Rule2021-11981
Schedules of Controlled Substances: Placement of Oliceridine in Schedule II
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
June 10, 2021
Effective
July 12, 2021
Issuing agencies
Justice DepartmentDrug Enforcement Administration
Abstract
This final rule adopts, with a change as mentioned below, an interim final rule with request for comments published in the Federal Register on October 30, 2020, placing oliceridine, N-[(3- methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6- oxaspiro[4.5]decan-9-yl]ethyl{time} )amine fumarate, including its isomers, esters, ethers, salts and salts of isomers, esters and ethers whenever the existence of such isomers, esters, ethers and salts is possible, in schedule II of the Controlled Substances Act. In response to an error in the chemical name of oliceridine as noted by one of the commenters to the interim final rule, the Drug Enforcement Administration makes a correction to the above mentioned chemical name of oliceridine by removing the word "fumarate" to read as N-[(3- methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6- oxaspiro[4.5]decan-9-yl]ethyl{time} amine. This change clarifies the control of oliceridine free base and its salts, to include the fumarate salt, by definition.
Full Text
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<title>Federal Register, Volume 86 Issue 110 (Thursday, June 10, 2021)</title>
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[Federal Register Volume 86, Number 110 (Thursday, June 10, 2021)]
[Rules and Regulations]
[Pages 30772-30775]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-11981]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-715]
Schedules of Controlled Substances: Placement of Oliceridine in
Schedule II
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final rule.
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SUMMARY: This final rule adopts, with a change as mentioned below, an
interim final rule with request for comments published in the Federal
Register on October 30, 2020, placing oliceridine, N-[(3-
methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-
oxaspiro[4.5]decan-9-yl]ethyl{time} )amine fumarate, including its
isomers, esters, ethers, salts and salts of isomers, esters and ethers
whenever the existence of such isomers, esters, ethers and salts is
possible, in schedule II of the Controlled Substances Act. In response
to an error in the chemical name of oliceridine as noted by one of the
commenters to the interim final rule, the Drug Enforcement
Administration makes a correction to the above mentioned chemical name
of oliceridine by removing the word ``fumarate'' to read as N-[(3-
methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-
oxaspiro[4.5]decan-9-yl]ethyl{time} amine. This change clarifies the
control of oliceridine free base and its salts, to include the fumarate
salt, by definition.
DATES: Effective July 12, 2021.
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:
Background and Legal Authority
On October 30, 2020, the Drug Enforcement Administration (DEA),
pursuant to 21 U.S.C. 811(j), published an interim final rule (IFR) to
place oliceridine (including its isomers, esters, ethers, salts and
salts of isomers, esters and ethers whenever the existence of such
isomers, esters, ethers and salts is possible), a medication approved
recently by the Food and Drug Administration (FDA) for medical use as
an intravenous drug for the management of acute pain severe enough to
require an intravenous opioid analgesic and for patients for whom
alternative treatments are inadequate, in schedule II of the Controlled
Substances Act (CSA). 85 FR 68749. The IFR provided an opportunity for
interested persons to submit comments, as well as file a request for
hearing or waiver of hearing, on or before November 30, 2020. DEA
received three comments and did not receive any requests for hearing or
waiver of hearing.
Comments Received
In response to the IFR, DEA received three comments. The
submissions were from individuals or anonymous commenters. One
commenter suggested that oliceridine be placed in schedule III rather
than schedule II, one commenter had a statement on the controlled name,
and the third commenter discussed another substance entirely that was
unrelated to oliceridine. As such, the third comment was outside the
scope of this current scheduling action.
Comment: One commenter suggested that oliceridine be placed in
schedule III of the CSA, rather than schedule II. The commenter
mentioned that placement of oliceridine in schedule II will limit its
medical applications and limit access to the drug due to schedule II
manufacturing quotas. The commenter stated that oliceridine has the
potential
[[Page 30773]]
to revolutionize gastrointestinal endoscopy because it does not cause
respiratory depression. Lastly, the commenter stated that since
oliceridine is not indicated for home-use, abuse of the medication by
drug users would be difficult.
DEA Response: DEA notes that FDA approved a New Drug Application
(NDA) for oliceridine and provided DEA with a scheduling recommendation
for oliceridine. The scheduling recommendation by Health and Human
Services (HHS) and their notification to DEA regarding the FDA approval
of the NDA initiated the DEA review and scheduling action. As stated in
the IFR, after careful consideration of data from preclinical and
clinical studies, DEA concurred with the HHS recommendation that
oliceridine has abuse potential comparable to other schedule II opioids
and therefore supported--and continues to support through this final
rule--placement of oliceridine in schedule II under the CSA. Contrary
to the commenter's opinion about schedule II controls on a drug
limiting its medical applications and access due to manufacturing quota
requirements, DEA notes that currently several schedule II drugs
(oxycodone, hydrocodone etc.) are extensively prescribed and used in
medical practice.
Comment: One commenter stated that the chemical name provided in
the interim final rule indicates oliceridine is ``N-[(3-
methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-
oxaspiro[4.5]decan-9-yl]ethyl{time} )amine fumarate'', though this is
the name of the fumarate salt of oliceridine. The commenter noted that
the other substances listed in 21 CFR 1308.12, and in most other
sections of the CSA list only the base form of the drug, and control
salts by definition. The commenter suggested to provide the chemical
name for oliceridine base, and the fumarate salt would be controlled
under the preamble in 12 CFR 1308.12.
DEA Response: DEA agrees with commenter regarding the error in the
chemical name of oliceridine and corrects appropriately by removing the
word ``fumarate'' to read oliceridine as, N-[(3-methoxythiophen-2-
yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-
yl]ethyl{time} )amine. The correction will make clear precisely which
substance is being controlled because the fumarate salt was not the
accurate designation for the controlled substance. The listing of the
base form and removal of the salt designation is consistent with other
controlled substance listings under the CFR and the substance
designated for control remains unchanged. The base form listing minus
the salt designation (``fumarate'') is readily understood by those
registered to handle the substance and would not be misunderstood by
the public. For this reason, DEA believes the change will not have an
impact.
Based on the rationale set forth in the interim final rule, DEA
adopts the IFR, with the above mentioned correction to the chemical
name of oliceridine.
Requirements for Handling Oliceridine
As indicated above, oliceridine has been a schedule II controlled
substance by virtue of an IFR issued by DEA in October 2020. Thus, this
final rule does not alter the regulatory requirements applicable to
handlers of oliceridine that have been in place since that time.
Nonetheless, for informational purposes, we restate here those
requirements. Oliceridine is subject to the CSA's schedule II
regulatory controls and administrative, civil, and criminal sanctions
applicable to the manufacture, distribution, reverse distribution,
dispensing, importing, exporting, research, and conduct of
instructional activities and chemical analysis with, and possession
involving schedule II substances, including the following:
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, dispenses, imports, exports, engages in research,
or conducts instructional activities or chemical analysis with, or
possesses) oliceridine, or who desires to handle oliceridine, must 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. Any person who currently handles or intends to handle
oliceridine, and is not registered with DEA, must submit an application
for registration and may not continue to handle oliceridine, unless DEA
has approved the application for registration, pursuant to 21 U.S.C.
822, 823, 957, and 958, and in accordance with 21 CFR parts 1301 and
1312. These registration requirements, however, are not applicable to
patients (end users) who possess oliceridine pursuant to a lawful
prescription.
2. Quota. Only registered manufacturers are permitted to
manufacture oliceridine in accordance with a quota assigned pursuant to
21 U.S.C. 826 and in accordance with 21 CFR part 1303.
3. Disposal of stocks. Any person who does not desire or is not
able to maintain a schedule II registration must surrender all
quantities of currently held oliceridine, or may transfer all
quantities of currently held oliceridine to a person registered with
DEA in accordance with 21 CFR part 1317, in addition to all other
applicable Federal, State, local, and tribal laws.
4. Security. Oliceridine is subject to schedule II security
requirements and must be handled and stored pursuant to 21 U.S.C. 821
and 823 and in accordance with 21 CFR 1301.71-1301.93. Non-
practitioners handling oliceridine must also comply with the employee
screening requirements of 21 CFR 1301.90-1301.93.
5. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of oliceridine must comply with 21 U.S.C. 825 and
958(e) and be in accordance with 21 CFR part 1302.
6. Inventory. Every DEA registrant who possesses any quantity of
oliceridine must take an inventory of oliceridine on hand, pursuant to
21 U.S.C. 827 and 958(e), and in accordance with 21 CFR 1304.03,
1304.04, and 1304.11.
Any person who becomes registered with DEA to handle oliceridine
must take an initial inventory of all stocks of controlled substances
containing oliceridine on hand on the date the registrant first engages
in the handling of controlled substances, pursuant to 21 U.S.C. 827 and
958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
After the initial inventory, every DEA registrant must take a new
inventory of all stocks of controlled substances (including
oliceridine) on hand every two years, pursuant to 21 U.S.C. 827 and
958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
7. Records and Reports. DEA registrants must maintain records and
submit reports for oliceridine, pursuant to 21 U.S.C. 827 and 958(e),
and in accordance with 21 CFR parts 1304, 1312, and 1317.
8. Orders for oliceridine. Every DEA registrant who distributes
oliceridine is required to comply with order form requirements,
pursuant to 21 U.S.C. 828, and in accordance with 21 CFR part 1305.
9. Prescriptions. All prescriptions for oliceridine or products
containing oliceridine must comply with 21 U.S.C. 829, and be issued in
accordance with 21 CFR parts 1306 and 1311, subpart C.
10. Manufacturing and Distributing. In addition to the general
requirements of the CSA and DEA regulations that are applicable to
manufacturers and distributors of schedule II controlled substances,
such registrants should be advised that (consistent with the foregoing
considerations) any manufacturing or distribution of oliceridine may
only be for the
[[Page 30774]]
legitimate purposes consistent with the drug's labeling, or for
research activities authorized by the Federal Food, Drug, and Cosmetic
Act, as applicable, and the CSA.
11. Importation and Exportation. All importation and exportation of
oliceridine must be in compliance with 21 U.S.C. 952, 953, 957, and
958, and in accordance with 21 CFR part 1312.
12. Liability. Any activity involving oliceridine not authorized
by, or in violation of, the CSA or its implementing regulations, is
unlawful, and may subject the person to administrative, civil, and/or
criminal sanctions.
Regulatory Analyses
Administrative Procedure Act
This final rule, with a correction in the chemical name of
oliceridine as discussed above, affirms the amendment made by the IFR
that is already in effect. Section 553 of the Administrative Procedure
Act (APA) (5 U.S.C. 553) generally requires notice and comment for
rulemaking. However, 21 U.S.C. 811(j) provides that in cases where a
certain new drug is: (1) Approved by HHS and (2) HHS recommends control
in CSA schedule II-V, DEA shall issue an IFR scheduling the drug within
90 days. Additionally, subsection (j) specifies that the rulemaking
shall become immediately effective as an interim final rule without
requiring DEA to demonstrate good cause. DEA issued an IFR on October
30, 2020, and solicited public comments on that rule. Subsection (j)
further provides that after giving interested persons the opportunity
to comment and to request a hearing, the Attorney General, as delegated
to the Administrator of DEA, shall issue a final rule in accordance
with the scheduling criteria of 21 U.S.C. 811(b) through (d) and
812(b). DEA is now responding to the comments submitted by the public
and issuing the final rule, in conformity with the APA and the
procedure required by 21 U.S.C. 811.
Executive Orders 12866 (Regulatory Planning and Review) and 13563
(Improving Regulation and Regulatory Review)
In accordance with 21 U.S.C. 811(a) and (j), this 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 procedures
and 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 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 rulemaking does not have federalism implications warranting
the application of E.O. 13132. The rule does not have substantial
direct effects on the States, on the relationship between the national
government and the States, or on the distribution of power and
responsibilities among the various levels of government.
Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments
This 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 Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to
rules that are subject to notice and comment under section 553(b) of
the APA. Under 21 U.S.C. 811(j), DEA is not required to publish a
general notice of proposed rulemaking. Consequently, the RFA does not
apply.
Unfunded Mandates Reform Act of 1995
In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., DEA has determined that this action would not
result in any Federal mandate that may result ``in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100 million or more (adjusted for inflation) in any
one year.'' Therefore, neither a Small Government Agency Plan nor any
other action is required under UMRA of 1995.
Paperwork Reduction Act of 1995
This action does not impose a new collection of information
requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. This action does 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.
Congressional Review Act
This rule is not a major rule as defined by the Congressional
Review Act (CRA), 5 U.S.C. 804. However, pursuant to the CRA, DEA is
submitting a copy of this final rule to both Houses of Congress and to
the Comptroller General.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
Accordingly, the interim final rule amending 21 CFR part 1308,
which published on October 30, 2020 (85 FR 68749), is adopted as a
final rule with the following amendment:
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. 1308.12 by revising paragraph (c)(18) to read as
follows:
Sec. 1308.12 Schedule II.
* * * * *
(c) * * *
(18) Oliceridine (N-[(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9- 9245
(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl{time} )amine)....
[[Page 30775]]
* * * * *
D. Christopher Evans,
Acting Administrator.
[FR Doc. 2021-11981 Filed 6-9-21; 8:45 am]
BILLING CODE 4410-09-P
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</html>Indexed from Federal Register on June 10, 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.