate
Regulatory Flexibility Act that may result ‘‘in the expenditure by
State, local, and tribal governments, in
The Administrator, in accordance DEPARTMENT OF STATE
the aggregate, or by the private sector, of
with the Regulatory Flexibility Act (5
$100,000,000 or more (adjusted for 22 CFR Parts 120, 123, 125, and 127
U.S.C. 601–612) (RFA), has reviewed
inflation) in any one year * * * .’’
this proposed rule and by approving it [Public Notice 9149]
Therefore, neither a Small Government
certifies that it will not have a
Agency Plan nor any other action is RIN 1400–AD70
significant economic impact on a
required under provisions of UMRA.
substantial number of small entities.
International Traffic in Arms: Revisions
The purpose of this rule is to remove Paperwork Reduction Act to Definitions of Defense Services,
[123I]ioflupane from the list of schedules
This action does not impose a new Technical Data, and Public Domain;
of the CSA. This action will remove
collection of information requirement Definition of Product of Fundamental
regulatory controls and administrative,
under the Paperwork Reduction Act, 44 Research; Electronic Transmission
civil, and criminal sanctions applicable
asabaliauskas on DSK5VPTVN1PROD with PROPOSALS

U.S.C. 3501–3521. This action would and Storage of Technical Data; and
to controlled substances for handlers
not impose recordkeeping or reporting Related Definitions
and proposed handlers of
[123I]ioflupane. Accordingly, it has the requirements on State or local AGENCY: Department of State.
potential for some economic impact in governments, individuals, businesses, or ACTION: Proposed rule.
the form of cost savings. organizations. An agency may not
If finalized, the proposed rule will conduct or sponsor, and a person is not SUMMARY: As part of the President’s
affect all persons who would handle, or required to respond to, a collection of Export Control Reform (ECR) initiative,
propose to handle, [123I]ioflupane. Due information unless it displays a the Department of State proposes to
to the wide variety of unidentifiable and currently valid OMB control number. amend the International Traffic in Arms

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Document Created: 2015-12-15 15:09:07
Document Modified: 2015-12-15 15:09:07

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Proposed Rules
Action		Notice of proposed rulemaking.
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 July 6, 2015. 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.
Contact		John R. Scherbenske, Office of Diversion
FR Citation		80 FR 31521
CFR Associated		Administrative Practice and Procedure; Drug Traffic Control and Reporting and Recordkeeping Requirements

80 FR 31521 - Schedules of Controlled Substances: Removal of [123

DEPARTMENT OF JUSTICEDrug Enforcement Administration

Federal Register Volume 80, Issue 106 (June 3, 2015)

DEPARTMENT OF JUSTICE
Drug Enforcement Administration