87 FR 148 pgs. 47428-47431 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-BUTINACA; Adinazolam; Bromazolam; Protonitazene (Propoxynitazene); Etazene (Etodesnitazene); Etonitazepyne (N-Pyrrolidino etonitazene); 2-Methyl-AP-237; Alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone; Request for Comments
Type: NOTICEVolume: 87Number: 148Pages: 47428 - 47431
Pages: 47428, 47429, 47430, 47431Docket number: [Docket No. FDA-2022-N-1625]
FR document: [FR Doc. 2022-16572 Filed 8-2-22; 8:45 am]
Agency: Health and Human Services Department
Sub Agency: Food and Drug Administration
Official PDF Version: PDF Version
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2022-N-1625]
International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-BUTINACA; Adinazolam; Bromazolam; Protonitazene (Propoxynitazene); Etazene (Etodesnitazene); Etonitazepyne (N-Pyrrolidino etonitazene); 2-Methyl-AP-237; Alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone; Request for Comments
AGENCY:
Food and Drug Administration, HHS.
ACTION:
Notice; request for comments.
SUMMARY:
The Food and Drug Administration (FDA or Agency) is inviting interested persons to submit comments concerning abuse potential, actual abuse, medical usefulness, trafficking, and impact of scheduling changes on availability for medical use of 10 drug substances. These comments will be considered in preparing a response from the United States to the World Health Organization (WHO) regarding the abuse liability and diversion of these drugs. WHO will use this information to consider whether to recommend that certain international restrictions be placed on these drug substances. This notice requesting comments is required by the Controlled Substances Act (CSA).
DATES:
Either electronic or written comments must be submitted by August 24, 2022.
ADDRESSES:
You may submit comments as follows. Please note that late, untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 11:59 p.m. Eastern Time at the end of August 24, 2022. Comments received by mail/hand delivery/courier (for written/paper submissions) will be considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
• Federal eRulemaking Portal: https://www.regulations.gov. Follow the instructions for submitting comments. Comments submitted electronically, including attachments, to https://www.regulations.gov will be posted to the docket unchanged. Because your comment will be made public, you are solely responsible for ensuring that your comment does not include any confidential information that you or a third party may not wish to be posted, such as medical information, your or anyone else's Social Security number, or confidential business information, such as a manufacturing process. Please note that if you include your name, contact information, or other information that identifies you in the body of your comments, that information will be posted on https://www.regulations.gov.
• If you want to submit a comment with confidential information that you do not wish to be made available to the public, submit the comment as a written/paper submission and in the manner detailed (see "Written/Paper Submissions" and "Instructions").
Written/Paper Submissions
Submit written/paper submissions as follows:
• Mail/Hand Delivery/Courier (for written/paper submissions): Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments submitted to the Dockets Management Staff, FDA will post your comment, as well as any attachments, except for information submitted, marked and identified, as confidential, if submitted as detailed in "Instructions."
Instructions: All submissions received must include the Docket No. FDA-2022-N-1625 for "International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on Narcotic Drugs; ADB-BUTINACA; Adinazolam; Bromazolam; Protonitazene (propoxynitazene); Etazene (etodesnitazene); Etonitazepyne (N-pyrrolidino etonitazene); 2-Methyl-AP-237; alpha-PiHP; 3-Methylmethcathinone (3-MMC); Zopiclone; Request for Comments" Received comments, those filed in a timely manner (see ADDRESSES ), will be placed in the docket and, except for those submitted as "Confidential Submissions," publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
[top] • 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
Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the "Search" box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT:
Edward (Greg) Hawkins, 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, 301-796-0727, edward.hawkins@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
The United States is a party to the 1971 Convention on Psychotropic Substances (Psychotropic Convention). Article 2 of the Psychotropic Convention provides that if a party to the convention or WHO has information about a substance, which in its opinion may require international control or change in such control, it shall so notify the Secretary-General of the United Nations (U.N. Secretary-General) and provide the U.N. Secretary-General with information in support of its opinion.
Section 201(d)(2)(A) of the CSA (21 U.S.C. 811(d)(2)(A)) (Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970) provides that when WHO notifies the United States under Article 2 of the Psychotropic Convention that it has information that may justify adding a drug or other substances to one of the schedules of the Psychotropic Convention, transferring a drug or substance from one schedule to another, or deleting it from the schedules, the Secretary of State must transmit the notice to the Secretary of Health and Human Services (Secretary of HHS). The Secretary of HHS must then publish the notice in the Federal Register and provide opportunity for interested persons to submit comments that will be considered by HHS in its preparation of the scientific and medical evaluations of the drug or substance.
II. WHO Notification
The Secretary of HHS received the following notice from WHO (nonrelevant text removed):
Ref.: C.L.27.2022
The World Health Organization (WHO) presents its compliments to Member States and Associate Members and has the pleasure of announcing that the 45th Expert Committee on Drug Dependence (ECDD) will meet from 10 to 14 October 2022, in Geneva, Switzerland. Given that WHO Expert Committee meetings are of a closed nature, this letter serves to notify Member States of the substances under review at the 45th ECDD, which are in the Annex I, attached for reference.
WHO is mandated by the 1961 and 1971 International Drug Control Conventions to make recommendations to the UN Secretary-General on the need for and level of international control of psychoactive substances based on the advice of its independent scientific advisory body, the ECDD. To assess whether or not a psychoactive substance should be placed under international control, the ECDD convenes annually to review the potential of this substance to cause dependence, abuse and harm to health, as well as any therapeutic applications. In order to perform this review and make evidence-based decisions, the ECDD conducts medical, scientific, and public health evaluations of the selected psychoactive substances using the best available information.
Although the meetings are of a closed nature, Member States are invited to contribute to the ECDD review process by joining the 45th ECDD Open Session on 10 October 2022. The Information Session will be held virtually and allow interested parties to learn about present and future activities of the ECDD Secretariat, and to present information concerning substances under review to the Expert Committee for consideration in its deliberations. Registration information will be made available on the ECDD website in due course: https://www.who.int/medicines/access/controlled-substances/en/.
As in the past and in line with the publication " Guidance on the WHO review of psychoactive substances for international control" (EB126/2010/REC1, Annex 6)? 1 , Member States can also contribute to the ECDD review process by providing accurate information concerning the substances under review in advance of the meeting. For this purpose, a questionnaire will be sent to Member States to gather country information on the legitimate use, harmful use, status of national control and potential impact of international control for each substance under evaluation.
In addition to the questionnaire, Member States are also encouraged to provide any additional relevant information (unpublished or published) on substances to be reviewed by the 45th ECDD.
The World Health Organization takes this opportunity to renew to Member States and Associate Members the assurance of its highest consideration.
GENEVA, 10 June 2021
1 https://apps.who.int/gb/ebwha/pdf_files/EB126-REC1/B126_REC1-en.pdf#page=58.
Annex I
45th Expert Committee on Drug Dependence (ECDD) Substances For Review 10-14 October 2022
Critical reviews: The substances listed below have never been formally reviewed by WHO and are not currently under international control. Information was brought to WHO's attention that these substances are clandestinely manufactured, of especially serious risk to public health and society, and of no recognized therapeutic use by any Party. The Expert Committee will consider whether information presented during a critical review may justify the scheduling or a change in the scheduling of the substance in the 1961 or 1971 Conventions.
Synthetic cannabinoid receptor agonists
1. ADB-BUTINACA
Benzodiazepines
2. Adinazolam
3. Bromazolam
Novel synthetic opioids
4. Protonitazene (propoxynitazene)
5. Etazene (etodesnitazene)
6. Etonitazepyne (N-pyrrolidino etonitazene)
7. 2-Methyl-AP-237
Cathinones/stimulants
8. alpha-PiHP
9. 3-Methylmethcathinone (3-MMC)
Pre-reviews: The substances listed below have been proposed for a pre-review. The purpose of a pre-review is to determine whether current information justifies an Expert Committee critical review. A pre-review is a preliminary analysis and findings at this stage should not determine whether the control status of a substance should be changed.
Medicines
1. Zopiclone
FDA has verified the website addresses contained in the WHO notice, as of the date this document publishes in the Federal Register , but websites are subject to change over time. Access to view the WHO questionnaire can be found at https://www.who.int/publications/m/item/45th-ecdd-questionnaire.
III. Substances Under WHO Review
[top] ADB-BUTINACA is a synthetic cannabinoid that has been sold online and is used to mimic the biological effects of tetrahydrocannabinol, the
Footnotes:
1 ?NFLIS-Drug is a national forensic laboratory reporting system that systematically collects drug identification results from drug cases submitted to and analyzed by Federal, State and local forensic laboratories in the United States. NFLIS-Drug data were queried on June 29, 2022.
Adinazolam is a designer benzodiazepine ( i.e., a structural or functional analog of other drugs in the benzodiazepine class) and is expected to have central nervous system (CNS) depressant-like effects similar to that of other known benzodiazepines. Adinazolam was first reported to NFLIS-Drug in 2019, and there were 87 reports in 2021. Adinazolam has appeared in toxicology reports in the United States. Adinazolam is not currently controlled in the United States.
Bromazolam is a designer benzodiazepine and is expected to have CNS depressant-like effects similar to that of other known benzodiazepines. Bromazolam was first reported to NFLIS-Drug in 2016, and there were 743 reports in 2021. Bromazolam has appeared in at least two overdose death reports in the United States and adverse effects associated with the use of bromazolam have been reported. Bromazolam is not currently controlled in the United States.
Protonitazene (propoxynitazene), etazene (etodesnitazene), and etonitazepyne ( N -pyrrolidino etonitazene) are novel synthetic opioid receptor agonists of the benzimidazole structural class. Law enforcement data indicates that these substances have appeared on the U.S. illicit markets as evidenced by their identification in forensic drug seizures and biological samples. Etazene was first reported to NFLIS-Drug in 2020, and there were 41 reports in 2021. Protonitazene and etonitazepyne were both first reported to NFLIS-Drug in 2021 with 20 and 129 reports in that year, respectively. The abuse of these benzimidazole opioids are similar to other synthetic opioids. Protonitazene, etazene, and etonitazepyne have been identified in toxicology and several post-mortem cases. The public health risks attendant to the abuse of mu-opioid receptor agonists are well established. These risks included large numbers of drug treatment admissions, emergency department visits, and fatal overdoses. On April 12, 2022, the U.S. Drug Enforcement Administration issued a temporary order to control these substances as schedule I substances under the CSA.
2-Methyl-AP-237 is a novel synthetic mu-opioid receptor agonist. It was first reported to NFLIS-Drug in 2019, and there were 45 reports in 2021. Abuse of 2-methyl-AP-237 is similar to other synthetic opioids, and has been associated with adverse health effects, including death. In the United States, there are at least 10 confirmed reports of fatal poisonings and several reports of emergency room visits, and non-fatal poisonings associated with 2-methyl-AP-237. 2-Methyl-AP-237 is not currently controlled in the United States. There are no commercial or approved medical uses of 2-methyl-AP-237.
Alpha-PiHP is a synthetic stimulant designer drug structurally similar to other schedule I synthetic cathinones. Alpha-PiHP is a monoamine transporter (dopamine transporter and norepinephrine transporter) uptake inhibitor. Adverse effects associated with synthetic cathinones abuse include agitation, hypertension, tachycardia, and death. Alpha-PiHP was first reported to NFLIS-Drug in 2017, and there were 332 reports in 2021. Alpha-PiHP has been confirmed to have played a role in fatal and non-fatal overdose events in the United States. Alpha-PiHP has no approved medical uses in the United States. As a positional isomer of alpha-PHP, alpha-PiHP is controlled in schedule I of the CSA.
3-Methylmethcathinone (3-MMC) is a designer drug of the phenethylamine class, which is structurally and pharmacologically similar to amphetamine, 3,4-methylenedioxymethamphetamine, cathinone and other related substances. 3-MMC is a monoamine transporter (dopamine transporter, serotonin transporter, and norepinephrine transporter) uptake inhibitor. Like other schedule I synthetic cathinones, 3-MMC is abused for its psychoactive effects. Adverse effects associated with synthetic cathinones abuse include agitation, hypertension, tachycardia, and death. 3-MMC was first reported to NFLIS-Drug in 2012, and there were three reports in 2021. 3-MMC has no approved medical uses in the United States. As a positional isomer of mephedrone, 3-MMC is controlled in schedule I of the CSA.
Zopiclone is a nervous system depressant drug used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. Zopiclone is approved for medical use in the United States as (S)-zopiclone (or eszopiclone), the active (S) isomer of zopiclone. Zopiclone has abuse potential and may be misused due to its ability to produce euphoric effects at high doses. Amnesia and hallucinations have been reported with higher doses. Zopiclone is controlled in schedule IV of the CSA.
IV. Opportunity To Submit Domestic Information
As required by section 201(d)(2)(A) of the CSA, FDA, on behalf of HHS, invites interested persons to submit comments regarding the 10 drug substances. Any comments received will be considered by HHS when it prepares a scientific and medical evaluation for drug substances that is responsive to the WHO Questionnaire for these drug substances. HHS will forward such evaluation of these drug substances to WHO, for WHO's consideration in deciding whether to recommend international control/decontrol of any of these drug substances. Such control could limit, among other things, the manufacture and distribution (import/export) of these drug substances and could impose certain recordkeeping requirements on them.
Although FDA is, through this notice, requesting comments from interested persons, which will be considered by HHS when it prepares an evaluation of these drug substances, HHS will not now make any recommendations to WHO regarding whether any of these drugs should be subjected to international controls. Instead, HHS will defer such consideration until WHO has made official recommendations to the Commission on Narcotic Drugs, which are expected to be made in late 2022. Any HHS position regarding international control of these drug substances will be preceded by another Federal Register notice soliciting public comments, as required by section 201(d)(2)(B) of the CSA.
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Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-16572 Filed 8-2-22; 8:45 am]
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