Schedules of Controlled Substances: Placement of 10 Specific Fentanyl-Related Substances in Schedule I, 12296-12305 [2021-04214]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 86, Number 40 (Wednesday, March 3, 2021)]
[Proposed Rules]
[Pages 12296-12305]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-04214]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-476]


Schedules of Controlled Substances: Placement of 10 Specific 
Fentanyl-Related Substances in Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration proposes placing N-(1-(2-
fluorophenethyl)piperidin-4-yl)-N-(2-fluorophenyl)propionamide (2'-
fluoro ortho-fluorofentanyl), N-(1-(4-methylphenethyl)piperidin-4-yl)-
N-phenylacetamide (4'-methyl acetyl fentanyl), N-(1-phenethylpiperidin-
4-yl)-N,3-diphenylpropanamide ([beta]'-phenyl fentanyl; 3-
phenylpropanoyl fentanyl), N-phenyl-N-(1-(2-phenylpropyl)piperidin-4-
yl)propionamide ([beta]-methyl fentanyl), N-(2-fluorophenyl)-N-(1-
phenethylpiperidin-4-yl)butyramide (ortho-fluorobutyryl fentanyl; 2-
fluorobutyryl fentanyl), N-(2-methylphenyl)-N-(1-phenethylpiperidin-4-
yl)acetamide (ortho-methyl acetylfentanyl; 2-methyl acetylfentanyl), 2-
methoxy-N-(2-methylphenyl)-N-(1-phenethylpiperidin-4-yl)acetamide 
(ortho-methyl methoxyacetylfentanyl), N-(4-methylphenyl)-N-(1-
phenethylpiperidin-4-yl)propionamide (para-methylfentanyl; 4-
methylfentanyl), N-(1-phenethylpiperidin-4-yl)-N-phenylbenzamide 
(phenyl fentanyl; benzoyl fentanyl), N-(1-phenethylpiperidin-4-yl)-N-
phenylthiophene-2-carboxamide (thiofuranyl fentanyl), including their 
isomers, esters, ethers, salts, and salts of isomers, esters, and 
ethers, in schedule I of the Controlled Substances Act. These ten 
specific substances fall within the definition of fentanyl-related 
substances set forth in the February 6, 2018, temporary scheduling 
order. Through the Temporary Reauthorization and Study of the Emergency 
Scheduling of Fentanyl Analogues Act, which became law on February 6, 
2020, Congress extended the temporary control of fentanyl-related 
substances until May 6, 2021. If finalized, this action would make 
permanent the existing regulatory controls and administrative, civil, 
and criminal sanctions applicable to schedule I controlled substances 
on persons who handle (manufacture, distribute, reverse

[[Page 12297]]

distribute, import, export, engage in research, conduct instructional 
activities or chemical analysis, or possess), or propose to handle 2'-
fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]'-phenyl 
fentanyl, [beta]-methyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl.

DATES: Comments must be submitted electronically or postmarked on or 
before April 2, 2021.
    Requests for hearing and waivers of an opportunity for a hearing or 
to participate in a hearing must be received on or before April 2, 
2021.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-476'' on all electronic and written correspondence, 
including any attachments.
     Electronic comments: Interested persons may file written 
comments on this proposal in accordance with 21 CFR 1308.43(g). The 
Drug Enforcement Administration (DEA) encourages that all comments be 
submitted electronically through the Federal eRulemaking Portal which 
provides the ability to type short comments directly into the comment 
field on the web page or to attach a file for lengthier comments. 
Please go to https://www.regulations.gov and follow the online 
instructions at that site for submitting comments. Upon completion of 
your submission you will receive a Comment Tracking Number for your 
comment. Please be aware that submitted comments are not 
instantaneously available for public view on Regulations.gov. If you 
have received a Comment Tracking Number, your comment has been 
successfully submitted and there is no need to resubmit the same 
comment. Commenters should be aware that the electronic Federal Docket 
Management System will not accept comments after 11:59 p.m. Easter Time 
on the last day of the comment period.
     Paper comments: Paper comments that duplicate the 
electronic submission are not necessary. Should you wish to mail a 
paper comment in lieu of an electronic comment, it should be sent via 
regular or express mail to: Drug Enforcement Administration, Attn: DEA 
Federal Register Representative/DPW, 8701 Morrissette Drive, 
Springfield, Virginia 22152.
     Hearing requests: Interested persons may file a request 
for hearing or waiver of hearing pursuant to 21 CFR 1308.44 and in 
accordance with 21 CFR 1316.45 and/or 1316.47, as applicable. All 
requests for hearing and waivers of participation must be sent to: Drug 
Enforcement Administration, Attn: Administrator, 8701 Morrissette 
Drive, Springfield, Virginia 22152. All requests for hearing and 
waivers of participation should also be sent to: (1) Drug Enforcement 
Administration, Attn: Hearing Clerk/OALJ, 8701 Morrissette Drive, 
Springfield, Virginia 22152; and (2) Drug Enforcement Administration, 
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive, 
Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug and Chemical 
Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Mailing Address: 8701 Morrissette Drive, Springfield, 
Virginia 22152; Telephone: (571) 362-3249

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

    Please note that all comments received in response to this docket 
are considered part of the public record. They will, unless reasonable 
cause is given, be made available by the Drug Enforcement 
Administration (DEA) for public inspection online at https://www.regulations.gov. Such information includes personal identifying 
information (such as your name, address, etc.) voluntarily submitted by 
the commenter. The Freedom of Information Act applies to all comments 
received. If you want to submit personal identifying information (such 
as your name, address, etc.) as part of your comment, but do not want 
it to be made publicly available, you must include the phrase 
``PERSONAL IDENTIFYING INFORMATION'' in the first paragraph of your 
comment. You must also place all of the personal identifying 
information you do not want made publicly available in the first 
paragraph of your comment and identify what information you want 
redacted.
    If you want to submit confidential business information as part of 
your comment, but do not want it to be made publicly available, you 
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the 
first paragraph of your comment. You must also prominently identify 
confidential business information to be redacted within the comment.
    Comments containing personal identifying information and 
confidential business information identified as directed above will be 
made publicly available in redacted form. If a comment has so much 
confidential business information or personal identifying information 
that it cannot be effectively redacted, all or part of that comment may 
not be made publicly available. Comments posted to https://www.regulations.gov may include any personal identifying information 
(such as name, address, and phone number) included in the text of your 
electronic submission that is not identified as directed above as 
confidential.
    An electronic copy of this document and supplemental information to 
this proposed rule are available at https://www.regulations.gov for easy 
reference.

Request for Hearing or Waiver of Participation in a Hearing

    Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking 
``on the record after opportunity for a hearing.'' Such proceedings are 
conducted pursuant to the provisions of the Administrative Procedure 
Act, 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316, 
subpart D. Interested persons may file requests for hearing or notices 
of intent to participate in a hearing in conformity with the 
requirements of 21 CFR 1308.44(a) or (b), and include a statement of 
interest in the proceeding and the objections or issues, if any, 
concerning which the person desires to be heard. Any interested person 
may file a waiver of an opportunity for a hearing or to participate in 
a hearing together with a written statement regarding the interested 
person's position on the matters of fact and law involved in any 
hearing as set forth in 21 CFR 1308.44(c).
    All requests for a hearing and waivers of participation must be 
sent to DEA using the address information provided above.

Legal Authority

    The Controlled Substances Act (CSA) provides that proceedings for 
the issuance, amendment, or repeal of the scheduling of any drug or 
other substance may be initiated by the Attorney General (delegated to 
the Administrator of DEA pursuant to 28 CFR 0.100) on his own motion. 
21 U.S.C. 811(a). This proposed action is supported by a recommendation 
from the Assistant Secretary for Health of U.S. Department of Health 
and Human Services (HHS) (Assistant Secretary) and an evaluation of all 
other relevant data by DEA. If finalized, this action would make 
permanent the existing temporary regulatory controls and 
administrative, civil, and criminal sanctions of schedule I controlled 
substances on any person who handles or proposes to handle 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]'-phenyl 
fentanyl, [beta]-methyl fentanyl, ortho-fluorobutyryl

[[Page 12298]]

fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl.

Background

    On February 6, 2018, pursuant to 21 U.S.C. 811(h)(1), the then-
Acting Administrator of DEA published an order in the Federal Register 
(83 FR 5188) temporarily placing fentanyl-related substances, as 
defined in that order, in schedule I of the CSA upon finding that these 
substances pose an imminent hazard to the public safety. The 10 
substances named in this proposed rule (2'-fluoro ortho-fluorofentanyl, 
4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
ortho-methyl methoxyacetyl fentanyl, para-methylfentanyl, phenyl 
fentanyl, and thiofuranyl fentanyl) meet the existing definition of 
fentanyl-related substances. On April 19, 2019, DEA specifically 
identified four of these 10 substances (2'-fluoro ortho-fluorofentanyl, 
[beta]'-phenyl fentanyl, ortho-methyl acetylfentanyl, and thiofuranyl 
fentanyl) as meeting the definition of fentanyl-related substances. 84 
FR 16397. Although DEA did not issue a Federal Register publication to 
identify the other six substances, the February 6, 2018, temporary 
scheduling order emphasized that, even still, a substance is controlled 
by virtue of the order if it falls within the definition of fentanyl-
related substances. 83 FR 5188, 5189. As discussed below in Factor 3, 
all 10 substances meet the definition as they are not otherwise 
controlled in any other schedule (i.e., not included under another 
Administration Controlled Substance Code Number) and are structurally 
related to fentanyl by one or more of the five modifications listed 
under the definition.
    That temporary order was effective upon the date of publication. 
Pursuant to 21 U.S.C. 811(h)(2), the temporary control of fentanyl-
related substances, a class of substances as defined in the order, as 
well as the 10 specific substances already covered by that order, was 
set to expire on February 6, 2020. However, as explained in DEA's April 
10, 2020, correcting amendment (85 FR 20155), Congress overrode and 
extended that expiration date until May 6, 2021, by enacting on 
February 6, 2020 the Temporary Reauthorization and Study of the 
Emergency Scheduling of Fentanyl Analogues Act (Pub. L. 116-114, sec. 
2, 134 Stat. 103). By operation of law, the temporary control of 
fentanyl-related substances, which includes these 10 covered 
substances, will remain in effect until May 6, 2021, unless DEA 
permanently places them in schedule I prior to May 6, 2021. As 
discussed in the above Legal Authority section, proceedings under 21 
U.S.C. 811(a) may be initiated by the Administrator of DEA on his own 
motion.
    The Acting Administrator, on his own motion, is initiating 
proceedings to permanently schedule the following 10 fentanyl-related 
substances: 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]'-phenyl fentanyl, [beta]-methyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl. DEA gathered the available information regarding the 
pharmacology, chemistry, trafficking, actual abuse, pattern of abuse, 
and the relative potential for abuse for these 10 fentanyl-related 
substances, as well as for six other fentanyl-related substances 
(benzodioxole fentanyl, crotonyl fentanyl, fentanyl carbamate, ortho-
fluoro isobutyryl fentanyl, ortho-fluoroacryl fentanyl, and para-fluoro 
furanyl fentanyl). On April 3, and October 2, 2019, the then-Acting 
Administrator submitted this data to the Assistant Secretary, and 
requested that HHS provide DEA with a scientific and medical evaluation 
and a scheduling recommendation for the 16 fentanyl-related substances 
named above, in accordance with 21 U.S.C. 811(b) and (c).
    Upon evaluating the scientific and medical evidence, on July 2, 
2020, the Assistant Secretary submitted to the Acting Administrator, 
HHS's scientific and medical evaluation and scheduling recommendation 
for 11 of the 16 fentanyl-related substances, including the 10 named 
substances in this proposed rule as well as crotonyl fentanyl.\1\ Upon 
receipt of the scientific and medical evaluation and scheduling 
recommendation from HHS, DEA reviewed these documents and all other 
relevant data, and conducted its own eight-factor analysis of the abuse 
potential of the 10 substances in accordance with 21 U.S.C. 811(c). On 
October 2, 2020, DEA issued a final order (85 FR 62215) for crotonyl 
fentanyl to remain as a schedule I substance under the CSA in order to 
meet the United States' obligations under the 1961 Single Convention on 
Narcotic Drugs (Single Convention), March 30, 1961, 18 U.S.T. 1407, 570 
U.N.T.S. 151, as amended.\2\ As such, crotonyl fentanyl will not be 
discussed further in this scheduling action.
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    \1\ HHS' scientific and medical evaluation for the other five 
fentanyl-related substances (benzodioxole fentanyl, fentanyl 
carbamate, ortho-fluoro isobutyryl fentanyl, ortho-fluoroacryl 
fentanyl, and para-fluoro furanyl fentanyl) is ongoing. DEA will not 
further discuss these five substances in this proposed rule.
    \2\ In November 2019, the Director-General of the World Health 
Organization recommended to the Secretary-General that crotonyl 
fentanyl be placed in Schedule I of the Single Convention. On May 7, 
2020, the Secretary-General advised the Secretary of State of the 
United States, by letter, that during its 63rd session in March 
2020, the Commission on Narcotic Drugs voted to place crotonyl 
fentanyl in Schedule I of the Single Convention (CND Mar/63/2).
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Proposed Determination To Permanently Schedule 2'-Fluoro ortho-
Fluorofentanyl, 4'-Methyl Acetyl Fentanyl, [bta]-Methyl Fentanyl, 
[bta]'-Phenyl Fentanyl, ortho-Fluorobutyryl fentanyl, ortho-Methyl 
Acetylfentanyl, ortho-Methyl Methoxyacetyl Fentanyl, para-
Methylfentanyl, Phenyl Fentanyl, and Thiofuranyl Fentanyl

    As discussed in the background section, the Acting Administrator is 
initiating proceedings to permanently add 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl to schedule 
I. DEA has reviewed the scientific and medical evaluation and 
scheduling recommendation from HHS, and all other relevant data, and 
conducted its own eight-factor analysis of the abuse potential of these 
10 substances. Included below is a brief summary of each factor as 
analyzed by HHS and DEA, and as considered by DEA in its proposed 
scheduling action. Please note that both the DEA and HHS 8-Factor 
analyses and the Assistant Secretary's July 2, 2020, letter are 
available in their entirety under the tab ``Supporting Documents'' of 
the public docket for this action at https://www.regulations.gov under 
Docket Number ``DEA-476.''
    1. The Drug's Actual or Relative Potential for Abuse: The term 
``abuse'' is not defined in the CSA. However, the legislative history 
of the CSA suggests that DEA consider the following criteria when 
determining whether a particular drug or substance has a potential for 
abuse:\3\
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    \3\ Comprehensive Drug Abuse Prevention and Control Act of 1970, 
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); reprinted in 1970 
U.S.C.C.A.N. 4566, 4603.

    (a) There is evidence that individuals are taking the drug or 
drugs containing such a substance in amounts sufficient to create a

[[Page 12299]]

hazard to their health or to the safety of other individuals or to 
the community; or
    (b) There is significant diversion of the drug or drugs 
containing such a substance from legitimate drug channels; or
    (c) Individuals are taking the drug or drugs containing such a 
substance on their own initiative rather than on the basis of 
medical advice from a practitioner licensed by law to administer 
such drugs in the course of his professional practice; or
    (d) The drug or drugs containing such a substance are new drugs 
so related in their action to a drug or drugs already listed as 
having a potential for abuse to make it likely that the drug will 
have the same potentiality for abuse as such drugs, thus making it 
reasonable to assume that there may be significant diversions from 
legitimate channels, significant use contrary to or without medical 
advice, or that it has a substantial capability of creating hazards 
to the health of the user or to the safety of the community.

    The abuse potential of 2'-fluoro ortho-fluorofentanyl, 4'-methyl 
acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, 
ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl is associated with their pharmacological 
similarity to other schedule I and II mu-opioid receptor agonist 
substances, which have a high potential for abuse. Similar to morphine 
and fentanyl, these 10 substances have been shown to bind and act as 
mu-opioid receptor agonists.
    These 10 substances have no approved medical use in the United 
States and have been encountered on the illicit drug market. The use of 
some fentanyl-related substances has been associated with adverse 
health outcomes, including death. The appearance of several substances 
structurally related to fentanyl in the illicit drug market has 
resulted in a significant increase in drug overdose deaths in the 
United States. According to the Centers for Disease Control and 
Prevention (CDC) overdose death data for 2018, there continues to be an 
increase in the number of deaths related to synthetic opioids. Opioids 
were involved in about 70 percent of all drug-involved overdose deaths 
in 2018. Further, CDC reports demonstrate that the increase in 
synthetic opioid overdose deaths are largely attributed to an increase 
in the supply of illicitly manufactured fentanyl and substances 
structurally related to fentanyl. Because 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl are not Food 
and Drug Administration (FDA)-approved drug products, a practitioner 
may not legally prescribe them, and these substances cannot be 
dispensed to an individual. Therefore, the use of 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl is without 
medical advice, and accordingly leads to the conclusion that these 10 
substances are abused for their opioidergic properties.
    There are no legitimate drug channels for 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl as marketed 
FDA-approved drug products, but these substances are available for 
purchase from legitimate chemical companies for research purposes. 
However, despite the limited legitimate research use of these 10 
substances, reports from public health and law enforcement data 
indicate that all 10 substances are being abused and taken in amounts 
sufficient to create a hazard to an individual's health. Data from 
forensic databases can be used as an indicator of illicit activity with 
drugs and abuse \4\ within the United States. According to the National 
Forensic Laboratory Information System (NFLIS),\5\ which collects and 
analyzes drug exhibits submitted to Federal, State, and local forensic 
laboratories, there were 235 total reports of seven of the 10 
substances (4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, ortho-
fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl) between 2017 
and 2020 (queried on July 16, 2020). In 2017 and 2018, U.S. Customs and 
Border Protection (CBP) reported that two other of the 10 substances 
(2'-fluoro ortho-fluorofentanyl and [beta]'-phenyl fentanyl) have been 
positively identified in seized drugs, respectively. In 2018, ortho-
methyl methoxyacetyl fentanyl was positively identified in an exhibit 
submitted to NMS laboratories for analysis by the Department of 
Homeland Security. Consequently, the positive identification of the 10 
substances in law enforcement encounters indicates that these 
substances are being abused, and thus pose safety hazards to the health 
of users.
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    \4\ While law enforcement data is not direct evidence of abuse, 
it can lead to an inference that a drug has been diverted and 
abused. See 76 FR 77330, 77332, Dec. 12, 2011.
    \5\ NFLIS is a DEA program and a national forensic laboratory 
reporting system that systematically collects results from drug 
chemistry analyses conducted by state and local forensic 
laboratories in the United States. The NFLIS database also contains 
Federal data from U.S. Customs and Border Protection (CBP). NFLIS 
only includes drug chemistry results from completed analyses.
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    2. Scientific Evidence of the Drug's Pharmacological Effects, if 
Known: 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl are pharmacologically similar to other schedule I and schedule 
II mu-opioid receptor agonist substances. The abuse potential (assessed 
by drug discriminative studies) of 2'-fluoro ortho-fluorofentanyl, 4'-
methyl acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
ortho-methyl methoxyacetyl fentanyl, para-methylfentanyl, phenyl 
fentanyl, and thiofuranyl fentanyl show that these substances share 
discriminative stimulus effects similar to fentanyl and morphine. 
Similar to schedule I and II opioid analgesics, these 10 substances 
bind to and activate the mu-opioid receptor. Additionally, behavioral 
studies in animals demonstrate these 10 substances produce analgesic 
effects similar to fentanyl and morphine. Pre-treatment with 
naltrexone, an opioid antagonist, attenuated analgesic effect of these 
10 substances, as well as fentanyl and morphine. These data indicate 
that the 10 substances are mu-opioid receptor agonists with effects on 
the central nervous system. Data from drug discrimination studies 
showed that these 10 substances share discriminative stimulus effects 
similar to those of morphine. Thus, it is concluded from in vitro and 
in vivo pharmacological studies that the effects of the 10 substances 
are similar to that of fentanyl and morphine and are mediated by mu-
opioid receptor agonism.
    3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance: 2'-Fluoro ortho-fluorofentanyl, 4'-methyl acetyl 
fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-
fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl are synthetic opioids of the 4-anilidopiperidine 
structural class, which includes fentanyl. As defined in the February 
6,

[[Page 12300]]

2018, temporary order, fentanyl-related substances include any 
substance not otherwise controlled in any schedule (i.e., not included 
under any other Administration Controlled Substance Code Number) that 
is structurally related to fentanyl by one or more of the following 
modifications:
    (A) Replacement of the phenyl portion of the phenethyl group by any 
monocycle, whether or not further substituted in or on the monocycle;
    (B) substitution in or on the phenethyl group with alkyl, alkenyl, 
alkoxyl, hydroxyl, halo, haloalkyl, amino or nitro groups;
    (C) substitution in or on the piperidine ring with alkyl, alkenyl, 
alkoxyl, ester, ether, hydroxyl, halo, haloalkyl, amino or nitro 
groups;
    (D) replacement of the aniline ring with any aromatic monocycle 
whether or not further substituted in or on the aromatic monocycle; 
and/or
    (E) replacement of the N-propionyl group by another acyl group.
    [GRAPHIC] [TIFF OMITTED] TP03MR21.102
    
    According to the February 6, 2018, temporary scheduling order, the 
existence of a substance with any one, or any combination, of above-
mentioned modifications (see Figure 1) would meet the structural 
requirements of the definition of fentanyl-related substances. The 
present 10 substances fall within the definition of fentanyl-related 
substances by the following modifications:
    1. 2'-Fluoro ortho-fluorofentanyl: Substitution on the phenethyl 
group with a halo group and substitution on the aniline ring (meets 
definition for modifications B and D);
    2. 4'-methyl acetyl fentanyl: Substitution on the phenethyl group 
with an alkyl group and replacement of the N-propionyl group by another 
acyl group (meets definition for modifications B and E);
    3. [beta]-methyl fentanyl: Substitution on the phenethyl group with 
an alkyl group (meets definition for modification B);
    4. [beta]'-phenyl fentanyl: Replacement of the N-propionyl group by 
another acyl group (meets definition for modification E);
    5. ortho-fluorobutyryl fentanyl: Substitution on the aniline ring 
and replacement of the N-propionyl group with another acyl group (meets 
definition for modifications D and E);
    6. ortho-methyl acetylfentanyl: Substitution on the aniline ring 
and replacement of the N-propionyl group with another acyl group (meets 
definition for modifications D and E);
    7. ortho-methyl methoxyacetylfentanyl: Substitution on the aniline 
ring and replacement of the N-propionyl group with another acyl group 
(meets definition for modifications D and E);
    8. para-methylfentanyl: Substitution on the aniline ring (meets 
definition for modification D);
    9. phenyl fentanyl: Replacement of the N-propionyl group by another 
acyl group (meets definition for modification E); and
    10. thiofuranyl fentanyl: Replacement of the N-propionyl group by 
another acyl group (meets definition for modification E).
    No study has been undertaken to evaluate the efficacy, toxicology, 
and safety of the 10 substances in humans. It can be inferred from data 
obtained from animal studies that these 10 substances have sufficient 
distribution to the brain to produce depressant effects similar to that 
of other mu-opioid receptor agonists such as fentanyl. Data from in 
vitro receptor binding studies show that these 10 substances, similar 
to fentanyl, display high selectivity for the mu-opioid receptor over 
other opioid receptor subtypes.
    There are no FDA-approved marketing applications for a drug product 
containing 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
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 10 substances.
    4. Its History and Current Pattern of Abuse: 2'-Fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl, like other 
substances structurally related to fentanyl, are disguised as a 
``legal''

[[Page 12301]]

alternative to fentanyl. Between 2017 and 2020, law enforcement 
officials in the United States encountered these 10 substances.
    5. The Scope, Duration, and Significance of Abuse: 2'-Fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl, similar to 
other substances structurally related to fentanyl, are often used as 
recreational drugs. The recreational use of these 10 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 10 substances are 
being abused and trafficked is confirmed by law enforcement encounters. 
NFLIS contained 235 reports of 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
para-methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl from 
Federal, State, and local forensic laboratories between 2017 and 2020. 
In 2017 and 2018, CBP reported that 2'-fluoro ortho-fluorofentanyl and 
[beta]'-phenyl fentanyl have been positively identified in seized 
drugs, respectively. In 2018, ortho-methyl methoxyacetyl fentanyl was 
positively identified in an exhibit submitted to NMS laboratories for 
analysis by the Department of Homeland Security.
    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, 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, 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl produced 
pharmacological effects similar to fentanyl. Thus, these 10 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 2017, opioid-related 
overdose deaths in the United States increased 90 percent from 25,052 
to 47,600. The increase in the number of opioid-related deaths was 
primarily driven by illicitly manufactured fentanyl.\6\ According to 
CDC 2018 provisional data, there were 68,500 drug overdose fatalities; 
of those, 47,600 (~69 percent) involved an opioid. The use of some 
fentanyl-related substances has been associated with adverse health 
outcomes, including death.
---------------------------------------------------------------------------

    \6\ If evidence of prescription or illicit use was not 
available, fentanyl was categorized as illicitly-manufactured 
fentanyl (``IMF'') because the vast majority of fentanyl overdose 
deaths involve IMF. Gladden RM, O'Donnell J, Mattson CL, Seth P. 
Changes in Opioid-Involved Overdose Deaths by Opioid Type and 
Presence of Benzodiazepines, Cocaine, and Methamphetamine--25 
States, July-December 2017 to January-June 2018. MMWR Morb Mortal 
Wkly Rep. 30; 68(34):737-744.
---------------------------------------------------------------------------

    7. Its Psychic or Physiological Dependence Liability: There are no 
pre-clinical and clinical studies that have evaluated the dependence 
potential of 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl. These 10 substances are mu-opioid 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: 2'-Fluoro ortho-fluorofentanyl, 4'-
methyl acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
ortho-methyl methoxyacetyl fentanyl, para-methylfentanyl, phenyl 
fentanyl, and thiofuranyl fentanyl are not considered immediate 
precursors of any controlled substance of the CSA as defined by 21 
U.S.C. 802(23).
    Conclusion: After considering the scientific and medical evaluation 
conducted by HHS, HHS's scheduling recommendation, and DEA's own eight-
factor analysis, DEA finds that the facts and all relevant data 
constitute substantial evidence of the potential for abuse of 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl. As such, DEA 
hereby proposes to permanently schedule 2'-fluoro ortho-fluorofentanyl, 
4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
ortho-methyl methoxyacetyl fentanyl, para-methylfentanyl, phenyl 
fentanyl, and thiofuranyl 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. 812(b). After consideration of the analysis and 
recommendation of the Assistant Secretary for Health of HHS and review 
of all other available data, the Acting Administrator of DEA, pursuant 
to 21 U.S.C. 811(a) and 21 U.S.C. 812(b)(1), finds that:
    (1) 2'-Fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl have a high potential for abuse.
    According to HHS, 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl 
fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-
fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl, similar to fentanyl, are mu-opioid receptor 
agonists. These

[[Page 12302]]

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 2'-
fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl fully 
substituted for the discriminative stimulus effects of morphine.
    (2) 2'-Fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl have no currently accepted medical use in treatment in the 
United States.
    According to HHS, there are no FDA-approved new drug applications 
for 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-
methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, 
ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl in the United 
States. There are no known therapeutical applications for these 
fentanyl-related substances and thus they have no currently accepted 
medical use in the United States.\7\
---------------------------------------------------------------------------

    \7\ Although there is no evidence suggesting that 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, 
ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, 
para-methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl have 
a currently accepted medical use in treatment in the United States, 
it bears noting that a drug cannot be found to have such medical use 
unless DEA concludes that it satisfies a five-part test. 
Specifically, with respect to a drug that has not been approved by 
the FDA, to have a currently accepted medical use in treatment in 
the United States, all of the following must be demonstrated:
     i. The drug's chemistry must be known and reproducible;
     ii. there must be adequate safety studies;
     iii. there must be adequate and well-controlled studies proving 
efficacy;
     iv. the drug must be accepted by qualified experts; and
     v. the scientific evidence must be widely available.
    57 FR 10499 (1992), pet. for rev. denied, Alliance for Cannabis 
Therapeutics v. DEA, 15 F.3d 1131, 1135 (D.C. Cir. 1994).
---------------------------------------------------------------------------

    (3) There is a lack of accepted safety for use of 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl under medical 
supervision.
    Because 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl have no FDA-approved medical use and have not been thoroughly 
investigated as new drugs, their safety for use under medical 
supervision is undetermined. Thus, there is a lack of accepted safety 
for use of 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl under medical supervision.
    Based on these findings, the Acting Administrator of DEA concludes 
that 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-
methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, 
ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl, including 
their isomers, esters, ethers, salts, and salts of isomers, esters, and 
ethers warrant continued control in schedule I of the CSA. 21 U.S.C. 
812(b)(1).
    Requirements for handling 2'-fluoro ortho-fluorofentanyl, 4'-methyl 
acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, 
ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl.
    If this rule is finalized as proposed, 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl would 
continue \8\ to be subject to the CSA's schedule I regulatory controls 
and administrative, civil, and criminal sanctions applicable to the 
manufacture, distribution, reverse distribution, dispensing, 
importation, exportation, research, and conduct of instructional 
activities, including the following:
---------------------------------------------------------------------------

    \8\ 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl, are covered by the February 6, 2018, temporary scheduling 
order, and are currently subject to schedule I controls on a 
temporary basis, pursuant to 21 U.S.C. 811(h). 83 FR 5188.
---------------------------------------------------------------------------

    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, dispenses, imports, exports, engages in research, 
or conducts instructional activities or chemical analysis with, or 
possesses) 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl, or who desires to handle 2'-fluoro ortho-fluorofentanyl, 4'-
methyl acetyl fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl 
fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, 
ortho-methyl methoxyacetyl fentanyl, para-methylfentanyl, phenyl 
fentanyl, and thiofuranyl fentanyl is required to be registered with 
DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 957, and 
958, and in accordance with 21 CFR parts 1301 and 1312.
    2. Security. 2'-Fluoro ortho-fluorofentanyl, 4'-methyl acetyl 
fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-
fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl are subject to schedule I security requirements 
and must be handled and stored pursuant to 21 U.S.C. 821, 823, and in 
accordance with 21 CFR 1301.71-1301.93. Non-practitioners handling 2'-
fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl also must 
comply with the employee screening requirements of 21 CFR 1301.90-
1301.93.
    3. Labeling and Packaging. All labels and labeling for commercial 
containers of 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl 
fentanyl, [beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-
fluorobutyryl fentanyl, ortho-methyl acetylfentanyl, ortho-methyl 
methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl must be in compliance with 21 U.S.C. 825 and 
958(e), and be in accordance with 21 CFR part 1302.

[[Page 12303]]

    4. Quota. Only registered manufacturers are permitted to 
manufacture 2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, 
[beta]-methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl 
fentanyl, ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl 
fentanyl, para-methylfentanyl, phenyl fentanyl, and thiofuranyl 
fentanyl in accordance with a quota assigned pursuant to 21 U.S.C. 826 
and in accordance with 21 CFR part 1303.
    5. Inventory. Any person registered with DEA to handle 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl must have an 
initial inventory of all stocks of controlled substances (including 
these substances) on hand on the date the registrant first engages in 
the handling of controlled substances pursuant to 21 U.S.C. 827 and 
958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl) on hand 
every two years pursuant to 21 U.S.C. 827 and 958, and in accordance 
with 21 CFR 1304.03, 1304.04, and 1304.11.
    6. Records and Reports. Every DEA registrant is required to 
maintain records and submit reports with respect to 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl, pursuant to 
21 U.S.C. 827 and 958(e), and in accordance with 21 CFR parts 1304 and 
1312.
    7. Order Forms. Every DEA registrant who distributes 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl is required 
to comply with the order form requirements, pursuant to 21 U.S.C. 828 
and 21 CFR part 1305.
    8. Importation and Exportation. All importation and exportation of 
2'-fluoro ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-
methyl fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, 
ortho-methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl must be in 
compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance 
with 21 CFR part 1312.
    9. Liability. Any activity involving 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl not 
authorized by, or in violation of, the CSA or its implementing 
regulations is unlawful, and could subject the person to 
administrative, civil, and/or criminal sanctions.

Regulatory Analyses

Executive Orders 12866 (Regulatory Planning and Review) and 13563 
(Improving Regulation and Regulatory Review)

    In accordance with 21 U.S.C. 811(a), this proposed scheduling 
action is subject to formal rulemaking procedures done ``on the record 
after opportunity for a hearing,'' which are conducted pursuant to the 
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for 
scheduling a drug or other substance. Such actions are exempt from 
review by the Office of Management and Budget (OMB) pursuant to section 
3(d)(1) of Executive Order (E.O.) 12866 and the principles reaffirmed 
in E.O. 13563.

Executive Order 12988, Civil Justice Reform

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors 
and ambiguity, minimize litigation, provide a clear legal standard for 
affected conduct, and promote simplification and burden reduction.

Executive Order 13132, Federalism

    This proposed rulemaking does not have federalism implications 
warranting the application of E.O. 13132. The proposed rule does not 
have substantial direct effects on the States, on the relationship 
between the National Government and the States, or the distribution of 
power and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This proposed rule does not have tribal implications warranting the 
application of E.O. 13175. It does not have substantial direct effects 
on one or more Indian tribes, on the relationship between the Federal 
Government and Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.

Regulatory Flexibility Act

    The Acting Administrator, in accordance with the Regulatory 
Flexibility Act, 5 U.S.C. 601-602, has reviewed this proposed rule and 
by approving it, certifies that it will not have a significant economic 
impact on a substantial number of small entities. On February 6, 2018, 
DEA published an order to temporarily place fentanyl-related 
substances, as defined in the order, in schedule I of the CSA pursuant 
to the temporary scheduling provisions of 21 U.S.C. 811(h). DEA 
estimates that all entities handling or planning to handle 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl have already 
established and implemented the systems and processes required to 
handle these substances which meet the definition of fentanyl-related 
substances.
    There are currently 57 registrations authorized to handle the 
fentanyl-related substances as a class, which include 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl, as well as a 
number of registered analytical labs that are authorized to handle 
schedule I controlled substances generally. These 57 registrations 
represent 51 entities, of which eight are small entities. Therefore, 
DEA estimates eight small entities are affected by this proposed rule.
    A review of the 57 registrations indicates that all entities that 
currently handle fentanyl-related substances, including 2'-fluoro 
ortho-fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl 
fentanyl, [beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-
methyl acetylfentanyl, ortho-methyl

[[Page 12304]]

methoxyacetyl fentanyl, para-methylfentanyl, phenyl fentanyl, and 
thiofuranyl fentanyl, also handle other schedule I controlled 
substances, and have established and implemented (or maintain) the 
systems and processes required to handle 2'-fluoro ortho-
fluorofentanyl, 4'-methyl acetyl fentanyl, [beta]-methyl fentanyl, 
[beta]'-phenyl fentanyl, ortho-fluorobutyryl fentanyl, ortho-methyl 
acetylfentanyl, ortho-methyl methoxyacetyl fentanyl, para-
methylfentanyl, phenyl fentanyl, and thiofuranyl fentanyl. Therefore, 
DEA anticipates that this proposed rule will impose minimal or no 
economic impact on any affected entities; and thus, will not have a 
significant economic impact on any of the eight affected small 
entities. Therefore, DEA has concluded that this proposed rule will not 
have a significant effect on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
2 U.S.C. 1501 et seq., DEA has determined and certifies that this 
action would not result in any Federal mandate that may result ``in the 
expenditure by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100 million or more (adjusted annually 
for inflation) in any 1 year . . . .'' Therefore, neither a Small 
Government Agency Plan nor any other action is required under UMRA of 
1995.

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information under 
the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-3521. This action 
would not impose recordkeeping or reporting requirements on State or 
local governments, individuals, businesses, or organizations. An agency 
may not conduct or sponsor, and a person is not required to respond to, 
a collection of information unless it displays a currently valid OMB 
control number.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.

    For the reasons set out above, DEA proposes to amend 21 CFR part 
1308 as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1308 continues to read as 
follows:

    Authority:  21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise 
noted.

0
2. In Sec.  1308.11:
0
a. Redesignate paragraph (75) as paragraph (b)(84);
0
b. Add paragraph (b)(83);
0
c. Redesignate paragraphs (b)(65) through (71) as paragraphs (b)(76) 
through (82);
0
d. Add a new paragraph (b)(75);
0
e. Redesignate paragraphs (b)(60) through (64) as paragraphs (b)(70) 
through (74);
0
f. Add a new paragraph (69);
0
g. Redesignate paragraphs (b)(56) through (59) as paragraphs (b)(65) 
through (68);
0
h. Add a new paragraph (64);
0
i. Redesignate paragraph (b)(55) as paragraph (b)(63);
0
j. Add new paragraphs (b)(61) and (62);
0
k. Redesignate paragraphs (b)(45) through (54) as paragraphs (b)(51) 
through (60);
0
l. Add new paragraph (b)(50);
0
m. Redesignate paragraphs (b)(37) through (44) as paragraphs (b)(42) 
through (49);
0
n. Add a new paragraph (b)(41);
0
o. Redesignate paragraph (b)(36) as paragraph (b)(40);
0
p. Add a reserved paragraph (b)(39);
0
q. Redesignate paragraphs (b)(22) through (35) as paragraphs (b)(25) 
through (38);
0
r. Add a reserved paragraph (b)(24);
0
s. Redesignate paragraphs (b)(17) through (21) as paragraphs (b)(19) 
through (23); and
0
t. Add new paragraphs (b)(17) and (18).
    The additions to read as follows:


Sec.  1308.11   Schedule I.

* * * * *
    (b) * * *

(17) Beta-methyl fentanyl (N-phenyl-N-(1-(2-                        9856
 phenylpropyl)piperidin-4-yl)propionamide; other name: [beta]-
 methyl fentanyl).............................................
(18) Beta'-phenyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N,3-      9842
 diphenylpropanamide; other names: [beta]'-phenyl fentanyl; 3-
 phenylpropanoyl fentanyl)....................................
 
                              * * * * * * *
(41) 2'-Fluoro ortho-fluorofentanyl (N-(1-(2-                       9829
 fluorophenethyl)piperidin-4-yl)-N-(2-
 fluorophenyl)propionamide; other name: 2'-fluoro 2-
 fluorofentanyl)..............................................
 
                              * * * * * * *
(50) 4'-Methyl acetyl fentanyl (N-(1-(4-                            9819
 methylphenethyl)piperidin-4-yl)-N-phenylacetamide)...........
 
                              * * * * * * *
(61) ortho-Fluorobutyryl fentanyl (N-(2-fluorophenyl)-N-(1-         9846
 phenethylpiperidin-4-yl)butyramide; other name: 2-
 fluorobutyryl fentanyl)......................................
(62) ortho-Methyl acetylfentanyl (N-(2-methylphenyl)-N-(1-          9848
 phenethylpiperidin-4-yl)acetamide; other name: 2-methyl
 acetylfentanyl)..............................................
 
                              * * * * * * *
(64) ortho-Methyl methoxyacetyl fentanyl (2-methoxy-N-(2-           9820
 methylphenyl)-N-(1-phenethylpiperidin-4-yl)acetamide; other
 name: 2-methyl methoxyacetyl fentanyl).......................
 
                              * * * * * * *
(69) para-Methylfentanyl (N-(4-methylphenyl)-N-(1-                  9817
 phenethylpiperidin-4-yl)propionamide; other name: 4-
 methylfentanyl)..............................................
 
                              * * * * * * *
(75) Phenyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-              9841
 phenylbenzamide; other name: benzoyl fentanyl................
 
                              * * * * * * *
(83) Thiofuranyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-         9839
 phenylthiophene-2-carboxamide; other names: 2-thiofuranyl
 fentanyl; thiophene fentanyl)................................
 


[[Page 12305]]

* * * * *

D. Christopher Evans,
Acting Administrator.
[FR Doc. 2021-04214 Filed 3-2-21; 8:45 am]
BILLING CODE 4410-09-P