81 FR 29487 - Schedules of Controlled Substances: Placement of Brivaracetam Into Schedule V

DEPARTMENT OF JUSTICE
Drug Enforcement Administration

Federal Register Volume 81, Issue 92 (May 12, 2016)

The Drug Enforcement Administration is placing the substance brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide) (also referred to as BRV; UCB-34714; Briviact) (including its salts) into schedule V 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.

[Federal Register Volume 81, Number 92 (Thursday, May 12, 2016)]
[Rules and Regulations]
[Pages 29487-29492]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-11245]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-435]


Schedules of Controlled Substances: Placement of Brivaracetam 
Into Schedule V

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 
brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide) 
(also referred to as BRV; UCB-34714; Briviact) (including its salts) 
into schedule V 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 rulemaking is May 12, 2016. 
Interested persons may file written comments on this rulemaking in 
accordance with 21 CFR 1308.43(g). Electronic comments must be 
submitted, and written comments must be postmarked, on or before June 
13, 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. Requests for 
hearing and waivers of an opportunity for a hearing or to participate 
in a hearing must be received on or before June 13, 2016.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-435'' 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, VA 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: Barbara J. Boockholdt, 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 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)-

[[Page 29488]]

(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 DEA using the address information provided above.

Legal Authority

    The DEA implements and enforces titles II and III of the 
Comprehensive Drug Abuse Prevention and Control Act of 1970, as 
amended. 21 U.S.C. 801-971. Titles II and III are referred to as the 
``Controlled Substances Act'' and the ``Controlled Substances Import 
and Export Act,'' respectively, and are collectively referred to as the 
``Controlled Substances Act'' or the ``CSA'' for the purpose of this 
action. The DEA publishes the implementing regulations for these 
statutes in title 21 of the Code of Federal Regulations (CFR), chapter 
II. The CSA and its implementing regulations are designed to prevent, 
detect, and eliminate the diversion of controlled substances and listed 
chemicals into the illicit market while providing for the legitimate 
medical, scientific, research, and industrial needs of the United 
States. Controlled substances have the potential for abuse and 
dependence and are controlled to protect the public health and safety.
    Under the CSA, controlled substances are classified into one of 
five schedules based upon their potential for abuse, their currently 
accepted medical use in treatment in the United States, and the degree 
of dependence the substance may cause. 21 U.S.C. 812. The initial 
schedules of controlled substances established by Congress are found at 
21 U.S.C. 812(c), and the current list of all scheduled substances is 
published at 21 CFR part 1308.
    Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule, 
``add to such a schedule or transfer between such schedules any drug or 
other substance if he * * * finds that such drug or other substance has 
a potential for abuse, and * * * makes 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 * 
* *'' The Attorney General has delegated this scheduling authority 
under 21 U.S.C. 811 to the Administrator of the DEA. 28 CFR 0.100.
    The CSA provides that scheduling of any drug or other substance may 
be initiated by the Attorney General (1) on her own motion; (2) at the 
request of the Secretary of Health and Human Services (HHS); or (3) on 
the petition of any interested party. 21 U.S.C. 811(a). This action 
imposes the regulatory controls and administrative, civil, and criminal 
sanctions of schedule V controlled substances for any person who 
handles or proposes to handle BRV.
    The Improving Regulatory Transparency for New Medical Therapies Act 
(Pub. L. 114-89) was signed into law on November 25, 2015. This law 
amended 21 U.S.C. 811 and states that in cases where a new drug is (1) 
approved by the Department of Health and Human Services (HHS) and (2) 
HHS recommends control in CSA schedule II-V, DEA shall issue an interim 
final rule scheduling the drug, within 90 days.
    The law further states that the 90-day timeframe starts the later 
of (1) the date DEA receives the HHS scientific and medical evaluation/
scheduling recommendation or (2) the date DEA receives notice of drug 
approval by HHS. In addition, the law specifies that the rulemaking 
shall become immediately effective as an interim final rule without 
requiring the DEA to demonstrate good cause therefor.
    Specifically, Public Law 114-89 revised section 201 of the CSA (21 
U.S.C. 811) by inserting after subsection (i) a new paragraph (j), 
which requires that with respect to a drug referred to in subsection 
(f), if the Secretary recommends that the Attorney General control the 
drug in schedule II, III, IV, or V pursuant to subsections (a) and (b), 
the Attorney General is required to, within 90 days, issue an interim 
final rule controlling the drug in accordance with such subsections and 
21 U.S.C. 812(b) using the specified procedures. For purposes of 
calculating the 90 days, Public Law 114-89 states that such date shall 
be the later of the date on which the Attorney General receives the 
scientific and medical evaluation and the scheduling recommendation 
from the Secretary in accordance with subsection (b), or the date on 
which the Attorney General receives notification from the Secretary 
that the Secretary has approved an application under section 505(c), 
512, or 571 of the Federal Food, Drug, and Cosmetic Act or section 
351(a) of the Public Health Service Act, or indexed a drug under 
section 572 of the Federal Food, Drug, and Cosmetic Act, with respect 
to the drug described in paragraph (1). Public Law 114-89 further 
stipulates that a rule issued by the Attorney General under paragraph 
(1) becomes immediately effective as an interim final rule without 
requiring the Attorney General to demonstrate good cause and requires 
that the interim final rule give interested persons the opportunity to 
comment and to request a hearing. After the conclusion of such 
proceedings, the Attorney General must issue a final rule in accordance 
with the scheduling criteria of subsections 21 U.S.C. 811(b), (c), and 
(d) of this section and 21 U.S.C. 812(b).

Background

    Brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] 
butanamide) (also referred to as BRV; UCB-34714; Briviact) is a new 
molecular entity with central nervous system (CNS) depressant 
properties. BRV is known to be a high affinity ligand for the synaptic 
vesicle protein, SV2A, which is found on excitatory synapses in the 
brain. On November 22, 2014, UCB Inc. (Sponsor) submitted three New 
Drug Applications (NDAs) to the U.S. Food and Drug Administration (FDA) 
for the tablet, oral, and intravenous formulations of BRV. The FDA 
accepted the NDA filings for BRV on January 21, 2015.
    On March 28, 2016 the DEA received notification that HHS/FDA 
approved BRV as an add-on treatment to other medications to treat 
partial onset seizures in patients age 16 years and older with 
epilepsy.

Determination to Schedule BRV

    Pursuant to 21 U.S.C. 811(a)(1), proceedings to add a drug or 
substance to those controlled under the CSA may be initiated by request 
of the Secretary

[[Page 29489]]

of the HHS.\1\ On September 8, 2015, the HHS provided the DEA with a 
scientific and medical evaluation document prepared by the FDA entitled 
``Basis for the Recommendation to Place Brivaracetam in Schedule V of 
the Controlled Substances Act.'' Pursuant to 21 U.S.C. 811(b), this 
document contained an eight-factor analysis of the abuse potential of 
BRV as a new drug, along with the HHS' recommendation to control BRV 
under schedule V of the CSA.
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    \1\ As set forth in a memorandum of understanding entered into 
by the HHS, the 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 the 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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    In response, in December 2015, the DEA 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 pursuant to 21 U.S.C. 811(c). The DEA concluded that 
BRV met the 21 U.S.C. 812(b)(5) criteria for placement in schedule V of 
the CSA. Subsequently, on March 28, 2016, the DEA received notification 
that HHS/FDA approved three NDAs for BRV (see Background section).
    Pursuant to the provisions of the Improving Regulatory Transparency 
for New Medical Therapies Act (Pub. L. 114-89), and based on the HHS 
recommendation, NDA approvals by HHS/FDA, and DEA's determination, DEA 
is issuing this interim final rule to schedule brivaracetam ((2S)-2-
[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide) (including its salts) 
as a controlled substance under 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 both the DEA and HHS analyses 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-435.'' 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: BRV is a new 
chemical entity and has not been marketed in the United States or in 
any other country; information on actual abuse of BRV is not available. 
The HHS characterized BRV as related in its action to lacasamide and 
ezogabine, which are both schedule V CNS depressant anti-epileptics 
(AEDs). Based on data submitted by the Sponsor in their NDAs, the HHS 
indicated that administration of BRV in mice, rats, and dogs resulted 
in CNS depressant effects, including decreased locomotor activity and 
reactivity, motor incoordination, and ataxia.
    BRV is not self-administered in animals and, unlike schedule IV 
benzodiazepines and the schedule III AED perampanel, lacks 
pentobarbital-like (schedule II) discriminative stimulus and 
reinforcing effects (HHS review, 2015). In humans, BRV is most similar 
to the schedule V AEDs lacosamide, ezogabine, and pregabalin in 
producing positive subjective effects without producing sedation and 
withdrawal following drug discontinuation that is observed with 
schedule IV benzodiazepines. Based on this collective evidence, the HHS 
concluded that BRV has an abuse potential that is most similar to AEDs 
in schedule V.
    2. Scientific Evidence of the Drug's Pharmacological Effects, if 
Known: BRV selectively binds with high affinity to synaptic vesicle 
protein 2A (SV2A). It produces reverse inhibition caused by negative 
modulators of gamma aminobutyric acid (GABA) and glycine and inhibits 
sodium (Na+) channels. These sites appear to underlie pharmacological 
activity of BRV.
    In rats, BRV at high doses partially generalizes to the schedule IV 
benzodiazepine chlordiazepoxide. BRV, across a wide range of doses, 
neither initiates nor maintains self-administration in rats trained to 
self-administer cocaine. Human studies have reported that healthy 
individuals may experience euphoria, sedation, and a drunken-like 
feeling following BRV administration. When treatment-emergent adverse 
events (TEAEs) \2\ were pooled across several clinical BRV studies, the 
most common TEAEs were dizziness and sedative-related events such as 
fatigue, extreme drowsiness, and extreme weakness. In a human abuse 
potential study, the oral abuse potential, safety, tolerability, and 
pharmacokinetics of BRV (50 mg, 200 mg, and 1000 mg) were compared to 
1.5 and 3.0 mg of the schedule IV CNS depressant alprazolam (ALP) and 
placebo. When surveyed, for all doses of BRV, there was an increase of 
drug likability, feeling of a high, and taking the drug again in 
comparison to placebo. The HHS mentioned that individuals who took BRV 
had fewer sedative, euphoric, stimulant, dizziness, and overall 
negative subjective effects compared to ALP.
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    \2\ Treatment-emergent adverse event (TEAE): An event or 
unexpected medical occurrence (e.g. adverse event) which first 
appears during treatment with a drug or substance. TEAEs are 
typically absent prior to the onset of treatment or would have been 
exacerbated relative to pre-treatment conditions.
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    3. The State of Current Scientific Knowledge Regarding 
Brivaracetam: The chemical name for brivaracetam is (2S)-2-[(4R)-2-oxo-
4-propylpyrrolidin-1-yl] butanamide. Other names include BRV and UCB-
34714. The Chemical Abstract Services number (CAS #) of BRV is: 357336-
20-0. BRV is a racetam derivative.\3\ As the HHS noted, BRV does not 
have structural similarities to any other scheduled AED or to any major 
classes of abused sedative drugs with noted euphoric effects. Chemical 
synthesis of BRV is considered highly complex and includes several 
steps, reagents and specialized equipment.
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    \3\ Racetams are a class of drugs that have a pyrrolidoline 
center.
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    BRV is readily soluble in water at up to 700 mg/mL. In an in vitro 
oral tablet dissolution evaluation, BRV oral tablets were placed in a 
buffer (pH 6.4) for 16 hours. Approximately 86-96% of BRV was released 
after 16 hours in the buffer; 14-30% of BRV was released following 1 
hour and 40-66% BRV was released after 4 hours.
    Following oral ingestion, BRV is rapidly and completely absorbed. 
In healthy young males, the half-life of BRV was determined to be 
approximately 9 hours. According to the HHS, the half-life of BRV is 
decreased to 6 hours when a repeated oral dose of 800 mg/day BRV is 
administered. The HHS noted that BRV binds weakly to plasma proteins 
and is extensively metabolized through several pathways. Clearance 
through the kidneys represents 5-10% of the total clearance and only 3-
7% of the parent compound (BRV) was detected in the urine. The three 
main metabolites of BRV were detected in urine and according to the 
HHS, these metabolites are relatively inactive. One BRV metabolite was 
characterized as having a potency that was 20 times less than BRV, and 
this metabolite was not detected in human plasma and represented less 
than 3% of the dose in urine.
    4. Its History and Current Pattern of Abuse: As noted by the HHS, 
information on the history and current pattern of abuse of BRV is not 
available since this drug is currently not marketed in any country. A 
review of the animal and human data indicates that BRV has an abuse 
potential similar to other schedule V AEDs. If BRV were to be

[[Page 29490]]

approved for medical use, the HHS indicated that BRV would be abused 
for its euphoric properties and other abuse-related TEAEs that were 
reported in human clinical studies. Based on the available information, 
the HHS concluded that the history and pattern of abuse of BRV will be 
similar to other schedule V CNS depressants.
    5. The Scope, Duration, and Significance of Abuse: As noted by the 
HHS, information on the scope, duration, and significance of abuse of 
BRV is not available since this drug is currently not marketed in any 
country. Results from animal and human studies suggest that there is 
abuse potential associated with BRV and if marketed in the United 
States, it is likely that BRV will be abused similar to other AEDs that 
are CNS depressants. The HHS stated that it is unlikely that epileptic 
individuals (the population expected to take this drug) will abuse BRV. 
The HHS concluded that based on abuse potential similarities between 
BRV and other schedule V AEDs, it is likely that the scope, duration, 
and significance of abuse of BRV will be similar to these compounds.
    6. What, if any, Risk There is to the Public Health: The HHS 
characterized BRV's drug abuse potential to be similar to schedule V 
AEDs. As such, the public health risk with BRV will also be similar to 
other schedule V AEDs. The HHS noted that if BRV were approved for 
medical use, it would be abused for its rewarding properties. In 
healthy volunteers administered 600 mg or higher of BRV, cognitive and 
motor impairment and sedation were observed. It is unknown how BRV 
would interact in combination with other CNS depressants and if the 
sedative effects would be additive or even a lethal combination. In an 
interaction study with BRV and intravenous ethanol in healthy 
individuals, it was determined that BRV enhanced the effects of 
ethanol.
    7. Its Psychic or Physiological Dependence Liability: BRV has 
limited psychological dependence and does not appear to have physical 
dependence. When rats were administered BRV for 30 days, no signs of 
physical dependence were noted in comparison to the schedule IV 
comparator, chlordiazepoxide. Similarly, in human clinical studies with 
healthy volunteers, there were no reports or adverse events that noted 
physical dependence or a withdrawal syndrome associated with BRV use. 
The low potential for physical dependence observed with BRV is 
consistent with other schedule V AEDs. There is limited evidence for 
psychological dependence with BRV. Clinical studies have reported 
individuals experiencing increasing euphoria with increasing doses of 
BRV. Tolerance does not appear to develop with respect to BRV treatment 
on epileptic seizure reduction.
    8. Whether the Substance is an Immediate Precursor of a Substance 
Already Controlled under the CSA: BRV is not an immediate precursor of 
any controlled substance.
    Conclusion: After considering the scientific and medical evaluation 
conducted by the HHS, the HHS' recommendation, and its own eight-factor 
analysis, the DEA has determined that these facts and all relevant data 
constitute substantial evidence of a potential for abuse of BRV. As 
such, the DEA hereby schedules BRV as a controlled substance under the 
CSA.

Determination of Appropriate Schedule

    The CSA outlines 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)(5), finds that:
    1. BRV has a low potential for abuse relative to the drugs or other 
substances in schedule IV. The overall abuse potential of BRV is 
comparable to schedule V controlled substances such as ezogabalin, 
pregabalin, and lacosamide;
    2. With FDA's approval of the new drug applications, BRV has a 
currently accepted medical use in the United States as adjunctive 
treatment of partial onset seizures in epileptic individuals ages 16 
and older; and
    3. Human and animal studies demonstrate that BRV has limited 
psychological dependence and does not appear to have physical 
dependence. There was no evidence of physical dependence associated 
with BRV in human and animal studies since there have been no reports 
of withdrawal syndromes or other physical dependence effects. Based on 
these data, abuse of BRV may lead to limited psychological dependence 
similar to schedule V AEDs but less than that of drugs in schedule IV.
    Based on these findings, the Acting Administrator of the DEA 
concludes that brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-
yl] butanamide) (also referred to as BRV; UCB-34714; Briviact), 
including its salts, warrants control in schedule V of the CSA. 21 
U.S.C. 812(b)(5).

Requirements for Handling Brivaracetam

    BRV is subject to the CSA's schedule V regulatory controls and 
administrative, civil, and criminal sanctions applicable to the 
manufacture, distribution, reverse distribution, dispensing, importing, 
exporting, research, and conduct of instructional activities and 
chemical analysis with, and possession involving schedule V substances, 
including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, dispenses, imports, exports, engages in research, 
or conducts instructional activities or chemical analysis with, or 
possesses) BRV, or who desires to handle BRV, 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. Any person 
who currently handles BRV, and is not registered with the DEA, must 
submit an application for registration and may not continue to handle 
BRV, unless the DEA has approved that application for registration, 
pursuant to 21 U.S.C. 822, 823, 957, and 958, and in accordance with 21 
CFR parts 1301 and 1312.
    2. Disposal of stocks. Any person who does not desire or is not 
able to obtain a schedule V registration must surrender all quantities 
of currently held BRV, or may transfer all quantities of currently held 
BRV to a person registered with the DEA in accordance with 21 CFR part 
1317, in additional to all other applicable federal, state, local, and 
tribal laws.
    3. Security. BRV is subject to schedule III-V security requirements 
and must be handled and stored pursuant to 21 U.S.C. 821, 823, and 
871(b), and in accordance with 21 CFR 1301.71-1301.93.
    4. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of BRV must comply with 21 U.S.C. 825 and 958(e), 
and be in accordance with 21 CFR part 1302.
    5. Inventory. Every DEA registrant who possesses any quantity of 
BRV must take an inventory of BRV 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 must take an initial 
inventory of all stocks of controlled substances (including BRV) 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.

[[Page 29491]]

    After the initial inventory, every DEA registrant must take a new 
inventory of all stocks of controlled substances (including BRV) 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 must maintain records 
and submit reports for BRV, or products containing BRV, pursuant to 21 
U.S.C. 827 and 958(e), and in accordance with 21 CFR parts 1304, 1312, 
and 1317.
    7. Prescriptions. All prescriptions for BRV or products containing 
BRV must comply with 21 U.S.C. 829, and be issued in accordance with 21 
CFR parts 1306 and 1311, subpart C.
    8. Importation and Exportation. All importation and exportation of 
BRV 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 BRV 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 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 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 in 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 part 1308:

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), unless otherwise noted.


0
2. Amend Sec.  1308.15 by redesignating paragraphs (e)(1) through 
(e)(3) as paragraphs (e)(2) through (e)(4) and adding new paragraph 
(e)(1) to read as follows:


Sec.  1308.15  Schedule V.

* * * * *
    (e) * * *

[[Page 29492]]



(1) Brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]       2710
 butanamide) (also referred to as BRV; UCB-34714; Briviact)
 (including its salts).........................................
 

* * * * *

    Dated: May 6, 2016.
Chuck Rosenberg,
Acting Administrator.
[FR Doc. 2016-11245 Filed 5-11-16; 8:45 am]
BILLING CODE 4410-09-P