Proposed Rule2021-15331
Schedules of Controlled Substances: Placement of Amineptine 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
July 22, 2021
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
The Drug Enforcement Administration proposes placing the substance amineptine (chemical name: 7-[(10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid), including its salts, isomers, and salts of isomers, in schedule I of the Controlled Substances Act. This action is being taken to enable the United States to meet its obligations under the 1971 United Nations 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 with, or possess), or propose to handle, amineptine.
Full Text
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<title>Federal Register, Volume 86 Issue 138 (Thursday, July 22, 2021)</title>
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[Federal Register Volume 86, Number 138 (Thursday, July 22, 2021)]
[Proposed Rules]
[Pages 38619-38624]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-15331]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-371]
Schedules of Controlled Substances: Placement of Amineptine 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 amineptine (chemical name: 7-[(10,11-dihydro-5H-
dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid), including its
salts, isomers, and salts of isomers, in schedule I of the Controlled
Substances Act. This action is being taken to enable the United States
to meet its obligations under the 1971 United Nations 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 with,
or possess), or propose to handle, amineptine.
DATES: Comments must be submitted electronically or postmarked, on or
before September 20, 2021.
Interested persons may file a request for 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 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 August
23, 2021.
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-371'' on all
electronic and written correspondence, including any attachments.
<bullet> Electronic comments: DEA encourages commenters to submit
all 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 on-line
instructions at that site for submitting comments. Upon completion of
your submission, you will receive a Comment Tracking Number. Submitted
comments are not instantaneously available for public view on <a href="http://www.regulations.gov">http://www.regulations.gov</a>. If you have received a Comment Tracking Number,
you have submitted your comment successfully, and there is no need to
resubmit the same comment.
<bullet> Paper comments: Paper comments that duplicate electronic
submissions are not necessary and are discouraged. Should you wish to
mail a paper comment in lieu of an electronic comment, send 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/LJ, 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: Terrence L. Boos, Drug & Chemical
Evaluation Section, Diversion Control Division, Drug Enforcement
Administration; Telephone: (571) 362-3249.
SUPPLEMENTARY INFORMATION:
Posting of Public Comments
All comments received in response to this docket are considered
part of the public record. The Drug Enforcement Administration (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 DEA to make it 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 generally make available in publicly redacted form
comments containing personal identifying information and 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.
[[Page 38620]]
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, 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D. Interested persons may file requests for a hearing or
notices of intent to participate in a hearing in conformity with the
requirements of 21 CFR 1308.44(a) or (b), and they shall include a
statement of interest in the proceeding and the objections or issues,
if any, concerning which the person desires to be heard. 21 CFR
1316.47(a). Any interested person may file a waiver of an opportunity
for a hearing or to participate in a hearing together with a written
statement regarding the interested person's position on the matters of
fact and law involved in any hearing as set forth in 21 CFR 1308.44(c).
All requests for 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.
Legal Authority
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 the
Department of Health and Human Services (HHS),\1\ 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 substance. 21 U.S.C. 811(d)(3). In the event that the Secretary
of HHS (Secretary) did not 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 may add to such a schedule any drug or other
substance, if he finds that such drug or other substance has a
potential for abuse, and makes the findings prescribed by 21 U.S.C.
812(b) for the schedule in which such drug is to be placed. The
Attorney General has delegated this scheduling authority to the
Administrator of DEA. 28 CFR 0.100.
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\1\ As discussed in a memorandum of understanding entered into
by the Food and Drug Administration (FDA) and the National Institute
on Drug Abuse (NIDA), FDA acts as the lead agency within HHS in
carrying out the Secretary's scheduling responsibilities under the
Controlled Substances Act, with the concurrence of NIDA. 50 FR 9518
(March 8, 1985). The Secretary of HHS has delegated to the Assistant
Secretary for Health of HHS the authority to make domestic drug
scheduling recommendations. 58 FR 35460 (July 1, 1993).
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Background
Amineptine is a synthetic tricyclic antidepressant with central
nervous system (CNS) stimulating properties that, according to HHS, has
no approved medical use and no known therapeutic application in the
United States. Pharmacological studies indicate that amineptine's
primary mode of action is to increase extracellular levels of dopamine
and norepinephrine as well as inhibit re-uptake of dopamine and
norepinephrine within the striatum and limbic areas of the brain.
In 1978, amineptine was approved for use in France as an
antidepressant and subsequently marketed in 66 countries throughout
Africa, Asia, Europe, and South America. As documented by the World
Health Organization's (WHO) Expert Committee on Drug Dependence in its
33rd report (2003) (WHO 2003 report), amineptine has been withdrawn
from the market in 49 of the 66 countries. The status of current
production of amineptine in other countries is not known, although a
small quantity is most likely produced for research purposes.
In April 2003, the United Nations Commission on Narcotic Drugs, on
the advice of the Director-General of the WHO, added amineptine to
Schedule II of the 1971 Convention, thus notifying all parties to the
1971 Convention.\2\ Because the procedures in 21 U.S.C. 811(d)(3) and
(4) for consultation and issuance of a temporary order for amineptine,
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 amineptine. Such scheduling would
satisfy the United States' international obligations.
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\2\ <a href="https://www.unodc.org/unodc/en/Resolutions/resolution_2003-04-08_1.html">https://www.unodc.org/unodc/en/Resolutions/resolution_2003-04-08_1.html</a>.
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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 amineptine. 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
accordance 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
[[Page 38621]]
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 Amineptine
Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on
amineptine and, on August 12, 2008, submitted it to the Assistant
Secretary for Health of HHS with a request for a scientific and medical
evaluation of available information and a scheduling recommendation for
amineptine. On November 8, 2011, HHS provided to DEA a written
scientific and medical evaluation and scheduling recommendation
entitled ``Basis for the Recommendation for Control of Amineptine in
Schedule I of the Controlled Substances Act.'' In this recommendation,
HHS presented its eight-factor analysis as required under 21 U.S.C.
811(b) and recommended that amineptine be added to schedule I of the
CSA.
In response, DEA reviewed the scientific and medical evaluation and
scheduling recommendation provided by HHS and all other relevant data
and conducted its own eight-factor analysis pursuant to 21 U.S.C.
811(c). Included below is a brief summary of each factor as analyzed by
HHS and DEA, and as considered by DEA in the scheduling decision. Both
DEA and HHS analyses are available in their entirety under ``Supporting
and Related Material'' of the public docket for this rule at <a href="http://www.regulations.gov">http://www.regulations.gov</a> under docket number DEA-371.
1. The Drug's Actual or Relative Potential for Abuse: As reported
by HHS, the WHO 2003 report showed strong evidence of abuse in Europe
and Asia, where amineptine was approved for use as an antidepressant.
Additional HHS findings showed that due to reports of hepatotoxicity
and abuse in Europe, Servier (a French pharmaceutical company)
voluntarily discontinued the French marketing authorization in France
and Spain for amineptine in 1999 (HHS, 2011; \3\ WHO, 2002 \4\).
However, as documented by the WHO 2003 report, the medical use of
amineptine and its abuse in developing countries still existed during
1990 to 2003. Clinical studies used between 100--200 mg of amineptine
(Lachatre et al., 1989; \5\ Sbarra et al., 1981 \6\); however, case
reports from various countries (none in the United States due to its
lack of approved medical use or known therapeutic application in the
United States) have reported hospitalizations due to amineptine abuse
and overdose following the ingestion of 2,000-4,300 mg and even up to
12 g daily. However, adverse effects at prescribed doses of amineptine
were still observed (see Factor 6).
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\3\ Health and Human Services (HHS) (2011). Basis for the
Recommendation for Control of Amineptine in Schedule I of the
Controlled Substances Act.
\4\ WHO's Critical Review of Psychoactive Substances prepared
for evaluation by the 33rd Meeting of the WHO Expert Committee on
Drug Dependence held in September, in Annex, 2002.1-14.
\5\ Lachatre, G., Piva, C., Riche, C., Dumont, D., Defrance, R.,
Mocaer, E., Nicot, G. (1989). Single-dose pharmacokinetics of
amineptine and of its main metabolite in healthy young adults.
Fundamental and Clinical Pharmacology, 3(1):19-26.
\6\ Sbarra, C., Castelli, M. G., Noseda, A., Fanelli, R. (1981).
Pharmacokinetics of amineptine in man. European Journal of Drug
Metabolism and Pharmacokinetics, 6(2), 123-126.
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Evidence shows that amineptine produces behavioral effects in
humans and animals that are similar to amphetamine and cocaine (both in
schedule II). Pharmacological studies have demonstrated that amineptine
has reinforcing effects as shown by the self-administration test and
has locomotor stimulant effects. Studies also have shown that
amineptine increases extracellular concentrations of dopamine in the
brain, particularly in the striatum and nucleus accumbens, which are
structures constituting the reward pathway and are known to be involved
in the abuse of drugs, including amphetamine and cocaine. The above
data indicate that amineptine has the potential for abuse similar to
other CNS stimulants controlled under the CSA, such as cocaine and
amphetamine.
2. Scientific Evidence of the Drug's Pharmacological Effects, if
Known: As stated by HHS, amineptine increases dopamine levels by
inducing the synaptosomal release and inhibition of dopamine re-uptake
and, to a lesser extent, increasing norepinephrine levels, a mode of
action mechanistically similar to the known schedule II CNS stimulants
amphetamine and cocaine. Animal behavioral studies have shown that
amineptine, in addition to its CNS stimulant properties, has anti-
depressant, locomotor, and anti-narcoleptic activities. Human
behavioral studies have demonstrated that amineptine works similarly to
other antidepressants, often with an earlier onset of therapeutic
effects. Studies have shown that amineptine administration lowers
depression rating scales in patients and results in a positive
subjective quality of sleep and subsequent increase in attention and
concentration upon waking.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: The chemical name of amineptine is 7-[(10,11-dihydro-
5H-dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid. It is a white,
crystalline powder and is soluble in water and in methanol. Humans
rapidly absorb amineptine after oral administration, with mean peak
plasma concentrations of amineptine and its main metabolite occurring
at 1 hour and 1.5 hours, respectively. Amineptine is metabolized in the
liver and rapidly excreted and eliminated through the kidneys with mean
half-lives of 0.8 hours for amineptine and 2.5 hours for its
metabolite. In humans, 70-75 percent of the administered dose of
amineptine was excreted in the urine within 48 hours, with most of the
elimination occurring within the first 12 hours.
Distribution of \14\C-amineptine was also evaluated in the Macaca
fascicularis monkey using whole body autoradiography. Results
demonstrated high levels of radio-labeled amineptine in the liver and
kidneys, with lower levels of activity in the blood, gastrointestinal
tract and spleen. In the brain, radioactivity was observed in the
cortex, putamen, caudate nucleus, globus pallidus, pulvinar, and
geniculate bodies, with lower levels noted in the hippocampus,
substantia nigra, and medulla.
4. Its History and Current Pattern of Abuse: As mentioned by HHS,
there are numerous published reports of amineptine abuse, including 186
cases of abuse between 1978 and 1988 reported to the Regional Centers
of Pharmacovigilance and the Laboratory Eutherapie in France, and 65
cases of abuse between 1990 and 1998 appearing in the Observation of
Illegal Drugs and Misuse of Psychotropic Medications database. Notably,
amineptine has not been approved for medical use in the United States
nor is there any
[[Page 38622]]
documented abuse in the United States of amineptine.
At the 16th French Pharmacovigilance meeting in November 1994, the
Fernand Widal Pharmacovigilance Centre reviewed 565 cases of amineptine
``overconsumption'' from 1978 to 1993, and reported multiple
characteristics of amineptine abuse including: (1) Amineptine abusers
typically had a history of alcoholism, drug abuse, and/or eating
disorders; (2) 28 percent of the cases of amineptine abuse resulted in
neuropsychiatric disorders; (3) 11 percent of patients developed acne-
like lesions from amineptine use; (4) withdrawal from amineptine abuse
was described as extremely difficult; (5) only 30 percent were
abstinent after one month of withdrawal and long-term abstinence was
uncommon; and (6) most patients obtained amineptine from pharmacists by
prescription theft or by fraudulent prescriptions. Collectively, these
three reports show that there has been a continued pattern of abuse
from 1978 to 1998.
DEA noted that in the WHO 2003 report, the WHO's Expert Committee
on Drug Dependence stated that the degree of risk to public health
associated with the abuse liability of amineptine is substantial, while
noting several adverse effects including hepatotoxicity, severe acne,
and anxiety. The committee also noted the limited therapeutic
usefulness of amineptine due to the availability of safer
antidepressants.
Queries of DEA's System to Retrieve Information from Drug Evidence
(STRIDE)/STARLiMS \7\ and the National Forensic Laboratory Information
System (NFLIS) \8\ databases on November 17, 2020, did not generate any
reports of amineptine, suggesting that it is not trafficked in the
United States.
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\7\ STRIDE is a database of drug exhibits sent to DEA
laboratories for analysis. Exhibits from the database are from DEA,
other federal agencies, and law enforcement agencies. On October 1,
2014, STARLiMS replaced STRIDE as DEA laboratory drug evidence data
system of record.
\8\ NFLIS is a national drug forensic laboratory reporting
system that systematically collects results from drug chemistry
analyses conducted by state and local forensic laboratories across
the country. The NFLIS participation rate, defined as the percentage
of the national drug caseload represented by laboratories that have
joined NFLIS, is over 97%. NFLIS includes drug chemistry results
from completed analyses only.
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5. The Scope, Duration, and Significance of Abuse: According to the
published case reports from 1984 to 2001 in France, Italy, Pakistan,
Singapore, and Spain, the majority of the reported cases of amineptine
abuse involved patients who were prescribed amineptine for an affective
disorder. In these cases, abuse normally began one year after
amineptine was prescribed for the treatment of depression by patients
independently increasing their dosage, especially in those with a
history of alcoholism, intravenous drug abuse, and eating disorders.
Amineptine abuse appears to be due to its psychostimulant effect.
Indeed, reasons cited for its abuse were increased energy, joy, work
output, alertness, and psychomotor performance. Presently, although
internet searches result in websites with purported amineptine for
sale, these sites do not list the formulation, purity, price, and
quantity for this purported amineptine. In addition, the 1971
Convention currently controls amineptine internationally as a Schedule
II substance. Amineptine is also controlled in Belgium, Canada, the
Czech Republic, Denmark, Estonia, Germany, Greece, Hungary, Italy,
Latvia, Lithuania, the Netherlands, Norway, Poland, Slovenia, and
Sweden.
6. What, if Any, Risk There is to the Public Health: As reported by
HHS, there are no known fatalities resulting from amineptine use or
abuse. Some of the main public health risks of amineptine are related
to its serious adverse effects, such as hepatotoxicity, severe acne,
and gastrointestinal (acute pancreatitis) effects. In addition,
neuropsychiatric symptoms including anxiety, insomnia, nervousness,
irritability, dysarthria, acute psychosis, delusions, hallucinations,
anorexia, agitation, psychotic disorders, and confusion have resulted
from abuse of amineptine.
7. Its Psychic or Physiological Dependence Liability: HHS stated
that amineptine has been shown to produce physical and psychological
dependence as supported by clinical evidence. While amineptine has no
clearly defined withdrawal syndrome, reports of withdrawal symptoms
include anxiety, dysphoria, nausea, brief psychotic episodes, tremor,
psychomotor agitation, somatic symptoms, and sleep disturbances. In
addition, a strong desire to take amineptine was noted in individuals
upon withdrawal of the drug, a typical characteristic of psychological
dependence.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled under the CSA: DEA and HHS find that amineptine is
not an immediate precursor of a substance already controlled under the
CSA.
Conclusion: Based on consideration of the scientific and medical
evaluation and accompanying recommendation of HHS, and based on DEA's
consideration of its own eight-factor analysis, DEA finds that these
facts and all relevant data constitute substantial evidence of
potential for abuse of amineptine. As such, DEA hereby proposes to
schedule amineptine as a 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 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 available data, the Administrator of DEA, pursuant to 21 U.S.C.
812(b)(1), finds that:
(1) Amineptine has a high potential for abuse. Amineptine has
stimulant and euphoric effects similar to cocaine and amphetamine,
which are both schedule II drugs. Amineptine has a high potential for
abuse that is equivalent to cocaine and amphetamine and has been abused
throughout Europe and Asia.
(2) Amineptine has no currently accepted medical use in treatment
in the United States. There are no approved New Drug Applications for
amineptine and no known therapeutic application for amineptine in the
United States. Therefore, amineptine has no currently accepted medical
use in treatment in the United States.\9\
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\9\ Although there is no evidence suggesting that amineptine 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, to have a currently accepted medical use in treatment in the
United States, all of the following must be demonstrated: i. the
drug's chemistry must be known and reproducible; ii. there must be
adequate safety studies; iii. there must be adequate and well-
controlled studies proving efficacy; iv. the drug must be accepted
by qualified experts; and v. the scientific evidence must be 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).
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(3) There is a lack of accepted safety for use of amineptine under
medical supervision. Clinical experience showed that patients taking
amineptine under medical supervision for depression misused and abused
the drug by stealing or falsifying prescriptions and taking doses that
were 10 to 20 times higher than prescribed. As a result of taking
higher doses, many patients developed hepatic, gastrointestinal,
cardiovascular, and psychiatric side effects. Amineptine was once
marketed in 66 countries throughout Europe, Africa, Asia, and
[[Page 38623]]
South America. However, amineptine was later withdrawn from the
majority of countries due to its abuse potential and lack of safety.
Therefore, there is a lack of accepted safety for the use of amineptine
under medical supervision.
Although the first finding shows amineptine to have similar effects
to schedule II substances such as cocaine and amphetamine, it bears
reiterating that there is only one possible schedule in the CSA--
schedule I--to place amineptine 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 of DEA concludes that
amineptine warrants control in schedule I of the CSA. 21 U.S.C.
812(b)(1). More precisely, because of its stimulant effects, DEA
proposes placing substance amineptine, including its salts, isomers,
and salts of isomers, in 21 CFR 1308.11(f) (the stimulants category of
schedule I).
Requirements for Handling Amineptine
If this rule is finalized as proposed, amineptine would be subject
to the CSA's schedule I regulatory controls and administrative, civil,
and criminal sanctions applicable to the manufacture, distribution,
reverse distribution, import, export, engagement in research, 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
instructional activities or chemical analysis with, or possesses)
amineptine, or who desires to handle amineptine, would need to be
registered with DEA to conduct such activities pursuant to 21 U.S.C.
822, 823, 957, 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 amineptine and is not registered with DEA would need
to submit an application for registration and may not continue to
handle amineptine 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
or to transfer all quantities of currently held amineptine 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,
amineptine 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. Amineptine would be subject to schedule I security
requirements and would need to be handled and stored pursuant to 21
U.S.C. 821 and 823 and in accordance with 21 CFR 1301.71-1301.93, as of
the effective date of a final scheduling action. Non-practitioners
handling amineptine 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 amineptine would need to be in compliance with
21 U.S.C. 825 and 958(e) and 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 amineptine 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
amineptine on the effective date of a final scheduling action would be
required to take an inventory of amineptine 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 on or after the
effective date of the final scheduling action would be required to take
an initial inventory of all stocks of controlled substances (including
amineptine) 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 would be required
to take a new inventory of all controlled substances (including
amineptine) 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 for amineptine, or products
containing amineptine, pursuant to 21 U.S.C. 827 and 958 and in
accordance with 21 CFR parts 1304, 1312, and 1317, as of the effective
date of a final scheduling action. Manufacturers and distributors would
be required to submit reports regarding amineptine 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 amineptine
would be required to comply with 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
amineptine 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 amineptine 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 and 13563, Regulatory Planning and Review, and
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
procedures and criteria for scheduling a drug or other substance. Such
actions are exempt from review by the Office of Management and Budget
pursuant to Section 3(d)(1) of Executive Order (E.O.) 12866 and the
principles reaffirmed in E.O. 13563.
Executive Order 12988, Civil Justice Reform
This proposed regulation meets the applicable standards set forth
in Sections 3(a) and 3(b)(2) of E.O. 12988, Civil Justice Reform, to
eliminate drafting errors and ambiguity, minimize litigation, provide a
clear legal standard for affected conduct, and promote simplification
and burden reduction.
Executive Order 13132, Federalism
This 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
[[Page 38624]]
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.
Paperwork Reduction Act of 1995
This action does not impose a new collection of information
requirement under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3521).
Regulatory Flexibility Act
The Administrator of DEA, in accordance with the Regulatory
Flexibility Act, 5 U.S.C. 601-612, has reviewed this proposed rule and,
by approving it, certifies that it will not have a significant economic
impact on a substantial number of small entities.
DEA proposes placing the substance amineptine, including its
isomers, salts, 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. If finalized, this action would
impose the regulatory controls and administrative, civil, and/or
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 with, or possess), or propose to handle, amineptine.
According to HHS, amineptine 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 commercial market for amineptine in the
United States. Additionally, queries of DEA's STRIDE/STARLiMS and the
NFLIS databases on November 17, 2020, did not generate any reports of
amineptine, suggesting that it is not trafficked in the United States.
Therefore, DEA estimates that no United States entity currently handles
amineptine and does not expect any United States entity to handle
amineptine in the foreseeable future. DEA concludes that no 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
On the basis of information contained in the ``Regulatory
Flexibility Act'' section above, DEA has determined pursuant to the
Unfunded Mandates Reform Act (UMRA) of 1995 (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 annually for inflation) in any 1 year * * *.'' Therefore,
neither a Small Government Agency Plan nor any other action is required
under provisions of the UMRA of 1995.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, 21 CFR part 1308 is proposed to be
amended to read as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
0
1. The authority citation for 21 CFR part 1308 continues to read as
follows:
Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise
noted.
0
2. Amend Sec. 1308.11 by re-designating paragraphs (f)(1) through
(f)(9) as paragraphs (f)(2) through (f)(10), and adding a new paragraph
(f)(1) to read as follows:
Sec. 1308.11 Schedule I.
* * * * *
(f) * * *
(1) Amineptine (7-[(10,11-dihydro-5H- 1219
dibenzo[a,d]cyclohepten-5-yl)amino]heptanoic acid).....
* * * * *
Anne Milgram,
Administrator.
[FR Doc. 2021-15331 Filed 7-21-21; 8:45 am]
BILLING CODE 4410-09-P
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</html>Indexed from Federal Register on July 22, 2021.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.