[Federal Register Volume 81, Number 166 (Friday, August 26, 2016)]
[Rules and Regulations]
[Pages 58834-58840]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-20463]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Parts 1301, 1305, and 1308

[Docket No. DEA-375]


Schedules of Controlled Substances: Placement of Thiafentanil 
Into Schedule II

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Interim final rule with request for comments.

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SUMMARY: The Drug Enforcement Administration is placing the substance 
thiafentanil (4-(methoxycarbonyl)-4-(N-phenmethoxyacetamido)-1-[2-
(thienyl)ethyl]piperidine), including its isomers, esters, ethers, 
salts and salts of isomers, esters and ethers as possible, into 
schedule II of the Controlled Substances Act. This scheduling action is 
pursuant to the Controlled Substances Act, as revised by the Improving 
Regulatory Transparency for New Medical Therapies Act which was signed 
into law on November 25, 2015.

DATES: The effective date of this rule is August 26, 2016. Interested 
persons may file written comments on this rule in accordance with 21 
U.S.C. 811(j)(3) and 21 CFR 1308.43(g). Electronic comments must be 
submitted, and written comments must be postmarked, on or before 
September 26, 2016. 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.
    Interested persons, defined at 21 CFR 1300.01 as those ``adversely 
affected or aggrieved by any rule or proposed rule issuable pursuant to 
section 201 of the Act (21 U.S.C. 811),'' 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 September 26, 
2016.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-375'' on all correspondence, including any 
attachments.
     Electronic comments: The 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 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 and are discouraged. 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/ODW, 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 also be sent 
to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 8701 
Morrissette Drive, Springfield, Virginia 22152; and (2) Drug 
Enforcement Administration, Attn: DEA Federal Register Representative/
ODW, 8701 Morrissette Drive, Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Michael J. Lewis, Office of Diversion 
Control, 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 are considered part of the 
public record. They will, unless reasonable cause is given, be made 
available by the Drug Enforcement

[[Page 58835]]

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 the 
confidential business information to be redacted within the comment.
    Comments containing personal identifying information and 
confidential business information identified as directed above will 
generally 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, 
including the complete Department of Health and Human Services and Drug 
Enforcement Administration eight-factor analyses, to this interim final 
rule are available at http://www.regulations.gov for easy reference.

Request for Hearing, Notice of Appearance at Hearing, or Waiver of 
Participation in 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. In accordance with 21 CFR 1308.44(a)-(c), requests for a 
hearing, notices of appearance, and waivers of an opportunity for a 
hearing or to participate in a hearing may be submitted only by 
interested persons, defined as those ``adversely affected or aggrieved 
by any rule or proposed rule issuable pursuant to section 201 of the 
Act (21 U.S.C. 811).'' 21 CFR 1300.01. Requests for a hearing and 
notices of participation must conform to the requirements of 21 CFR 
1308.44(a) or (b), as applicable, and include a statement of the 
interest of the person in the proceeding and the objections or issues, 
if any, concerning which the person desires to be heard. Any waiver of 
an opportunity for a hearing must conform to the requirements of 21 CFR 
1308.44(c), including a written statement regarding the interested 
person's position on the matters of fact and law involved in any 
hearing.
    Please note that pursuant to 21 U.S.C. 811(a), the purpose and 
subject matter of the hearing are restricted to ``(A) find[ing] that 
such drug or other substance has a potential for abuse, and (B) 
mak[ing] with respect to such drug or other substance the findings 
prescribed by subsection (b) of section 812 of this title for the 
schedule in which such drug is to be placed . . . .'' Requests for a 
hearing and waivers of participation in the hearing should be submitted 
to the DEA on or before the deadline specified above, using the address 
information provided therein.

Background, Legal Authority, and Basis for This Scheduling Action

    Thiafentanil, known chemically as 4-(methoxycarbonyl)-4-(N-
phenylmethoxyacetamido)-1-[2-(2-thienyl)ethyl]piperidine, a potent 
opioid, is an analogue of fentanyl. The product Thianil (thiafentanil 
oxalate, a salt form of thiafentanil) was reviewed by the Food and Drug 
Administration (FDA) to determine whether it meets the requirements for 
addition to the Index of Legally Marketed Unapproved New Animal Drugs 
for Minor Species (the Index) (21 U.S.C. 360ccc-1) as set forth by the 
Minor Use and Minor Species Animal Health Act of 2004 (MUMS Act, 2004). 
The MUMS Act amended the Federal Food, Drug, and Cosmetic Act (FDCA) to 
allow for the legal marketing of unapproved new animal drugs intended 
for use in minor species. In a letter from the Department of Health and 
Human Services (HHS) dated June 20, 2016, the DEA received notification 
that HHS/FDA added Thianil (thiafentanil oxalate) to the Index under 
section 572 of the FDCA. In this same notification, HHS/FDA stated that 
on June 16, 2016, HHS/FDA granted the request for the addition of 
Thianil to the Index under Minor Species Index File (MIF) 900000. 
Thianil is indicated for use in the immobilization of non-domestic, 
non-food-producing minor species hoofstock.
    Thiafentanil will be marketed as thiafentanil oxalate, 4-
(methoxycarbonyl)-4-(N-phenylmethoxyacetamido)-1-[2-(2-
thienyl)ethyl]piperidinium oxalate. Thiafentanil should not be confused 
with thiofentanyl (N-phenyl-N-(1-(2-(thiophen-2-yl)ethyl)piperidin-4-
yl)propionamide), which is currently listed as a controlled schedule I 
substance.
    Under the Controlled Substances Act (CSA), as amended in 2015 by 
the Improving Regulatory Transparency for New Medical Therapies Act 
(Pub. L. 114-89), where the DEA receives notification from HHS that the 
Secretary has indexed a drug under section 572 of the FDCA, the DEA is 
required to issue an interim final rule controlling the drug not later 
than 90 days after receiving such notification from HHS. 21 U.S.C. 
811(j). Accordingly, the DEA is issuing this interim final rule 
controlling thiafentanil.
    When controlling a drug pursuant to section 811(j), the DEA must 
apply the scheduling criteria of subsections 811(b), (c), and (d) and 
section 812(b). 21 U.S.C. 811(j)(3). In accordance with these criteria, 
the DEA has reviewed the scientific and medical evaluation and 
scheduling recommendation provided by the HHS, along with all other 
relevant data, and completed its own eight-factor review document on 
thiafentanil pursuant to 21 U.S.C. 811(c). As explained below, based on 
these considerations, the DEA concludes that thiafentanil meets the 
criteria for placement in schedule II of the CSA.
    On November 28, 2011, the HHS provided the DEA with its initial 
scientific and medical evaluation and scheduling recommendation 
regarding thiafentanil. Pursuant to 21 U.S.C. 811(b), this document 
contained an eight-factor analysis of the abuse potential of 
thiafentanil as a new drug, along with the HHS' recommendation to 
control thiafentanil and its salts under schedule II of the CSA. 
Subsequently, on March 23, 2016, the HHS provided the DEA with a 
supplement to its 2011 analysis, which indicated that the HHS/FDA 
planned to add Thianil (thiafentanil oxalate) to the Index for use in 
the immobilization of non-domestic, non-food-producing minor species 
hoofstock and reiterated their recommendation that thiafentanil be 
placed in schedule II of the CSA. By

[[Page 58836]]

letter dated June 20, 2016, the DEA received notification from the HHS 
that the FDA had granted the request on June 16, 2016, for Thianil 
(thiafentanil oxalate) to be added to the Index.
    Pursuant to 21 U.S.C. 811(j), and based on the HHS recommendation, 
MUMS Act indication by the HHS/FDA, and the DEA's determination, the 
DEA finds that thiafentanil has a high potential for abuse, a currently 
accepted medical use with severe restrictions, and that abuse of 
thiafentanil may lead to severe psychological or physical dependence. 
Accordingly, the DEA is issuing this interim final rule to add 
thiafentanil (4-(methoxycarbonyl)-4-(N-phenylmethoxyacetamido)-1-[2-(2-
thienyl)ethyl]piperidine) and its isomers, esters, ethers, salts and 
salts of isomers, esters and ethers, whenever the existence of such, to 
schedule II of the CSA.
    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 scheduling action. 
Please note that the DEA and HHS analyses, along with the HHS 
supplement, are available in their entirety under ``Supporting 
Documents'' in the public docket for this interim final rule at http://www.regulations.gov, under Docket Number ``DEA-375.'' Full analysis of, 
and citations to, the information referenced in the summary may also be 
found in the supporting and related material.
    1. The Drug's Actual or Relative Potential for Abuse: Thiafentanil 
is a chemical substance that has not been marketed in the United 
States, however, it is approved and marketed in the Republic of South 
Africa as a salt form under the brand name Thianil (thiafentanil 
oxalate). There is no information available which details actual abuse 
of thiafentanil.
    According to the HHS, thiafentanil is a synthetic analogue of 
fentanyl and is structurally related to other fentanyl-like opioids 
such as sufentanil (schedule II) and carfentanil (schedule II). It acts 
as a potent [micro]-opioid receptor agonist and produces strong 
morphine-like effects in animals. It is only intended for the 
immobilization of non-domestic, non-food-producing minor species 
hoofstock. Thiafentanil has been used in a manner similar to other 
opioid immobilizing agents such as etorphine hydrochloride (schedule 
II) and carfentanil (schedule II), which are approved only for 
veterinary use as animal immobilization agents. The abuse potential of 
thiafentanil has not been evaluated in humans or in animal behavioral 
models that are predictors of abuse by humans. Because thiafentanil 
shares chemical and pharmacological similarities with schedule II 
fentanyl and its analogues, the abuse potential of thiafentanil is 
considered similar to that of schedule II opioid substances such as 
sufentanil and carfentanil.
    Pharmacologically, as a potent [micro] opioid receptor agonist, 
thiafentanil is slightly less potent than carfentanil, which is 100 
times more potent than fentanyl and 10,000 times more potent than 
morphine. Thiafentanil is a potent fentanyl analogue. Thus, it is 
reasonable to assume that there will be potentially significant 
diversion of thiafentanil from legitimate channels by people who have 
access to it, and that thiafentanil would be used without medical 
advice, therefore causing substantial hazards to the users or to the 
safety of the community if not controlled. The chemical and potent 
opioid-like pharmacological properties of thiafentanil predict that its 
risk to the public health is likely to be similar to fentanyl (schedule 
II) and its analogues such as carfentanil (schedule II), sufentanil 
(schedule II) and alpha-methylfentanyl (schedule I).
    2. Scientific Evidence of the Drug's Pharmacological Effects, if 
Known: According to HHS' scientific and medical review, there are no 
data on the effects of thiafentanil in humans. Thiafentanil's effects 
in humans are predicted from its effects in animals and its chemical 
and pharmacological similarity to other schedule II potent opioids such 
as fentanyl and carfentanil.
    The HHS eight-factor review document described a study directly 
comparing the immobilizing effects of thiafentanil (15 mg) and 
carfentanil (2 or 4 mg) in elk in which thiafentanil produced a faster 
immobilization effect (0.7 to 2.2 minutes) than carfentanil. In 
addition, the elk returned to standing 0.9 to 1.4 minutes faster under 
the thiafentanil condition. This study appears to support a faster 
immobilization and recovery time with thiafentanil relative to 
carfentanil. However, the authors stated that the role of the increased 
dose of thiafentanil is unknown.
    Animal studies described by the HHS demonstrated that the effects 
of thiafentanil and carfentanil are completely reversed by naltrexone. 
As a [micro]-opioid receptor antagonist, naltrexone can reverse the 
effects of a variety of opioid drugs including thiafentanil and 
carfentanil. Those studies suggest that thiafentanil possesses a neuro-
pharmacological mechanism of action similar to other schedule II opioid 
drugs with a high abuse potential.
    According to HHS' review, Thianil (thiafentanil) is currently 
approved and registered for use in the Republic of South Africa. 
Thiafentanil oxalate is suggested as a drug of choice in the capture of 
exotic and ungulate wildlife species.
    3. The State of Current Scientific Knowledge Regarding 
Thiafentanil: The chemical name of free base thiafentanil is 4-
(methoxycarbonyl)-4-(N-phenylmethoxyacetamido)-1-[2-(2-
thienyl)ethyl]piperidine. It has a molecular formula of 
C22H28N2O4S and a molecular 
weight of 416.52 g/mol with a Chemical Abstract Registry Number (CAS) 
of 101345-60-2. Thiafentanil oxalate is also known as A3080 with a CAS 
number of 101365-73-5 and has a molecular formula of 
C24H30N2O8S with a 
molecular weight of 506.57 g/mol. Thiafentanil oxalate is a white 
crystalline powder with a melting point of 190-192 [deg]C and its salt 
crystalizes from absolute alcohol. Thiafentanil should not be confused 
with thiofentanyl (N-phenyl-N-(1-(2-(thiophen-2-yl)ethyl)piperidin-4-
yl)propionamide), which is currently listed as a schedule I substance.
    4. Its History and Current Pattern of Abuse: According to the HHS' 
review, there are no reports of actual abuse and misuse of 
thiafentanil. This may be due to the limited use of thiafentanil as an 
immobilizing agent by trained veterinarians.
    Current data from the National Forensic Laboratory System 
(NFLIS),\1\ the System to Retrieve Information from Drug Evidence 
(STRIDE),\2\ and the STARLiMS databases show that there is no evidence 
of law enforcement encounters of thiafentanil in the United States. 
However, thiafentanil's pharmacological and structural properties 
suggest that its pattern of abuse would be similar to other potent

[[Page 58837]]

schedule II [micro]-opioid receptor agonists such as fentanyl and 
carfentanil.
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    \1\ The National Forensic Laboratory System (NFLIS) is a program 
of the DEA, Office of Diversion Control. NFLIS systematically 
collects drug identification results and associated information from 
drug cases submitted to and analyzed by State and local forensic 
laboratories. NFLIS represents an important resource in monitoring 
illicit drug abuse and trafficking, including the diversion of 
legally manufactured pharmaceuticals into illegal markets. NFLIS is 
a comprehensive information system that includes data from forensic 
laboratories that handle approximately 90% of an estimated 1.0 
million distinct annual State and local drug analysis cases. NFLIS 
includes drug chemistry results from completed analyses only. While 
NFLIS 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.
    \2\ The System to Retrieve Information from Drug Evidence 
(STRIDE) is a database of drug exhibits sent to DEA laboratories for 
analysis. Exhibits from the database are from the DEA, other federal 
agencies, and local law enforcement agencies. Reporting via STRIDE 
ceased on September 30, 2014. STRIDE was succeeded by STARLiMS.
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    5. The Scope, Duration, and Significance of Abuse: An assessment of 
the scope, duration, and significance of thiafentanil abuse is not 
available since it has only been used in a limited market. However, as 
stated in the HHS review, the structural and pharmacological properties 
of thiafentanil suggest that it could lead to an abuse pattern with a 
scope, duration, and significance of abuse similar to that observed 
with other opioid drugs and opioid analogues if it were marketed in a 
non-controlled status or were the subject of clandestine synthesis. The 
HHS and DEA note that thiafentanil is not known to be or to have been 
the subject of abuse in the United States.
    6. What, if any, Risk There is to the Public Health: The HHS review 
indicates that thiafentanil presents a significant risk to the public 
health and, in this vein, that thiafentanil should only be used in 
certain animals for very limited purposes and with extreme caution. 
Based on the review of the structural and pharmacological properties of 
thiafentanil, the HHS concluded that the abuse of thiafentanil is 
likely to pose a similar risk to public health as that of other potent 
opioid drugs such as sufentanil (schedule II), fentanyl (schedule II), 
carfentanil (schedule II) and clandestinely synthesized alpha-
methylfentanyl (schedule I). Thus, inappropriate use of thiafentanil 
poses a high risk to the public health. Among other things, HHS noted 
that as a fentanyl derivative, and assuming that thiafentanil can be 
aerosolized, the use of thiafentanil presents a significant risk to the 
public health.
    HHS described that thiafentanil's labeling indicates that it is 
solely intended for use by zoologic, wildlife, or exotic animal 
veterinarians or field biologists who have received training and are 
supervised by veterinarians. The sponsor recommends the use of handling 
protocols similar to those in place for other scheduled potent opioids 
such as carfentanil. HHS further indicated that thiafentanil should be 
handled in teams consisting of at least two individuals knowledgeable 
about the hazards of working with potent [mu]-opioid agonist 
substances. Personal protective equipment such as latex gloves and 
protective eyewear should be used and syringes must be disposed of 
properly. If exposure to thiafentanil occurs in a remote or distant 
environment, veterinary naltrexone is recommended for use as a reversal 
agent. The label information will further state that thiafentanil must 
never be used unless an adequate amount of reversal agent (naltrexone 
hydrochloride) is immediately available.
    HHS also describes the risk of thiafentanil intoxication upon 
ingestion of animals immobilized with thiafentanil. The label 
information states that thiafentanil is not intended for human or 
animal consumption or in non-food producing minor species that become 
eligible for consumption by humans or food-producing animals. Because 
thiafentanil, similar to carfentanil, etorphine hydrochloride and 
diprenorphine, is a potent [mu]-opioid receptor agonist, it will be 
subject to specialized handling, distribution and storage procedures 
similar to those applicable for carfentanil, etorphine hydrochloride 
and diprenorphine as set forth in 21 CFR parts 1301 and 1305. As a 
result, this interim final rule revises 21 CFR 1301.74(g), 1301.75(e), 
1305.07 introductory text and paragraph (a), and 1305.17(d) to include 
``thiafentanil.''
    7. Its Psychic or Physiological Dependence Liability: HHS' review 
states that the structural and pharmacological properties of 
thiafentanil suggest that it possesses a psychic and physiological 
dependence liability that is similar to other schedule II related 
[micro]-opioid receptor agonist drugs such as sufentanil, fentanyl and 
carfentanil.
    As cited by the HHS review, a double-blind abuse liability study 
examining intravenous fentanyl, buprenorphine, heroin, morphine, and 
oxycodone in methadone-maintained patients reported that fentanyl 
produced subjective effects similar to heroin (schedule I) on several 
outcome measures indicating that the two drugs produce similar 
subjective effects. It also demonstrates the psychic dependence 
liability of fentanyl, and thiafentanil is expected to produce effects 
similar to fentanyl and to present a similar risk of psychic and 
physiological dependence. There has been a major increase in abuse of 
opioids analgesics in the United States (HHS review document, 2011; 
Compton and Volkow, 2006). Thiafentanil, similar to these opioid 
analgesics, presents a risk of severe psychic and physiological 
dependence.
    8. Whether the Substance is an Immediate Precursor of a Substance 
Already Controlled under the CSA: Thiafentanil is not considered an 
immediate precursor of any controlled substance.

Determination of Appropriate Schedule

    The CSA lists the findings required to place a drug or other 
substance in any particular schedule (I, II, III, IV, or V). 21 U.S.C. 
812(b). After consideration of the analysis and recommendation of the 
Assistant Secretary for Health of the HHS and review of all available 
data, the Acting Administrator of the DEA, pursuant to 21 U.S.C. 
812(b)(2), finds that:
    1. Thiafentanil has a high potential for abuse. Based on its 
structural and pharmacological properties, thiafentanil has an abuse 
potential that is comparable to other schedule II opioid drugs such as 
fentanyl, carfentanil, and sufentanil;
    2. FDA determined that Thianil (thiafentanil oxalate) meets the 
requirements for addition to the Index as set forth by the MUMS Act, 
2004 and accordingly added Thianil (thiafentanil oxalate) to the Index 
of Legally Marketed Unapproved New Animal Drugs for Minor Species (the 
Index) under section 572 of the Federal Food, Drug, and Cosmetic Act. 
Thianil (thiafentanil oxalate) will be legally marketed in the United 
States and will have an accepted medical use with severe restrictions; 
\3\ and
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    \3\ According to the HHS analysis, ``[u]se of a new animal 
indexed drug is subject to significant restrictions. For example, 
use of an indexed new animal drug for minor species is limited to a 
minor species for which there is a reasonable certainty that the 
animal or edible products from the animal will not be consumed by 
humans or food producing animals. 21 U.S.C. Sec.  360ccc-l(a)(1). 
The requester must label, distribute, and promote the new animal 
drug in accordance with the Index entry, and the FDA may remove a 
new animal drug from the Index if the conditions and limitations of 
use have not been followed. 21 U.S.C. 360ccc-l(d)(l)(G); (f)(l)(F). 
The labeling of an indexed new animal drug must prominently state 
that the extra-label use of the product is prohibited. 21 U.S.C. 
360ccc-l(h). Such restrictions are not imposed upon approved human 
or animal drugs.''
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    3. Due to the chemical and pharmacological similarities of 
thiafentanil to other schedule II fentanyl derivatives, abuse of 
thiafentanil may lead to severe psychological or physical dependence.
    Based on these findings, the Acting Administrator of the DEA 
concludes that thiafentanil, including its isomers, esters, ethers, 
salts and salts of isomers, esters and ethers whenever the existences 
of such isomers, esters, ethers, and salts is possible warrants control 
in schedule II of the CSA. 21 U.S.C. 812(b)(2).

Requirements for Handling Thiafentanil

    Thiafentanil is subject to the CSA's schedule II regulatory 
controls and administrative, civil, and criminal sanctions applicable 
to the manufacture, distribution, reverse distribution, dispensing, 
importing, exporting, research, and conduct of instructional

[[Page 58838]]

activities and chemical analysis with, and possession involving 
schedule II substances, including the following:
    1. Registration. Any person who desires to handle thiafentanil 
(manufacture, distribute, reverse distribute, dispense, import, export, 
engage in research, or conduct instructional activities or chemical 
analysis with, or possess), must 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. Quota. Only registered manufacturers are permitted to 
manufacture thiafentanil in accordance with a quota assigned pursuant 
to 21 U.S.C. 826 and in accordance with 21 CFR part 1303.
    3. Disposal of stocks. Upon obtaining a schedule II registration to 
handle thiafentanil, and if subsequently, any person who does not 
desire or is not able to maintain a schedule II registration must 
surrender all quantities of currently held thiafentanil, or may 
transfer all quantities of currently held thiafentanil to a person 
registered with the DEA in accordance with 21 CFR part 1317, in 
addition to all other applicable federal, state, local, and tribal 
laws.
    4. Security. Thiafentanil is subject to schedule II security 
requirements and must be handled and stored pursuant to 21 U.S.C. 821 
and 823, and in accordance with 21 CFR 1301.71-1301.93.
    5. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of thiafentanil must comply with 21 U.S.C. 825 
and 958(e), and be in accordance with 21 CFR part 1302. In addition, 
thiafentanil is subject to additional labeling requirements provided by 
FDA. Thiafentanil must be labeled, distributed, and promoted in 
accordance with the Index entry of the new animal drug and the FDA may 
remove a new animal drug from the Index if the conditions and 
limitations of use have not been followed. 21 U.S.C. 360ccc-l(d)(l)(G); 
(f)(l)(F). The labeling of an indexed new animal drug must prominently 
state that the extra-label use of the product is prohibited. 21 U.S.C. 
360ccc-l(h).
    6. Inventory. Every DEA registrant who desires to possess any 
quantity of thiafentanil must take an inventory of thiafentanil on 
hand, pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 
1304.03, 1304.04, and 1304.11.
    Any person who becomes registered with the DEA to handle 
thiafentanil must take an initial inventory of all stocks of controlled 
substances (including thiafentanil) 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 
thiafentanil) 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.
    7. Records and Reports. Every DEA registrant must maintain records 
and submit reports for thiafentanil, or products containing 
thiafentanil, pursuant to 21 U.S.C. 827 and 958(e), and in accordance 
with 21 CFR parts 1304, 1312, and 1317.
    8. Orders for thiafentanil. Every DEA registrant who distributes 
thiafentanil is required to comply with order form requirements, 
pursuant to 21 U.S.C. 828, and in accordance with 21 CFR part 1305.
    9. Prescriptions and other dispensing. All prescriptions for 
thiafentanil or products containing thiafentanil must comply with 21 
U.S.C. 829, and be issued in accordance with 21 CFR parts 1306 and 
1311, subpart C. Moreover, given that thiafentanil is not the subject 
of an approved new drug application under the FDCA, and that it is only 
allowed under the MUMS Act amendments to the FDCA to be marketed for 
extremely limited use in minor species, DEA would not consider any 
dispensing of thiafentanil for human use to be for a legitimate medical 
purpose within the meaning of the CSA. Likewise, DEA would not consider 
any dispensing of thiafentanil for animal use beyond the scope of the 
drug's labeling authorized under the MUMS Act amendments to the FDCA to 
be for a legitimate medical purpose within the meaning of the CSA.
    10. Manufacturing and Distributing. In addition to the general 
requirements of the CSA and DEA regulations that are applicable to 
manufacturers and distributors of schedule II controlled substances, 
such registrants should be advised that (consistent with the foregoing 
considerations) any manufacturing or distribution of thiafentanil may 
only be for the legitimate purposes consistent with the drug's labeling 
authorized under the MUMS Act, or for research activities authorized by 
the FDCA and CSA.
    11. Importation and Exportation. All importation and exportation of 
thiafentanil must be in compliance with 21 U.S.C. 952, 953, 957, and 
958, and in accordance with 21 CFR part 1312.
    12. Liability. Any activity involving thiafentanil not authorized 
by, or in violation of, the CSA or its implementing regulations, is 
unlawful, and may subject the person to administrative, civil, and/or 
criminal sanctions.

Regulatory Analyses

Administrative Procedure Act

    Public Law 114-89 was signed into law, amending 21 U.S.C. 811. This 
amendment provides that in cases where a new drug is (1) approved or 
indexed by the Department of Health and Human Services (HHS) and (2) 
HHS recommends control in CSA schedule II-V, the DEA shall issue an 
interim final rule scheduling the drug within 90 days. Additionally, 
the law specifies that the rulemaking shall become immediately 
effective as an interim final rule without requiring the DEA to 
demonstrate good cause. Therefore, the DEA has determined that the 
notice and comment requirements of section 553 of the APA, 5 U.S.C. 
553, do not apply to this scheduling action.

Executive Orders 12866, Regulatory Planning and Review, and 13563, 
Improving Regulation and Regulatory Review

    In accordance with Public Law 114-89, this scheduling action is 
subject to formal rulemaking procedures performed ``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 procedures 
and 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.

Executive Order 12988, Civil Justice Reform

    This 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 rulemaking does not have federalism implications warranting 
the application of Executive Order 13132. The rule does not have 
substantial direct effects on the States, on the relationship between 
the national government and the States, or on the distribution of power 
and

[[Page 58839]]

responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal 
Governments

    This 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

    In accordance with 5 U.S.C. 603(a), ``[w]henever an agency is 
required by [5 U.S.C. 553], or any other law, to publish general notice 
of proposed rulemaking for any proposed rule, or publishes a notice of 
proposed rulemaking for an interpretive rule involving the internal 
revenue laws of the United States, the agency shall prepare and make 
available for public comment an initial regulatory flexibility 
analysis.'' As noted in the above discussion regarding applicability of 
the Administrative Procedure Act, the DEA has determined that the 
notice and comment requirements of section 553 of the APA, 5 U.S.C. 
553, do not apply to this scheduling action. Consequently, the RFA does 
not apply to this interim final rule.

Unfunded Mandates Reform Act of 1995

    In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995, 
2 U.S.C. 1501 et seq., the 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 for 
inflation) in any one 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 
requirement 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.

Congressional Review Act

    This rule is not a major rule as defined by section 804 of the 
Small Business Regulatory Enforcement Fairness Act of 1996 
(Congressional Review Act (CRA)). This rule will not result in: An 
annual effect on the economy of $100,000,000 or more; a major increase 
in costs or prices for consumers, individual industries, Federal, 
State, or local government agencies, or geographic regions; or 
significant adverse effects on competition, employment, investment, 
productivity, innovation, or on the ability of U.S.-based companies to 
compete with foreign based companies in domestic and export markets. 
However, pursuant to the CRA, the DEA has submitted a copy of this 
interim final rule to both Houses of Congress and to the Comptroller 
General.

List of Subjects

21 CFR Part 1301

    Administrative practice and procedure, Drug traffic control, 
Security measures.

21 CFR Part 1305

    Drug traffic control, Reporting and recordkeeping requirements.

21 CFR Part 1308

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

    For the reasons set out above, the DEA amends 21 CFR parts 1301, 
1305 and 1308 as follows:

PART 1301--REGISTRATION OF MANUFACTURERS, DISTRIBUTORS, AND 
DISPENSERS OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR part 1301 continues to read as 
follows:

    Authority: 21 U.S.C. 821, 822, 823, 824, 831, 871(b), 875, 877, 
886a, 951, 952, 953, 956, 957, 958, 965.


0
2. In Sec.  1301.74, revise paragraph (g) to read as follows:


Sec.  1301.74  Other security controls for non-practitioners; narcotic 
treatment programs and compounders for narcotic treatment programs.

* * * * *
    (g) Before the initial distribution of thiafentanil, carfentanil, 
etorphine hydrochloride and/or diprenorphine to any person, the 
registrant must verify that the person is authorized to handle the 
substance(s) by contacting the Drug Enforcement Administration.
* * * * *

0
3. In Sec.  1301.75, revise paragraph (e) to read as follows:


Sec.  1301.75  Physical security controls for practitioners.

* * * * *
    (e) Thiafentanil, carfentanil, etorphine hydrochloride and 
diprenorphine shall be stored in a safe or steel cabinet equivalent to 
a U.S. Government Class V security container.

PART 1305--ORDERS FOR SCHEDULE I AND II CONTROLLED SUBSTANCES

0
4. The authority citation for 21 CFR part 1305 continues to read as 
follows:

    Authority: 21 U.S.C. 821, 828, 871(b), unless otherwise noted.


0
5. In Sec.  1305.07, revise the introductory text and paragraph (a) to 
read as follows:


Sec.  1305.07  Special procedure for filling certain orders.

    A supplier of thiafentanil, carfentanil, etorphine hydrochloride, 
or diprenorphine, if he or she determines that the purchaser is a 
veterinarian engaged in zoo and exotic animal practice, wildlife 
management programs, or research, and is authorized by the 
Administrator to handle these substances, may fill the order in 
accordance with the procedures set forth in Sec.  1305.17 except that:
    (a) A DEA Form 222 or an electronic order for thiafentanil, 
carfentanil, etorphine hydrochloride, and diprenorphine must contain 
only these substances in reasonable quantities.
* * * * *

0
6. In Sec.  1305.17, revise paragraph (d) to read as follows:


Sec.  1305.17  Preservation of DEA Forms 222.

* * * * *
    (d) The supplier of thiafentanil, carfentanil, etorphine 
hydrochloride, and diprenorphine must maintain DEA Forms 222 for these 
substances separately from all other DEA Forms 222 and records required 
to be maintained by the registrant.

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

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

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


0
8. In Sec.  1308.12, add paragraph (c)(29) to read as follows:


Sec.  1308.12  Schedule II.

* * * * *
    (c) * * *

(29) Thiafentanil...............................................    9729
 

* * * * *


[[Page 58840]]


    Dated: August 18, 2016.
Chuck Rosenberg,
Acting Administrator.
[FR Doc. 2016-20463 Filed 8-25-16; 8:45 am]
 BILLING CODE 4410-09-P