[Federal Register Volume 85, Number 20 (Thursday, January 30, 2020)]
[Proposed Rules]
[Pages 5356-5361]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-01681]



[[Page 5356]]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-565]


Schedules of Controlled Substances: Placement of cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl Into 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 
cyclopentyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-
phenylcyclopentanecarboxamide), isobutyryl fentanyl (N-(1-
phenethylpiperidin-4-yl)-N-phenylisobutyramide), para-chloroisobutyryl 
fentanyl (N-(4-chlorophenyl)-N-(1-phenethylpiperidin-4-
yl)isobutyramide), para-methoxybutyryl fentanyl (N-(4-methoxyphenyl)-N-
(1-phenethylpiperidin-4-yl)butyramide), and valeryl fentanyl (N-(1-
phenethylpiperidin-4-yl)-N-phenylpentanamide), including their isomers, 
esters, ethers, salts, and salts of isomers, esters and ethers whenever 
the existence of such isomers, esters, ethers and salts is possible, in 
schedule I of the Controlled Substances Act. 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, 
import, export, engage in research, conduct instructional activities or 
chemical analysis, or possess), or propose to handle cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl.

DATES: Comments must be submitted electronically or postmarked on or 
before March 2, 2020.
    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. Requests for hearing and waivers 
of an opportunity for a hearing or to participate in a hearing must be 
received on or before March 2, 2020.

ADDRESSES: Interested persons may file written comments on this 
proposal in accordance with 21 CFR 1308.43(g). Commenters should be 
aware that the electronic Federal Docket Management System will not 
accept comments after 11:59 p.m. Eastern Time on the last day of the 
comment period. To ensure proper handling of comments, please reference 
``Docket No. DEA-565'' on all electronic and written correspondence, 
including any attachments.
     Electronic comments: Drug Enforcement Administration 
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 http://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.
     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/DRW, 8701 Morrissette Drive, 
Springfield, Virginia 22152.
     Hearing requests: 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 be sent to: 
Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 8701 
Morrissette Drive, Springfield, Virginia 22152; and (2) Drug 
Enforcement Administration, Attn: DEA Federal Register Representative/
DRW, 8701 Morrissette Drive, Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Scott A. Brinks, Diversion Control 
Division, Drug Enforcement Administration; Mailing Address: 8701 
Morrissette Drive, Springfield, Virginia 22152; Telephone: (202) 598-
6812.

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 http://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 (FOIA) 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 http://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 http://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 (APA), 5 U.S.C. 551-559. (21 CFR 1308.41-1308.45; 21 CFR part 1316, 
subpart D). Such requests or notices must conform to the requirements 
of 21 CFR 1308.44(a) or (b), and 1316.47 or 1316.48, as applicable, and 
include a

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statement of the person's interests in the proposed scheduling action, 
whether the person is adversely affected or aggrieved, and the 
objections or issues, if any, concerning which the person desires to be 
heard at a hearing. Any waiver must conform to the requirements of 21 
CFR 1308.44(c) and may include a written statement regarding the 
interested person's position on the matters of fact and law involved in 
any hearing.

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 (1) on his own 
motion; (2) at the request of the Secretary of the Department of Health 
and Human Services (HHS),\1\ or (3) on the petition of any interested 
party. 21 U.S.C. 811(a). This proposed action is supported by a 
recommendation from the Assistant Secretary for Health of the HHS 
(Assistant Secretary) and an evaluation of all other relevant data by 
the 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 cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl.
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    \1\ As discussed in a memorandum of understanding entered into 
by the Food and Drug Administration (FDA) and the National Institute 
on Drug Abuse (NIDA), the FDA acts as the lead agency within the HHS 
in carrying out the Secretary's scheduling responsibilities under 
the CSA, with the concurrence of NIDA. 50 FR 9518, Mar. 8, 1985. The 
Secretary of the HHS has delegated to the Assistant Secretary for 
Health of the HHS the authority to make domestic drug scheduling 
recommendations. 58 FR 35460, July 1, 1993.
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Background

    On February 1, 2018, DEA published an order in the Federal Register 
amending 21 CFR 1308.11(h) to temporarily place cyclopentyl fentanyl 
(N-(1-phenethylpiperidin-4-yl)-N-phenylcyclopentanecarboxamide), 
isobutyryl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-
phenylisobutyramide), para-chloroisobutyryl fentanyl (N-(4-
chlorophenyl)-N-(1-phenethylpiperidin-4-yl)isobutyramide), para-
methoxybutyryl fentanyl (N-(4-methoxyphenyl)-N-(1-phenethylpiperidin-4-
yl)butyramide), and valeryl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-
phenylpentanamide), along with two other substances,\2\ in schedule I 
of the CSA pursuant to the temporary scheduling provisions of 21 U.S.C. 
811(h). 83 FR 4580. That temporary scheduling order was effective on 
the date of publication, and was based on findings by the former Acting 
Administrator of DEA (Acting Administrator) that the temporary 
scheduling of these seven substances was necessary to avoid an imminent 
hazard to public safety pursuant to 21 U.S.C. 811(h)(1). Section 
201(h)(2) of the CSA, 21 U.S.C. 811(h)(2), requires that the temporary 
control of these substances expire two years from the effective date of 
the scheduling order, which was February 1, 2018. However, the CSA also 
provides that during the pendency of proceedings under 21 U.S.C. 
811(a)(1) with respect to the substance, the temporary scheduling of 
that substance could be extended for up to one year. Proceedings for 
the scheduling of a substance under 21 U.S.C. 811(a) may be initiated 
by the Attorney General (delegated to the Administrator of the DEA 
pursuant to 28 CFR 0.100) on his own motion, at the request of the 
Secretary of HHS,\3\ or on the petition of any interested party. An 
extension of the existing temporary order is being ordered by the 
Acting Administrator in a separate action, and is published elsewhere 
in this issue of the Federal Register.
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    \2\ Those two other substances, ocfentanil (N-(2-fluorophenyl)-
2-methoxy-N-(phenethylpiperidin-4-yl)acetamide) and para-
fluorobutyryl fentanyl (N-(4-fluorophenyl)-N-(1-phenethylpiperidin-
4-yl)butyramide, were subsequently permanently placed in schedule I 
on November 29, 2018 (83 FR 61320) and October 25, 2019 (84 FR 
57327), respectively, pursuant to 21 U.S.C. 811(d)(1).
    \3\ Because the Secretary of HHS has delegated to the Assistant 
Secretary the authority to make domestic drug scheduling 
recommendations, for purposes of this proposed rulemaking, all 
subsequent references to ``Secretary'' have been replaced with 
``Assistant Secretary.''
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    The Acting Administrator, on his own motion pursuant to 21 U.S.C. 
811(a), is initiating proceedings under 21 U.S.C. 811(a)(1) to 
permanently schedule cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl. DEA has gathered and reviewed the available information 
regarding the pharmacology, chemistry, trafficking, actual abuse, 
pattern of abuse, and the relative potential for abuse for these 
substances. On November 5, 2018, the Acting Administrator submitted a 
request to the Assistant Secretary to provide DEA with a scientific and 
medical evaluation of available information and a scheduling 
recommendation for cyclopropyl fentanyl, para-fluorobutyryl fentanyl, 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl, in 
accordance with 21 U.S.C. 811(b) and (c).
    In a letter dated September 6, 2019, DEA notified HHS that it no 
longer needed scientific and medical evaluations for cyclopropyl 
fentanyl and para-fluorobutyryl fentanyl. Subsequently, DEA permanently 
placed these two substances in schedule I of the CSA on October 25, 
2019, pursuant to 21 U.S.C. 811(d)(1). (84 FR 57323).
    On November 12, 2019, the Assistant Secretary submitted HHS's 
scientific and medical evaluation and scheduling recommendation \4\ for 
cyclopropyl fentanyl and para-fluorobutyryl fentanyl, cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl to the Acting 
Administrator. Upon receipt of the scientific and medical evaluation 
and scheduling recommendation from the HHS, in accordance with 21 
U.S.C. 811(c), the DEA reviewed the documents and all other relevant 
data, and conducted its own eight-factor analysis of the abuse 
potential of cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl.
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    \4\ Although HHS provided information on cyclopropyl fentanyl 
and para-fluorobutyryl fentanyl, these two substances will not be 
discussed in this notice of proposed rulemaking because they are 
already permanently controlled.
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Proposed Determination to Permanently Schedule Cyclopentyl fentanyl, 
Isobutyryl fentanyl, para-Chloroisobutyryl fentanyl, para-
Methoxybutyryl fentanyl, and Valeryl fentanyl

    As discussed in the background section, the Acting Administrator is 
initiating proceedings, pursuant to 21 U.S.C. 811(a)(1), to add 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl 
permanently to schedule I. DEA has reviewed the scientific and medical 
evaluation and scheduling recommendation received from HHS, and all 
other relevant data and conducted its own eight-factor analysis of the 
abuse potential of these five substances pursuant to 21 U.S.C. 811(c). 
Included below is a brief summary of each factor as analyzed by the HHS 
and the DEA, and as considered by the DEA in its proposed scheduling 
action. Please note that both DEA 8-Factor and HHS 8-Factor analysis 
and the Assistant

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Secretary's November 12, 2019, letter are available in their entirety 
under the tab ``Supporting Documents'' of the public docket for this 
action at http://www.regulations.gov under Docket Number ``DEA-565.''
    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 DEA consider the following criteria when 
determining whether a particular drug or substance has a potential for 
abuse:\5\
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    \5\ 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 
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 cyclopentyl fentanyl, isobutyryl fentanyl, 
para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and 
valeryl fentanyl is associated with its pharmacological similarity to 
other schedule I and II mu-opioid receptor agonist substances which 
have a high potential for abuse. Similar to morphine, fentanyl and 
several schedule I opioid substances that are structurally related to 
fentanyl, cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl have been shown to bind and act as mu-opioid receptor 
agonists.
    Cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl have no 
approved medical use in the United States and have been encountered on 
the illicit drug market. The use of cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
and valeryl fentanyl has been associated with adverse outcomes to 
include intoxications for para-chloroisobutyryl fentanyl and para-
methoxybutyryl fentanyl. Because these five substances 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 cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
and valeryl fentanyl is without medical advice, and accordingly, leads 
to the conclusion that these five substances are abused for their 
opioid-like properties. There are no legitimate channels for these five 
substances to be marketed as FDA-approved drug products but they are 
available for purchase from legitimate chemical companies to be used in 
scientific research. However, despite the limited legitimate use of 
these substances, reports from public health and law enforcement 
indicate that cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl 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 \6\ 
within the United States. According to drug seizure data from STRIDE 
and STARLiMS \7\ and the National Forensic Laboratory Information 
System (NFLIS),\8\ cyclopentyl fentanyl, isobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl are being encountered in 
the United States. Although there have been no law enforcement 
encounters for para-chloroisobutyryl fentanyl thus far, this substance 
poses the same qualitative public health risks as heroin, fentanyl, and 
other opioid analgesic substances.
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    \6\ 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.
    \7\ October 1, 2014, the DEA implemented STARLiMS (a web-based, 
commercial laboratory information management system) to replace the 
System to Retrieve Information from Drug Evidence (STRIDE) as its 
laboratory drug evidence data system of record. DEA laboratory data 
submitted after September 30, 2014, are reposited in STARLiMS. 
STRIDE/STARLiMS data were queried on 11/20/2019.
    \8\ 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. NFLIS 
data were queried 11/20/2019. NFLIS is still reporting data from 
2018-2019 due to normal lag time in reporting.
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    2. Scientific Evidence of the Drug's Pharmacological Effects, if 
Known: Cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl are 
pharmacologically similar to other schedule I and schedule II mu-opioid 
receptor agonist substances. Non-clinical and clinical studies 
conducted on abuse potential of mu-opioid receptor agonists such as 
morphine and fentanyl indicate that these substances share 
discriminative stimulus effects and have reinforcing properties. 
Similar to schedule I and II opioid analgesics, cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl bind to and activate the 
mu-opioid receptor. Additionally, behavioral studies in animals 
demonstrate that similar to fentanyl and morphine, cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl produce analgesic 
effects. Pre-treatment with naltrexone, an opioid antagonist, 
attenuated analgesic effects of cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
valeryl fentanyl, fentanyl, and morphine. Thus, it is concluded from in 
vitro and in vivo pharmacological studies that effects of cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl are similar to that of 
fentanyl and morphine and mediated by mu-opioid receptor agonism.
    3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance: Cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl are synthetic opioids in the 4-anilidopiperidine structural 
class which includes fentanyl. These five substances differ in chemical 
structure from fentanyl by modification at the acyl group. Fentanyl is 
substituted with an ethyl group at this position. Modifications of this 
group include cycloalkyl groups (cyclopentyl fentanyl), branched alkyl 
groups (isobutyryl fentanyl and para-chloroisobutyryl fentanyl), or 
other linear alkyl groups by adding one methylene group to give a 
propyl group (para-methoxybutyryl fentanyl) or two

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methylene groups to give a butyl group (valeryl fentanyl). In addition 
to modification of the acyl group, para-methoxybutyryl fentanyl and 
para-chloroisobutyryl fentanyl are substituted at the para-position of 
the N-phenyl ring with a methoxy group or a chlorine atom, 
respectively. No study has been undertaken to evaluate the efficacy, 
toxicology, and safety of cyclopentyl fentanyl, isobutyryl fentanyl, 
para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, or 
valeryl fentanyl in humans. It can be inferred from medical examiner 
reports and data obtained from animal studies that these five 
substances have sufficient distribution to the brain to produce 
depressant effects similar to that of mu-opioid receptor agonists.
    There are no FDA-approved marketing applications for drug products 
containing cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, or valeryl 
fentanyl for any therapeutic indication in the United States. Moreover, 
there are no clinical studies or petitioners which have claimed an 
accepted medical use in the United States for these substances.
    4. Its History and Current Pattern of Abuse: Cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl have recently been 
encountered by law enforcement and/or public health officials in the 
United States or elsewhere. Evidence suggests that the pattern of abuse 
of these five substances parallels that of prescription opioid 
analgesics. The first reports of cyclopentyl fentanyl and valeryl 
fentanyl in the United States were in 2015. Para-methoxybutyryl 
fentanyl followed in 2016 and isobutyryl fentanyl was first reported in 
2017. While there are no drug seizure reports for para-chloroisobutyryl 
fentanyl, one intoxication was associated with this substance in 
Sweden.
    5. The Scope, Duration, and Significance of Abuse: Cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl, similar to other 
substances structurally related to fentanyl, are often used as 
recreational drugs. The recreational use of these substances continues 
to be of significant concern in the United States. These substances are 
distributed to users often with unpredictable outcomes. Currently, the 
United States is in the midst of an illicit opioid abuse epidemic.
    NFLIS and STARLiMS data indicate that law enforcement encounters 
for isobutyryl fentanyl and valeryl fentanyl have increased over the 
years, with valeryl fentanyl nearly doubling from 2018 to 2019. 
Cyclopentyl fentanyl was found in three exhibits in 2017 and para-
methoxybutyryl fentanyl was found in one exhibit in 2016; these two 
substances haven't been reported since. para-Chloroisobutyryl fentanyl 
has not been found in any drug seizure reports. DEA notes that the data 
from pharmacological testing of cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
and valeryl fentanyl are consistent with those of other opioids such as 
fentanyl and other related opioid agonists. Thus, it can be inferred 
that the abuse potential of these substances is similar to mu-opioid 
receptor agonists such as fentanyl and morphine.
    6. What, if Any, Risk There is to the Public Health: Available 
evidence on the overall public health risks associated with cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl can be measured by 
hospitalization or fatalities associated with the use of such 
substances. Other countries have identified fatal and non-fatal 
intoxications from toxicological samples for para-methoxybutyryl 
fentanyl and para-chloroisobutyryl fentanyl. Abusers of these 
substances may not know the origin, identity, or purity of these 
substances, thus posing significant adverse health risks when compared 
to abuse of pharmaceutical preparations of opioid analgesics, such as 
morphine and oxycodone. The abuse of cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
and valeryl fentanyl leads to the same qualitative public health risks 
as heroin, fentanyl and other opioid analgesic substances. Taken 
together, evidence posits that individuals experimenting with 
substances with unknown potency are at high risk of adverse health 
outcomes.
    7. Its Psychic or Physiological Dependence Liability: There are no 
pre-clinical or clinical studies that have evaluated the psychic or 
physiologic dependence of cyclopentyl fentanyl, isobutyryl fentanyl, 
para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and 
valeryl fentanyl. Several studies have shown that due to fentanyl's 
short duration of action, more frequent dosing is often required that 
can lead to a fast induction of tolerance, dependence and opiate 
withdrawal syndrome. Opioid withdrawal includes nausea and vomiting, 
depression, agitation, anxiety, craving, sweats, hypertension, 
diarrhea, and fever. These five substances act as agonists at the mu-
opioid receptors and exhibit a full and dose-dependent substitution for 
the discriminative stimulus effects produced by morphine. Thus, the 
pharmacological similarity and pattern of abuse of cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl to fentanyl are 
indicative of their potential to possess a psychic and physiological 
dependence liability similar to that of other mu-opioid receptor 
agonist substances, such as heroin and fentanyl.
    8. Whether the Substance is an Immediate Precursor of a Substance 
Already Controlled Under the CSA: Cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
and valeryl fentanyl are not 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 the HHS, the HHS's recommendation, and the DEA's own 
eight-factor analysis, the DEA finds that the facts and all relevant 
data constitute substantial evidence of the potential for abuse of 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl. As such, 
DEA hereby proposes to permanently schedule cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl as schedule I controlled 
substances under 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 HHS and review of all 
other available data, the Acting Administrator of the DEA, pursuant to 
21 U.S.C. 811(a) and 21 U.S.C. 812(b)(1), finds that:
    1. Cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl have a 
high potential for abuse as indicated either by law enforcement data, 
intoxications reported by scientific literature, or

[[Page 5360]]

pharmacological testing of these substances;
    2. Cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl have no 
currently accepted medical use in treatment in the United States; \9\ 
and
---------------------------------------------------------------------------

    \9\ Although there is no evidence suggesting that cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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).
---------------------------------------------------------------------------

    3. There is a lack of accepted safety for use of cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl under medical 
supervision.
    Based on these findings, Acting Administrator of DEA concludes that 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl, including 
their isomers, esters, ethers, salts, and salts of isomers, esters and 
ethers whenever the existence of such isomers, esters, ethers and salts 
is possible, warrant continued control in schedule I of the CSA. (21 
U.S.C. 812(b)(1)).

Requirements for Handling cyclopentyl fentanyl, isobutyryl fentanyl, 
para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and 
valeryl fentanyl

    If this rule is finalized as proposed, cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl would continue \10\ to be 
subject to the CSA's schedule I regulatory controls and administrative, 
civil, and criminal sanctions applicable to the manufacture, 
distribution, dispensing, importing, exporting, research, and conduct 
of instructional activities, including the following:
---------------------------------------------------------------------------

    \10\ Cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl are currently subject to schedule I controls on a temporary 
basis, pursuant to 21 U.S.C. 811(h). 83 FR 4580, February 1, 2018.
---------------------------------------------------------------------------

    1. Registration. Any person who handles, manufactures, distributes, 
dispenses, imports, exports, engages in research, or conducts 
instructional activities or chemical analysis with, or possesses 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl, or who 
desires to handle cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl, is required to be registered with the 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. Cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
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.
    3. Labeling and Packaging. All labels and labeling for commercial 
containers of cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
fentanyl must be in compliance with 21 U.S.C. 825 and 958(e), and be in 
accordance with 21 CFR part 1302.
    4. Quota. Only registered manufacturers are permitted to 
manufacture cyclopentyl fentanyl, isobutyryl fentanyl, para-
chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, and valeryl 
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 cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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 cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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 cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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 cyclopentyl 
fentanyl, isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl 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 cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl 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, 13563, and 13771, Regulatory Planning and 
Review, Improving Regulation and Regulatory Review, and Reducing 
Regulation and Controlling Regulatory Costs

    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 12866 and the principles reaffirmed in 
Executive Order 13563.
    This proposed rule does not meet the definition of an Executive 
Order 13771 regulatory action, and the repeal and cost offset 
requirements of Executive Order 13771 have not been triggered. OMB has 
previously determined that formal rulemaking actions concerning the 
scheduling of controlled substances, such as this rule, are not 
significant

[[Page 5361]]

regulatory actions under Section 3(f) of Executive Order 12866.

Executive Order 12988, Civil Justice Reform

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of Executive Order 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 Executive Order 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 Executive Order 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 Administrator, in accordance with the Regulatory Flexibility 
Act (RFA), 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 1, 2018, 
the DEA published an order to temporarily place cyclopentyl fentanyl, 
isobutyryl fentanyl, para-chloroisobutyryl fentanyl, para-
methoxybutyryl fentanyl, and valeryl fentanyl 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 
cyclopentyl fentanyl, isobutyryl fentanyl, para-chloroisobutyryl 
fentanyl, para-methoxybutyryl fentanyl, and valeryl fentanyl have 
already established and implemented the systems and processes required 
to handle these substances.
    There are currently 34 registrations authorized to handle one or 
more of the following substances: Cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
or valeryl fentanyl, as well as a number of registered analytical labs 
that are authorized to handle schedule I controlled substances 
generally. These 34 registrations represent 26 entities, of which 8 are 
small entities. Therefore, DEA estimates 8 small entities are affected 
by this proposed rule. A review of the 34 registrations indicates that 
all entities that currently handle cyclopentyl fentanyl, isobutyryl 
fentanyl, para-chloroisobutyryl fentanyl, para-methoxybutyryl fentanyl, 
or valeryl fentanyl also handle other schedule I controlled substances 
and have established and implemented (or maintain) the systems and 
processes required to handle these substances. Therefore, the 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 
economic impact 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 $100,000,000 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 paragraphs (b)(56) through (70) as (b)(60) through (74);
0
b. Redesignate paragraphs (b)(54) and (55) as (b)(57) and (58);
0
c. Redesignate paragraphs (b)(39) through (53) as (b)(41) through (55);
0
d. Redesignate paragraphs (b)(22) through (38) as (b)(23) through (39);
0
e. Add new paragraphs (b)(22), (40), (56), (59), and (75); and
0
f. Remove and reserve paragraphs (h)(23), and (h)(25) through (28).
    The additions read as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

 
 
 
(22) Cyclopentyl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-       (9847)
 phenylcyclopentanecarboxamide)...............................
 
                                * * * * *
(40) Isobutyryl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-        (9827)
 phenylisobutyramide).........................................
 
                                * * * * *
(56) para-Chloroisobutyryl fentanyl (N-(4-chlorophenyl)-N-(1-     (9826)
 phenethylpiperidin-4-yl)isobutyramide........................
 
                                * * * * *
(59) para-Methoxybutyryl fentanyl (N-(4-methoxyphenyl)-N-(1-      (9837)
 phenethylpiperidin-4-yl)butyramide)..........................
 
                                * * * * *
(75) Valeryl fentanyl (N-(1-phenethylpiperidin-4-yl)-N-           (9804)
 phenylpentanamide)...........................................
 

* * * * *

    Dated: January 23, 2020.
Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-01681 Filed 1-29-20; 8:45 am]
BILLING CODE 4410-09-P