Schedules of Controlled Substances: Removal of Samidorphan From Control

• Published date: 19 April 2021
• Citation: 86 FR 20284
• Record Number: 2021-07884
• Section: Rules and Regulations
• Court: Drug Enforcement Administration,Justice Department

20284

Federal Register / Vol. 86, No. 73 / Monday, April 19, 2021 / Rules and Regulations

PART 892—RADIOLOGY DEVICES

■10. The authority citation for part 892

continues to read as follows:

Authority: 21 U.S.C. 351, 360, 360c, 360e,

360j, 360l, 371.

■11. Amend § 892.2010 by revising

paragraph (a) to read as follows:

§ 892.2010 Medical image storage device.

(a) Identification: A medical image

storage device is a hardware device that

provides electronic storage and retrieval

functions for medical images. Examples

include electronic hardware devices

employing magnetic and optical discs,

magnetic tapes, and digital memory.

* * * * *

■12. Amend § 892.2020 by revising

paragraph (a) to read as follows:

§ 892.2020 Medical image communications

device.

(a) Identification. A medical image

communications device provides

electronic transfer of medical image data

between medical devices. It may

include a physical communications

medium, modems, and interfaces. It

may provide simple image review

software functionality for medical image

processing and manipulation, such as

grayscale window and level, zoom and

pan, user delineated geometric

measurements, compression, or user

added image annotations. The device

does not perform advanced image

processing or complex quantitative

functions. This does not include

electronic transfer of medical image

software functions.

* * * * *

■13. Amend § 892.2050 by revising the

section heading and paragraph (a) to

read as follows:

§ 892.2050 Medical image management

and processing system.

(a) Identification. A medical image

management and processing system is a

device that provides one or more

capabilities relating to the review and

digital processing of medical images for

the purposes of interpretation by a

trained practitioner of disease detection,

diagnosis, or patient management. The

software components may provide

advanced or complex image processing

functions for image manipulation,

enhancement, or quantification that are

intended for use in the interpretation

and analysis of medical images.

Advanced image manipulation

functions may include image

segmentation, multimodality image

registration, or 3D visualization.

Complex quantitative functions may

include semi-automated measurements

or time-series measurements.

* * * * *

Dated: April 8, 2021.

Janet Woodcock,

Acting Commissioner of Food and Drugs.

Dated: April 13, 2021.

Xavier Becerra,

Secretary, Department of Health and Human

Services.

[FR Doc. 2021–07860 Filed 4–16–21; 8:45 am]

BILLING CODE 4164–01–P

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA–665]

Schedules of Controlled Substances:

Removal of Samidorphan From Control

AGENCY

: Drug Enforcement

Administration, Department of Justice.

ACTION

: Final rule.

SUMMARY

: With the issuance of this final

rule, the Acting Administrator of the

Drug Enforcement Administration

removes samidorphan (3-carboxamido-

4-hydroxy naltrexone) and its salts from

the schedules of the Controlled

Substances Act. This scheduling action

is pursuant to the Controlled Substances

Act which requires that such actions be

made on the record after opportunity for

a hearing through formal rulemaking.

Prior to the effective date of this rule,

samidorphan was a schedule II

controlled substance because it can be

derived from opium alkaloids. This

action removes the regulatory controls

and administrative, civil, and criminal

sanctions applicable to controlled

substances, including those specific to

schedule II controlled substances, on

persons who handle (manufacture,

distribute, reverse distribute, dispense,

conduct research, import, export, or

conduct chemical analysis) or propose

to handle samidorphan.

DATES

: Effective April 19, 2021.

FOR FURTHER INFORMATION CONTACT

:

Terrence L. Boos, Drug & Chemical

Evaluation Section, Diversion Control

Division, Drug Enforcement

Administration; Mailing Address: 8701

Morrissette Drive, Springfield, Virginia

22152; Telephone: (571) 362–3261.

SUPPLEMENTARY INFORMATION

:

Legal Authority

Under the Controlled Substances Act

(CSA), each controlled substance is

classified into one of five schedules

based upon its potential for abuse, its

currently accepted medical use in

treatment in the United States, and the

degree of dependence the drug or other

substance may cause. 21 U.S.C. 812. The

initial schedules of controlled

substances established by Congress are

found at 21 U.S.C. 812(c) and the

current list of scheduled substances is

published at 21 CFR part 1308.

Pursuant to 21 U.S.C. 811(a)(2), the

Attorney General may, by rule, ‘‘remove

any drug or other substance from the

schedules if he finds that the drug or

other substance does not meet the

requirements for inclusion in any

schedule.’’ The Attorney General has

delegated scheduling authority under 21

U.S.C. 811 to the Acting Administrator

of the Drug Enforcement Administration

(DEA). 28 CFR 0.100.

The CSA provides that proceedings

for the issuance, amendment, or repeal

of the scheduling of any drug or other

substance may be initiated by the

Attorney General on the petition of any

interested party. 21 U.S.C. 811(a)(3).

This action was initiated by one petition

to remove samidorphan from the list of

scheduled controlled substances of the

CSA, and is supported by, inter alia, a

recommendation from the Assistant

Secretary of the HHS and an evaluation

of all relevant data by DEA. This action

removes the regulatory controls and

administrative, civil, and criminal

sanctions applicable to controlled

substances, including those specific to

schedule II controlled substances, on

persons who handle or propose to

handle samidorphan.

Background

Samidorphan (3-carboxamido-4-

hydroxy naltrexone), is a chemical

entity that is structurally similar to

naltrexone, a mu (m)-opioid receptor

antagonist. Samidorphan (other

developmental code names: RDC–0313

or ALKS 33) is a mu-opioid receptor

antagonist with a weak partial agonist

activity at the kappa- and delta-opioid

receptors. According to HHS, products

containing samidorphan are currently

being developed for medical use.

Samidorphan is currently controlled in

schedule II of the CSA, as defined in 21

CFR 1308.12(b)(l), because it can be

derived from opium alkaloids. On April

14, 2014, DEA received a petition to

initiate proceedings to amend 21 CFR

1308.12(b)(1) so as to decontrol

samidorphan from schedule II of the

CSA. The petition complied with the

requirements of 21 CFR 1308.43(b) and

was accepted for filing. The petitioner

contended that samidorphan has been

characterized as an opioid receptor

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Federal Register / Vol. 86, No. 73 / Monday, April 19, 2021 / Rules and Regulations

1

As discussed in a memorandum of

understanding entered into by the Food and Drug

Administration (FDA) and the National Institute on

Drug Abuse (NIDA), the FDA acts as the lead agency

within the HHS in carrying out the Secretary’s

scheduling responsibilities under the CSA, with the

concurrence of NIDA. 50 FR 9518, Mar. 8, 1985.

The Secretary of the HHS has delegated to the

Assistant Secretary for Health of the HHS the

authority to make domestic drug scheduling

recommendations. 58 FR 35460, July 1, 1993.

antagonist, a class of drugs with no

abuse potential.

DEA and HHS Eight Factor Analyses

Pursuant to 21 U.S.C. 811(b), DEA

gathered the necessary data on

samidorphan and forwarded the data,

the sponsor’s petition, and a request for

scheduling recommendation on

samidorphan to HHS on April 24, 2015.

On January 9, 2020, DEA received

from HHS a scientific and medical

evaluation (dated December 19, 2019)

conducted by the Food and Drug

Administration (FDA)

1

entitled ‘‘Basis

for the Recommendation to Remove

Samidorphan (3-Carboxamido-4-

Hydroxy Naltrexone) and its Salts from

All Schedules of Control Under the

Controlled Substances Act’’ and a

scheduling recommendation. Following

consideration of the eight factors and

findings related to the substance’s abuse

potential, legitimate medical use, and

dependence liability, HHS

recommended that samidorphan and its

salts be removed from all schedules of

control of the CSA. In response, DEA

conducted its own eight factor analysis

of samidorphan pursuant to 21 U.S.C.

811(c). Both DEA and HHS analyses are

available in their entirety in the public

docket of this rule (Docket Number

DEA–665) at http://www.regulations.gov

under ‘‘Supporting and Related

Material.’’

Determination To Decontrol

Samidorphan

After a review of the available data,

including the scientific and medical

evaluation and the recommendation to

decontrol samidorphan from HHS, the

Acting Administrator of DEA published

in the Federal Register a notice of

proposed rulemaking (NPRM) entitled

‘‘Schedules of Controlled Substances:

Removal of Samidorphan from Control’’

which proposed removal of

samidorphan and its salts from the

schedules of the CSA. 85 FR 79450,

December 10, 2020. The proposed rule

provided an opportunity for interested

persons to file a request for a hearing in

accordance with DEA regulations by

January 11, 2021. No requests for such

a hearing were received by DEA. The

NPRM also provided an opportunity for

interested persons to submit written

comments on the proposal on or before

January 11, 2021.

Comments Received

DEA received two comments on the

proposed rule to remove samidorphan

from control. Both commenters

supported decontrol of samidorphan.

Support

One commenter, a psychiatrist,

clinical investigator and pain

management expert, who participated as

a principal investigator in clinical trials

that examined the safety and efficacy of

samidorphan and olanzapine

combination product, stated that

samidorphan counters weight gain

associated with clinical use of

olanzapine as antipsychotic medication

and this combination product offers

significant advancement relative to

olanzapine alone, and thus supported

this scheduling action.

Another commenter, on behalf of the

sponsor of a samidorphan and

olanzapine combination drug product

currently under review by FDA for

marketing approval, stated that

samidorphan when combined with

olanzapine has the potential to improve

the safety profile of olanzapine by

mitigating the weight gain associated

with olanzapine treatment without

altering its antipsychotic efficacy. This

commenter agreed with DEA’s

conclusion that samidorphan lacks

abuse or dependence potential and

stated that samidorphan and its salts

should be removed from the CSA

schedules. This commenter further

mentioned that the samidorphan and

olanzapine combination product, which

is currently under review by FDA for

marketing approval, is an important

new therapeutic option for patients and

any delay in its availability for

therapeutic use would negatively affect

stakeholders, and therefore this final

rule should be made effective

immediately.

DEA Response: DEA appreciates the

comments in support of this

rulemaking.

Scheduling Conclusion

Based on the consideration of all

comments, the scientific and medical

evaluation and accompanying

recommendation of HHS, and based on

DEA’s consideration of its own eight-

factor analysis, the Acting

Administrator finds that these facts and

all relevant data demonstrate that

samidorphan does not meet the

requirements for inclusion in any

schedule, and will be removed from

control under the CSA.

Regulatory Analyses

Executive Orders 12866 and 13563

In accordance with 21 U.S.C. 811(a),

this scheduling action is subject to

formal rulemaking procedures done ‘‘on

the record after opportunity for a

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

This 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

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

Federal government and the States, or

the distribution of power and

responsibilities among the various

levels of government.

Executive Order 13175

This rule does not have tribal

implications warranting the application

of E.O. 13175. This rule does not have

substantial direct effects on one or more

Indian tribes, on the relationship

between the Federal government and

Indian tribes, or on the distribution of

power and responsibilities between the

Federal government and Indian tribes.

Regulatory Flexibility Act

The Acting Administrator, in

accordance with the Regulatory

Flexibility Act (5 U.S.C. 601–612)

(RFA), has reviewed this rule and by

approving it certifies that it will not

have a significant economic impact on

a substantial number of small entities.

The purpose of this rule is to remove

samidorphan from the list of schedules

of the CSA. This action removes

regulatory controls and administrative,

civil, and criminal sanctions applicable

to controlled substances for handlers

and proposed handlers of samidorphan.

Accordingly, it has the potential for

some economic impact in the form of

cost savings.

This rule will affect all persons who

would handle, or propose to handle,

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Federal Register / Vol. 86, No. 73 / Monday, April 19, 2021 / Rules and Regulations

samidorphan. Samidorphan is not

currently available or marketed in any

country. Due to the wide variety of

unidentifiable and unquantifiable

variables that potentially could

influence the distribution and

dispensing rates, if any, of samidorphan,

DEA is unable to determine the number

of entities and small entities which

might handle samidorphan. In some

instances where a controlled

pharmaceutical drug is removed from

the schedules of the CSA, DEA is able

to quantify the estimated number of

affected entities and small entities

because the handling of the drug is

expected to be limited to DEA

registrants even after removal from the

schedules. In such instances, DEA’s

knowledge of its registrant population

forms the basis for estimating the

number of affected entities and small

entities. However, DEA does not have a

basis to estimate whether samidorphan

is expected to be handled by persons

who hold DEA registrations, by persons

who are not currently registered with

DEA to handle controlled substances, or

both. Therefore, DEA is unable to

estimate the number of entities and

small entities who plan to handle

samidorphan.

Although DEA does not have a

reliable basis to estimate the number of

affected entities and quantify the

economic impact of this final rule, a

qualitative analysis indicates that this

rule is likely to result in some cost

savings. Any person planning to handle

samidorphan will realize cost savings in

the form of saved DEA registration fees,

and the elimination of physical security,

recordkeeping, and reporting

requirements. Because of these factors,

DEA projects that this rule will not

result in a significant economic impact

on a substantial number of small

entities.

Administrative Procedure Act

DEA finds that good cause exists for

adopting this rule as a final rule with an

immediate effective date under 5 U.S.C.

553(d) because this final rule relieves a

restriction.

Unfunded Mandates Reform Act of 1995

On the basis of information contained

in the RFA section above, DEA has

determined and certifies pursuant to the

Unfunded Mandates Reform Act of 1995

(UMRA), 2 U.S.C. 1501 et seq., that this

action would not result in any federal

mandate that may result ‘‘in the

expenditure by State, local, and tribal

governments, in the aggregate, or by the

private sector, of $100 million or more

(adjusted for inflation) in any one

year. . . .’’ Therefore, neither a Small

Government Agency Plan nor any other

action is required under provisions of

UMRA.

Paperwork Reduction Act

This action does not impose a new

collection of information requirement

under the Paperwork Reduction Act, 44

U.S.C. 3501–3521. This action would

not impose recordkeeping or reporting

requirements on State or local

governments, individuals, businesses, or

organizations. An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

Congressional Review Act

This rule is not a major rule as

defined by section 804 of the Small

Business Regulatory Enforcement

Fairness Act of 1996 (Congressional

Review Act (CRA)). This rule will not

result in: an annual effect on the

economy of $100 million or more; a

major increase in costs or prices for

consumers, individual industries,

Federal, State, or local government

agencies, or geographic regions; or

significant adverse effects on

competition, employment, investment,

productivity, innovation, or on the

ability of United States-based

companies to compete with foreign-

based companies in domestic and

export markets. 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.

For the reasons set out above, 21 CFR

part 1308 is amended to read as follows:

PART 1308—SCHEDULES OF

CONTROLLED SUBSTANCES

■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.

■2. In § 1308.12, revise paragraph (b)(1)

introductory text to read as follows:

§ 1308.12 Schedule II.

* * * * *

(b) * * *

(1) Opium and opiate, and any salt,

compound, derivative, or preparation of

opium or opiate excluding

apomorphine, thebaine-derived

butorphanol, dextrorphan, nalbuphine,

naldemedine, nalmefene, naloxegol,

naloxone, 6b-naltrexol, naltrexone, and

samidorphan, and their respective salts,

but including the following:

* * * * *

D. Christopher Evans,

Acting Administrator.

[FR Doc. 2021–07884 Filed 4–16–21; 8:45 am]

BILLING CODE 4410–09–P

DEPARTMENT OF STATE

22 CFR Part 62

[Public Notice: 10818]

RIN 1400–AF03

Change to Certification Authority for

the Alien Physician Category of the

Exchange Visitor Program

AGENCY

: Department of State.

ACTION

: Final rule.

SUMMARY

: The Department of State

(Department) is changing the

certification authority for alien

physicians from the American Board of

Medical Specialties (ABMS) to the

Accreditation Council for Graduate

Medical Education (ACGME).

DATES

: This rule is effective May 19,

2021.

FOR FURTHER INFORMATION CONTACT

: G.

Kevin Saba, Director, Office of Policy

and Program Support, Office of Private

Sector Exchange, Bureau of Educational

and Cultural Affairs, U.S. Department of

State, SA–4E, 2201 C Street NW,

Washington, DC 20522; email at

JExchanges@state.gov; or, (202) 634–

4710.

SUPPLEMENTARY INFORMATION

: In 22 CFR

62.27(e)(1) and (e)(4)(i), there is a

reference to the ‘‘American Board of

Medical Specialties’’ (ABMS). These

provisions, last amended in 1993, state

that ABMS will perform certain

certification functions for the Secretary

of State.

ABMS no longer produces the

publication, Marquis Who’s Who,

referenced in 22 CFR part 62.

Furthermore, ABMS has confirmed that

it is also no longer the appropriate

organization to comment on programs of

graduate medical education. The

Department has confirmed that the

Accreditation Council for Graduate

Medical Education (ACGME) has

responsibility to accredit and recognize

institutions offering programs of

graduate medical education, and is

replacing the reference to the ABMS

with the ACGME in § 62.27.

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