[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 [www.gpo.gov]
[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