Voglio sapere a riguardo di…

jbell on DSKJLSW7X2PROD with PROPOSALS

Federal Register / Vol. 86, No. 51 / Thursday, March 18, 2021 / Proposed Rules There are no FDA-approved marketing applications for a drug product containing fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl for any therapeutic indication in the United States.
Moreover, there are no clinical studies or petitions which have claimed an accepted medical use in the United States for these four substances.
4. Its History and Current Pattern of Abuse: Fentanyl carbamate, orthofluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl, like other substances structurally related to fentanyl, are disguised as a legal alternative to fentanyl. Between 2017 and 2020, law enforcement officials in the United States encountered these four substances.
5. The Scope, Duration, and Significance of Abuse: Fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl, similar to other substances structurally related to fentanyl, are often used as recreational drugs. The recreational use of these four substances and other fentanyl-related substances continues to be of significant concern as the United States currently is in the midst of an opioid epidemic.
These substances are distributed to users, often with unpredictable outcomes. Because users of these fentanyl-related substances and their associated drug products are likely to obtain these substances through unregulated sources, the identity, purity, and quantity are uncertain and inconsistent, thus posing significant adverse health risks to abusers.
Evidence that these four substances are being abused and trafficked is confirmed by law enforcement encounters. NFLIS contained 187
reports of fentanyl carbamate, orthofluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl from Federal, State, and local forensic laboratories between 2017
and 2020.
6. What, if Any, Risk There Is to the Public Health: The increase in opioid overdose deaths in the United States has been exacerbated by the availability of potent synthetic opioids such as fentanyl and structurally related substances in the illicit drug market.
These substances have a history of being trafficked as replacements for heroin and other synthetic opioids.
Increasingly, law enforcement has encountered fentanyl and substances structurally related to fentanyl in counterfeit prescription opioids, heroin, and other street drugs such as cocaine,
VerDate Sep<11>2014

16:14 Mar 17, 2021

Jkt 253001

methamphetamine, and synthetic cannabinoids. Fentanyl is a potent synthetic opioid that is primarily prescribed for acute and chronic pain and is approximately 100 times more potent than morphine. As such, fentanyl has a high risk of abuse, dependence, and overdose that can lead to death.
Because fentanyl-related substances, as defined in the February 6, 2018, temporary order, have similar chemical structure to fentanyl, these substances are expected to have similar biological effects. In in vitro and in vivo studies, fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl produced pharmacological effects similar to fentanyl. Thus, these four substances pose the same qualitative public health risks as heroin, fentanyl, and other mu-opioid receptor agonists.
According to a CDC report, from 2013
to 2019, deaths involving synthetic opioids other than methadone increased by 1,040 percent from 3,105 to 36,359.
The increase in the number of opioidrelated deaths was primarily driven by illicitly manufactured fentanyl.7
According to CDC 2019 data, there were 70,630 drug overdose fatalities; of those, 49,860 approximately 71 percent involved an opioid. The use of some fentanyl-related substances has been associated with adverse health outcomes, including death.
7. Its Psychic or Physiological Dependence Liability: There are no preclinical and clinical studies that have evaluated the dependence potential of fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl. These four substances are muopioid receptor agonists, and discontinuation of the use of mu-opioid receptor agonists such as fentanyl and morphine is known to cause withdrawal indicative of physical dependence.
Opioid withdrawal includes nausea and vomiting, depression, agitation, anxiety, craving, sweats, hypertension, diarrhea, and fever.
8. Whether the Substance Is an Immediate Precursor of a Substance Already Controlled Under the CSA:
Fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl 7 If evidence of prescription or illicit use was not available, fentanyl was categorized as illicitlymanufactured fentanyl IMF because the vast majority of fentanyl overdose deaths involve IMF.
Gladden RM, ODonnell J, Mattson CL, Seth P.
Changes in Opioid-Involved Overdose Deaths by Opioid Type and Presence of Benzodiazepines, Cocaine, and Methamphetamine25 States, July December 2017 to JanuaryJune 2018. MMWR Morb Mortal Wkly Rep. 30; 6834:737744.

PO 00000

Frm 00017

Fmt 4702

Sfmt 4702

14711

fentanyl are not considered immediate precursors of any controlled substance of the CSA as defined by 21 U.S.C.
80223.
Conclusion: After considering the scientific and medical evaluation conducted by HHS, HHSs scheduling recommendation, and DEAs own eightfactor analysis, DEA finds that the facts and all relevant data constitute substantial evidence of the potential for abuse of fentanyl carbamate, orthofluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl. As such, DEA hereby proposes to permanently schedule fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl in schedule I of the CSA.
Proposed Determination of Appropriate Schedule The CSA establishes five schedules of controlled substances known as schedules I, II, III, IV, and V. The CSA
also outlines the findings required to place a drug or other substance in any particular schedule. 21 U.S.C. 812b.
After consideration of the analysis and recommendation of the Acting Assistant Secretary for Health of HHS and review of all other available data, the Acting Administrator of DEA, pursuant to 21
U.S.C. 811a and 21 U.S.C. 812b1, finds that:
1 Fentanyl carbamate, orthofluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl have a high potential for abuse.
According to HHS, fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl, similar to fentanyl, are mu-opioid receptor agonists. These substances have analgesic effects, and these effects are mediated by mu-opioid receptor agonism. HHS states that substances that produce mu-opioid receptor agonist effects in the central nervous system e.g., morphine and fentanyl are considered as having a high potential for abuse. Data obtained from drug discrimination studies indicate that fentanyl carbamate, ortho-fluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl fully substituted for the discriminative stimulus effects of morphine.
2 Fentanyl carbamate, orthofluoroacryl fentanyl, ortho-fluoro isobutyryl fentanyl, and para-fluoro furanyl fentanyl have no currently accepted medical use in treatment in the United States.

E:FRFM18MRP1.SGM

18MRP1