8586 Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

Helena Sviglin, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, Rm. 1197, 

Silver Spring, MD 20993–0002, 301– 

796–5331, cderdatastandards@

fda.hhs.gov, or Stephen Ripley, Center 

for Biologics Evaluation and Research, 

Food and Drug Administration, Bldg. 

71, Rm. 7301, Silver Spring, MD 20993– 

0002, 240–402–7911. 

SUPPLEMENTARY INFORMATION: FDA’s 

CBER and CDER are issuing this Federal 

Register notice to announce the date 

that support begins for version 3.1.1 of 

the CDISC SENDIG and the date that 

this version update is required in 

certain submissions. The FDA guidance 

for industry ‘‘Providing Regulatory 

Submissions in Electronic Format— 

Standardized Study Data’’ (June 2021) 

(eStudy Data guidance), posted on 

FDA’s Study Data Standards Resources 

web page at https://www.fda.gov/ 

forindustry/datastandards/studydata

standards/default.htm, implements the 

electronic submission requirements of 

section 745A(a) of the Federal Food, 

Drug, and Cosmetic Act (21 U.S.C. 

379k–1(a)) for study data contained in 

NDAs, ANDAs, certain BLAs, and 

certain INDs submitted to CDER or 

CBER by specifying the format for 

electronic submissions. The eStudy Data 

guidance states that a Federal Register 

notice will specify any new standards 

and version updates to FDA-supported 

study data standards that will be added 

to the Catalog, when the support for 

such standards and version updates 

begins or ends, and when the 

requirement to use such standards and 

version updates in submissions begins 

or ends. 

Support for version 3.1.1 of the CDISC 

SENDIG begins February 15, 2022. The 

transition date for this version update is 

March 15, 2022. The requirement for 

electronic submissions to be submitted 

using version 3.1.1 of the CDISC 

SENDIG is March 15, 2023, for NDAs, 

ANDAs, certain BLAs, and certain INDs. 

Dated: February 9, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–03225 Filed 2–14–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2022–N–0105] 

International Drug Scheduling; 

Convention on Psychotropic 

Substances; Single Convention on 

Narcotic Drugs; World Health 

Organization; Scheduling 

Recommendations; Brorphine; 

Metonitazene; Eutylone; Request for 

Comments 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is providing 

interested persons with the opportunity 

to submit written comments concerning 

recommendations by the World Health 

Organization (WHO) to impose 

international manufacturing and 

distributing restrictions, under 

international treaties, on certain drug 

substances. The comments received in 

response to this notice will be 

considered in preparing the United 

States’ position on these proposals for a 

meeting of the United Nations 

Commission on Narcotic Drugs (CND) in 

Vienna, Austria, in March 2022. This 

notice is issued under the Controlled 

Substances Act (CSA). 

DATES: Submit either electronic or 

written comments by February 28, 2022. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. Electronic comments must 

be submitted on or before February 28, 

2022. The https://www.regulations.gov 

electronic filing system will accept 

comments until 11:59 p.m. Eastern Time 

at the end of February 28, 2022. 

Comments received by mail/hand 

delivery/courier (for written/paper 

submissions) will be considered timely 

if they are received on or before that 

date. 

Electronic Submissions 

Submit electronic comments in the 

following way: 

• Federal eRulemaking Portal: 

https://www.regulations.gov. Follow the 

instructions for submitting comments. 

Comments submitted electronically, 

including attachments, to https://

www.regulations.gov will be posted to 

the docket unchanged. Because your 

comment will be made public, you are 

solely responsible for ensuring that your 

comment does not include any 

confidential information that you or a 

third party may not wish to be posted, 

such as medical information, your or 

anyone else’s Social Security number, or 

confidential business information, such 

as a manufacturing process. Please note 

that if you include your name, contact 

information, or other information that 

identifies you in the body of your 

comments, that information will be 

posted on https://www.regulations.gov. 

• If you want to submit a comment 

with confidential information that you 

do not wish to be made available to the 

public, submit the comment as a 

written/paper submission and in the 

manner detailed (see ‘‘Written/Paper 

Submissions’’ and ‘‘Instructions’’). 

Written/Paper Submissions 

Submit written/paper submissions as 

follows: 

• Mail/Hand Delivery/Courier (for 

written/paper submissions): Dockets 

Management Staff (HFA–305), Food and 

Drug Administration, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852. 

• For written/paper comments 

submitted to the Dockets Management 

Staff, FDA will post your comment, as 

well as any attachments, except for 

information submitted, marked and 

identified, as confidential, if submitted 

as detailed in ‘‘Instructions.’’ 

Instructions: All submissions received 

must include the Docket No. FDA– 

2022–N–0105 for ‘‘International Drug 

Scheduling; Convention on 

Psychotropic Substances; Single 

Convention on Narcotic Drugs; World 

Health Organization; Scheduling 

Recommendations; Brorphine; 

Metonitazene; Eutylone; Request for 

Comments.’’ Received comments, those 

filed in a timely manner (see 

ADDRESSES), will be placed in the docket 

and, except for those submitted as 

‘‘Confidential Submissions,’’ publicly 

viewable at https://www.regulations.gov 

or at the Dockets Management Staff 

between 9 a.m. and 4 p.m., Monday 

through Friday, 240–402–7500. 

• Confidential Submissions—To 

submit a comment with confidential 

information that you do not wish to be 

made publicly available, submit your 

comments only as a written/paper 

submission. You should submit two 

copies total. One copy will include the 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 8587 

information you claim to be confidential 

with a heading or cover note that states 

‘‘THIS DOCUMENT CONTAINS 

CONFIDENTIAL INFORMATION.’’ The 

Agency will review this copy, including 

the claimed confidential information, in 

its consideration of comments. The 

second copy, which will have the 

claimed confidential information 

redacted/blacked out, will be available 

for public viewing and posted on 

https://www.regulations.gov. Submit 

both copies to the Dockets Management 

Staff. If you do not wish your name and 

contact information to be made publicly 

available, you can provide this 

information on the cover sheet and not 

in the body of your comments and you 

must identify this information as 

‘‘confidential.’’ Any information marked 

as ‘‘confidential’’ will not be disclosed 

except in accordance with 21 CFR 10.20 

and other applicable disclosure law. For 

more information about FDA’s posting 

of comments to public dockets, see 80 

FR 56469, September 18, 2015, or access 

the information at: https://

www.govinfo.gov/content/pkg/FR-2015- 

09-18/pdf/2015-23389.pdf. 

Docket: For access to the docket to 

read background documents or the 

electronic and written/paper comments 

received, go to https://

www.regulations.gov and insert the 

docket number, found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

James R. Hunter, Center for Drug 

Evaluation and Research, Controlled 

Substance Staff, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 51, Rm. 5150, Silver Spring, 

MD 20993–0002, 301–796–3156, 

james.hunter@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

The United States is a party to the 

1971 Convention on Psychotropic 

Substances (1971 Convention). Section 

201(d)(2)(B) of the CSA (21 U.S.C. 

811(d)(2)(B)) provides that when the 

United States is notified under Article 2 

of the 1971 Convention that the CND 

proposes to decide whether to add a 

drug or other substance to one of the 

schedules of the 1971 Convention, 

transfer a drug or substance from one 

schedule to another, or delete it from 

the schedules, the Secretary of State 

must transmit notice of such 

information to the Secretary of Health 

and Human Services (Secretary of HHS). 

The Secretary of HHS must then publish 

a summary of such information in the 

Federal Register and provide 

opportunity for interested persons to 

submit comments. The Secretary of HHS 

must then evaluate the proposal and 

furnish a recommendation to the 

Secretary of State that shall be binding 

on the representative of the United 

States in discussions and negotiations 

relating to the proposal. 

As detailed in the following 

paragraphs, the Secretary of State has 

received notification from the SecretaryGeneral of the United Nations (the 

Secretary-General) regarding one 

substance to be considered for control 

under the 1971 Convention. This 

notification reflects the 

recommendation from the 44th WHO 

Expert Committee for Drug Dependence 

(ECDD), which met in October 2021. In 

the Federal Register of July 23, 2021 (86 

FR 39038), FDA announced the WHO 

ECDD review and invited interested 

persons to submit information for 

WHO’s consideration. 

The full text of the notification from 

the Secretary-General is provided in 

section II of this document. Section 

201(d)(2)(B) of the CSA requires the 

Secretary of HHS, after receiving a 

notification proposing scheduling, to 

publish a notice in the Federal Register 

to provide the opportunity for interested 

persons to submit information and 

comments on the proposed scheduling 

action. 

The United States is also a party to 

the 1961 Single Convention on Narcotic 

Drugs (1961 Convention). The Secretary 

of State has received a notification from 

the Secretary-General regarding two 

substances to be considered for control 

under this convention. The CSA does 

not require HHS to publish a summary 

of such information in the Federal 

Register. Nevertheless, to provide 

interested and affected persons an 

opportunity to submit comments 

regarding the WHO recommendations 

for drugs under the 1961 Convention, 

the notification regarding these 

substances is also included in this 

Federal Register notice. The comments 

will be shared with other relevant 

Agencies to assist the Secretary of State 

in formulating the position of the 

United States on the control of these 

substances. The HHS recommendations 

are not binding on the representative of 

the United States in discussions and 

negotiations relating to the proposal 

regarding control of substances under 

the 1961 Convention. 

II. United Nations Notification 

The formal notification from the 

United Nations that identifies the drug 

substances and explains the basis for the 

scheduling recommendations is 

reproduced as follows (non-relevant text 

removed): 

Reference: 

NAR/CL.13/2021 

WHO/ECDD44; 1961C-Art.3, 1971C-Art.2 

CU 2021/453/DTA/SGB 

The Secretariat of the United Nations 

presents its compliments to the Permanent 

Mission of the United States of America and 

has the honour to inform the Government 

that in a letter dated 18 November 2021, the 

Director-General of the World Health 

Organization (WHO), pursuant to article 3, 

paragraphs 1 and 3 of the Single Convention 

on Narcotic Drugs of 1961 as amended by the 

1972 Protocol (1961 Convention), and article 

2, paragraphs 1 and 4 of the Convention on 

Psychotropic Substances of 1971 (1971 

Convention), notified the Secretary-General 

of the following recommendations of the 

forty-third Meeting of the WHO’s Expert 

Committee on Drug Dependence (ECDD): 

Substance recommended to be added to 

Schedule I of the 1961 Convention: 

—Brorphine 

IUPAC (International Union of Pure and 

Applied Chemistry) name: 1-[1-[1-(4- 

Bromophenyl)ethyl]-piperidin-4-yl]-1,3- 

dihydro-2H-imidazol-2-one 

—Metonitazene 

IUPAC name: N,N-Diethyl-2-(2-(4- 

methoxybenzyl)-5-nitro-1Hbenzo[d]imidazol-1-yl)ethan-1-amine 

Substances recommended to be added to 

Schedule II of the 1971 Convention: 

—Eutylone (alternate name: 3,4- 

methylenedioxy-alpha-ethylamino 

butiophenone) 

IUPAC names: 1-(Benzo[d][1,3]dioxol-5-yl)-2- 

(ethylamino)butan-1-one 1-(1,3- 

Benzodioxol-5-yl)-2-(ethylamino)butan-1- 

one 

Substances to be kept under surveillance: 

In the letter from the Director-General of 

WHO to the Secretary-General, reference is 

also made to the recommendation made by 

the WHO Expert Committee on Drug 

Dependence (ECDD), at its forty-fourth 

meeting, to keep the following substances 

under surveillance: 

—4F–MDMB–BICA (alternate name: 4F– 

MDMB–BUTICA) 

IUPAC names: Methyl 2-({[1-(4-fluorobutyl)- 

1H-indol-3-yl]carbonyl}amino)-3,3- 

dimethylbutanoate; Methyl 2-(1-(4- 

fluorobutyl)-1H-indole-3-carbaxamido)-3,3- 

dimethylbutanoate 

—Benzylone (alternate name: 3,4- 

Methylenedioxy-N-benzylcathinone) 

IUPAC name: 1-(Benzo[d][1,3]dioxol-5-yl)-2- 

(benzylamino)propan-1-one 

—Kratom, mitragynine, and 7- 

hydroxymitragynine 

—Phenibut (alternate name: 4-amino-3- 

phenyl-butyric acid) 

IUPAC name: 4-Amino-3-phenylbutanoic 

acid 

In accordance with the provisions of article 

3, paragraph 2, of the 1961 Convention and 

article 2, paragraph 2, of the 1971 

Convention, the notification is hereby 

transmitted as annex I to the present note. In 

connection with the notification, WHO also 

submitted a summary of the assessments and 


lotter on DSK11XQN23PROD with NOTICES1
8588 Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 

findings for these recommendations made by 

ECDD, which is transmitted as annex II. 

Also, in accordance with the same 

provisions, the notification from WHO will 

be brought to the attention of the sixty-fifth 

session of the Commission on Narcotic Drugs 

(14–18 March 2022, tent.) in a pre-session 

document that will be made available in the 

six official languages of the United Nations 

on the website of the 65th session of the 

Commission on Narcotic Drugs: https://

www.unodc.org/unodc/en/commissions/ 

CND/session/65_Session_2022/65CND_

Main.html. 

In order to assist the Commission in 

reaching a decision, it would be appreciated 

if the Permanent Mission could communicate 

any comments it considers relevant to the 

possible scheduling of substances 

recommended by WHO to be placed under 

international control under the 1961 

Convention, namely: 

—Brorphine 

—Metonitazene; as well as any economic, 

social, legal, administrative or other factors 

that it considers relevant to the possible 

scheduling of substances recommended by 

WHO to be placed under international 

control under the 1971 Convention, 

namely: 

—Eutylone (alternate name: 3,4- 

methylenedioxy-alpha-ethylamino 

butiophenone). 

The Secretariat of the United Nations 

avails itself of this opportunity to renew to 

the Permanent Mission of the United States 

of America to the United Nations (Vienna) 

the assurances of its highest consideration. 

8 December 2021 

Annex I 

Letter addressed to the Secretary-General 

of the United Nations from the DirectorGeneral of the World Health Organization, 

dated 18 November 2021 

‘‘The Forty-fourth Meeting of the World 

Health Organization (WHO)’s Expert 

Committee on Drug Dependence (ECDD) was 

convened in a virtual format from 11 to 15 

October 2021 and was coordinated from the 

WHO headquarters in Geneva. 

WHO is mandated by the 1961 and 1971 

International Drug Control Conventions to 

make recommendations to the United 

Nations Secretary-General on the need for, 

and level of, international control of 

psychoactive substances based on the advice 

of its independent scientific advisory body, 

the ECDD. In order to recommend if a 

psychoactive substance should be placed 

under international control or if its level of 

control should be changed, the WHO 

convenes the ECDD annually to thoroughly 

review the potential for abuse, dependence, 

and harm to health of a psychoactive 

substance, as well as any therapeutic 

applications. 

The Forty-fourth WHO ECDD Meeting 

critically reviewed five new psychoactive 

substances, including one synthetic 

cannabinoid receptor agonist (4F–MDMB– 

BICA), two novel synthetic opioids 

(brorphine; metonitazene), and two 

cathinones/stimulants (eutylone; benzylone). 

These substances had not previously been 

formally reviewed by WHO and are currently 

not under international control. Information 

was brought to WHO’s attention that these 

substances are clandestinely manufactured, 

of especially serious risk to public health and 

society, and of no recognised therapeutic use 

by any Party. Therefore, a critical review to 

consider international scheduling measures 

was undertaken for each substance so that 

the Expert Committee could consider 

whether information available about these 

substances may justify the scheduling or a 

change in scheduling of a substance in the 

1961 or 1971 Conventions. 

In addition, the Forty-fourth ECDD Meeting 

carried out pre-reviews of kratom, 

mitragynine, and 7-hydroxymitragynine; and 

phenibut to consider whether current 

information justified a critical review. 

With reference to Article 3, paragraphs 1 

and 3 of the Single Convention on Narcotic 

Drugs (1961), as amended by the 1972 

Protocol, and Article 2, paragraphs 1 and 4 

of the Convention on Psychotropic 

Substances (1971), WHO is pleased to 

endorse and submit the following 

recommendations of the Forty-fourth Meeting 

of the ECDD: 

To be added to Schedule I of the Single 

Convention on Narcotic Drugs (1961): 

—Brorphine 

IUPAC (International Union of Pure and 

Applied Chemistry) name: 1-[1-[1-(4- 

Bromophenyl)ethyl]- piperidin-4-yl]-1,3- 

dihydro-2H- imidazol-2- one 

—Metonitazene 

IUPAC name: N,N-Diethyl-2-(2-(4- 

methoxybenzyl)-5-nitro-1Hbenzo[d]imidazol-1-yl)ethan-1-amine 

To be added to Schedule II of the 

Convention on Psychotropic Substances 

(1971): 

—Eutylone (alternate name: 3,4- 

methylenedioxy-alpha-ethylamino 

butiophenone) 

IUPAC names: 1-(Benzo[d][1,3]dioxol-5-yl)-2- 

(ethylamino)butan-1-one; 1-(1,3- 

Benzodioxol-5-yl)-2-(ethylamino)butan-1- 

one 

To be kept under surveillance: 

—4F–MDMB–BICA (alternate name: 4F– 

MDMB–BUTICA) 

IUPAC names: Methyl 2-({[1-(4-fluorobutyl)- 

1H-indol-3-yl]carbonyl}amino)-3,3- 

dimethylbutanoate; Methyl 2-(1-(4- 

fluorobutyl)-1H-indole-3- carbaxamido)- 

3,3- dimethylbutanoate 

—Benzylone (alternate name: 3,4- 

Methylenedioxy-N-benzylcathinone) 

IUPAC name: 1-(Benzo[d][1,3]dioxol-5-yl)-2- 

(benzylamino)propan-1-one 

—Kratom, mitragynine, 7- 

hydroxymitragynine 

—Phenibut (alternate name: 4-amino-3- 

phenyl-butyric acid) 

IUPAC name: 4-Amino-3-phenylbutanoic 

acid 

The assessments and findings on which 

these recommendations are based are set out 

in detail in the Forty-fourth ECDD Meeting 

Report of the WHO Expert Committee on 

Drug Dependence. A summary of the 

assessments and findings for these 

recommendations made by the ECDD is 

contained in Annex 1 to this letter. 

I am very pleased with the ongoing 

collaboration between WHO, the United 

Nations Office on Drugs and Crime and the 

International Narcotics Control Board, and in 

particular, how this collaboration has 

benefited the work of the WHO Expert 

Committee on Drug Dependence and more 

generally, the implementation of the 

operational recommendations of the United 

Nations General Assembly Special Session 

2016.’’ 

Annex II 

Summary assessment and 

recommendations of the 44th Expert 

Committee on Drug Dependence, 11–15 

October 2021 

Substances to be added to Schedule I of 

the Single Convention on Narcotic Drugs 

(1961): 

Brorphine 

Substance Identification 

Brorphine (IUPAC chemical name: 1-[1-[1- 

(4-bromophenyl)ethyl]-piperidin-4-yl]-1,3- 

dihydro-2H-imidazol-2-one) has a chemical 

structure similar to bezitramide, an opioid 

listed in Schedule I of the 1961 Convention. 

Brorphine freebase has been described as a 

white or off-white solid, and the 

hydrochloride salt as a neat solid, with 

seized samples described as white, 

yellowish, gray, purple, or white powder, or 

in crystal form. It is also found in tablets and 

capsules as falsified opioid medicines. It is 

reported to be used by the oral, inhalation, 

and intravenous routes of administration. 

WHO Review History 

Brorphine has not been formally reviewed 

by WHO and is not currently under 

international control. Information was 

brought to WHO’s attention that this 

substance is manufactured clandestinely, 

poses a risk to public health, and is of no 

recognized therapeutic use. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Brorphine is a full agonist at the m-opioid 

receptor, with greater potency than 

morphine, and less potency than fentanyl. It 

has analgesic effects that are reversed by an 

opioid antagonist and, based on its 

mechanism of action, it would be expected 

to produce other typical opioid effects such 

as respiratory depression and sedation. 

Brorphine may be convertible to bezitramide, 

which is an opioid listed in Schedule I of the 

1961 Single Convention on Narcotic Drugs. 

Dependence Potential 

No controlled animal or human studies 

have examined the dependence potential of 

brorphine. As a potent m-opioid agonist, it 

would be expected to produce dependence 

similar to other opioid substances. 

Unverified online reports describe tolerance 

and withdrawal following repeated brorphine 

use. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

In an animal model predictive of abuse 

potential, brorphine was shown to produce 

effects similar to morphine and fentanyl. 

Deaths involving brorphine have been 

reported in several countries. Deaths 

commonly occur after use of brorphine in 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 8589 

combination with other opioids or with 

benzodiazepines such as flualprazolam. 

Brorphine has been identified in falsified 

opioid medicines, suggesting that sometimes 

its use may be unintentional. Fatal and nonfatal intoxications due to brorphine share 

features with intoxications due to other 

opioids, such as pulmonary oedema. 

Brorphine has been detected with other 

substances in biological fluids in cases of 

driving under the influence. 

Seizures have been reported in multiple 

countries and regions. 

Therapeutic Usefulness 

Brorphine is not known to have any 

therapeutic use. 

Recommendation 

The mechanism of action of brorphine 

indicates that it is liable to have similar 

abuse potential and ill effects as opioids that 

are controlled under Schedule I of the 1961 

Single Convention on Narcotic Drugs. 

Its use has been reported in a number of 

countries and has been associated with 

adverse effects, including death. It has no 

known therapeutic use and is likely to cause 

substantial harm. 

Recommendation: The Committee 

recommended that brorphine (IUPAC 

chemical name: 1-[1-[1-(4- 

bromophenyl)ethyl]-piperidin-4-yl]-1,3- 

dihydro-2H-imidazol-2-one) be added to 

Schedule I of the 1961 Single Convention on 

Narcotic Drugs. 

Metonitazene 

Substance Identification 

Metonitazene (IUPAC chemical name: N,NDiethyl-2-(2-(4-methoxybenzyl)-5-nitro-1Hbenzo[d]imidazol-1-yl)ethan-1-amine) 

belongs to the series of 2- 

benzylbenzimidazole opioid compounds. It is 

a white or off-white/beige or coloured 

powder, and is sometimes crystalline in 

consistency. Reports suggest that it is used 

intranasally and by intravenous injection. 

WHO Review History 

Metonitazene has not been formally 

reviewed by WHO and is not currently under 

international control. Information was 

brought to WHO’s attention that this 

substance is manufactured clandestinely, 

poses a risk to public health, and has no 

recognized therapeutic use. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Metonitazene is a chemical analogue of 

etonitazene and isotonitazene, both of which 

are Schedule I compounds under the Single 

Convention on Narcotic Drugs, 1961. 

Metonitazene is a potent opioid analgesic 

with a rapid onset of action and greater 

potency than fentanyl and hydromorphone. 

Limited early clinical research demonstrated 

that metonitazene produces analgesia and 

typical opioid adverse effects including 

sedation, respiratory depression, nausea, and 

vomiting. The effects of metonitazene have 

been shown to be reversed by an opioid 

antagonist. 

Dependence Potential 

Animal studies have demonstrated that 

metonitazene suppresses opioid withdrawal 

and has potent m-opioid agonist effects. No 

controlled human studies have reported on 

the dependence potential of metonitazene, 

but as a potent m-opioid agonist, it would be 

expected to produce dependence similar to 

other opioids. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

No controlled studies have been reported 

on the abuse potential of metonitazene, but 

as it is a potent m-opioid receptor agonist, it 

would be expected to have high abuse 

liability. Online reports from people who 

report use of metonitazene describe its 

euphoric and opioid-like effects. 

A number of deaths have been reported in 

association with use of metonitazene. In 

many of these cases metonitazene has been 

used in combination with other opioids or 

benzodiazepines. However, in some fatalities, 

metonitazene was the sole substance 

identified in the analyzed biological samples. 

Trafficking and use of metonitazene have 

been reported from a number of countries 

across several regions. 

Therapeutic Usefulness 

Metonitazene is not known to have any 

therapeutic use. 

Recommendation 

The mechanism of action and effects of 

metonitazene indicate that it is liable to have 

similar abuse potential and ill effects as 

opioids that are controlled under Schedule I 

of the 1961 Single Convention on Narcotic 

Drugs. Its use has been reported in a number 

of countries and been associated with 

adverse effects, including death. 

Metonitazene has no known therapeutic use 

and is likely to cause substantial harm. 

Recommendation: The Committee 

recommended that metonitazene (IUPAC 

chemical name: N,N-Diethyl-2-(2-(4- 

methoxybenzyl)-5-nitro-1Hbenzo[d]imidazol-1-yl)ethan-1-amine) be 

added to Schedule I of the 1961 Single 

Convention on Narcotic Drugs. 

Substances to be added to Schedule II of 

the Convention on Psychotropic Substances 

(1971): 

Eutylone (3,4-methylenedioxy-alphaethylamino butiophenone) 

Substance Identification 

Eutylone (IUPAC chemical name: 1- 

(Benzo[d][1,3]dioxol-5-yl)-2- 

(ethylamino)butan-1-one) is a synthetic 

cathinone of the phenethylamine class. The 

hydrochloride salt of eutylone has been 

described as a crystalline solid. Eutylone is 

mostly found as tablets, capsules, and 

crystals. It is used orally and intranasally. 

WHO Review History 

Eutylone has not been formally reviewed 

by WHO and is not currently under 

international control. Information was 

brought to WHO’s attention that this 

substance is manufactured clandestinely, 

poses a risk to public health, and has no 

recognized therapeutic use. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Eutylone is a synthetic cathinone with a 

mechanism of action and effects similar to 

other cathinones and to stimulants such as 

methamphetamine. Related cathinones, such 

as methylone and N-ethylnorpentylone, are 

listed under Schedule II of the Convention on 

Psychotropic Substances of 1971. The 

clinical features described are similar to 

other cathinones, including 

sympathomimetic effects and 

psychostimulant effects such as euphoria, 

insomnia, tachycardia, agitation, anxiety, 

delirium and psychosis. 

Dependence Potential 

No animal or human studies have been 

conducted on the dependence potential of 

eutylone. Based on its overall profile of 

effects, eutylone would be expected to 

produce dependence similar to other 

psychostimulants. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

In an animal model predictive of abuse 

potential, eutylone has been shown to 

produce effects similar to those of 

methamphetamine. Online reports from 

people reporting use of eutylone suggest that 

it has high abuse potential. 

Eutylone has been detected in biological 

samples from forensic, post-mortem, and 

driving under the influence cases. Published 

case reports describe fatalities as a result of 

eutylone use. In addition to the effects 

described above, reported adverse events in 

these cases have included rhabdomyolysis, 

hyperthermia, hypertension, and seizures. 

Eutylone has been detected in seized 

materials in multiple countries across several 

regions. 

Therapeutic Usefulness 

Eutylone is not known to have any 

therapeutic use. 

Recommendation 

Eutylone has effects similar to those of 

related cathinones listed under Schedule II of 

the Convention on Psychotropic Substances 

of 1971. 

There is evidence that this substance is 

used in multiple countries in various regions. 

Eutylone causes substantial harm, including 

severe adverse events and fatal intoxications. 

Its mode of action suggests a likelihood of 

abuse and it poses a substantial risk to public 

health. It has no known therapeutic 

usefulness. 

Recommendation: The Committee 

recommended that eutylone (IUPAC 

chemical name: 1-(Benzo[d][1,3]dioxol-5-yl)- 

2-(ethylamino)butan-1-one) be added to 

Schedule II of the Convention on 

Psychotropic Substances of 1971. 

Substances to be kept under surveillance: 

4F–MDMB–BICA (4F–MDMB–BUTICA) 

Substance Identification 

4F–MDMB–BICA (IUPAC chemical name: 

Methyl 2-({[1-(4-fluorobutyl)-1H-indol-3- 

yl]carbonyl}amino)-3,3-dimethylbutanoate) 

has a chemical structure similar to a number 

of synthetic cannabinoids. It has been 

identified in seized materials as a white, offwhite, brown or orange powder, and has been 

identified in herbal blends, vaping solutions, 

and infused onto paper. It is also available as 

a reference material as crystalline solid. 


lotter on DSK11XQN23PROD with NOTICES1
8590 Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 

WHO Review History 

4F–MDMB–BICA has not been formally 

reviewed by WHO and is not currently under 

international control. Information was 

brought to WHO’s attention that this 

substance is manufactured clandestinely, 

poses a risk to public health, and has no 

recognized therapeutic use. 

Similarity to Known Substances and Effects 

on Central Nervous System 

4F–MDMB–BICA is a synthetic 

cannabinoid, structurally related to 5F– 

MDMB–PICA, a synthetic cannabinoid, 

which is included in Schedule II of the 

United Nations Single Convention on 

Psychotropic Substances of 1971. Some data 

suggest that 4F–MDMB–BICA has activity at 

the cannabinoid CB1 receptor, but this action 

may not be identical to that exerted by other 

CB1 agonists. No animal or human studies 

have evaluated the effects of 4F–MDMB– 

BICA, and there is insufficient data on 4F– 

MDMB–BICA overdose cases to confirm that 

it has typical cannabinoid effects. 

Dependence Potential 

No studies have been reported in animals 

or humans on the dependence potential of 

4F–MDMB–BICA. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

No studies have been reported in animals 

or humans to indicate the likelihood of abuse 

of 4F–MDMB–BICA. A number of countries 

in various regions have reported use of 4F– 

MDMB–BICA. Its use has been associated 

with multiple deaths and Emergency 

Department visits, although multiple 

substances have been present in analysed 

biological samples, and the relationship 

between 4F–MDMB–BICA exposure and 

cause of death is not established. 

Theraputic Usefulness 

4F–MDMB–BICA is not known to have any 

therapeutic use. 

Recommendation 

4F–MDMB–BICA has a structure similar to 

other synthetic cannabinoids, but its 

mechanism of action has yet to be confirmed. 

The magnitude of harm due to 4F–MDMB– 

BICA alone is unclear, and no animal or 

human studies have examined the effects or 

abuse potential of 4F–MDMB–BICA. Based 

on the limited information available 

concerning abuse, dependence and risks to 

public health, there is insufficient evidence 

to justify placing 4F–MDMB–BICA under 

international control. 

Recommendation: The Committee 

recommended that 4F–MDMB–BICA (IUPAC 

chemical name: Methyl 2-({[1-(4- 

fluorobutyl)-1H-indol-3-yl]carbonyl}amino)- 

3,3-dimethylbutanoate) be kept under 

surveillance by the WHO Secretariat. 

Benzylone (3,4-Methylenedioxy-Nbenzylcathinone) 

Substance Identification 

Benzylone (IUPAC chemical name: 1- 

(Benzo[d][1,3]dioxol-5-yl)-2- 

(benzylamino)propan-1-one) is a ringsubstituted synthetic cathinone. Benzylone is 

a white powder. The hydrochloride salt of 

benzylone is a crystalline solid. 

WHO Review History 

Benzylone has not been formally reviewed 

by WHO and is not currently under 

international control. Information was 

brought to WHO’s attention that this 

substance is manufactured clandestinely, 

poses a risk to public health, and has no 

recognized therapeutic use. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Benzylone has a mode of action suggestive 

of stimulant effects similar to other 

cathinones. However, these effects are 

relatively weak and it fails to produce 

stimulant effects in animal models. 

Limited information is available on its 

effects in humans. 

Dependence Potential 

There is no information available on the 

dependence potential of benzylone in 

animals or humans 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

In an animal model predictive of abuse 

potential, benzylone did not produce effects 

similar to MDMA, and its similarity to 

methamphetamine is unclear. No human 

studies have been conducted to assess abuse 

liability. 

Benzylone has been detected in seized 

materials in multiple countries across several 

regions. 

There is little information concerning the 

adverse effects of benzylone. Although it has 

been detected in postmortem samples along 

with other substances, there is no significant 

evidence of benzylone playing a causative 

role in deaths. 

Therapeutic Usefulness 

Benzylone is not known to have any 

therapeutic use. 

Recommendation 

Benzylone is a synthetic cathinone that has 

some effects in common with substances 

listed under Schedule II of the Convention on 

Psychotropic Substances of 1971. However, 

its effects are relatively weak and there is no 

consistent evidence supporting the 

likelihood of abuse or dependence. In 

addition, there is no consistent evidence of 

the extent of public health and social 

problems related to use of benzylone. 

Recommendation: The Committee 

recommended that benzylone (IUPAC 

chemical name: 1-(Benzo[d][1,3]dioxol-5-yl)- 

2-(benzylamino)propan-1-one) be kept under 

surveillance by the WHO Secretariat. 

Kratom, mitragynine, and 7- 

hydroxymitragynine 

Substance Identification 

Kratom is the common term for Mitragyna 

speciosa, a tree native to Southeast Asia. 

Kratom use is almost exclusively oral, 

typically by chewing the leaves, ingesting 

powdered leaf, or drinking a kratom infusion 

or decoction, or by ingesting powdered leaf 

as a capsule or pill or dissolved in a 

beverage. Other forms such as extracts and 

resins are also used. 

Several alkaloids have been detected in 

kratom plants. The main known psychoactive 

components of kratom are mitragynine and 7- 

hydroxymitragynine, both of which are found 

in the leaves of Mitragyna speciosa. 

Mitragynine is the most abundant alkaloid in 

kratom. 

Whilst 7-hydroxymitragynine is a minor 

alkaloid, it is also a metabolite of 

mitragynine. 

WHO Review History 

Kratom has been under ECDD surveillance 

since 2020 due to a country level report 

indicating the potential for abuse, 

dependence, and harm to public health from 

mitragynine and 7-hydroxymitragynine, and 

a report from an international organization 

regarding documented fatalities associated 

with kratom use. A pre-review on kratom, 

mitragynine, and 7-hydroxymitragynine was 

initiated following consideration of these 

reports. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Mitragynine and 7-hydroxymitragynine are 

partial agonists at the mu-opioid receptor. 

Human studies demonstrate the analgesic 

effects of kratom, while kratom extract, 

mitragynine and 7-hydroxymitragynine have 

been shown to be antinociceptive in animal 

models. The antinociceptive effects are 

reversed by an opioid antagonist. 

Mitragynine also binds to adrenergic 

receptors, serotonergic and dopamine 

receptors. Although there is limited 

information regarding its effects at these 

receptors, kratom extracts and mitragynine 

have been reported in animal studies to have 

a variety of non-opioid-like behavioural 

effects, including antidepressant and 

antipsychotic effects. 

Reported adverse effects as a result of 

kratom intoxication have included 

neuropsychiatric (agitation, confusion, 

sedation, hallucinations, tremor, seizure, 

coma), cardiovascular (tachycardia, 

hypertension), gastrointestinal (abdominal 

pain, nausea, vomiting) and respiratory 

(respiratory depression) symptoms. A 

number of cases of kratom-associated liver 

toxicity have been documented. 

Dependence Potential 

In animal models, repeated dosing with 

mitragynine produced dependence, 

evidenced by naloxone-precipitated 

withdrawal. The withdrawal syndrome from 

kratom appears to be less severe than 

withdrawal from morphine. 

In humans, opioid-like withdrawal 

symptoms have been reported following 

cessation of kratom use. Limited 

epidemiological evidence indicates that 

withdrawal is usually mild. There are a small 

number of cases of neonatal opioid 

withdrawal symptoms in neonates born to 

mothers who used kratom regularly. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

Animal studies with kratom extracts have 

not shown abuse liability in one animal 

model. Mitragynine and 7- 

hydroxymitragynine have effects indicative 

of abuse liability in some animal models but 

not in others. Mitragynine is not selfadministered by animals, while 7- 

hydroxymitragynine has been shown to be 


lotter on DSK11XQN23PROD with NOTICES1
Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 8591 

self-administered, supporting a likely abuse 

liability. 

Kratom can produce serious toxicity in 

people who use high doses, but the number 

of cases is probably low as a proportion of 

the total number of people who use kratom. 

Although mitragynine has been analytically 

confirmed in a number of deaths, almost all 

involve use of other substances, so the degree 

to which kratom use has been a contributory 

factor to fatalities is unclear. 

Kratom and mitragynine have been 

associated with cases of driving under the 

influence, but their role in driving 

impairment could not be established in most 

instances. 

Multiple countries across various regions 

report nonmedical use of kratom. Seizures of 

kratom and related products have been 

reported in several countries. 

Therapeutic Usefulness 

People report using kratom to self-medicate 

a variety of disorders and conditions, 

including pain, opioid withdrawal, opioid 

use disorder, anxiety, and depression. 

Kratom is being used as a part of traditional 

medicine in some countries. 

Research is ongoing to determine the basic 

pharmacology and the potential therapeutic 

value of kratom, mitragynine, and 7- 

hydroxymitragynine. 

Recommendation 

Kratom contains multiple alkaloids. The 

two main known psychoactive alkaloids, 

mitragynine and 7-hydroxymitragynine, 

produce at least some effects similar to 

opioids under international control. 

Mitragynine, the most abundant of these 

alkaloids, also has non-opioid actions, the 

significance of which is unclear. There is 

mixed evidence on the abuse liability of 

mitragynine in animal models. Kratom is 

used for self-medication for a variety of 

disorders but there is limited evidence of 

abuse liability in humans. 

Cessation of regular use of kratom may lead 

to withdrawal symptoms. 

The Committee considered information 

regarding the traditional use and 

investigation into possible medical 

applications of kratom. 

The Committee concluded that there is 

insufficient evidence to recommend a critical 

review of kratom. With respect to 

mitragynine and 7-hydroxymitragynine, the 

Committee, except for one member, also 

concluded that there is insufficient evidence 

to recommend a critical review at this time. 

Recommendation: The Committee 

recommended that kratom, mitragynine, and 

7-hydroxymitragynine be kept under 

surveillance by the WHO Secretariat. 

Phenibut (4-amino-3-phenyl-butyric acid) 

Substance Identification 

Phenibut (IUPAC chemical name: 4- 

Amino-3-phenylbutanoic acid) is a structural 

analogue of baclofen and gabapentin. It is 

produced in various formulations including 

tablets and powder for oral use, and 

crystalline form. Phenibut is a registered 

pharmaceutical in some countries and is also 

marketed online for a number of uses 

including as a sleep aid, mood enhancer, 

treatment for anxiety and a cognitive 

enhancer. 

WHO Review History 

Phenibut has not been formally reviewed 

by WHO and is not currently under 

international control. Phenibut has been 

under ECDD surveillance since 2017 due to 

reports from Member States of its abuse and 

dependence potential. A pre-review was 

initiated following consideration of these 

reports. 

Similarity to Known Substances and Effects 

on Central Nervous System 

Phenibut acts primarily as an agonist at the 

GABAB receptor, similar to baclofen, and at 

the a2-d subunit of voltage dependent 

calcium channels, similar to gabapentin. 

Animal studies show that phenibut has 

dose-dependent analgesic, antidepressant, 

and anxiolytic effects, which are mediated 

both by its GABAB agonist effects and actions 

at voltage dependent calcium channels. 

Phenibut intoxication has presented with 

central nervous system depressive symptoms 

including decreased level of consciousness, 

muscle tone, stupor, depressed respiration, 

temperature dysregulation, hyper- or 

hypotension, and coma. However, in other 

cases individuals have presented with 

agitation, hallucinations, seizures, and 

delirium. 

Dependence Potential 

There are no studies conducted in animals 

examining the dependence potential of 

phenibut. People who use phenibut describe 

escalating dosing suggestive of tolerance and 

difficulty in cessation. 

There are a limited number of case reports 

of withdrawal symptoms following abrupt 

discontinuation of high dose phenibut use. 

Reported symptoms have included insomnia, 

psychomotor agitation, delusions, psychosis, 

disorganized thought patterns, auditory/ 

visual hallucinations, anxiety, depression, 

fatigue, dizziness, seizures, decreased 

appetite, nausea and vomiting, palpitations, 

and tachycardia. However, in most cases the 

use of phenibut was not verified analytically, 

and the clinical picture was complicated by 

the use of other drugs. 

Actual Abuse and/or Evidence of Likelihood 

of Abuse 

No controlled animal or human studies 

have examined the abuse potential of 

phenibut. 

There are reports from different countries 

of adverse effects due to nonmedical use of 

phenibut. Medically unsupervised use of 

phenibut obtained via the internet is often at 

doses much higher than those used 

clinically. However, many cases involve 

multiple drugs, and the role of phenibut in 

these cases remains unclear. 

Multiple countries over several regions 

report seizures of phenibut. However, the 

extent of non-medical use is unknown. 

Therapeutic Usefulness 

Phenibut is approved in a few countries as 

a medicine for a range of psychiatric and 

neurological conditions. 

Recommendation 

The Committee noted that there has been 

concern in several countries regarding the 

nonmedical use of phenibut. While there are 

reports of adverse effects and of a withdrawal 

syndrome following cessation of use, the 

information on these cases is very limited. In 

addition, there is very little information on 

the abuse liability of phenibut, on the 

magnitude of its misuse or abuse, and on its 

similarity to currently internationally 

controlled substances. 

The Committee also noted that phenibut is 

used therapeutically in a small number of 

countries. 

Recommendation: The Committee 

recommended that phenibut (IUPAC 

chemical name: 4-Amino-3-phenylbutanoic 

acid) should not proceed to critical review 

but should be kept under surveillance by the 

WHO Secretariat. 

III. Discussion 

Although WHO has made specific 

scheduling recommendations for each of 

the drug substances, the CND is not 

obliged to follow the WHO 

recommendations. Options available to 

the CND for substances considered for 

control under the 1971 Convention 

include the following: (1) Accept the 

WHO recommendations; (2) accept the 

recommendations to control but control 

the drug substance in a schedule other 

than that recommended; or (3) reject the 

recommendations entirely. 

Brorphine (chemical name: 1-(1-(1-(4- 

bromophenyl)ethyl)piperidin-4-yl)-1,3- 

dihydro-2H-benzo[d]imidazol-2-one) is 

a potent synthetic opioid encountered 

as both a single substance of abuse and 

in combination with other opioid 

substances, such as heroin and fentanyl. 

The appearance of brorphine on the 

illicit drug market is similar to other 

designer drugs trafficked for their 

psychoactive effects. Beginning in June 

2019, brorphine emerged in the United 

States illicit, synthetic drug market as 

evidenced by its identification in drug 

seizures. The use of brorphine has been 

associated with at least seven fatalities 

between June and July 2020 in the 

United States. Brorphine is not 

approved for medical use in the United 

States. On March 1, 2021, the U.S. Drug 

Enforcement Administration (DEA) 

issued a temporary order to control 

brorphine as a Schedule I substance 

under the CSA, therefore additional 

permanent controls may be needed if 

brorphine is placed in Schedule I of the 

1961 Convention. 

Metonitazene (chemical name: N,Ndiethyl-2-(2-(4-methoxybenzyl)-5-nitro1H-benzo[d]imidazol-1-yl)ethan-1- 

amine) belongs to the series of 2- 

benzylbenzimidazole opioid 

compounds and is classified as a potent 

opioid structurally resembling 

etonitazene and dissimilar in structure 

to other synthetic opioids such as 

fentanyl analogues. Novel opioids such 

as metonitazene have been reported to 


lotter on DSK11XQN23PROD with NOTICES1
8592 Federal Register / Vol. 87, No. 31 / Tuesday, February 15, 2022 / Notices 

cause psychoactive effects and adverse 

events, including deaths similar to 

heroin, fentanyl, and other opioids. As 

of January 2021, metonitazene has been 

identified in eight blood specimens 

associated with postmortem death 

investigations in the United States. 

There are no commercial or approved 

medical uses for metonitazene. On 

December 7, 2021, the DEA issued a 

temporary order (86 FR 69182) to 

control metonitazene as a Schedule I 

substance under the CSA, therefore 

additional permanent controls may be 

needed if metonitazene is placed in 

Schedule I of the 1961 Convention. 

Eutylone (chemical name: 1-(1,3- 

benzodioxol-5-yl)-2-(ethylamino)butan1-one) is a designer drug of the 

phenethylamine class. Eutylone is a 

synthetic cathinone with chemical 

structural and pharmacological 

similarities to Schedule I and II 

amphetamines and cathinones, such as 

to 3,4- 

methylenedioxymethamphetamine, 

methylone, and pentylone. Eutylone 

emerged in the United States illicit, 

synthetic drug market in 2014 as 

evidenced by its identification in drug 

seizures. Other evidence indicates that 

eutylone, like other Schedule I synthetic 

cathinones, is abused for its 

psychoactive effects. Adverse effects 

associated with synthetic cathinones 

abuse include agitation, hypertension, 

tachycardia, and death. Eutylone is not 

approved for medical use in the United 

States. As a positional isomer of 

pentylone, eutylone is controlled in 

Schedule I of the CSA. As such, 

additional permanent controls will not 

be needed if eutylone is placed in 

Schedule II of the Convention on 

Psychotropic Substances. 

FDA, on behalf of the Secretary of 

HHS, invites interested persons to 

submit comments on the notifications 

from the United Nations concerning 

these drug substances. FDA, in 

cooperation with the National Institute 

on Drug Abuse, will consider the 

comments on behalf of HHS in 

evaluating the WHO scheduling 

recommendations. Then, under section 

201(d)(2)(B) of the CSA, HHS will 

recommend to the Secretary of State 

what position the United States should 

take when voting on the 

recommendations for control of 

substances under the 1971 Convention 

at the CND meeting in March 2022. 

Comments regarding the WHO 

recommendations for control of 

brorphine and metonitazene under the 

1961 Single Convention will also be 

forwarded to the relevant Agencies for 

consideration in developing the U.S. 

position regarding narcotic substances 

at the CND meeting. 

Dated: February 9, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–03229 Filed 2–14–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket Nos. FDA–2010–D–0575 and FDA– 

2021–N–0764] 

Compliance Policy Guide Sec. 510.800 

Beverages—Serving Size Labeling; 

Compliance Policy Guide Sec. 540.420 

Raw Breaded Shrimp—Microbiological 

Criteria for Evaluating Compliance 

With Current Good Manufacturing 

Practice Regulations; and Compliance 

Policy Guide Sec. 562.800 Vending 

Machine Food—Labeling; Withdrawal 

of Guidances 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; withdrawal. 

SUMMARY: The Food and Drug 

Administration (FDA or we) is 

announcing the withdrawal of three 

compliance policy guides (CPG) entitled 

‘‘Compliance Policy Guide Sec. 510.800 

Beverages—Serving Size Labeling,’’ 

‘‘Compliance Policy Guide Sec. 540.420 

Raw Breaded Shrimp—Microbiological 

Criteria for Evaluating Compliance with 

Current Good Manufacturing Practice 

Regulations,’’ and ‘‘Compliance Policy 

Guide Sec. 562.800 Vending Machine 

Food—Labeling.’’ We are withdrawing 

these CPGs because they have become 

outdated or have been superseded by 

subsequent FDA actions. 

DATES: The withdrawal is applicable 

February 15, 2022. 

ADDRESSES: For access to the docket, go 

to https://www.regulations.gov and 

insert docket number FDA–2010–D– 

0575 for ‘‘Compliance Policy Guide Sec. 

510.800 Beverages—Serving Size 

Labeling’’ or FDA–2021–N–0764 for 

‘‘Compliance Policy Guide Sec. 540.420 

Raw Breaded Shrimp—Microbiological 

Criteria for Evaluating Compliance with 

Current Good Manufacturing Practice 

Regulations’’ and ‘‘Compliance Policy 

Guide Sec. 562.800 Vending Machine 

Food—Labeling’’ into the ‘‘Search’’ box 

and follow the prompts and/or go to the 

Dockets Management Staff, 5630 Fishers 

Lane, Rm. 1061, Rockville, MD 20852, 

240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

Kevin Kwon, Office of Compliance 

(HFS–605), Center for Food Safety and 

Applied Nutrition, Food and Drug 

Administration, 5001 Campus Dr., 

College Park, MD 20740, 240–402–4597; 

or Alexandra Jurewitz, Office of 

Regulations and Policy (HFS–024), 

Center for Food Safety and Applied 

Nutrition, Food and Drug 

Administration, 5001 Campus Dr., 

College Park, MD 20740, 240–402–2378. 

SUPPLEMENTARY INFORMATION: 

I. Background 

We are announcing the withdrawal of 

three CPGs entitled ‘‘Compliance Policy 

Guide Sec. 510.800 Beverages—Serving 

Size Labeling,’’ ‘‘Compliance Policy 

Guide Sec. 540.420 Raw Breaded 

Shrimp—Microbiological Criteria for 

Evaluating Compliance with Current 

Good Manufacturing Practice 

Regulations,’’ and ‘‘Compliance Policy 

Guide Sec. 562.800 Vending Machine 

Food—Labeling.’’ 

CPG Sec. 510.800 entitled 

‘‘Beverages—Serving Size Labeling’’ was 

first issued in December 2010. This CPG 

provided guidance for FDA staff and 

industry as to when we would typically 

consider not taking enforcement action 

in connection to a ‘‘12 [fluid ounce] 

(360 [milliliter])’’ labeled serving size on 

specific types of beverages larger than 

20 fluid ounces. On May 27, 2016, FDA 

issued a final rule entitled ‘‘Food 

Labeling: Serving Sizes of Foods That 

Can Reasonably Be Consumed at One 

Eating Occasion; Dual-Column Labeling; 

Updating, Modifying, and Establishing 

Certain Reference Amounts Customarily 

Consumed; Serving Size for Breath 

Mints; and Technical Amendments’’ (81 

FR 34000). The final rule amended the 

Reference Amounts Customarily 

Consumed (RACCs) that are used by 

manufacturers to determine serving 

sizes for certain foods, including certain 

beverages. Our regulations, at 21 CFR 

101.12(b), table 2, lists the categories for 

each type of food product and each 

category’s current RACC. Due to the 

updated RACCs for certain beverages, 

CPG Sec. 510.800 is now obsolete, and 

the enforcement discretion provided in 

this CPG is no longer applicable. 

Therefore, CPG Sec. 510.800 is being 

withdrawn. 

CPG Sec. 540.420 entitled ‘‘Raw 

Breaded Shrimp—Microbiological 

Criteria for Evaluating Compliance with 

Current Good Manufacturing Practice 

Regulations’’ was first issued in August 

1983. This CPG used data collected in 

fiscal year 1978 and listed an outdated 

sampling and compliance structure. The 

compliance criteria and the 

methodology used in the CPG have 

become outdated and are no longer 

useful. This CPG is superseded by the 


lotter on DSK11XQN23PROD with NOTICES1