International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; World Health Organization; Scheduling Recommendations; AH-7921; Gamma-Butyrolactone; 1,4-Butanediol; Ketamine; 9 Additional Substances; Request for Comments, 4283-4288 [2015-01408]

Download as PDF asabaliauskas on DSK5VPTVN1PROD with NOTICES Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 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 In the Federal Register of February 4, 2013 (78 FR 7786), FDA published a notice announcing the availability of a draft guidance entitled ‘‘S10 Photosafety Evaluation of Pharmaceuticals.’’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 VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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 https://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 https:// www.regulations.gov. III. Electronic Access Persons with access to the Internet may obtain the document at https:// www.regulations.gov, https:// www.fda.gov/Drugs/Guidance ComplianceRegulatoryInformation/ Guidances/default.htm, or https:// www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatory Information/default.htm. 1 See 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 https://www.fda.gov/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/default.htm. PO 00000 Frm 00041 Fmt 4703 Sfmt 4703 4283 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. 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 https:// 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: SUMMARY: E:\FR\FM\27JAN1.SGM 27JAN1 asabaliauskas on DSK5VPTVN1PROD with NOTICES 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 VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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 PO 00000 Frm 00042 Fmt 4703 Sfmt 4703 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 (4methylmethcathinone) 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); 1,4butanediol; 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 E:\FR\FM\27JAN1.SGM 27JAN1 asabaliauskas on DSK5VPTVN1PROD with NOTICES Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices 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 VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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 PO 00000 Frm 00043 Fmt 4703 Sfmt 4703 4285 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-[(2methoxyphenyl)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-[(2methoxyphenyl)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 E:\FR\FM\27JAN1.SGM 27JAN1 asabaliauskas on DSK5VPTVN1PROD with NOTICES 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-[(2methoxyphenyl)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 1benzyl-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(1pentyl-1H-indol-3-yl)methanone. VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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 PO 00000 Frm 00044 Fmt 4703 Sfmt 4703 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, 4MMC) 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 E:\FR\FM\27JAN1.SGM 27JAN1 Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices asabaliauskas on DSK5VPTVN1PROD with NOTICES 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-(3,4dichlorobenzamidomethyl) 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. 1,4Butanediol is not controlled under the CSA in the United States, but it is VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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-3yl)-1-naphthalenyl-methanone (JWH018) and [1-(5-fluoropentyl)-1H-indol-3- PO 00000 Frm 00045 Fmt 4703 Sfmt 4703 4287 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 3,4methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxy-N-methylcathinone (beta-keto-MDMA; methylone), and 4methylmethcathinone (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 (https://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 E:\FR\FM\27JAN1.SGM 27JAN1 4288 Federal Register / Vol. 80, No. 17 / Tuesday, January 27, 2015 / Notices asabaliauskas on DSK5VPTVN1PROD with 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 https://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 https:// 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 VerDate Sep<11>2014 18:01 Jan 26, 2015 Jkt 235001 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. PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 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 https:// 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 https://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. E:\FR\FM\27JAN1.SGM 27JAN1

Agencies

[Federal Register Volume 80, Number 17 (Tuesday, January 27, 2015)]
[Notices]
[Pages 4283-4288]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-01408]

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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; Gamma-Butyrolactone;
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 https://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:

[[Page 4284]]

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 Secretary-General 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 Director-General 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 25I-NBOMe (2C-I-NBOMe), be placed in
Schedule I of the Convention on Psychotropic Substances (1971) and
that:
--N-benzylpiperazine (BZP); JWH-018; AM-2201; 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

[[Page 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 Secretary-General 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{time} benzamide.
AH-7921 had not been previously pre-reviewed 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 ``morphine-like'' 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 pre-review 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 gamma-hydroxybutyric 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 pre-review 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 pre-reviewed 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 pre-reviewed 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

[[Page 4286]]

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 pre-reviewed 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 aryl-substituted 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 pre-reviewed 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 pre-reviewed 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 pre-reviewed 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 pre-reviewed 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)propan-1-one.

Mephedrone had not been previously pre-reviewed 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

[[Page 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 [micro]-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
gamma-hydroxybutyric 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-B-NBOMe), 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 25B-NBOMe, 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
(JWH-018) and [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-
methanone (AM-2201) are classified as synthetic cannabinoids with
pharmacological properties like tetrahydrocannabinol. The WHO ECDD at
its 36th meeting recommended that JWH-018 and AM-2201 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 (https://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 rapid-acting 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

[[Page 4288]]

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 AH-7921
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 https://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 https://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

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