39038 Federal Register / Vol. 86, No. 139 / Friday, July 23, 2021 / Notices 

We have adjusted the estimate of 

burden we associate with the 

information collection 

recommendations in the guidance to 

reflect an increase of 2,000 hours and 

100 responses annually. 

Dated: July 16, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–15653 Filed 7–22–21; 8:45 am] 

BILLING CODE 4161–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0739] 

International Drug Scheduling; 

Convention on Psychotropic 

Substances; Single Convention on 

Narcotic Drugs; 4F-MDMB-BICA (4FMDMB-BUTICA); Brorphine; 

Metonitazene; Eutylone (bk-EBDB); 

BMDP (3,4-Methylenedioxy-Nbenzylcathinone); Kratom 

(mitragynine, 7-hydroxymitragynine); 

Phenibut; Request for Comments 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice; request for comments. 

SUMMARY: The Food and Drug 

Administration (FDA or Agency) is 

inviting interested persons to submit 

comments concerning abuse potential, 

actual abuse, medical usefulness, 

trafficking, and impact of scheduling 

changes on availability for medical use 

of seven drug substances. These 

comments will be considered in 

preparing a response from the United 

States to the World Health Organization 

(WHO) regarding the abuse liability and 

diversion of these drugs. WHO will use 

this information to consider whether to 

recommend that certain international 

restrictions be placed on these drug 

substances. This notice requesting 

comments is required by the Controlled 

Substances Act (CSA). 

DATES: Submit either electronic or 

written comments by August 9, 2021. 

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 August 9, 

2021. The https://www.regulations.gov 

electronic filing system will accept 

comments until 11:59 p.m. Eastern Time 

at the end of August 9, 2021. Comments 

received by mail/hand delivery/courier 

(for written/paper submissions) will be 

considered timely if they are 

postmarked or the delivery service 

acceptance receipt is 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– 

2021–N–0739 for ‘‘International Drug 

Scheduling; Convention on 

Psychotropic Substances; Single 

Convention on Narcotic Drugs; 4FMDMB-BICA (4F-MDMB-BUTICA); 

Brorphine; Metonitazene; Eutylone (bkEBDB); BMDP (3,4-Methylenedioxy-Nbenzylcathinone); Kratom (mitragynine, 

7-hydroxymitragynine); Phenibut; 

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 

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 (Psychotropic Convention). 

Article 2 of the Psychotropic 

Convention provides that if a party to 

the convention or WHO has information 

about a substance, which in its opinion 


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Federal Register / Vol. 86, No. 139 / Friday, July 23, 2021 / Notices 39039 

1https://www.npsdiscovery.org/positivity-of-newsynthetic-cannabinoid-4f-mdmb-bica-increasing-inu-s-as-prevalence-of-5f-mdmb-pica-wanes/. 

may require international control or 

change in such control, it shall so notify 

the Secretary-General of the United 

Nations (U.N. Secretary-General) and 

provide the U.N. Secretary-General with 

information in support of its opinion. 

Paragraph (d)(2)(A) of the CSA (21 

U.S.C. 811) (Title II of the 

Comprehensive Drug Abuse Prevention 

and Control Act of 1970) provides that 

when WHO notifies the United States 

under Article 2 of the Psychotropic 

Convention that it has information that 

may justify adding a drug or other 

substances to one of the schedules of the 

Psychotropic Convention, transferring a 

drug or substance from one schedule to 

another, or deleting it from the 

schedules, the Secretary of State must 

transmit the notice to the Secretary of 

Health and Human Services (Secretary 

of HHS). The Secretary of HHS must 

then publish the notice in the Federal 

Register and provide opportunity for 

interested persons to submit comments 

that will be considered by HHS in its 

preparation of the scientific and medical 

evaluations of the drug or substance. 

II. WHO Notification 

The Secretary of HHS received the 

following notice from WHO 

(nonrelevant text removed): 

Ref.: C.L.20.2021 

The World Health Organization (WHO) 

presents its compliments to Member States 

and Associate Members and has the pleasure 

of announcing that the 44th Expert 

Committee on Drug Dependence (ECDD) will 

meet from 11 to 15 October 2021, 

coordinated from Geneva, Switzerland. Given 

that WHO Expert Committee meetings are of 

a closed nature, this letter serves to notify 

Member States of the substances under 

review at the 44th ECDD, which are in the 

Annex I, attached for reference. 

WHO is mandated by the 1961 and 1971 

International Drug Control Conventions to 

make recommendations to the UN SecretaryGeneral on the need for and level of 

international control of psychoactive 

substances based on the advice of its 

independent scientific advisory body, the 

ECDD. To assess the appropriate control of a 

psychoactive substance, the ECDD convenes 

annually to review the potential of this 

substance to cause dependence, abuse and 

harm to health, as well as any therapeutic 

applications. In order to perform this review 

and make scientific and evidence-based 

decisions, the ECDD conducts medical, 

scientific, and public health evaluations of 

the selected psychoactive substances using 

the best available information. 

Although the meetings are of a closed 

nature, Member States are invited to 

contribute to the ECDD review process by 

joining the 44th ECDD Open Session on 11 

October 2021. The Open Session will allow 

interested parties to learn about present and 

future activities of the ECDD Secretariat, and 

to present information concerning substances 

under review to the Expert Committee 

Registration information will be made 

available on the ECDD website: https://

www.who.int/medicines/access/controlledsubstances/en/. 

As in the past and in line with the 

publication ‘‘Guidance on the WHO review of 

psychoactive substances for international 

control’’ (EB126/2010/REC1, Annex 6),1

Member States can also contribute to the 

ECDD review process by providing accurate 

information concerning the substances under 

review in advance of the meeting. For this 

purpose, a questionnaire will be sent to 

Member States to gather country information 

on the legitimate use, harmful use, status of 

national control and potential impact of 

international control for each substance 

under evaluation. 

In addition to the questionnaire, Member 

States are also encouraged to provide any 

additional relevant information (unpublished 

or published) on substances to be reviewed 

by the 44th ECDD by emailing 

ecddsecretariat@who.int with the subject 

‘‘Ref: C.L.20.2021’’. 

The World Health Organization takes this 

opportunity to renew to Member States and 

Associate Members the assurance of its 

highest consideration. 

GENEVA, 10 June 2021 

1https://apps.who.int/gb/ebwha/pdf_files/ 

EB126-REC1/B126_REC1-en.pdf#page=58. 

Annex I 

44th Expert Committee on Drug Dependence 

(ECDD) 11–15 October 2021, Substances For 

Review 

Critical reviews: The substances listed 

below have never been formally reviewed by 

WHO and are not currently 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 recognized therapeutic use 

by any Party. The Expert Committee will 

consider whether information presented 

during a critical review may justify the 

scheduling or a change in the scheduling of 

the substance in the 1961 or 1971 

Conventions. 

Synthetic cannabinoid receptor agonists 

1. 4F-MDMB-BICA (4F-MDMB-BUTICA) 

Novel synthetic opioids 

2. Brorphine 

3. Metonitazene 

Cathinones/stimulants 

4. Eutylone (bk-EBDB) 

5. BMDP (3,4-Methylenedioxy-Nbenzylcathinone), benzylone 

Pre-reviews: The substances listed below 

have been proposed for a pre-review. The 

purpose of a pre-review is to determine 

whether current information justifies an 

Expert Committee critical review. A prereview is a preliminary analysis and findings 

at this stage should not determine whether 

the control status of a substance should be 

changed. 

Herbal drugs 

6. Kratom, mitragynine, 7- 

hydroxymitragynine 

Medicines 

7. Phenibut 

FDA has verified the website 

addresses contained in the WHO notice, 

as of the date this document publishes 

in the Federal Register, but websites are 

subject to change over time. Access to 

view the WHO questionnaire can be 

found at https://www.who.int/groups/ 

who-expert-committee-on-drugdependence/forty-fourth-ecdddocuments. 

III. Substances Under WHO Review 

4F-MDMB-BICA (4F-MDMB-BUTICA) 

is a synthetic cannabinoid that has been 

sold online and used to mimic the 

biological effects of 

tetrahydrocannabinol, the main 

psychoactive constituent in marijuana. 

Research and clinical reports have 

demonstrated that synthetic 

cannabinoids are applied onto plant 

material so that the material may be 

smoked as users attempt to obtain a 

euphoric and psychoactive ‘‘high.’’ 

Synthetic cannabinoids have been 

marketed under the guise of ‘‘herbal 

incense,’’ and promoted by drug 

traffickers as legal alternatives to 

marijuana. According to the National 

Forensic Laboratory Information System 

database, 4F-MDMB-BICA emerged in 

the United States in May 2020 through 

identification in drug seizures. Per NPS 

Discovery,1 4F-MDMB-BICA has been 

identified in at least 26 toxicology cases 

associated with postmortem and driving 

under the influence of drugs 

investigations in the United States. 

There are no commercial or approved 

medical uses for 4F-MDMB-BICA, and it 

is not a controlled substance under the 

CSA but may be considered an analogue 

of other Schedule I substances. 

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 issued a 


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39040 Federal Register / Vol. 86, No. 139 / Friday, July 23, 2021 / Notices 

temporary order to control brorphine as 

a Schedule I substance under the CSA. 

Eutylone (bk-EBDB) (chemical name: 

1-(1,3-benzodioxol-5-yl)-2- 

(ethylamino)butan-1-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. 

BMDP (chemical name: 3,4- 

Methylenedioxy-N-benzylcathinone) is 

a designer drug of the phenethylamine 

class. BMDP is a synthetic cathinone 

with chemical structural and 

pharmacological similarities to 

Schedule I and II amphetamines (e.g., 

methamphetamine and 3,4- 

methylenedioxymethamphetamine) and 

cathinones (e.g., methylone). Law 

enforcement has seen an increase in the 

encounters of BMDP in 2019 in the 

United States illicit, synthetic drug 

market as evidenced by its identification 

in drug seizures. BMDP has no 

commercial or approved medical uses, 

and it is not controlled under the CSA. 

However, if BMDP is found to meet the 

criteria outlined in Title 21 of the 

United States Code, section 802(32) (21 

U.S.C. 802(32)), and it is intended for 

human consumption, it may be treated 

as a Schedule I controlled substance 

analogue for the purpose of Federal law 

pursuant to 21 U.S.C. 813. 

Mitragynine and 7- 

hydroxymitragynine are the main active 

constituents of the plant Mitragyna 

speciosa, commonly known as kratom, 

an indigenous plant of Southeast Asia. 

Kratom is abused for its ability to 

produce opioid-like effects. Kratom is 

available in several different forms to 

include dried/crushed leaves, powder, 

capsules, tablets, liquids, and gum/ 

resin. Kratom is an increasingly popular 

drug of abuse and readily available on 

the recreational drug market in the 

United States. Evidence suggests that 

kratom is abused individually and with 

other psychoactive substances. Kratom 

does not have an approved medical use 

in the United States and has not been 

studied as a treatment agent in the 

United States. Kratom has a history of 

being used as an opium substitute in 

Southeast Asia. In the United States, 

kratom is misused to self-treat chronic 

pain and opioid withdrawal symptoms. 

Consumption of kratom can lead to a 

number of health impacts, including, 

among others, respiratory depression, 

vomiting, nervousness, weight loss, and 

constipation. Kratom has been reported 

to have both narcotic and stimulant-like 

effects, and withdrawal symptoms may 

include hostility, aggression, excessive 

tearing, aching of muscles and bones, 

and jerky limb movements. Kratom is 

not a controlled substance under the 

CSA. 

Phenibut (chemical name: Betaphenyl-gamma-aminobutyric acid HCl) 

is a neuropsychotropic drug that is used 

in Russia to treat alcohol withdrawal, 

anxiety, insomnia, and vestibular 

disorders. It has anxiolytic and 

nootropic (cognition enhancing) effects. 

Phenibut acts as a gamma-aminobutyric 

acid (GABA)-mimetic, primarily at 

GABA(B) and, to some extent, at 

GABA(A) receptors. Phenibut is sold 

online as a supplement to improve 

cognitive function, memory, creativity 

in healthy persons, and used to selfmedicate anxiety, insomnia, and alcohol 

cravings. There are reports of people 

taking phenibut arriving to emergency 

departments with agitation, 

intoxication, altered mental status, and 

withdrawal, and also reports of 

phenibut in toxicology urinalysis 

reports from a prison facility, where 

inmates were abusing multiple drugs, 

including phenibut. There is no 

approved medical use for phenibut in 

the United States, and phenibut is not 

a controlled substance under the CSA. 

IV. Opportunity To Submit Domestic 

Information 

As required by paragraph (d)(2)(A) of 

the CSA, FDA, on behalf of HHS, invites 

interested persons to submit comments 

regarding the 11 drug substances. Any 

comments received will be considered 

by HHS when it prepares a scientific 

and medical evaluation for drug 

substances that is responsive to the 

WHO Questionnaire for these drug 

substances. HHS will forward such 

evaluation of these drug substances to 

WHO, for WHO’s consideration in 

deciding whether to recommend 

international control/decontrol of any of 

these drug substances. Such control 

could limit, among other things, the 

manufacture and distribution (import/ 

export) of these drug substances and 

could impose certain recordkeeping 

requirements on them. 

Although FDA is, through this notice, 

requesting comments from interested 

persons, which will be considered by 

HHS when it prepares an evaluation of 

these drug substances, HHS will not 

now make any recommendations to 

WHO regarding whether any of these 

drugs should be subjected to 

international controls. Instead, HHS will 

defer such consideration until WHO has 

made official recommendations to the 

Commission on Narcotic Drugs, which 

are expected to be made in late 2021. 

Any HHS position regarding 

international control of these drug 

substances will be preceded by another 

Federal Register notice soliciting public 

comments, as required by paragraph 

(d)(2)(B) of the CSA. 

Dated: July 19, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–15685 Filed 7–22–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2020–N–1584] 

Authorization of Emergency Use of 

Certain Medical Devices During 

COVID–19; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

issuance of Emergency Use 

Authorizations (EUAs) (the 

Authorizations) for certain medical 

devices related to the Coronavirus 

Disease 2019 (COVID–19) public health 

emergency. FDA has issued the 

Authorizations listed in this document 

under the Federal Food, Drug, and 

Cosmetic Act (FD&C Act). These 

Authorizations contain, among other 

things, conditions on the emergency use 

of the authorized products. The 

Authorizations follow the February 4, 

2020, determination by the Secretary of 

Health and Human Services (HHS) that 

there is a public health emergency that 

has a significant potential to affect 

national security or the health and 

security of U.S. citizens living abroad, 

and that involves the virus that causes 

COVID–19, and the subsequent 

declarations on February 4, 2020, March 

2, 2020, and March 24, 2020, that 

circumstances exist justifying the 

authorization of emergency use of in 

vitro diagnostics for detection and/or 


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