83 FR 50938 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-FUBINACA; ADB-CHMINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; para-Fluoro Butyrfentanyl; Tramadol; Pregabalin; Cannabis Plant and Resin; and Eight Additional Substances; Request for Comments
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration Federal Register Volume 83, Issue 196 (October 10, 2018)
Food and Drug Administration
Federal Register Volume 83, Issue 196 (October 10, 2018)
| Page Range | 50938-50942 | |
| FR Document | 2018-21954 |
[Federal Register Volume 83, Number 196 (Wednesday, October 10, 2018)] [Notices] [Pages 50938-50942] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2018-21954] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2018-N-3685] International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-FUBINACA; ADB- CHMINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; para-Fluoro Butyrfentanyl; Tramadol; Pregabalin; Cannabis Plant and Resin; and Eight Additional Substances; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. ----------------------------------------------------------------------- SUMMARY: The Food and Drug Administration (FDA) is requesting interested persons to submit comments concerning abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of 16 drug substances. These comments will be considered in preparing a response from the United States to the World Health Organization (WHO) regarding the abuse liability and diversion of these drugs. WHO will use this information to consider whether to recommend that certain international restrictions be placed on these drugs. This notice requesting comments is required by the Controlled Substances Act (the CSA). DATES: Submit either electronic or written comments by October 31, 2018. ADDRESSES: You may submit comments as follows. Please note that late, untimely filed comments will not be considered. Electronic comments must be submitted on or before (enter date), 2018. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of October 31, 2018. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are postmarked or the delivery service acceptance receipt is on or before that date. Electronic Submissions Submit electronic comments in the following way:Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any [[Page 50939]] confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov. If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see ``Written/Paper Submissions'' and ``Instructions''). Written/Paper Submissions Submit written/paper submissions as follows: Mail/Hand delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in ``Instructions.'' Instructions: All submissions received must include the Docket No. FDA-2018-N-3685 for ``International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB- FUBINACA; FUB-AMB(MMB-FUBINACA_AMB-FUBINACA); ADB-CHMINACA; CUMYL-4CN- BINACA; Cyclopropyl Fentanyl; Methoxyacetyl Fentanyl; Ortho- Fluorofentanyl; Para-Fluoro Butyrfentanyl; Para-Methoxybutyrfentanyl; N-Ethylnorpentylone; Tramadol; Pregabalin; Cannabis Plant and Resin; Extracts and Tinctures of Cannabis; Delta-9-Tetrahydrocannabinol; Stereoisomers of Tetrahydrocannabinol; Request for Comments.'' Received comments, those filed in a timely manner (see ADDRESSES), will be placed in the docket and, except for those submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday. Confidential Submissions--To submit a comment with confidential information that you do not wish to be made publicly available, submit your comments only as a written/paper submission. You should submit two copies total. One copy will include the information you claim to be confidential with a heading or cover note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ``confidential.'' Any information marked as ``confidential'' will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA's posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https://www.thefederalregister.org/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ``Search'' box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. 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, email: [email protected]. SUPPLEMENTARY INFORMATION: I. Background The United States is a party to the 1971 Convention on Psychotropic Substances (Psychotropic Convention). Article 2 of the Psychotropic Convention provides that if a party to the convention or WHO has information about a substance, which in its opinion may require international control or change in such control, it shall so notify the Secretary-General of the United Nations (the U.N. Secretary-General) and provide the U.N. Secretary-General with information in support of its opinion. Paragraph (d)(2)(A) of the CSA (21 U.S.C. 811) (Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970) provides that when WHO notifies the United States under Article 2 of the Psychotropic Convention that it has information that may justify adding a drug or other substances to one of the schedules of the Psychotropic Convention, transferring a drug or substance from one schedule to another, or deleting it from the schedules, the Secretary of State must transmit the notice to the Secretary of Health and Human Services (Secretary of HHS). The Secretary of HHS must then publish the notice in the Federal Register and provide opportunity for interested persons to submit comments that will be considered by HHS in its preparation of the scientific and medical evaluations of the drug or substance. II. WHO Notification The Secretary of HHS received the following notice from WHO (non- relevant text removed): Ref.: C.L.26.2018 The World Health Organization (WHO) presents its compliments to Member States and Associate Members and has the pleasure of informing that the 41th Expert Committee on Drug Dependence (ECDD) will meet in Geneva from 12 to 16 November 2018. The 41th ECDD will convene to review psychoactive substances on their potential to cause dependence, abuse and harm to health, and their potential therapeutic applications. WHO will make recommendations to the UN Secretary-General on the need for and level of international control of these substances. Member States are invited to collaborate, as in the past, in this process by providing pertinent information as requested in the questionnaire and concerning substances under review. At its 126th session in January 2010, the Executive Board approved the publication ``Guidance on the WHO review of psychoactive substances for international control'' (EB126/2010/REC1, Annex 6) which requires the Secretariat to request relevant information from Ministers of Health in Member States to prepare a report for submission to the ECDD. For this purpose, a questionnaire was designed to gather information on the legitimate use, harmful use, status of national control and potential impact of international control for each substance under evaluation. A list of substances for which Member States will receive questionnaires is attached. Kindly note that Member States who submitted questionnaire responses that were reviewed at the 40th ECDD on cannabis and cannabis-related substances will not be requested to re-submit questionnaires for those substances for the 41st ECDD. However, if Member States would like to amend their responses or submit additional information on cannabis and cannabis-related substances, it is requested that they inform the Secretariat. It would be appreciated if a person from the Ministry of Health could be designated as the focal point responsible for coordinating answers to the questionnaires. A list of focal [[Page 50940]] points designated by Member States for the 40th ECDD in June 2018 is attached. It is requested that if a focal point's contact details including email address are to be added or amended, that Member States inform the Secretariat by 17 September 2018. Any additions or amendments to focal point designations should be emailed to [email protected]. If no additions or amendments to focal point details are made by this date, the focal point from 2018 will be approached by the Secretariat for questionnaire completion. Where there is a competent National Authority under the International Drug Control Treaties, it is kindly requested that the questionnaires be completed in collaboration with such body. Once the Secretariat has received the contact details, focal points will be given further instructions and direct access to an online questionnaire. The questionnaires will be analysed by the Secretariat and prepared as a report that will be shared with the Committee for review. Member States are also encouraged to provide any additional relevant information (unpublished or published) that is available on these substances to: [email protected]. This information will be an invaluable contribution to the ECDD and all submissions will be treated as confidential. The WHO takes this opportunity to renew to Member States and Associate Members the assurance of its highest consideration. GENEVA, 21 August 2018 Attachment: 41st WHO Expert Committee on Drug Dependence Member State Questionnaire Substances SYNTHETIC CANNABINOIDS ADB-FUBINACA FUB-AMB (MMB-FUBINACA, AMB-FUBINACA) ADB-CHMINACA CUMYL-4CN-BINACA FENTANYLS Cyclopropyl Fentanyl Methoxyacetyl Fentanyl Ortho-Fluorofentanyl Para-Fluoro Butyrfentanyl Para-Methoxybutyrfentanyl (METH)CATHINONE N-Ethylnorpentylone MEDICINES Tramadol Pregabalin FDA has verified the website addresses contained in the WHO notice, as of the date this document publishes in the Federal Register, but websites are subject to change over time. Access to view the WHO questionnaire can be found at http://www.who.int/medicines/access/controlled-substances/ecdd_41_meeting/en/. III. Substances Under WHO Review ADB-FUBINACA (chemical name: N-[1-(aminocarbonyl)-2,2- dimethylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide) is an indazole-based synthetic cannabinoid that is a potent, full agonist at CB1 receptors. This substance functionally (biologically) mimics the effects of the structurally unrelated delta-9- tetrahydrocannabinol (THC), a Schedule I substance, and the main psychoactive chemical constituent in the cannabis (marijuana) plant. Synthetic cannabinoids have been marketed under the guise of ``herbal incense,'' and promoted by drug traffickers as legal alternatives to marijuana. ADB-FUBINACA use has been associated with serious adverse events including death in the United States. There are no commercial or approved medical uses for ADB-FUBINACA. On April 10, 2017, ADB-FUBINACA was temporarily controlled as a Schedule I substance under the CSA. FUB-AMB (other names: MMB-FUBINACA; AMB-FUBINACA; chemical name: methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3- methylbutanoate) is an indazole-based synthetic cannabinoid that is a potent full agonist at CB1 receptors. This substance functionally (biologically) mimics the effects of the structurally unrelated THC, a Schedule I substance, and the main psychoactive chemical constituent in marijuana. Synthetic cannabinoids have been marketed under the guise of ``herbal incense,'' and promoted by drug traffickers as legal alternatives to marijuana. FUB-AMB use has been associated with serious adverse events including death in the United States. There are no commercial or approved medical uses for FUB-AMB. On November 3, 2017, FUB-AMB was temporarily controlled as a Schedule I substance under the CSA. ADB-CHMINACA (other name: MAB-CHMINACA; chemical name: N-(1-amino- 3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indole-3- carboxamide) is an indazole-based synthetic cannabinoid that is a potent full agonist at CB1 receptors. This substance functionally (biologically) mimics the effects of the structurally THC, a Schedule I substance, and the main psychoactive chemical constituent in marijuana. Synthetic cannabinoids have been marketed under the guise of ``herbal incense,'' and promoted by drug traffickers as legal alternatives to marijuana. ADB-CHMINACA use has been associated with serious adverse events including death in the United States. There are no commercial or approved medical uses for ADB-CHMINACA. On February 5, 2016, ADB- CHMINACA was temporarily controlled as a Schedule I substance under the CSA. CUMYL-4CN-BINACA (chemical name: 1-(4-cyanobutyl)-N-(2- phenylpropan-2-yl)-1 H-indazole-3-carboxamide) is a clandestinely produced indazole-3-carboxamide based synthetic cannabinoid that has been sold online and used to mimic the biological effects of THC, the main psychoactive chemical constituent in marijuana. Synthetic cannabinoids have been marketed under the guise of ``herbal incense,'' and promoted by drug traffickers as legal alternatives to marijuana. Hospital, scientific publications and law enforcement reports show that CUMYL-4CN-BINACA is abused for its psychoactive properties. CUMYL-4CN- BINACA has been associated with serious adverse events in the United States, in addition to multiple deaths in Europe. CUMYL-4CN-BINACA has no commercial or medical uses. On July 10, 2018, CUMYL-4CN-BINACA was temporarily controlled as a Schedule I substance under the CSA. Cyclopropyl fentanyl is a synthetic opioid that has a pharmacological profile similar to other Schedule I and II controlled opioid substances such as acetyl fentanyl, fentanyl, and other related mu-opioid receptor agonist substances. This clandestinely produced analog of fentanyl is associated with adverse events typically associated with opioid use such as respiratory depression, anxiety, constipation, tiredness, hallucinations, and withdrawal. Cyclopropyl fentanyl has been associated with numerous fatalities. At least 115 confirmed overdose deaths involving cyclopropyl fentanyl abuse have been reported in the United States. Cyclopropyl fentanyl has no commercial or currently accepted medical uses in the United States. On January 4, 2018, cyclopropyl fentanyl was temporarily placed into Schedule I of the CSA. Methoxyacetyl fentanyl has a pharmacological profile similar to other Schedule I and II opioid substances such as acetyl fentanyl, fentanyl, and other related mu-opioid receptor agonist substances. Evidence suggests that the pattern of abuse of fentanyl analogues, including methoxyacetyl fentanyl is similar to heroin and prescription opioid analgesics. Law enforcement and public health reports demonstrate that methoxyacetyl fentanyl is being illicitly distributed and abused. The Drug Enforcement Administration (DEA) is aware of at least two overdose deaths associated with the abuse of methoxyacetyl fentanyl in the United [[Page 50941]] States. Methoxyacetyl fentanyl has no currently accepted medical use in treatment in the United States. On October 26, 2017, methoxyacetyl fentanyl was temporarily placed into Schedule I of the CSA. Ortho-fluorofentanyl has a pharmacological profile similar to fentanyl and other related mu-opioid receptor agonist. Ortho- fluorofentanyl has no currently accepted medical use in treatment in the United States. Ortho-fluorofentanyl has been encountered by law enforcement and public health officials. The DEA has received reports for at least 13 confirmed overdose deaths involving ortho- fluorofentanyl abuse in the United States. On October 26, 2017, ortho- fluorofentanyl was temporarily placed into Schedule I of the CSA. Para-fluorobutyrfentanyl shares pharmacological profile with other Schedule I (e.g., butyryl fentanyl) and II (e.g., fentanyl) opioid substances. Para-fluorobutyrfentanyl has no currently accepted medical use in treatment in the United States. The abuse of para- fluorobutyrfentanyl carries public health risks similar to that of heroin, fentanyl, and prescription opioid analgesics. On February 1, 2018, para-fluorobutyrfentanyl was temporarily placed into Schedule I of the CSA. Para-methoxybutyrfentanyl shares pharmacological profile with other Schedule I (e.g., butyryl fentanyl) and II (e.g., fentanyl) opioid substances. Para-methoxybutyrfentanyl has no currently accepted medical use in treatment in the United States. The abuse of para- methoxybutyrfentanyl carries public health risks similar to that of heroin, fentanyl, and prescription opioid analgesics. On February 1, 2018, para-methoxybutyrfentanyl was temporarily placed into Schedule I of the CSA. N-ethylnorpentylone (other name: N-ethylpentylone) is a synthetic cathinone with stimulant and psychoactive properties similar to cathinone, a Schedule I substance. N-ethylpentylone abuse has been associated with adverse health effects leading to emergency department admissions, and deaths. N-ethylpentylone has no currently accepted medical use in treatment in the United States. On August 31, 2018, N- ethylnorpentylone was temporarily controlled as a Schedule I substance under the CSA. Tramadol, an opioid analgesic, was first approved by the FDA for medical use in March of 1995 for the treatment of moderate to moderately severe pain. It is available as immediate-release, extended- release, and combination products containing acetaminophen. Tramadol has been abused alone or in combination with other psychoactive substances. On July 2, 2014, the DEA issued a Final Rule controlling tramadol as a Schedule IV substance under the CSA with effective date of August 18, 2014. The ECDD pre-reviewed tramadol at its 39th meeting in November 2017 noting growing evidence of abuse of tramadol in many countries, in some cases serious, accompanied by adverse reactions and tramadol-associated deaths and recommending that tramadol be subject to a critical review at a subsequent meeting. Pregabalin is an FDA-approved medication in the United States and is available as an oral capsule and oral solution and approved for the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and adjunctive therapy for partial onset seizures, fibromyalgia, and neuropathic pain associated with spinal cord injury. Although the mechanism of action of pregabalin is unknown, pregabalin is thought to produce its therapeutic effects on neuropathic pain via binding with high affinity to the alpha 2-delta receptor site (a subunit of voltage gated calcium channels) within the central nervous system. Reports indicate that patients are self- administering higher than recommended doses to achieve euphoria, especially patients who have a history of substance abuse, particularly opioids. While effects of excessively high doses are generally non- lethal, gabapentinoids such as pregabalin are increasingly being identified in postmortem toxicology analyses. Pregabalin is a Schedule V controlled substance in the United States under the CSA. At its 39th meeting in November 2017, the WHO Expert Committee on Drug Dependence (ECDD) pre-reviewed pregabalin and, noting increasing evidence of misuse and abuse in many countries, the ECDD recommended that pregabalin be subject to a future critical review. Cannabis, also known as marijuana, is a plant known by biological names Cannabis sativa or Cannabis indica. It is a complex plant substance containing multiple cannabinoids and other compounds, including the psychoactive chemical THC and other structurally similar compounds. Cannabinoids are defined as having activity at cannabinoid 1 and 2 (CB1 and CB2 respectively) receptors. Agonists of CB1 receptors are widely abused and are known to modulate motor coordination, memory processing, pain, and inflammation, and have anxiolytic effects. The principal cannabinoids in the cannabis plant include THC, cannabidiol (CBD), and cannabinol. These substances are controlled in Schedule I under the CSA. The synthetically derived single pure stereoisomer, (-)-trans-delta-9-THC (also known as dronabinol) is the active ingredient in two approved drug products in the United States, MARINOL (dronabinol) capsules (and generics) and SYNDROS (dronabinol) oral solution. MARINOL is controlled in Schedule III, while SYNDROS is controlled in Schedule II under the CSA. Both MARINOL and SYNDROS are approved to treat anorexia associated with weight loss in patients with acquired immunodeficiency syndrome (AIDS), and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional treatment. CBD is another cannabinoid constituent of the cannabis plant. In the United States, one CBD-containing product, Epidiolex oral solution, has received marketing approval by FDA for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients 2 years of age and older. The CBD in Epidiolex is extracted and purified from the cannabis plant. Currently, CBD is controlled generally as a Schedule I substance under the CSA. However, the recent scheduling action on September 28, 2018, by the DEA for Epidiolex, and any future, similar formulations of CBD that become FDA-approved medications, places these FDA-approved CBD formulations in Schedule V under the CSA.\1\ CBD is not specifically listed in the schedules of the 1961, 1971, or 1988 International Drug Control conventions. --------------------------------------------------------------------------- \1\ https://www.ecfr.gov/cgi-bin/text-idx?SID=f43ff6b6883b0b81774fab03dcea8fa5&mc=true&node=pt21.9.1308&rgn=div5#se21.9.1308_115. --------------------------------------------------------------------------- At the 40th (2018) meeting of the ECDD, the committee critically- reviewed CBD and pre-reviews of cannabis plant and resin; extracts and tinctures of cannabis; THC; and isomers of THC. The 40th ECDD recommended that preparations considered to be pure CBD should not be scheduled within the International Drug Control Conventions, and that cannabis plant and resin; extracts and tinctures of cannabis; THC; and isomers of THC proceed to a Critical Review. IV. Opportunity To Submit Domestic Information As required by paragraph (d)(2)(A) of the CSA, FDA, on behalf of HHS, invites [[Page 50942]] interested persons to submit comments regarding the 16 drug substances. Any comments received will be considered by HHS when it prepares a scientific and medical evaluation for drug substances that is responsive to the WHO Questionnaire for these drug substances. HHS will forward such evaluation of these drug substances to WHO, for WHO's consideration in deciding whether to recommend international control/ decontrol of any of these drug substances. Such control could limit, among other things, the manufacture and distribution (import/export) of these drug substances and could impose certain recordkeeping requirements on them. Although FDA is, through this notice, requesting comments from interested persons, which will be considered by HHS when it prepares an evaluation of these drug substances, HHS will not now make any recommendations to WHO regarding whether any of these drugs should be subjected to international controls. Instead, HHS will defer such consideration until WHO has made official recommendations to the Commission on Narcotic Drugs, which are expected to be made in mid- 2018. Any HHS position regarding international control of these drug substances will be preceded by another Federal Register notice soliciting public comments, as required by paragraph (d)(2)(B) of the CSA. Dated: October 3, 2018. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2018-21954 Filed 10-9-18; 8:45 am] BILLING CODE 4164-01-P
![50938 Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
RPG CROSS-SITE EVALUATION ANNUALIZED BURDEN ESTIMATES—Continued
Number of Average
Total Estimated Total
responses per burden hours
Data collection activity number of total annual
respondent per response
respondents burden hours burden hours
(each year) (in hours)
Partner survey ...................................................................... 135 .33 0.42 56.3 18.8
Enrollment, client and service data
Semi-annual progress reports ............................................. 27 2 16.5 2,673 891
Case enrollment data ........................................................... 81 43 0.25 2,612.3 870.8
Case closure ........................................................................ 81 43 0.017 174.2 58.1
Case closure—prenatal ....................................................... 81 33 0.017 133.7 44.6
Service log entries ............................................................... 162 2,288 0.03 37,065 12,355
Outcome and impact data
Administrative Data:
Obtain access to administrative data ........................... 27 1 42.6 3,450.6 1150.2
Report administrative data ............................................ 27 2 144 23,328 7,776
Standardized instruments:
Review and adopt reporting templates ......................... 27 .33 8 216 72
Data entry for standardized instruments ...................... 27 130 1.25 13,162.5 4,387.5
Review records and submit ................................................. 27 2 25 4,050 1,350
Data entry for comparison study sites (22 grantees) .......... 22 130 1.25 10,725 3,575
Estimated Total Burden Hours ..................................... ........................ ........................ ........................ 97,827 32,609
In compliance with the requirements comments and suggestions within 60 Organization (WHO) regarding the abuse
of Section 3506(c)(2)(A) of the days of this publication. liability and diversion of these drugs.
Paperwork Reduction Act of 1995, the WHO will use this information to
Robert Sargis,
Children’s Bureau within the consider whether to recommend that
Reports Clearance Officer. certain international restrictions be
Administration for Children and
[FR Doc. 2018–22020 Filed 10–9–18; 8:45 am] placed on these drugs. This notice
Families is soliciting public comment
on the specific aspects of the BILLING CODE 4184–29–P requesting comments is required by the
information collection described above. Controlled Substances Act (the CSA).
Copies of the proposed collection of DATES: Submit either electronic or
DEPARTMENT OF HEALTH AND
information can be obtained and HUMAN SERVICES written comments by October 31, 2018.
comments may be forwarded by writing ADDRESSES: You may submit comments
to Administration for Children and Food and Drug Administration as follows. Please note that late,
Families, Office of Administration, untimely filed comments will not be
[Docket No. FDA–2018–N–3685]
Office of Planning, Research and considered. Electronic comments must
Evaluation, 330 C Street SW, International Drug Scheduling; be submitted on or before (enter date),
Washington, DC 20201, Attn: ACF Convention on Psychotropic 2018. The https://www.regulations.gov
Reports Clearance Officer. Email Substances; Single Convention on electronic filing system will accept
address: infocollection@acf.hhs.gov. All Narcotic Drugs; ADB–FUBINACA; comments until 11:59 p.m. Eastern Time
requests should be identified by the title ADB–CHMINACA; Cyclopropyl at the end of October 31, 2018.
of the information collection. Fentanyl; Methoxyacetyl Fentanyl; Comments received by mail/hand
para-Fluoro Butyrfentanyl; Tramadol; delivery/courier (for written/paper
The Department specifically requests submissions) will be considered timely
comments on: (a) Whether the proposed Pregabalin; Cannabis Plant and Resin;
and Eight Additional Substances; if they are postmarked or the delivery
collection of information is necessary service acceptance receipt is on or
for the proper performance of the Request for Comments
before that date.
function of the agency, including AGENCY: Food and Drug Administration,
whether the information shall have Electronic Submissions
HHS.
practical utility; (b) the accuracy of the ACTION: Notice; request for comments. Submit electronic comments in the
agency’s estimate of the burden of the following way:
proposed collection of information; (c) SUMMARY: The Food and Drug • Federal eRulemaking Portal:
the quality, utility, and clarity of the Administration (FDA) is requesting https://www.regulations.gov. Follow the
information to be collected; and (d) interested persons to submit comments instructions for submitting comments.
amozie on DSK3GDR082PROD with NOTICES1
ways to minimize the burden of the concerning abuse potential, actual Comments submitted electronically,
collection of information on abuse, medical usefulness, trafficking, including attachments, to https://
respondents, including through the use and impact of scheduling changes on www.regulations.gov will be posted to
of automated collection techniques or availability for medical use of 16 drug the docket unchanged. Because your
other forms of information technology. substances. These comments will be comment will be made public, you are
Consideration will be given to considered in preparing a response from solely responsible for ensuring that your
the United States to the World Health comment does not include any
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![50940 Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
points designated by Member States for the dimethylpropyl]-1-[(4- ADB–CHMINACA was temporarily
40th ECDD in June 2018 is attached. It is fluorophenyl)methyl]-1H-indazole-3- controlled as a Schedule I substance
requested that if a focal point’s contact carboxamide) is an indazole-based under the CSA.
details including email address are to be CUMYL–4CN–BINACA (chemical
synthetic cannabinoid that is a potent,
added or amended, that Member States
full agonist at CB1 receptors. This name: 1-(4-cyanobutyl)-N-(2-
inform the Secretariat by 17 September 2018.
Any additions or amendments to focal point substance functionally (biologically) phenylpropan-2-yl)-1 H-indazole-3-
designations should be emailed to mimics the effects of the structurally carboxamide) is a clandestinely
ecddsecretariat@who.int. unrelated delta-9-tetrahydrocannabinol produced indazole-3-carboxamide based
If no additions or amendments to focal (THC), a Schedule I substance, and the synthetic cannabinoid that has been
point details are made by this date, the focal main psychoactive chemical constituent sold online and used to mimic the
point from 2018 will be approached by the in the cannabis (marijuana) plant. biological effects of THC, the main
Secretariat for questionnaire completion. Synthetic cannabinoids have been psychoactive chemical constituent in
Where there is a competent National marijuana. Synthetic cannabinoids have
marketed under the guise of ‘‘herbal
Authority under the International Drug
Control Treaties, it is kindly requested that incense,’’ and promoted by drug been marketed under the guise of
the questionnaires be completed in traffickers as legal alternatives to ‘‘herbal incense,’’ and promoted by drug
collaboration with such body. marijuana. ADB–FUBINACA use has traffickers as legal alternatives to
Once the Secretariat has received the been associated with serious adverse marijuana. Hospital, scientific
contact details, focal points will be given events including death in the United publications and law enforcement
further instructions and direct access to an States. There are no commercial or reports show that CUMYL–4CN–
online questionnaire. The questionnaires will approved medical uses for ADB– BINACA is abused for its psychoactive
be analysed by the Secretariat and prepared FUBINACA. On April 10, 2017, ADB– properties. CUMYL–4CN–BINACA has
as a report that will be shared with the been associated with serious adverse
FUBINACA was temporarily controlled
Committee for review.
Member States are also encouraged to as a Schedule I substance under the events in the United States, in addition
provide any additional relevant information CSA. to multiple deaths in Europe. CUMYL–
(unpublished or published) that is available FUB–AMB (other names: MMB– 4CN–BINACA has no commercial or
on these substances to: ecddsecretariat@ FUBINACA; AMB–FUBINACA; medical uses. On July 10, 2018,
who.int. This information will be an chemical name: methyl 2-(1-(4- CUMYL–4CN–BINACA was temporarily
invaluable contribution to the ECDD and all fluorobenzyl)-1H-indazole-3- controlled as a Schedule I substance
submissions will be treated as confidential. carboxamido)-3-methylbutanoate) is an under the CSA.
The WHO takes this opportunity to renew indazole-based synthetic cannabinoid Cyclopropyl fentanyl is a synthetic
to Member States and Associate Members the that is a potent full agonist at CB1 opioid that has a pharmacological
assurance of its highest consideration.
receptors. This substance functionally profile similar to other Schedule I and
GENEVA, 21 August 2018
(biologically) mimics the effects of the II controlled opioid substances such as
Attachment: structurally unrelated THC, a Schedule acetyl fentanyl, fentanyl, and other
41st WHO Expert Committee on Drug I substance, and the main psychoactive related mu-opioid receptor agonist
Dependence chemical constituent in marijuana. substances. This clandestinely produced
Member State Questionnaire Substances Synthetic cannabinoids have been analog of fentanyl is associated with
marketed under the guise of ‘‘herbal adverse events typically associated with
SYNTHETIC CANNABINOIDS opioid use such as respiratory
incense,’’ and promoted by drug
ADB–FUBINACA traffickers as legal alternatives to depression, anxiety, constipation,
FUB–AMB (MMB–FUBINACA, AMB– marijuana. FUB–AMB use has been tiredness, hallucinations, and
FUBINACA) withdrawal. Cyclopropyl fentanyl has
ADB–CHMINACA
associated with serious adverse events
CUMYL–4CN–BINACA including death in the United States. been associated with numerous
There are no commercial or approved fatalities. At least 115 confirmed
FENTANYLS medical uses for FUB–AMB. On overdose deaths involving cyclopropyl
Cyclopropyl Fentanyl November 3, 2017, FUB–AMB was fentanyl abuse have been reported in the
Methoxyacetyl Fentanyl temporarily controlled as a Schedule I United States. Cyclopropyl fentanyl has
Ortho-Fluorofentanyl substance under the CSA. no commercial or currently accepted
Para-Fluoro Butyrfentanyl ADB–CHMINACA (other name: medical uses in the United States. On
Para-Methoxybutyrfentanyl MAB–CHMINACA; chemical name: January 4, 2018, cyclopropyl fentanyl
(METH)CATHINONE N-(1-amino-3,3-dimethyl-1-oxobutan-2- was temporarily placed into Schedule I
N-Ethylnorpentylone yl)-1-(cyclohexylmethyl)-1H-indole-3- of the CSA.
carboxamide) is an indazole-based Methoxyacetyl fentanyl has a
MEDICINES synthetic cannabinoid that is a potent pharmacological profile similar to other
Tramadol full agonist at CB1 receptors. This Schedule I and II opioid substances
Pregabalin substance functionally (biologically) such as acetyl fentanyl, fentanyl, and
FDA has verified the website mimics the effects of the structurally other related mu-opioid receptor agonist
addresses contained in the WHO notice, THC, a Schedule I substance, and the substances. Evidence suggests that the
as of the date this document publishes main psychoactive chemical constituent pattern of abuse of fentanyl analogues,
in the Federal Register, but websites are in marijuana. Synthetic cannabinoids including methoxyacetyl fentanyl is
subject to change over time. Access to have been marketed under the guise of similar to heroin and prescription
view the WHO questionnaire can be ‘‘herbal incense,’’ and promoted by drug opioid analgesics. Law enforcement and
amozie on DSK3GDR082PROD with NOTICES1
found at http://www.who.int/medicines/ traffickers as legal alternatives to public health reports demonstrate that
access/controlled-substances/ecdd_41_ marijuana. ADB–CHMINACA use has methoxyacetyl fentanyl is being illicitly
meeting/en/. been associated with serious adverse distributed and abused. The Drug
events including death in the United Enforcement Administration (DEA) is
III. Substances Under WHO Review States. There are no commercial or aware of at least two overdose deaths
ADB–FUBINACA (chemical name: approved medical uses for ADB– associated with the abuse of
N-[1-(aminocarbonyl)-2,2- CHMINACA. On February 5, 2016, methoxyacetyl fentanyl in the United
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![50942 Federal Register / Vol. 83, No. 196 / Wednesday, October 10, 2018 / Notices
interested persons to submit comments ‘‘Assessing Adhesion with Transdermal • Mail/Hand delivery/Courier (for
regarding the 16 drug substances. Any Delivery Systems and Topical Patches written/paper submissions): Dockets
comments received will be considered for ANDAs,’’ which was announced in Management Staff (HFA–305), Food and
by HHS when it prepares a scientific the Federal Register on June 1, 2016. Drug Administration, 5630 Fishers
and medical evaluation for drug This revised draft guidance provides Lane, Rm. 1061, Rockville, MD 20852.
substances that is responsive to the recommendations for the design and • For written/paper comments
WHO Questionnaire for these drug conduct of studies evaluating the submitted to the Dockets Management
substances. HHS will forward such adhesive performance of a transdermal Staff, FDA will post your comment, as
evaluation of these drug substances to or a topical delivery system (collectively well as any attachments, except for
WHO, for WHO’s consideration in referred to as TDS). Depending on the information submitted, marked and
deciding whether to recommend objectives of a TDS product identified, as confidential, if submitted
international control/decontrol of any of development program, applicants may as detailed in ‘‘Instructions.’’
these drug substances. Such control choose to evaluate TDS adhesion in Instructions: All submissions received
could limit, among other things, the clinical studies performed to evaluate must include the Docket No. FDA 2016–
manufacture and distribution (import/ TDS adhesion only or in clinical studies D–1254 for ‘‘Assessing Adhesion With
export) of these drug substances and performed with a combined purpose Transdermal and Topical Delivery
could impose certain recordkeeping (e.g., for the simultaneous evaluation of Systems for ANDAs.’’ Received
requirements on them. adhesion and bioequivalence (BE) with comments will be placed in the docket
Although FDA is, through this notice, pharmacokinetic (PK) endpoints). The and, except for those submitted as
requesting comments from interested recommendations in this revised draft ‘‘Confidential Submissions,’’ publicly
persons, which will be considered by guidance relate exclusively to studies viewable at https://www.regulations.gov
HHS when it prepares an evaluation of submitted in support of an abbreviated or at the Dockets Management Staff
these drug substances, HHS will not new drug application (ANDA). between 9 a.m. and 4 p.m., Monday
now make any recommendations to through Friday.
DATES: Submit either electronic or • Confidential Submissions—To
WHO regarding whether any of these written comments on the revised draft submit a comment with confidential
drugs should be subjected to guidance by December 10, 2018 to information that you do not wish to be
international controls. Instead, HHS will ensure that the Agency considers your made publicly available, submit your
defer such consideration until WHO has comment on this revised draft guidance comments only as a written/paper
made official recommendations to the before it begins work on the final submission. You should submit two
Commission on Narcotic Drugs, which version of the guidance. copies total. One copy will include the
are expected to be made in mid-2018. ADDRESSES: You may submit comments information you claim to be confidential
Any HHS position regarding on any guidance at any time as follows: with a heading or cover note that states
international control of these drug
Electronic Submissions ‘‘THIS DOCUMENT CONTAINS
substances will be preceded by another
CONFIDENTIAL INFORMATION.’’ The
Federal Register notice soliciting public Submit electronic comments in the Agency will review this copy, including
comments, as required by paragraph following way: the claimed confidential information, in
(d)(2)(B) of the CSA. • Federal eRulemaking Portal: its consideration of comments. The
Dated: October 3, 2018. https://www.regulations.gov. Follow the second copy, which will have the
Leslie Kux, instructions for submitting comments. claimed confidential information
Associate Commissioner for Policy. Comments submitted electronically, redacted/blacked out, will be available
[FR Doc. 2018–21954 Filed 10–9–18; 8:45 am] including attachments, to https:// for public viewing and posted on
BILLING CODE 4164–01–P
www.regulations.gov will be posted to https://www.regulations.gov. Submit
the docket unchanged. Because your both copies to the Dockets Management
comment will be made public, you are Staff. If you do not wish your name and
DEPARTMENT OF HEALTH AND solely responsible for ensuring that your contact information to be made publicly
HUMAN SERVICES comment does not include any available, you can provide this
confidential information that you or a information on the cover sheet and not
Food and Drug Administration third party may not wish to be posted, in the body of your comments and you
such as medical information, your or must identify this information as
[Docket No. FDA 2016–D–1254]
anyone else’s Social Security number, or ‘‘confidential.’’
Assessing Adhesion With Transdermal confidential business information, such Any information marked as
and Topical Delivery Systems for as a manufacturing process. Please note ‘‘confidential’’ will not be disclosed
Abbreviated New Drug Applications; that if you include your name, contact except in accordance with 21 CFR 10.20
Revised Draft Guidance for Industry; information, or other information that and other applicable disclosure law. For
Availability identifies you in the body of your more information about FDA’s posting
comments, that information will be of comments to public dockets, see 80
AGENCY: Food and Drug Administration, posted on https://www.regulations.gov. FR 56469, September 18, 2015, or access
HHS. • If you want to submit a comment the information at: https://www.gpo.gov/
ACTION: Notice of availability. with confidential information that you fdsys/pkg/FR-2015-09-18/pdf/2015-
do not wish to be made available to the 23389.pdf.
SUMMARY: The Food and Drug public, submit the comment as a Docket: For access to the docket to
amozie on DSK3GDR082PROD with NOTICES1
Administration (FDA or Agency) is written/paper submission and in the read background documents or the
announcing the availability of a revised manner detailed (see ‘‘Written/Paper electronic and written/paper comments
draft guidance for industry entitled Submissions’’ and ‘‘Instructions’’). received, go to https://
‘‘Assessing Adhesion With Transdermal www.regulations.gov and insert the
and Topical Delivery Systems for Written/Paper Submissions docket number, found in brackets in the
ANDAs.’’ This revised draft guidance Submit written/paper submissions as heading of this document, into the
supersedes the draft guidance entitled follows: ‘‘Search’’ box and follow the prompts
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Document Created: 2018-10-10 17:39:16
Document Modified: 2018-10-10 17:39:16
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Notices | |
| Action | Notice; request for comments. | |
| Dates | Submit either electronic or written comments by October 31, 2018. | |
| 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, email: [email protected] | |
| FR Citation | 83 FR 50938 |
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