[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