Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 4283 

1See the ICH guidance ‘‘M3(R2) Nonclinical 

Safety Studies for the Conduct of Human Clinical 

Trials and Marketing Authorization for 

Pharmaceuticals,’’ available on the Internet at 

http://www.fda.gov/Drugs/GuidanceCompliance

RegulatoryInformation/Guidances/default.htm. 

initiatives to be developed with input 

from both regulatory and industry 

representatives. FDA also seeks input 

from consumer representatives and 

others. ICH is concerned with 

harmonization of technical 

requirements for the registration of 

pharmaceutical products among three 

regions: The European Union, Japan, 

and the United States. The six ICH 

sponsors are the European Commission; 

the European Federation of 

Pharmaceutical Industries Associations; 

the Japanese Ministry of Health, Labour, 

and Welfare; the Japanese 

Pharmaceutical Manufacturers 

Association; CDER and CBER, FDA; and 

the Pharmaceutical Research and 

Manufacturers of America. The ICH 

Secretariat, which coordinates the 

preparation of documentation, is 

provided by the International 

Federation of Pharmaceutical 

Manufacturers Associations (IFPMA). 

The ICH Steering Committee includes 

representatives from each of the ICH 

sponsors and the IFPMA, as well as 

observers from the World Health 

Organization, Health Canada, and the 

European Free Trade Area. 

In the Federal Register of February 4, 

2013 (78 FR 7786), FDA published a 

notice announcing the availability of a 

draft guidance entitled ‘‘S10 Photosafety 

Evaluation of Pharmaceuticals.’’ The 

notice gave interested persons an 

opportunity to submit comments by 

March 21, 2013. Changes made to the 

guidance took into consideration 

written comments received. In addition 

to editorial changes primarily for 

clarification, the major changes are as 

follows: 

• The guidance further emphasizes 

the flexibility and optional nature of 

assessments for photosafety. This is 

reflected in revisions to Figure 1 and 

related text. 

• The discussion about 

pharmaceuticals given via ocular routes 

was reduced because the ICH working 

group did not have useful guidance to 

provide for these products. 

After consideration of the comments 

received and revisions to the guidance, 

a final draft of the guidance was 

submitted to the ICH Steering 

Committee and endorsed by the three 

participating regulatory Agencies in 

November 2013. 

The ICH S10 guidance provides 

guidance on when photosafety testing is 

warranted, and on possible testing 

strategies. It represents the consensus 

that exists regarding assessment of 

photosafety to support clinical 

development and marketing 

authorization of pharmaceuticals. It 

supplements the ICH M3(R2) guidance,1

which: (1) Provides certain information 

regarding timing of photosafety testing 

relative to clinical development and (2) 

recommends that an initial assessment 

of photoreactive potential be conducted 

and, if appropriate, an experimental 

evaluation be undertaken before 

exposure of large numbers of subjects. 

The guidance describes a flexible, 

integrated process that involves 

photochemical characteristics, data from 

nonclinical studies, and human safety 

information. Although the strategy is 

flexible and the options selected are the 

developer’s choice, characterization of 

the ultraviolet-visible absorption 

spectrum is recommended as the initial 

assessment and can obviate any further 

photosafety evaluation. Results of the 

evaluation determine the need for risk 

minimization measures to prevent 

adverse events in humans. 

This guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The guidance represents the Agency’s 

current thinking on this topic. It does 

not create or confer any rights for or on 

any person and does not operate to bind 

FDA or the public. An alternative 

approach may be used if such approach 

satisfies the requirements of the 

applicable statutes and regulations. 

II. Comments 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set of 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday, and 

will be posted to the docket at http://

www.regulations.gov. 

III. Electronic Access 

Persons with access to the Internet 

may obtain the document at http://

www.regulations.gov, http://

www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/

Guidances/default.htm, or http://

www.fda.gov/BiologicsBloodVaccines/

GuidanceComplianceRegulatory

Information/default.htm. 

Dated: January 22, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–01406 Filed 1–26–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2015–N–0045] 

International Drug Scheduling; 

Convention on Psychotropic 

Substances; Single Convention on 

Narcotic Drugs; World Health 

Organization; Scheduling 

Recommendations; AH-7921; GammaButyrolactone; 1,4-Butanediol; 

Ketamine; 9 Additional Substances; 

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 and to 

request an informal public meeting 

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 and/or public 

meeting 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 

2015. This notice is issued under the 

Controlled Substances Act (the CSA). 

DATES: Submit either electronic or 

written comments by February 26, 2015. 

Submit requests for a public meeting on 

or before February 6, 2015. (For 

additional information, see also section 

IV of this document). 

ADDRESSES: Submit electronic 

comments to http://

www.regulations.gov. Submit written 

comments to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. 

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: 


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4284 Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 

I. Background 

The United States is a party to the 

1971 Convention on Psychotropic 

Substances (Psychotropic 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 Psychotropic 

Convention that the CND proposes to 

decide whether to add a drug or other 

substance to one of the schedules of the 

Psychotropic 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 13 

substances to be considered for control 

under the Psychotropic Convention. 

This notification reflects the 

recommendation from the 36th WHO 

Expert Committee for Drug Dependence 

(ECDD), which met in June 2014. In the 

Federal Register of December 30, 2013 

(78 FR 79465), 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 Single Convention). The 

Secretary of State has received a 

notification from the Secretary-General 

regarding a substance 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, in an 

effort to provide interested and affected 

persons an opportunity to submit 

comments regarding the WHO 

recommendations for narcotic drugs, the 

notification regarding this substance 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 this substance. 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 Single 

Convention. 

II. United Nations Notification 

The formal notification from the 

United Nations that identifies the drug 

substances and explains the basis for the 

recommendations is reproduced as 

follows: 

Reference: 

NAR/CL.11/2014 

WHO/ECDD36; 1961C–Art.3; 1971C–Art.2 

CU 2014/288/DTA/SGB 

The Secretary-General of the United 

Nations presents his compliments to the 

Secretary of State of the United States of 

America and has the honour to inform the 

Government that 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 1and 4 

of the Convention on Psychotropic 

Substances of 1971 (1971 Convention) 

notified the Secretary-General of the 

following recommendations: 

AH-7921 be placed in Schedule I of the 1961 

Convention 

and 

Gamma-butyrolactone (GBL) 

1,4-butanediol 

25B-NBOMe (2C-B-NBOMe) 

25C-NBOMe (2C-C-NBOMe) 

25I-NBOMe (2C-I-NBOMe) 

be placed in Schedule I of the 1971 

Convention 

and 

N-benzylpiperazine (BZP) 

JWH-018 

AM-2201 

3,4-methylenedioxypyrovalerone (MDPV) 

Methylone (beta-keto-MDMA) 

Mephedrone 

be placed in Schedule II of the 1971 

Convention. 

In accordance with the provisions of article 

3, paragraph 2 of the 1961 Convention and 

article 2, paragraph 2 of the 1971 Convention, 

the Secretary-General hereby transmits the 

notification as annex I to the present note. 

Also in accordance with the same provisions, 

the notification from WHO will be brought to 

the attention of the fifty-eighth session of the 

Commission on Narcotic Drugs, 9–17 March 

2015. 

His Excellency 

Mr. John Kerry 

Secretary of State of the United States of 

America 

In connection with the notification, WHO 

has also submitted the relevant extract from 

the report of the thirty-sixth session of the 

WHO Expert Committee on Drug Dependence 

which is hereby transmitted as annex II. 

Reference is made to the notification 

concerning the proposed recommendation for 

international control of mephedrone (4- 

methylmethcathinone) by the Government of 

the United Kingdom of Great Britain and 

Northern Ireland and to the respective note 

NAR/CL.2/2014 of 7 February 2014 of the 

Secretary-General to all Member States. 

Furthermore reference is made to the 

notification concerning the proposed 

recommendation for international control of 

ketamine by the Government of the People’s 

Republic of China and to the respective note 

NAR/CL.4/2014 of 14 March 2014 by the 

Secretary-General to all Member States, as 

well as to the recommendation of the Expert 

Committee on Drug Dependence related to 

ketamine (see annex I, page 2). 

In order to assist the Commission in 

reaching a decision, it would be appreciated 

if the Government could communicate any 

economic, social, legal, administrative or 

other factors that it considers relevant to the 

possible scheduling of the afore-mentioned 

substances under the 1961 Convention and 

the 1971 Convention, at the latest by 30 

January 2015 to the Executive Director of the 

United Nations Office on Drugs and Crime, 

c/o Secretary, Commission on Narcotic 

Drugs, P.O. Box 500, 1400 Vienna, Austria, 

fax: +43–1–26060–5885, email: sgb@

unodc.org. 

17 December 2014 

NAR/CL.11/2014 

Annex I 

Annex I 

Letter Addressed to the Secretary-General of 

the United Nations From the DirectorGeneral of the World Health Organization 

‘‘With reference to Article 2, paragraphs 1, 

4 and 6 of the Convention on Psychotropic 

Substances (1971) and Article 3, paragraphs 

1, 3 and 5 of the Single Convention on 

Narcotic Drugs (1961), as amended by the 

1972 Protocol, and following the 36th 

meeting of the Expert Committee on Drug 

Dependence in June 2014, I am pleased to 

submit recommendations of the World 

Health Organization. 

The recommendations are that: 

—AH-7921, be placed in Schedule I of the 

Single Convention on Narcotic Drugs 

(1961), that: 

—Gamma-butyrolactone (GBL); 1,4- 

butanediol; 25B-NBOMe (2C-B-NBOMe); 

25C-NBOMe (2C-C-NBOMe) and 25INBOMe (2C-I-NBOMe), be placed in 

Schedule I of the Convention on 

Psychotropic Substances (1971) and that: 

—N-benzylpiperazine (BZP); JWH-018; AM2201; 3,4-methylenedioxypyrovalerone 

(MDPV); Methylone (beta-keto-MDMA); 

Mephedrone, be placed in Schedule II of 

the Convention on Psychotropic 

Substances (1971). 

The recommendations and the assessments 

and findings on which they are based are set 

out in detail in the Report of the 36th Expert 

Committee on Drug Dependence, which is 


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Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 4285 

the Committee that advises me on these 

issues. An extract of the Committee’s Report 

is attached in Annex 1 to this letter. 

A notification has been made by the United 

Kingdom of Great Britain and Northern 

Ireland, pursuant to article 2, paragraphs 1 

and 3 of the Convention on Psychotropic 

Substances, 1971 concerning a proposed 

recommendation for international control of 

mephedrone. The Expert Committee 

critically reviewed this substance and 

considered that the degree of risk to public 

health and society associated with the abuse 

liability of mephedrone is substantial and 

therefore considered that the evidence of its 

abuse warranted its placement under 

international control, in Schedule II of the 

Convention on Psychotropic Substances 

(1971). 

Following a notification under Article 2, 

paragraph 1 of the Convention on 

Psychotropic Substances (1971) by the 

Government of the People’s Republic of 

China concerning proposed recommendation 

for international control of ketamine, the 

Expert Committee critically reviewed this 

substance, following its previous critical 

reviews of ketamine at its 35th and 34th 

meeting and the pre-review undertaken at its 

33rd meeting. The information provided by 

China with its notification to the SecretaryGeneral was brought to the Expert 

Committee’s attention. The Expert 

Committee’s assessment was that ketamine 

‘‘is widely used as an anaesthetic in human 

and veterinary medicine, and is included in 

the WHO Model List of Essential Medicines 

and the WHO Model List of Essential 

Medicines for Children as well as in many 

national lists of essential medicines’’. The 

Expert Committee found that it was 

presented with ‘‘compelling evidence [. . .] 

about the prominent place of ketamine as an 

anaesthetic in developing countries and 

crisis situations’’. While the Expert 

Committee ‘‘acknowledged the concerns 

raised by some countries and UN 

organizations’’, it stated that ‘‘ketamine abuse 

currently does not appear to pose a sufficient 

public-health risk of global scale to warrant 

scheduling’’ and recommended ‘‘that 

ketamine not be placed under international 

control at this time’’. ‘‘Countries with serious 

abuse problems may decide to introduce or 

maintain control measures, but should 

ensure ready access to ketamine for surgery 

and anaesthesia for human and veterinary 

care’’. 

During its meeting, the Expert Committee 

also discussed the importance of having 

reliable and sufficient data that could inform 

the review process in particular for New 

Psychoactive Substances (NPS), 

acknowledging the fact that more and more 

NPS will likely be reviewed in the future, for 

which data will not always be readily 

available. UNODC and WHO will hold an 

international experts consultation in 

December 2014 to identify selection criteria 

for prioritisation of NPS to be reviewed by 

the Committee as well as relevant indicators, 

methods and tools for data collection on 

NPS. 

I am very pleased with the ongoing 

collaboration between WHO, UNODC and 

INCB for improving access to controlled 

medicines while preventing misuse and 

trafficking and for preparing the Special 

Session of the United Nations General 

Assembly on the World Drug Problem in 

2016.’’ 

NAR/CL.11/2014 

Annex II 

Annex II 

Extract From the Report of the 36th Expert 

Committee on Drug Dependence 

Substance recommended to be scheduled 

in Schedule I of the Single Convention on 

Narcotic Drugs (1961), as amended by the 

1972 Protocol: 

AH-7921 

AH-7921 is an N-substituted 

cyclohexylmethylbenzamide and is 

chemically 3,4-dichloro-N-{[1- 

(dimethylamino)cyclohexyl]methyl}benza

mide. 

AH-7921 had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

AH-7921 is clandestinely manufactured, of 

especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

AH-7921 is an opioid with ‘‘morphinelike’’ effects. The Committee considered that 

the degree of risk to public health and society 

associated with the abuse liability and 

accompanying evidence warranted its 

placement under international control. The 

Committee recommended that AH-7921 be 

placed in Schedule I of the Single 

Convention on Narcotic Drugs (1961), as 

amended by the 1972 Protocol. 

Substances recommended to be scheduled 

in Schedule I of the Convention on 

Psychotropic Substances (1971): 

Gamma-butyrolactone (GBL) 

Gamma-butyrolactone (GBL) is chemically 

oxolan-2-one. GBL can be synthesised from 

gamma-hydroxybutyric acid (GHB) or 

tetrahydrofuran. 

During the discussion of GHB at the 34th 

Meeting of the WHO Expert Committee on 

Drug Dependence (ECDD), the Committee 

‘‘noted information relating to the abuse of 

GBL itself (convertible to GHB in the body) 

and suggested this substance for pre-review’’. 

Based on the evidence presented in the prereview of GBL during its 35th Meeting, given 

its close association with GHB, and the 

recommendation made by the Committee to 

reschedule GHB from Schedule IV to 

Schedule II of the Convention on 

Psychotropic Substances (1971), the 

Committee recommended that a critical 

review of GBL be undertaken. 

The Committee considered that the degree 

of risk to public health and society associated 

with the abuse liability of GBL is especially 

serious. Whilst the Committee recognized 

widespread and important industrial use, it 

has no defined therapeutic usefulness. The 

Committee considered that the evidence of 

its abuse warranted its placement under 

international control within Schedule I of the 

Convention on Psychotropic Substances 

(1971). 

1,4-butanediol 

1,4-butanediol (butane-1,4-diol, 1,4-BDO or 

1,4-BD) is one of four stable isomers of 

butanediol. 

During the discussion of gammahydroxybutyric acid (GHB) at its 34th 

Meeting, the Committee ‘‘noted information 

relating to the abuse of 1,4-BD itself 

(convertible to GHB in the body) and 

suggested this substance for pre-review’’. 

Based on the evidence presented in the prereview of GBL during its 35th Meeting, given 

its close association with GHB, and the 

recommendation made by the Committee to 

reschedule GHB from Schedule IV to 

Schedule II of the Convention on 

Psychotropic Substances (1971), the 

Committee recommended that a critical 

review of 1,4-BD be undertaken. 

1,4-butanediol produces its effects in the 

body through the in vivo formation of the 

scheduled substance GHB. The Committee 

considered that the degree of risk to public 

health and society associated with the abuse 

liability of 1,4-butanediol is especially 

serious. Whilst the Committee recognized 

widespread and important industrial use, it 

has no defined therapeutic usefulness. The 

Committee considered that the evidence of 

its abuse warranted its placement under 

international control within Schedule I of the 

Convention on Psychotropic Substances 

(1971). 

25B-NBOMe 

25B-NBOMe (2C-B-NBOMe) is chemically 2- 

(4-bromo-2,5-dimethoxyphenyl)-N-[(2- 

methoxyphenyl)methyl]ethanamine. 

25B-NBOMe had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

25B-NBOMe is clandestinely manufactured, 

of especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee noted the challenges 

associated with the evidence base concerning 

the substance. The Committee considered 

that the degree of risk to public health and 

society associated with the abuse liability of 

25B-NBOMe is especially serious. Whilst the 

Committee noted its use in medical research, 

it has no recorded therapeutic use. 

The Committee considered that the 

evidence of its abuse warranted its placement 

under international control and 

recommended that 25B-NBOMe be placed in 

Schedule I of the Convention on 

Psychotropic Substances (1971). 

25C-NBOMe 

25C-NBOMe (2C-C-NBOMe) is chemically 2- 

(4-chloro-2,5-dimethoxyphenyl)-N-[(2- 

methoxyphenyl)methyl]ethanamine. 

25C-NBOMe had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

25C-NBOMe is clandestinely manufactured, 

of especially serious risk to public health and 

society, and of no recognized therapeutic use 


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4286 Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee noted the challenges 

associated with the evidence base concerning 

the substance. The Committee considered 

that the degree of risk to public health and 

society associated with the abuse liability of 

25C-NBOMe is especially serious. Whilst the 

Committee noted its use in medical research, 

it has no recorded therapeutic use. The 

Committee considered that the evidence of 

its abuse warranted its placement under 

international control and recommended that 

25C-NBOMe be placed in Schedule I of the 

Convention on Psychotropic Substances 

(1971). 

25I-NBOMe 

25I-NBOMe (2C-I-NBOMe) is chemically 2- 

(4-iodo-2,5-dimethoxyphenyl)-N-[(2- 

methoxyphenyl)methyl]ethanamine. 

25I-NBOMe had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

25I-NBOMe is clandestinely manufactured, 

of especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee noted the challenges 

associated with the evidence base concerning 

the substance. The Committee considered 

that the degree of risk to public health and 

society associated with the abuse liability of 

25I-NBOMe is especially serious. Whilst the 

Committee noted its use in medical research, 

it has no recorded therapeutic use. The 

Committee considered that the evidence of 

its abuse warranted its placement under 

international control and recommended that 

25I-NBOMe be placed in Schedule I of the 

Convention on Psychotropic Substances 

(1971). 

Substances recommended to be scheduled 

in Schedule II of the Convention on 

Psychotropic Substances (1971): 

N-benzylpiperazine (BZP) 

N-benzylpiperazine (BZP) is an arylsubstituted piperazine and is chemically 1- 

benzyl-1,4-diazacyclohexane. 

BZP was pre-reviewed at the 35th ECDD 

meeting and based on the reported 

psychostimulant effects, evidence of abuse 

and adverse effects, the Expert Committee 

concluded that a critical review was 

warranted. 

BZP has been shown to have effects similar 

to amphetamine. The Committee considered 

that the degree of risk to public health and 

society associated with the abuse liability of 

BZP is substantial. Its therapeutic usefulness 

has been assessed to be little, as it is not 

currently licensed for use. The Committee 

considered that the evidence of its abuse 

warranted its placement under international 

control. The Committee recommended that 

BZP be placed in Schedule II of the 

Convention on Psychotropic Substances 

(1971). 

JWH-018 

JWH-018 is chemically naphthalen-1-yl(1- 

pentyl-1H-indol-3-yl)methanone. 

JWH-018 had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

JWH-018 is clandestinely manufactured, of 

especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee noted the challenges 

associated with the evidence base concerning 

the substance. The Committee noted 

analytically confirmed cases of non-fatal and 

fatal intoxications involving JWH-018. The 

Committee therefore considered that the 

degree of risk to public health associated 

with the abuse liability of JWH-018 is 

substantial. Its therapeutic usefulness has 

been assessed to be none. As per the 

Guidance on the WHO review of 

psychoactive substances for international 

control, higher regard was made to the 

substantial public health risk as opposed to 

the lack of therapeutic usefulness [p.18, 

paragraph 56, penultimate sentence]. The 

Committee recommended that JWH-018 be 

placed under international control in 

Schedule II of the Convention on 

Psychotropic Substances (1971). 

AM-2201 

AM-2201 is chemically [1-(5-fluoropentyl)- 

1H-indol-3-yl]-naphthalen-1-ylmethanone. 

AM-2201 had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

AM-2201 is clandestinely manufactured, of 

especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee noted the challenges 

associated with the evidence base concerning 

the substance. The Committee noted 

analytically confirmed cases of non-fatal and 

fatal intoxications involving AM-2201. The 

Committee therefore considered that the 

degree of risk to public health associated 

with the abuse liability of AM-2201 is 

substantial. Its therapeutic usefulness has 

been assessed to be none. As per the 

Guidance on the WHO review of 

psychoactive substances for international 

control, higher regard was made to the 

substantial public health risk as opposed to 

the lack of therapeutic usefulness [p.18, 

paragraph 56, penultimate sentence]. The 

Committee recommended that AM-2201 be 

placed under international control in 

Schedule II of the Convention on 

Psychotropic Substances (1971). 

3,4-methylenedioxypyrovalerone (MDPV) 

3,4-methylenedioxypyrovalerone (MDPV) is 

chemically (R,S)-1-(1,3-benzodioxol-5-yl)- 

2-(pyrrolidin-1-yl)pentan-1-one. 

MDPV had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

MDPV is clandestinely manufactured, of 

especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee considered that the degree 

of risk to public health and society associated 

with the abuse liability of MDPV is 

substantial. Its therapeutic usefulness has 

been assessed to be none. The Committee 

considered that the evidence of its abuse 

warranted its placement under international 

control. As per the Guidance on the WHO 

review of psychoactive substances for 

international control, higher regard was made 

to the substantial public health risk as 

opposed to the lack of therapeutic usefulness 

[p.18 paragraph 56, penultimate sentence]. 

The Committee recommended that MDPV be 

placed in Schedule II of the Convention on 

Psychotropic Substances (1971). 

Methylone (bk-MDMA) 

Methylone (beta-keto-MDMA) is chemically 

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

(methylamino)propan-1-one. 

Methylone had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

methylone is clandestinely manufactured, of 

especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm and that it has no medical use. 

The Committee considered that the degree 

of risk to public health and society associated 

with the abuse liability of methylone is 

substantial. Its therapeutic usefulness has 

been assessed to be none. The Committee 

considered that the evidence of its abuse 

warranted its placement under international 

control. As per the Guidance on the WHO 

review of psychoactive substances for 

international control, higher regard was made 

to the substantial public health risk as 

opposed to the lack of therapeutic usefulness 

[p.18, paragraph 56, penultimate sentence]. 

The Committee recommended that 

methylone be placed in Schedule II of the 

Convention on Psychotropic Substances 

(1971). 

Mephedrone 

Mephedrone (4-methylmethcathinone, 4- 

MMC) is chemically (R,S)-2- 

(methylamino)-1-(4-methylphenyl)propan1-one. 

Mephedrone had not been previously prereviewed or critically reviewed. A direct 

critical review was proposed based on 

information brought to WHO’s attention that 

mephedrone is clandestinely manufactured, 

of especially serious risk to public health and 

society, and of no recognized therapeutic use 

by any party. Preliminary data collected from 

literature and different countries indicated 

that this substance may cause substantial 

harm. A critical review was further 

undertaken by the Committee given that the 

Government of the United Kingdom of Great 

Britain and Northern Ireland had made a 

notification concerning a proposed 

recommendation for international control of 

mephedrone (4-methylmethcathinone), under 


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Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 4287 

article 2, paragraphs 1 and 3 of the 

Convention on Psychotropic Substances, 

1971. 

The Committee considered that the degree 

of risk to public health and society associated 

with the abuse liability of mephedrone is 

substantial. Its therapeutic usefulness has 

been assessed to be none. The Committee 

considered that the evidence of its abuse 

warranted its placement under international 

control. As per the Guidance on the WHO 

review of psychoactive substances for 

international control, higher regard was made 

to the substantial public health risk as 

opposed to the lack of therapeutic usefulness 

[p.18, paragraph 56, penultimate sentence]. 

The Committee recommended that 

mephedrone be placed in Schedule II of the 

Convention on Psychotropic Substances 

(1971). 

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 Psychotropic 

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. 

AH-7921, or 1-(3,4- 

dichlorobenzamidomethyl) 

cyclohexyldimethylamine, is an opioid 

analgesic drug substance selective for 

the m-opioid receptor. The WHO ECDD 

met in June 2014 and recommended that 

AH-7921 be placed in Schedule I of the 

1961 Single Convention. AH-7921 is not 

controlled under the CSA in the United 

States. As such, additional controls will 

be necessary to fulfill U.S. obligations if 

AH-7921 is controlled under Schedule I 

of the 1961 Single Convention. 

Gamma-butyrolactone (GBL) is used 

as an industrial solvent. GBL can be 

converted in the body to the central 

nervous system depressant drug gammahydroxybutyric acid (GHB). GBL is 

controlled as a List I chemical in the 

United States under the CSA. The WHO 

ECDD met in June 2014 and 

recommended that GBL be placed in 

Schedule I of the Psychotropic 

Convention. Additional controls will be 

necessary to fulfill U.S. obligations if 

GBL is controlled under Schedule I of 

the Psychotropic Convention. 

1,4-Butanediol is used as an industrial 

solvent for manufacturing and also used 

for the synthesis of GBL. 1,4-Butanediol 

can also be converted to the central 

nervous depressant drug GHB. It has no 

medical use in the United States. 1,4- 

Butanediol is not controlled under the 

CSA in the United States, but it is 

subject to controls in several States 

under state law. 1,4-Butanediol was 

reviewed by the WHO ECDD at its 36th 

meeting, at which the WHO ECDD 

recommended that 1,4-butanediol be 

placed in Schedule I of the Psychotropic 

Convention. Additional controls will be 

necessary to fulfill U.S. obligations if 

1,4-butanediol is controlled under 

Schedule I of the Psychotropic 

Convention. 

The substances 25B-NBOMe (2C-BNBOMe), 25C-NBOMe (2C-C-NBOMe), 

and 25I-NBOMe (2C-I-NBOMe) are 

synthetic 2C phenethylamine 

substances and were developed for use 

in mapping and investigating the 

serotonin receptors in the mammalian 

brain. The WHO ECDD at its 36th 

meeting recommended that 25BNBOMe, 25C-NBOMe, and 25I-NBOMe 

be placed in Schedule I of the 

Psychotropic Convention. On November 

15, 2013, 25B-NBOMe, 25C-NBOMe, 

and 25I-NBOMe were temporarily 

placed in Schedule I of the CSA under 

the temporary scheduling provision of 

section 201(h) of the CSA. These 

provisions provide the Attorney General 

with the authority to temporarily place 

a substance into Schedule I of the CSA 

for 2 years, without regard to the 

requirements of 21 U.S.C. 811(b), if he 

finds that such action is necessary to 

avoid an imminent hazard to the public 

safety. In addition, if proceedings to 

control a substance are initiated under 

21 U.S.C. 811(a)(1), the Attorney 

General may extend the temporary 

scheduling for up to 1 year (21 U.S.C. 

811(h)(2)). Therefore, considering the 

previously mentioned time limitations 

of temporary scheduling under section 

201(h) of the CSA, additional controls 

will be necessary to fulfill U.S. 

obligations if 25B-NBOMe, 25C-NBOMe, 

and 25I-NBOMe are controlled under 

Schedule I of the Psychotropic 

Convention. 

N-benzylpiperazine (BZP) is used as 

an intermediate in chemical synthesis 

but has been taken orally as either 

powder or tablets and by other routes, 

including smoking or snorting. It has no 

medical use in the United States. The 

WHO ECDD at its 36th meeting 

recommended that BZP be placed in 

Schedule II of the Psychotropic 

Convention on Psychotropic Substances 

(1971). BZP is controlled in Schedule I 

under the CSA in the United States. As 

such, no additional controls will be 

necessary to fulfill U.S. obligations if 

these substances are controlled under 

Schedule II of the Psychotropic 

Convention. 

The substances 1-pentyl-1H-indol-3- 

yl)-1-naphthalenyl-methanone (JWH018) and [1-(5-fluoropentyl)-1H-indol-3- 

yl]-1-naphthalenyl-methanone (AM2201) are classified as synthetic 

cannabinoids with pharmacological 

properties like tetrahydrocannabinol. 

The WHO ECDD at its 36th meeting 

recommended that JWH-018 and AM2201 be placed in Schedule II of the 

Psychotropic Convention. These two 

substances are controlled in Schedule I 

under the CSA in the United States. As 

such, no additional controls will be 

necessary to fulfill U.S. obligations if 

JWH-018 and AM-2201 are controlled 

under Schedule II of the Psychotropic 

Convention. 

The substances 3,4- 

methylenedioxypyrovalerone (MDPV), 

3,4-methylenedioxy-N-methylcathinone 

(beta-keto-MDMA; methylone), and 4- 

methylmethcathinone (4-MMC; 

mephedrone) are classified as synthetic 

cathinones in the phenethylamine class 

and are structurally and 

pharmacologically similar to 

amphetamine. The WHO ECDD at its 

36th meeting recommended that MDPV, 

methylone, and mephedrone be placed 

in Schedule II of the Psychotropic 

Convention. MDPV, methylone, and 

mephedrone are controlled in Schedule 

I under the CSA in the United States. As 

such, no additional controls will be 

necessary to fulfill U.S. obligations if 

these three substances are controlled 

under Schedule II of the Psychotropic 

Convention. 

In addition to the above substances 

recommended for international control 

by the WHO Expert Committee at its 

36th meeting, the United Nations 

Economic and Social Council published 

recommendations for action to be taken 

by the CND at the March 2015 meeting 

(http://www.un.org/Docs/journal/asp/

ws.asp?m=E/CN.7/2015/7). Among 

these recommendations is that the CND 

should decide whether it wishes to 

place ketamine in Schedule I of the 

Psychotropic Convention or, if not, what 

other action, if any, might be required. 

Pursuant to article 2, paragraph 1, of the 

Convention on Psychotropic Substances 

of 1971, the Government of China, in its 

correspondence dated 8 March 2014, 

notified the Secretary-General of the 

United Nations that China 

recommended that ketamine be placed 

in Schedule I of the 1971 Convention. 

In accordance with article 2 of the 

Psychotropic Convention, this proposal 

has been recommended for 

consideration by the CND. 

Ketamine is classified as a rapidacting general anesthetic agent used for 

short diagnostic and surgical procedures 

that do not require skeletal muscle 

relaxation. It is marketed in the United 

States as an injectable. Ketamine is 

controlled in Schedule III of the CSA in 


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4288 Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 

the United States. It is not controlled 

internationally under the Convention on 

Psychotropic Substances or the Single 

Convention on Narcotic Drugs. The 

WHO Expert Committee on Drug 

Dependence reviewed ketamine at its 

34th, 35th, and 36th meetings. Ketamine 

is controlled in schedule III of the CSA 

in the United States, and additional 

controls may be necessary to fulfill U.S. 

obligations if ketamine is controlled 

under Schedule I of the Psychotropic 

Convention. 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 Psychotropic 

Convention at the CND meeting in 

March 2015. 

Comments regarding the WHO 

recommendations for control of AH7921 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. 

IV. Submission of Comments and 

Opportunity for Public Meeting 

Interested persons may submit either 

electronic comments regarding this 

document to http://www.regulations.gov 

or written comments to the Division of 

Dockets Management (see ADDRESSES). It 

is only necessary to send one set of 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday, and 

will be posted to the docket at http://

www.regulations.gov. 

FDA does not presently plan to hold 

a public meeting. If any person believes 

that, in addition to written comments, a 

public meeting would contribute to the 

development of the U.S. position on the 

substances to be considered for control 

under the Psychotropic Convention, a 

request for a public meeting and the 

reasons for such a request should be 

sent to James R. Hunter (see FOR

FURTHER INFORMATION CONTACT) on or 

before February 6, 2015. 

The short time period for the 

submission of comments and requests 

for a public meeting is needed to ensure 

that HHS may, in a timely fashion, carry 

out the required action and be 

responsive to the United Nations. 

Dated: January 21, 2015. 

Leslie Kux, 

Associate Commissioner for Policy. 

[FR Doc. 2015–01408 Filed 1–26–15; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2015–N–0001] 

American Association of 

Pharmaceutical Scientists/American 

College of Clinical Pharmacology/

American Society for Clinical 

Pharmacology and Therapeutics/Food 

and Drug Administration Cosponsored 

Workshop on ‘‘Evaluating and 

Modernizing Our Approaches for FoodEffect Assessment’’ 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of public workshop. 

The Food and Drug Administration 

(FDA) is announcing a public workshop 

entitled ‘‘Evaluating and Modernizing 

our Approaches for Food-Effect 

Assessment,’’ cosponsored with the 

American Association of 

Pharmaceutical Scientists (AAPS), the 

American College of Clinical 

Pharmacology (ACCP), and the 

American Society for Clinical 

Pharmacology and Therapeutics 

(ASCPT). The goals of this public 

workshop are to facilitate discussion on 

current scientific approaches on 

assessing the effect of food on the 

pharmacokinetics and 

pharmacodynamics of drugs and to 

initiate constructive discussion and 

information sharing among relevant 

stakeholders on the influence of foodeffects on the pharmacokinetic 

properties of therapeutics in order to 

optimize dose and dosing regimens. 

Date and Time: The workshop will be 

held on February 2, 2015, from 8 a.m. 

to 5 p.m., February 3, 2015, from 8 a.m. 

to 5 p.m., and February 4, 2015, from 8 

a.m. to 12:15 p.m. 

Location: The workshop will be held 

at the Renaissance Baltimore 

Harborplace Hotel, 202 East Pratt St., 

Baltimore, MD 21202. 

Contacts: FDA: Padmaja Mummaneni, 

Food and Drug Administration, Center 

for Drug Evaluation and Research, 

10903 New Hampshire Ave., Bldg. 51, 

Rm. 2164, Silver Spring, MD 20993, 

301–796–2027, padmaja.mummaneni@

fda.hhs.gov. 

AAPS: For questions related to this 

event, please contact AAPS at 

registration@aaps.org. 

Registration: Workshop information 

and the registration link are posted at 

the AAPS meetings and professional 

development conference site. To register 

for the workshop, please visit http://

www.aaps.org/Meetings_and_

Professional_Development/Conference_

Mini_Sites/AAPS_WS_Food/Register/. 

The cost of registration is as follows: 

Member $1,690 

Nonmember $2,070 

Government $650 

Student $100 

The registration fee will be waived for 

50 FDA employees. If you need special 

accommodations because of disability, 

please contact AAPS at registration@

aaps.org. Onsite registration on the day 

of the workshop is available. 

Additional Information about the 

Workshop: The workshop agenda and 

additional background materials will be 

accessible at http://www.fda.gov/Drugs/ 

NewsEvents/ucm428914.htm to all 

registrants. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA’s guidance for industry entitled 

‘‘Food-Effect Bioavailability and Fed 

Bioequivalence Studies’’ (Food-Effect 

Guidance) is an important tool in the 

development of new oral therapeutics. 

Studies are conducted according to the 

principles described for every new drug 

that is intended to be administered by 

the oral route. The Food-Effect 

Guidance was first published in 2002. 

Since that time, numerous studies have 

been reported in the literature in an 

effort to address a number of different 

aspects related to assessing the effect of 

food on the pharmacokinetics and 

pharmacodynamics of drugs. 

Predominantly, these studies have 

addressed the impact of food 

composition on the physiology of drug 

absorption. In vitro studies have aimed 

at elucidating the individual 

mechanism(s) of drug absorption, and a 

number of in vivo studies have 

addressed the effects of different meal 

compositions on the pharmacokinetics 

of drugs. 

FDA has undertaken an effort to 

revise the 2002 Food-Effect Guidance 

and is seeking feedback from academia, 

industry, and other stakeholders on 

several issues. FDA, AAPS, ACCP, and 

ASCPT agreed to cosponsor this 

workshop to provide a forum for input 

on the best available science on this 

topic from academia, industry, other 

stakeholders, and regulators. 


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