Proposed Rule2023-20439
Schedules of Controlled Substances: Placement of Ethylphenidate in Schedule I
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
September 22, 2023
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing the substance ethylphenidate (chemical name: ethyl 2-phenyl-2-(piperidin-2- yl)acetate), including its salts, isomers, and salts of isomers, in schedule I of the Controlled Substances Act. This action is being taken, in part, to enable the United States to meet its obligations under the 1971 Convention on Psychotropic Substances. If finalized, this action would impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess) or propose to handle ethylphenidate.
Full Text
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<title>Federal Register, Volume 88 Issue 183 (Friday, September 22, 2023)</title>
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[Federal Register Volume 88, Number 183 (Friday, September 22, 2023)]
[Proposed Rules]
[Pages 65330-65336]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-20439]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-1142]
Schedules of Controlled Substances: Placement of Ethylphenidate
in Schedule I
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: The Drug Enforcement Administration proposes placing the
substance ethylphenidate (chemical name: ethyl 2-phenyl-2-(piperidin-2-
yl)acetate), including its salts, isomers, and salts of isomers, in
schedule I of the Controlled Substances Act. This action is being
taken, in part, to enable the United States to meet its obligations
under the 1971 Convention on Psychotropic Substances. If finalized,
this action would impose the regulatory controls and administrative,
civil, and criminal sanctions applicable to schedule I controlled
substances on persons who handle (manufacture, distribute, reverse
distribute, import, export, engage in research, conduct instructional
activities or chemical analysis, or possess) or propose to handle
ethylphenidate.
DATES: Comments must be submitted electronically or postmarked on or
before November 21, 2023.
Interested persons may file a request for a hearing or waiver of
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.45 and/or 1316.47, as applicable. Requests for a hearing and
waivers of an opportunity for a hearing or to participate in a hearing,
together with a written statement of position on the matters of fact
and law asserted in the hearing, must be received on or before October
23, 2023.
ADDRESSES: Interested persons may file written comments on this
proposal in accordance with 21 CFR 1308.43(g). 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. To ensure proper
handling of comments, please reference ``Docket No. DEA-1142'' on all
electronic and written correspondence, including any attachments.
<bullet> Electronic comments: The Drug Enforcement Administration
(DEA) encourages commenters to submit comments electronically through
the Federal eRulemaking Portal, which provides the ability to type
short comments directly into the comment field on the web page or
attach a file for lengthier comments. Please go to <a href="http://www.regulations.gov">http://www.regulations.gov</a> and follow the online instructions at that site for
submitting comments. Upon completion of your submission you will
receive a Comment Tracking Number for your comment. Please be aware
that submitted comments are not instantaneously available for public
view on <a href="http://regulations.gov">regulations.gov</a>. If you have received a Comment Tracking
Number, your comment has been successfully submitted and there is no
need to resubmit the same comment. 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.
[[Page 65331]]
<bullet> Paper comments: Paper comments that duplicate the
electronic submissions are not necessary and are discouraged. Should
you wish to mail a paper comment, in lieu of an electronic comment, it
should be sent via regular or express mail to: Drug Enforcement
Administration, Attn: DEA Federal Register Representative/DPW, 8701
Morrissette Drive, Springfield, Virginia 22152.
<bullet> Hearing requests: All requests for a hearing and waivers
of participation, together with a written statement of position on the
matters of fact and law asserted in the hearing, must be sent to: Drug
Enforcement Administration, Attn: Administrator, 8701 Morrissette
Drive, Springfield, Virginia 22152. All requests for hearing and
waivers of participation should also be sent to: (1) Drug Enforcement
Administration, Attn: Hearing Clerk/OALJ, 8701 Morrissette Drive,
Springfield, Virginia 22152; and (2) Drug Enforcement Administration,
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive,
Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Dr. Terrence L. Boos, Drug and
Chemical Evaluation Section, Diversion Control Division, Drug
Enforcement Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION: In this proposed rule, the Drug Enforcement
Administration (DEA) intends to place ethyl 2-phenyl-2-(piperidin-2-
yl)acetate (ethylphenidate) including its salts, isomers, and salts of
isomers in schedule I of the Controlled Substances Act (CSA).
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. DEA will make comments available, unless
reasonable cause is given, for public inspection online at <a href="http://www.regulations.gov">http://www.regulations.gov</a>. Such information includes personal identifying
information (such as your name, address, etc.) voluntarily submitted by
the commenter. The Freedom of Information Act applies to all comments
received. If you want to submit personal identifying information (such
as your name, address, etc.) as part of your comment, but do not want
DEA to make it 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.
DEA will make available publicly in redacted form comments
containing personal identifying information or confidential business
information identified as directed above. If a comment has so much
confidential business information that DEA cannot effectively redact
it, DEA may not make available publicly all or part of that comment.
Comments posted to <a href="http://www.regulations.gov">http://www.regulations.gov</a> may include any personal
identifying information (such as name, address, and phone number)
included in the text of your electronic submission that is not
identified as confidential as directed above.
An electronic copy of this document and supplemental information to
this proposed rule are available at <a href="http://www.regulations.gov">http://www.regulations.gov</a> for easy
reference.
Request for Hearing or Appearance; Waiver
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).\1\ Interested persons, as defined in 21 CFR 1300.01(b), may
file requests for a hearing in conformity with the requirements of 21
CFR 1308.44(a) and 1316.47(a), and such requests must:
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\1\ 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D.
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(1) state with particularity the interest of the person in the
proceeding;
(2) state with particularity the objections or issues concerning
which the person desires to be heard; and
(3) state briefly the position of the person with regarding to the
objections or issues.
Any interested person may file a waiver of an opportunity for a
hearing or to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(c), together with a written statement of
position on the matters of fact and law involved in any hearing.\2\
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\2\ 21 CFR 1316.49.
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All requests for a hearing and waivers of participation, together
with a written statement of position on the matters of fact and law
involved in such hearing, must be sent to DEA using the address
information provided above. The decision whether a hearing will be
needed to address such matters of fact and law in the rulemaking will
be made by the Administrator. If a hearing is needed, DEA will publish
a notice of hearing on the proposed rulemaking in the Federal
Register.\3\ Further, once the Administrator determines a hearing is
needed to address such matters of fact and law in rulemaking, she will
then designate an Administrative Law Judge (ALJ) to preside over the
hearing. The ALJ's functions shall only commence upon designation, as
provided in 21 CFR 1316.52.
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\3\ 21 CFR 1308.44(b), 1316.53.
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In accordance with 21 U.S.C. 811 and 812, the purpose of a hearing
would be to determine whether ethylphenidate meets the statutory
criteria for placement in schedule I.
Legal Authority
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 (delegated to the Administrator of
DEA pursuant to 28 CFR 0.100) on his own motion.\4\ This proposed
action is supported by a recommendation from the Assistant Secretary
for Health of the Department of Health and Human Services (HHS).
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\4\ 21 U.S.C. 811(a).
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In addition, the United States is a party to the 1971 United
Nations Convention on Psychotropic Substances (1971 Convention),
February 21, 1971, 32 U.S.T. 543, 1019 U.N.T.S. 175, as amended.
Procedures respecting changes in drug schedules under the 1971
Convention are governed domestically by 21 U.S.C. 811(d)(2)-(4). When
the United States receives notification of a scheduling decision
pursuant to Article 2 of the 1971 Convention indicating that a drug or
other substance has been added to a schedule specified in the
notification, the Secretary of HHS (Secretary),\5\ after consultation
with the Attorney General, shall first determine whether existing legal
controls under subchapter I of the Controlled Substances Act (CSA) and
the Federal Food, Drug, and Cosmetic Act meet the requirements of the
schedule specified in the notification with respect to the specific
drug or
[[Page 65332]]
substance.\6\ In the event that the Secretary did not so consult with
the Attorney General, and the Attorney General did not issue a
temporary order, as provided under 21 U.S.C. 811(d)(4), the procedures
for permanent scheduling set forth in 21 U.S.C. 811(a) and (b) control.
Pursuant to 21 U.S.C. 811(a)(1), the Attorney General (as delegated to
the Administrator of DEA) may, by rule, add to such a schedule or
transfer between such schedules any drug or other substance, if he
finds that such drug or other substance has a potential for abuse, and
makes with respect to such drug or other substance the findings
prescribed by 21 U.S.C. 812(b) for the schedule in which such drug or
other substance is to be placed.
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\5\ As discussed in a memorandum of understanding entered into
by the 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 has delegated to the
Assistant Secretary for Health of HHS the authority to make domestic
drug scheduling recommendations. 58 FR 35460 (July 1, 1993).
\6\ 21 U.S.C. 811(d)(3).
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Background
Ethylphenidate is a central nervous system (CNS) stimulant and
shares structural and pharmacological similarities with other schedule
II stimulants such as methylphenidate. On April 21, 2017, the
Secretary-General of the United Nations advised the Secretary of State
of the United States that during its 60th session, on March 16, 2017,
the Commission on Narcotic Drugs voted to place ethyl 2-phenyl-2-
(piperidin-2-yl)acetate (ethylphenidate) in Schedule II of the 1971
Convention (CND Dec/60/7). Because the procedures in 21 U.S.C.
811(d)(3) and (4) for consultation and issuance of a temporary order
for ethylphenidate, discussed in the above legal authority section,
were not followed, DEA is utilizing the procedures for permanent
scheduling set forth in 21 U.S.C. 811(a) and (b) to control
ethylphenidate. Such scheduling would satisfy the United States'
international obligations.
Article 2, paragraph 7(b), of the 1971 Convention sets forth the
minimum requirements that the United States must meet when a substance
has been added to Schedule II of the 1971 Convention. Pursuant to the
1971 Convention, the United States must require licenses for the
manufacture, export and import, and distribution of ethylphenidate.
This license requirement is accomplished by the CSA's registration
requirement as set forth in 21 U.S.C. 822, 823, 957, 958 and in ance
with 21 CFR parts 1301 and 1312. In addition, the United States must
adhere to specific export and import provisions set forth in the 1971
Convention. This requirement is accomplished by the CSA's export and
import provisions established in 21 U.S.C. 952, 953, 957, 958 and in
accordance with 21 CFR part 1312. Likewise, under Article 13,
paragraphs 1 and 2, of the 1971 Convention, a party to the 1971
Convention may notify through the UN Secretary-General another party
that it prohibits the importation of a substance in Schedule II, III,
or IV of the 1971 Convention. If such notice is presented to the United
States, the United States shall take measures to ensure that the named
substance is not exported to the notifying country. This requirement is
also accomplished by the CSA's export provisions mentioned above. Under
Article 16, paragraph 4, of the 1971 Convention, the United States is
required to provide annual statistical reports to the International
Narcotics Control Board (INCB). Using INCB Form P, the United States
shall provide the following information: (1) in regard to each
substance in Schedule I and II of the 1971 Convention, quantities
manufactured in, exported to, and imported from each country or region
as well as stocks held by manufacturers; (2) in regard to each
substance in Schedule II and III of the 1971 Convention, quantities
used in the manufacture of exempt preparations; and (3) in regard to
each substance in Schedule II-IV of the 1971 Convention, quantities
used for the manufacture of non-psychotropic substances or products.
Lastly, under Article 2 of the 1971 Convention, the United States must
adopt measures in accordance with Article 22 to address violations of
any statutes or regulations that are adopted pursuant to its
obligations under the 1971 Convention. Persons acting outside the legal
framework established by the CSA are subject to administrative, civil,
and/or criminal action; therefore, the United States complies with this
provision.
DEA notes that there are differences between the schedules of
substances in the 1971 Convention and the CSA. The CSA has five
schedules (schedules I-V) with specific criteria set forth for each
schedule. Schedule I is the only possible schedule in which a drug or
other substance may be placed if it has high potential for abuse and no
currently accepted medical use in treatment in the United States. See
21 U.S.C. 812(b). In contrast, the 1971 Convention has four schedules
(Schedules I-IV) but does not have specific criteria for each schedule.
The 1971 Convention simply defines its four schedules, in Article 1, to
mean the correspondingly numbered lists of psychotropic substances
annexed to the Convention, and altered in accordance with Article 2.
Proposed Determination To Schedule Ethylphenidate
On April 3, 2019, the Drug Enforcement Administration (DEA)
requested that the Department of Health and Human Services (HHS)
conduct a scientific and medical evaluation and provide a scheduling
recommendation for ethylphenidate. On October 26, 2020, HHS provided
DEA a scientific and medical evaluation (dated August 25, 2020)
entitled ``Basis for the recommendation to place ethylphenidate in
schedule I of the Controlled Substances Act'' and a scheduling
recommendation. Pursuant to 21 U.S.C. 811(b), following consideration
of the eight-factors and findings related to the substance's abuse
potential, legitimate medical use, safety, and dependence liability,
HHS recommended that ethylphenidate be controlled in schedule I of the
CSA under 21 U.S.C. 812(b). Upon receipt of the scientific and medical
evaluation and scheduling recommendation from HHS, DEA reviewed the
documents and all other relevant data and conducted its own eight-
factor analysis in accordance with 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 its proposed scheduling action. Please note that
both DEA and HHS eight-factor analyses are available in their entirety
under the tab ``Supporting Documents'' of the public docket of this
rulemaking action at <a href="http://www.regulations.gov">http://www.regulations.gov</a>, under docket number
``DEA-1142.''
1. The Drug's Actual or Relative Potential for Abuse: The term
``abuse'' is not defined in the CSA. However, the legislative history
of the CSA suggests that DEA consider the following criteria when
determining whether a particular drug or substance has a potential for
abuse: \7\
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\7\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted in 1970
U.S.C.C.A.N. 4566, 4603.
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(a) 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;
or
(b) There is significant diversion of the drug or drugs containing
such a substance from legitimate drug channels; or
(c) 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
[[Page 65333]]
administer such drugs in the course of his professional practice; or
(d) The drug or drugs containing such a substance are new drugs so
related in their action to a drug or drugs already listed as having a
potential for abuse to make it likely that the drug 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 it has a substantial capability of creating hazards to the health
of the user or to the safety of the community.
Both DEA and HHS eight-factor analyses found that ethylphenidate
has abuse potential associated with its abilities to produce
psychoactive effects that are similar to those produced by schedule II
stimulants such as methylphenidate that have a high potential for
abuse. In particular, the responses in humans to ethylphenidate are
stimulant-like and include tachycardia, anxiety, hallucinations,
impaired thinking, paranoia and hypertension.
Ethylphenidate does not have an approved medical use in the United
States. Thus, because this substance is not an approved drug product, a
practitioner may not legally prescribe it, and it cannot be dispensed
to an individual. DEA and HHS conclude that ethylphenidate is being
abused for its psychoactive properties because it is being used without
medical advice.
Reports from the public health sector and law enforcement suggest
that ethylphenidate is being abused and taken in amounts sufficient to
create a hazard to an individual's health. This hazard is evidenced by
deaths associated with ethylphenidate use which represents a safety
issue for those in the community. Further, ethylphenidate was first
reported to the National Forensic Laboratory Information System (NFLIS-
Drug) \8\ database in 2013; a January 2023 query of this database for
ethylphenidate reports indicated a total of 191 such reports through
2022 from 23 states by participating Federal, State, and local forensic
laboratories. Consequently, the data indicate that ethylphenidate is
being abused, and presents safety hazards to the health of individuals
who consume it due to its stimulant properties, making it a hazard to
the safety of the community.
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\8\ NFLIS represents an important resource in monitoring illicit
drug trafficking, including the diversion of legally manufactured
pharmaceuticals into illegal markets. NFLIS-Drug is a comprehensive
information system that includes data from forensic laboratories
that handle the nation's drug analysis cases. NFLIS-Drug
participation rate, defined as the percentage of the national drug
caseload represented by laboratories that have joined NFLIS-Drug, is
currently 98.5 percent. NFLIS-Drug includes drug chemistry results
from completed analyses only. While NFLIS-Drug data is not direct
evidence of abuse, it can lead to an inference that a drug has been
diverted and abused. See 76 FR 77330, 77332, December 12, 2011.
NFLIS data were queried on January 20, 2023.
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2. Scientific Evidence of the Drug's Pharmacological Effects, if
Known: As described by HHS, studies show that ethylphenidate produces
pharmacological effects that are similar to those produced by
methylphenidate, a schedule II substance. Similar to these schedule II
substances, ethylphenidate binds to monoamine transporters for dopamine
and norepinephrine and blocks the uptake of these neurotransmitters at
their transporters. Functionally, ethylphenidate, similar to
methylphenidate and cocaine, inhibits norepinephrine and dopamine
uptake. The potency of ethylphenidate in inhibiting norepinephrine
uptake is about 6.75-fold less than that of methylphenidate and 1.7-
fold less than cocaine. With respect to behavioral data, according to
HHS, while ethylphenidate is pharmacodynamically similar to
methylphenidate, it is less potent than methylphenidate in the
locomotor activity assay. Specifically, ethylphenidate is approximately
80% as effective as methylphenidate in producing locomotor effect.
Self-reports by users of ethylphenidate demonstrate that the drug
produces typical stimulant-like effects, including euphoria and
psychological and psychomotor stimulation. Overall, these data indicate
that ethylphenidate produces stimulant-like pharmacological effects and
behaviors that are similar to those of schedule II substances
methylphenidate and methamphetamine.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: Ethylphenidate is structurally similar to the schedule
II substance methylphenidate. As stated in the HHS review,
ethylphenidate is chemically known as ethyl 2-phenyl-2-piperidin-2-
ylacetate, (RS)-ethyl 2-phenyl-2-(piperidin-2-yl)acetate and dl-
ethylphenidate. Another name for ethylphenidate is EPH.
Ethylphenidate user reports suggest that following insufflation,
the pharmacokinetics of the drug are relatively rapid, with the onset
of effects occurring approximately 13 minutes after administration
(with a range of 0 to 35 minutes). Additionally, following oral
ingestion, the mean onset of action is 23 minutes (ranging from 5 to 31
minutes). According to published scientific literature, the mean
duration of action of ethylphenidate is approximately 2 hours.
As stated by HHS, there are no published clinical or nonclinical
toxicology studies using ethylphenidate. Furthermore, the only evidence
of the toxicological effects of ethylphenidate come from anecdotal user
reports and fatal overdoses that implicated its role in a death.
Neither DEA nor HHS is aware of any currently accepted medical use
for ethylphenidate. According to HHS's August 2020 scientific and
medical evaluation and scheduling recommendation, the Food and Drug
Administration (FDA) has not approved a marketing application for a
drug product containing ethylphenidate for any therapeutic indication,
nor is HHS aware of any reports of clinical studies or claims of an
accepted medical use for ethylphenidate in the United States.
Although there is no evidence to suggest ethylphenidate has a
currently accepted medical use in treatment in the United States, it
bears noting that a drug cannot be found to have such medical use
unless DEA concludes that it satisfies a five-part test. Specifically,
with respect to a drug that has not been approved by FDA, all of the
following must be demonstrated: the drug's chemistry is known and
reproducible; there are adequate safety studies; there are adequate and
well-controlled studies proving efficacy; the drug is accepted by
qualified experts; and the scientific evidence is widely available. 57
FR 10499 (1992), pet. for rev. denied, Alliance for Cannabis
Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994). Based on this
analysis, ethylphenidate has no currently accepted medical use in the
United States. Furthermore, DEA has not found any references regarding
clinical testing of ethylphenidate in the scientific and medical
literature. Taken together with HHS's conclusion, DEA finds that there
is no legitimate medical use for ethylphenidate in the United States.
4. History and Current Pattern of Abuse: As described by DEA and
HHS, ethylphenidate is a stimulant and is structurally and
pharmacologically similar to the schedule II substance,
methylphenidate. Ethylphenidate has been trafficked and abused in North
America and Europe since its first report of abuse in 2011. In
addition, ethylphenidate has been identified in law enforcement
seizures in the United States since 2013 and has persisted through 2020
(There were no ethylphenidate-related NFLIS-Drug reports in 2021 and
2022). Thus, ethylphenidate abuse occurs worldwide.
[[Page 65334]]
5. Scope, Duration and Significance of Abuse: Forensic laboratories
have confirmed the presence of ethylphenidate in drug exhibits received
from State, local, and Federal law enforcement agencies. Law
enforcement data show that ethylphenidate first appeared in the illicit
drug market in 2013 with 10 encounters. Overall, from 2013 through
2022, NFLIS registered 191 reports from Federal, State and local
forensic laboratories identifying this substance in drug-related
exhibits from 23 states. Thus, ethylphenidate abuse is wide-spread.
6. What, if Any, Risk There Is to the Public Health: Based on the
review of both HHS and DEA, public health risks of ethylphenidate
result from its ability to induce stimulant-like responses, which may
lead to adverse events that include psychological and cognitive
impairment. Furthermore, risk to the public health is associated with
adverse reactions in humans, which include hallucinations, impaired
thinking, and paranoia. Nineteen deaths in the United Kingdom involving
ethylphenidate have occurred between July 2013 and December 2014. A
majority of these deaths involved males from East of Scotland with a
history of current or previous heroin abuse. Additionally, according to
the 2016 WHO Critical Review, these cases were almost exclusively
associated with poly-drug use, with benzodiazepines, methadone, and
other opioids being the most commonly detected drugs. Thus, the public
health risks associated with ethylphenidate are confirmed by the
pharmacological profile along with the fatalities associated with
ethylphenidate use.
7. Its Psychic or Physiological Dependence Liability: According to
HHS, the psychic or physiological dependence liability of
ethylphenidate can be inferred based on case reports and from data on
substances that have similar pharmacological actions. As noted by HHS,
scientific literature of published case reports demonstrate the
propensity of ethylphenidate re-dosing by its users. Furthermore,
according to self-reports users of ethylphenidate typically experience
stimulant-like behavioral effects. In addition, DEA notes that because
ethylphenidate shares pharmacological properties with schedule II
stimulant substances such as methylphenidate and methamphetamine,
ethylphenidate likely has a dependence profile similar to these
substances, which are known to cause substance dependence.
In summary, data suggests that ethylphenidate produces behavioral
effects in animals and humans similar to those of schedule II
stimulants. Although there are no clinical studies evaluating
dependence liabilities specific for ethylphenidate, the pharmacological
profile of this substance suggests that it possesses dependence
liabilities qualitatively similar to schedule II substances such as
methylphenidate and methamphetamine.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA: Ethylphenidate is not an immediate
precursor of any controlled substance under the CSA as defined by 21
U.S.C. 802(23).
Conclusion: After considering the scientific and medical evaluation
conducted by HHS, HHS's scheduling recommendation, and DEA's own eight-
factor analysis, DEA finds that the facts and all relevant data
constitute substantial evidence of the potential for abuse of
ethylphenidate. As such, DEA hereby proposes to permanently schedule
ethylphenidate as a schedule I controlled substance under the CSA.
Proposed Determination of Appropriate Schedule
The CSA establishes five schedules of controlled substances known
as schedules I, II, III, IV, and V. The CSA also outlines the findings
required to place a drug or other substance in any particular schedule.
21 U.S.C. 812(b). After consideration of the analysis and
recommendation of the Assistant Secretary for Health of HHS and review
of all other available data, the Administrator of DEA, pursuant to 21
U.S.C. 811(a) and 812(b)(1), finds that:
1. Ethylphenidate has a high potential for abuse.
Ethylphenidate, similar to the schedule II stimulants
methylphenidate and methamphetamine, is a stimulant with a high
potential for abuse. In animals, behavioral locomotor studies show that
ethylphenidate produces stimulation similar to that of methylphenidate.
Additionally, typical stimulant effects such as euphoria, psychomotor
stimulation, and anxiety have been described from self-reports of
ethylphenidate abusers. These effects are similar to those of schedule
II stimulant such as methylphenidate and methamphetamine. These data
collectively indicate that ethylphenidate has a high potential for
abuse similar to other substances in schedule II such as
methylphenidate and methamphetamine.
2. Ethylphenidate currently has no accepted medical use in
treatment in the United States.
According to HHS, FDA has not approved a marketing application for
a drug product containing ethylphenidate for any therapeutic
indication. As HHS states, there are also no clinical studies or
petitioners that claim an accepted medical use in the United States. In
addition, as discussed above in the Factor 3 analysis, ethylphenidate
does not satisfy DEA's five-part test for having a currently accepted
medical use in treatment in the United States.
3. There is a lack of accepted safety for use of ethylphenidate
under medical supervision.
Currently, ethylphenidate does not have an accepted medical use as
noted by HHS. Because ethylphenidate has no approved medical use in
treatment in the United States and has not been investigated as a new
drug, its safety for use under medical supervision has not been
determined. Thus, there is a lack of accepted safety for use of
ethylphenidate under medical supervision.
Although the first finding shows ethylphenidate to have similar
effects to schedule II substances such as methylphenidate and
methamphetamine, it bears reiterating that there is only one possible
schedule in the CSA--schedule I--to place ethylphenidate since it has
no currently accepted medical use in treatment in the United States.
See the background section for additional discussion.
Based on these findings, the Administrator concludes that
ethylphenidate (chemical name: ethyl 2-phenyl-2-(piperidin-2-
yl)acetate), including its salts, isomers, and salts of isomers,
warrants control in schedule I of the CSA. 21 U.S.C. 812(b)(1). More
precisely, because of its stimulant-like effects, DEA is proposing to
place ethylphenidate in 21 CFR 1308.11(f) (the stimulants category of
schedule I). As such, the proposed control of ethylphenidate also
includes its salts, isomers, and salts of isomers.
Requirements for Handling Ethylphenidate
If this rule is finalized as proposed, ethylphenidate would be
subject to the CSA's schedule I regulatory controls and administrative,
civil, and criminal sanctions applicable to the manufacture,
distribution, reverse distribution, importation, exportation,
engagement in research, and conduct of instructional activities or
chemical analysis with, and possession of schedule I controlled
substances including the following:
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, imports, exports, engages in research, or conducts
[[Page 65335]]
instructional activities or chemical analysis with, or possesses)
ethylphenidate, or who desires to handle ethylphenidate, is required to
be registered with DEA to conduct such activities pursuant to 21 U.S.C.
822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and
1312 as of the effective date of a final scheduling action. Any person
who currently handles ethylphenidate, and is not registered with DEA,
would need to submit an application for registration and may not
continue to handle ethylphenidate as of the effective date of a final
scheduling action, unless DEA has approved that application for
registration pursuant to 21 U.S.C. 822, 823, 957, 958, and in
accordance with 21 CFR parts 1301 and 1312.
2. Disposal of stocks. Any person who does not desire or is not
able to obtain a schedule I registration would be required to surrender
all quantities of currently held ethylphenidate or to transfer all
quantities of currently held ethylphenidate to a person registered with
DEA before the effective date of a final scheduling action, in
accordance with all applicable Federal, State, local, and Tribal laws.
As of the effective date of a final scheduling action, ethylphenidate
would be required to be disposed of in accordance with 21 CFR part
1317, in addition to all other applicable Federal, State, local, and
Tribal laws.
3. Security. Ethylphenidate would be subject to schedule I security
requirements and would need to be handled and stored pursuant to 21
U.S.C. 821, 823, 871(b) and in accordance with 21 CFR 1301.71-1301.93
as of the effective date of a final scheduling action. Non-
practitioners handling ethylphenidate would also need to comply with
the employee screening requirements of 21 CFR 1301.90 -1301.93.
4. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of ethylphenidate would need to be in compliance
with 21 U.S.C. 825 and 958(e) and be in accordance with 21 CFR part
1302 as of the effective date of a final scheduling action.
5. Quota. Only registered manufacturers would be permitted to
manufacture ethylphenidate in accordance with a quota assigned pursuant
to 21 U.S.C. 826 and in accordance with 21 CFR part 1303 as of the
effective date of a final scheduling action.
6. Inventory. Every DEA registrant who possesses any quantity of
ethylphenidate on the effective date of a final scheduling action would
be required to take an inventory of ethylphenidate on hand at that
time, pursuant to 21 U.S.C. 827 and 958 and in accordance with 21 CFR
1304.03, 1304.04, and 1304.11(a) and (d).
Any person who becomes registered with DEA to handle ethylphenidate
on or after the effective date of a final scheduling action would be
required to have an initial inventory of all stocks of controlled
substances (including ethylphenidate) on hand on the date the
registrant first engages in the handling of controlled substances
pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR
1304.03, 1304.04, and 1304.11(a) and (b).
After the initial inventory, every DEA registrant must take an
inventory of all controlled substances (including ethylphenidate) on
hand every two years, pursuant to 21 U.S.C. 827 and 958, and in
accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
7. Records and Reports. Every DEA registrant would be required to
maintain records and submit reports with respect to ethylphenidate
pursuant to 21 U.S.C. 827 and 958(e) and in accordance with 21 CFR
parts 1304 and 1312, as of the effective date of a final scheduling
action. Manufacturers and distributors would be required to submit
reports regarding ethylphenidate to the Automation of Reports and
Consolidated Order System pursuant to 21 U.S.C. 827 and in accordance
with 21 CFR parts 1304 and 1312, as of the effective date of a final
scheduling action.
8. Order Forms. Every DEA registrant who distributes ethylphenidate
would be required to comply with the order form requirements, pursuant
to 21 U.S.C. 828 and in accordance with 21 CFR part 1305, as of the
effective date of a final scheduling action.
9. Importation and Exportation. All importation and exportation of
ethylphenidate would need to be in compliance with 21 U.S.C. 952, 953,
957, and 958, and in accordance with 21 CFR part 1312, as of the
effective date of a final scheduling action.
10. Liability. Any activity involving ethylphenidate not authorized
by, or in violation of, the CSA or its implementing regulations would
be unlawful, and may subject the person to administrative, civil, and/
or criminal sanctions.
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 proposed scheduling
action is subject to formal rulemaking procedures performed ``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 scheduling a drug or other substance. Such actions are
exempt from review by the Office of Management and Budget (OMB)
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 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 proposed 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 national 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. It 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. 601-602, 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.
DEA proposes placing the substance ethylphenidate (chemical name:
ethyl 2-phenyl-2-(piperidin-2-yl)acetate), including its salts,
isomers, and salts of isomers, in schedule I of the CSA. This action is
being taken to enable the United States to meet its obligations under
the 1971 Convention on Psychotropic Substances. If finalized, this
action would impose the regulatory controls and administrative, civil,
and criminal sanctions applicable to
[[Page 65336]]
schedule I controlled substances on persons who handle (manufacture,
distribute, reverse distribute, import, export, engage in research,
conduct instructional activities or chemical analysis with, or
possess), or propose to handle, ethylphenidate.
According to HHS, ethylphenidate has a high potential for abuse,
has no currently accepted medical use in treatment in the United
States, and lacks accepted safety for use under medical supervision.
DEA's research confirms that there is no legitimate commercial market
for ethylphenidate in the United States. Therefore, DEA estimates that
no United States entity currently handles ethylphenidate and does not
expect any United States entity to handle ethylphenidate in the
foreseeable future. DEA concludes that no legitimate United States
entity would be affected by this rule if finalized. As such, the
proposed rule will not have a significant effect 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 and certifies 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 million 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 under
the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-3521.
Signing Authority
This document of the Drug Enforcement Administration was signed on
September 7, 2023, by Administrator Anne Milgram. That document with
the original signature and date is maintained by DEA. For
administrative purposes only, and in compliance with requirements of
the Office of the Federal Register, the undersigned DEA Federal
Register Liaison Officer has been authorized to sign and submit the
document in electronic format for publication, as an official document
of DEA. This administrative process in no way alters the legal effect
of this document upon publication in the Federal Register.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, DEA proposes to amend 21 CFR part
1308 as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for part 1308 continues to read as follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. Amend Sec. 1308.11 by:
0
a. Redesignating paragraph (f)(6) through (12) as (f)(7) through (13);
and
0
b. Adding a new paragraph (f)(6)
The addition reads as follows:
Sec. 1308.11 Schedule I.
* * * * *
(f) * * *
------------------------------------------------------------------------
------------------------------------------------------------------------
* * * * * * *
(6) Ethylphenidate (ethyl 2-phenyl-2-(piperidin-2- 1727
yl)acetate)............................................
* * * * * * *
------------------------------------------------------------------------
* * * * *
Scott Brinks,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2023-20439 Filed 9-21-23; 8:45 am]
BILLING CODE 4410-09-P
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</html>Indexed from Federal Register on September 22, 2023.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.