Schedules of Controlled Substances: Placement of Serdexmethylphenidate in Schedule IV, 24487-24492 [2021-09738]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 86, Number 87 (Friday, May 7, 2021)]
[Rules and Regulations]
[Pages 24487-24492]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-09738]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-808]


Schedules of Controlled Substances: Placement of 
Serdexmethylphenidate in Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Interim final rule with request for comments.

-----------------------------------------------------------------------

SUMMARY: On March 2, 2021, the United States Food and Drug 
Administration approved a new drug application for AZSTARYS capsules 
for oral use, a combination drug product containing 
serdexmethylphenidate chloride and

[[Page 24488]]

dexmethylphenidate hydrochloride, for the treatment of Attention 
Deficit Hyperactivity Disorder in patients six years of age or older. 
The Department of Health and Human Services provided the Drug 
Enforcement Administration with a scheduling recommendation to place 
serdexmethylphenidate and its salts in schedule IV of the Controlled 
Substances Act. In accordance with the Controlled Substances Act, as 
amended by the Improving Regulatory Transparency for New Medical 
Therapies Act, Drug Enforcement Administration is hereby issuing an 
interim final rule placing serdexmethylphenidate, including its salts, 
isomers, and salts of isomers, in schedule IV of the Controlled 
Substances Act, thereby facilitating the commercial distribution of 
AZSTARYS as a lawful controlled substance.

DATES: The effective date of this rulemaking is May 7, 2021. Interested 
persons may file written comments on this rulemaking 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 June 
7, 2021. 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 may file a request for hearing or waiver of 
hearing in accordance with 21 U.S.C. 811(j)(3) and 21 CFR 1308.44. 
Requests for hearing and waivers of an opportunity for a hearing or to 
participate in a hearing, together with a written statement of position 
on the matters of fact and law asserted in the hearing, must be 
received on or before June 7, 2021.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-808'' on all correspondence, including any 
attachments.
     Electronic comments: The Drug Enforcement Administration 
(DEA) encourages that all comments be submitted electronically through 
the Federal eRulemaking Portal, which provides the ability to type 
short comments directly into the comment field on the web page or 
attach a file for lengthier comments. Please go to https://www.regulations.gov and follow the online instructions at that site for 
submitting comments. Upon completion of your submission, you will 
receive a Comment Tracking Number for your comment. Please be aware 
that submitted comments are not instantaneously available for public 
view on Regulations.gov. If you have received a Comment Tracking 
Number, your comment has been successfully submitted and there is no 
need to resubmit the same comment.
     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/DPW, 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/OALJ, 8701 
Morrissette Drive, Springfield, Virginia 22152; and (2) Drug 
Enforcement Administration, Attn: DEA Federal Register Representative/
DPW, 8701 Morrissette Drive, Springfield, Virginia 22152.

FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Drug & Chemical 
Evaluation Section, Diversion Control Division, Drug Enforcement 
Administration; Telephone: (571) 362-3249.

SUPPLEMENTARY INFORMATION: This interim final rule refers to the single 
entity, serdexmethylphenidate. The chloride salt of 
serdexmethylphenidate is chemically known as 3-[[[(1S)-1-carboxy-2-
hydroxyethyl]-amino]carbonyl]-1-[[[[(2R)-2-[(1R)-2-methoxy-2-oxo-1-
phenylethyl]-1-piperidinyl] carbonyl]oxy]methyl]pyridinium chloride. 
This rule places serdexmethylphenidate, including its salts, isomers, 
and salts of isomers, in schedule IV of the Controlled Substances Act 
(CSA), thereby facilitating the commercial distribution of AZSTARYS as 
a controlled substance.

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 https://www.regulations.gov. Such information 
includes personal identifying information (such as your name, address, 
etc.) voluntarily submitted by the commenter. The Freedom of 
Information Act applies to all comments received. If you want to submit 
personal identifying information (such as your name, address, etc.) as 
part of your comment, but do not want it to be made publicly available, 
you must include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the 
first paragraph of your comment. You must also place all of the 
personal identifying information you do not want made publicly 
available in the first paragraph of your comment and identify what 
information you want redacted. If you want to submit confidential 
business information as part of your comment, but do not want it to be 
made publicly available, you must include the phrase ``CONFIDENTIAL 
BUSINESS INFORMATION'' in the first paragraph of your comment. You must 
also prominently identify 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 https://www.regulations.gov may include any personal identifying information 
(such as name, address, and phone number) included in the text of your 
electronic submission that is not identified as directed above as 
confidential.
    An electronic copy of this document and supplemental information, 
including the complete Department of Health and Human Services (HHS) 
and DEA eight-factor analyses, to this interim final rule are available 
at https://www.regulations.gov for easy reference.

Request for Hearing or Waiver of Participation in a Hearing

    Pursuant to 21 U.S.C. 811(a), this action is a formal rulemaking 
``on the record after opportunity for a hearing.'' Such proceedings are 
conducted pursuant to the provisions of the Administrative Procedure 
Act (APA), 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316, 
subpart D. Such requests or notices must conform to the requirements of 
21 CFR 1308.44(a) or (b), and 1316.47 or 1316.48, as applicable, and 
include a statement of the person's interests in the proceeding and the 
objections or issues, if any, concerning which the person desires to be 
heard. Any waiver must conform to the requirements of 21 CFR 1308.44(c) 
and may include a written statement regarding the interested

[[Page 24489]]

person's position on the matters of fact and law involved in any 
hearing.
    All requests for a hearing and waivers of participation must be 
sent to DEA using the address information provided above.

Background and Legal Authority

    Under the CSA, as amended in 2015 by the Improving Regulatory 
Transparency for New Medical Therapies Act (section 2(b) of Pub. L. 
114-89), DEA is required to commence an expedited scheduling action 
with respect to certain new drugs approved by the Food and Drug 
Administration (FDA). As provided in 21 U.S.C. 811(j), this expedited 
scheduling is required where both of the following conditions apply: 
(1) The Secretary of HHS has advised DEA that a New Drug Application 
(NDA) has been submitted for a drug that has a stimulant, depressant, 
or hallucinogenic effect on the central nervous system (CNS), and that 
it appears that such drug has an abuse potential; and (2) the Secretary 
of HHS recommends that DEA control the drug in schedule II, III, IV, or 
V pursuant to 21 U.S.C. 811(a) and (b). In these circumstances, DEA is 
required to issue an interim final rule controlling the drug within 90 
days.
    Subsection (j)(2) states that the 90-day timeframe starts the later 
of (1) the date DEA receives HHS' scientific and medical evaluation/
scheduling recommendation, or (2) the date DEA receives notice of the 
NDA approval by HHS. Subsection (j)(3) specifies that the rulemaking 
shall become immediately effective as an interim final rule without 
requiring DEA to demonstrate good cause therefore. Thus, the purpose of 
subsection (j) is to speed the process by which DEA schedules newly 
approved drugs that are currently either in schedule I or not 
controlled (but which have sufficient abuse potential to warrant 
control) so that such drugs may be marketed without undue delay 
following FDA approval.\1\
---------------------------------------------------------------------------

    \1\ Given the parameters of subsection (j), in DEA's view, it 
would not apply to a reformulation of a drug containing a substance 
currently in schedules II through V for which an NDA has recently 
been approved.
---------------------------------------------------------------------------

    Subsection (j)(3) further provides that the interim final rule 
shall give interested persons the opportunity to comment and to request 
a hearing. After the conclusion of such proceedings, DEA must issue a 
final rule in accordance with the scheduling criteria of 21 U.S.C. 
811(b) through (d) and 812(b).
    Serdexmethylphenidate chloride (3-[[[(1S)-1-carboxy-2-
hydroxyethyl]-amino]carbonyl]-1-[[[[(2R)-2-[(1R)-2-methoxy-2-oxo-1-
phenylethyl]-1-piperidinyl]carbonyl]oxy]methyl]pyridinium chloride) is 
a new molecular entity (NME) without CNS activity. However, according 
to HHS, because serdexmethylphenidate chloride (SDX) is metabolized in 
the large intestine to dexmethylphenidate (d-MPH), a schedule II drug 
and a CNS stimulant, SDX is a prodrug of d-MPH.
    On March 2, 2020, Commave Therapeutics S.A. submitted an NDA to 
FDA, in partnership with KemPharm, Inc., for a combination drug product 
containing SDX and d-MPH, both as chloride salts. On March 2, 2021, DEA 
received notification that FDA, on the same date, approved this NDA for 
AZSTARYS capsules for oral use, a combination drug product containing 
dexmethylphenidate hydrochloride and serdexmethylphenidate chloride, 
under section 505(c) of the Federal Food, Drug, and Cosmetic Act 
(FDCA), for the treatment of Attention Deficit Hyperactivity Disorder 
(ADHD) in patients six years of age or older. According to the FDA-
approved product label, AZSTARYS contains 28 mg/6 mg, 42 mg/9 mg, or 56 
mg/12 mg of serdexmethylphenidate chloride/dexmethylphenidate 
hydrochloride (equivalent to 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, and 52.3 
mg/10.4 mg of serdexmethylphenidate/dexmethylphenidate, 
respectively).\2\
---------------------------------------------------------------------------

    \2\ https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212994s000lbl.pdf.
---------------------------------------------------------------------------

    The 90-day time frame, as stipulated to in subsection 811(j)(2) and 
discussed above, was triggered on March 2, 2021. Therefore, DEA must 
issue an interim final rule controlling serdexmethylphenidate on or 
before May 31, 2021.

Determination To Schedule Serdexmethylphenidate

    On March 2, 2021, DEA received from HHS a scientific and medical 
evaluation entitled ``Basis for the Recommendation to Control 
Serdexmethylphenidate and its Salts in schedule IV of the Controlled 
Substances Act'' and a scheduling recommendation. Pursuant to 21 U.S.C. 
811(b) and (c), this document contained an eight-factor analysis of the 
abuse potential, legitimate medical use, and dependence liability of 
serdexmethylphenidate, along with HHS's recommendation to control 
serdexmethylphenidate and its salts under schedule IV of the CSA.
    In response, DEA reviewed the scientific and medical evaluation and 
scheduling recommendation provided by HHS, along with all other 
relevant data, and completed its own eight-factor review pursuant to 21 
U.S.C. 811(c). DEA concluded that SDX meets the 21 U.S.C. 812(b)(4) 
criteria for placement in schedule IV of the CSA.
    Pursuant to subsection 811(j), and based on HHS' scheduling 
recommendation, the approval of the NDA by HHS/FDA, and DEA's 
determination, DEA is issuing this interim final rule to schedule SDX 
as a schedule IV controlled substance under the CSA.
    Included below is a brief summary of each factor as analyzed by HHS 
and DEA, and as considered by DEA in its scheduling action. Please note 
that both DEA and HHS analyses are available in their entirety under 
``Supporting Documents'' in the public docket for this interim final 
rule at https://www.regulations.gov, under Docket Number ``DEA-808.'' 
Full analysis of, and citations to, the information referenced in the 
summary may also be found in the supporting and related material.

1. Its Actual or Relative Potential for Abuse

    SDX is an NME that has not been marketed in the United States or 
any country. Thus, evidence regarding its diversion and actual abuse is 
lacking. SDX only recently became available for medical treatment, has 
not been diverted from legitimate sources, and individuals have not 
taken this substance in amounts sufficient to create a hazard to public 
health and safety. DEA notes that there are no reports for SDX in the 
National Forensic Laboratory Information System (NFLIS),\3\ which 
collects drug cases submitted to and analyzed by state and local 
forensic laboratories.
---------------------------------------------------------------------------

    \3\ NFLIS represents an important resource in monitoring illicit 
drug 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 more than 96% 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. NFLIS data were queried on March 4, 2021.
---------------------------------------------------------------------------

    As stated by HHS, clinical studies show that SDX, when taken by the 
oral route, produces effects that are similar to other stimulant drugs 
in schedule IV, such as phentermine. The pharmacological mechanism of 
action of SDX is based on its prodrug characteristics, as it must be 
metabolized to d-MPH to exert its effects. In clinical studies, SDX 
demonstrated a lower potential for

[[Page 24490]]

abuse when compared to d-MPH and similar potential for abuse when 
compared to phentermine. This evidence demonstrates that SDX is related 
in action and effect to the schedule IV substance phentermine, and can 
therefore be expected to have a similar potential for abuse.

2. Scientific Evidence of Its Pharmacological Effects, if Known

    SDX itself has no CNS activity and must be metabolized to d-MPH to 
exert its effect. As HHS notes, in vitro binding studies demonstrated 
that SDX does not interact with dopamine and norepinephrine 
transporters, which are the sites of action for d-MPH, a schedule II 
drug. Moreover, SDX does not bind to any other receptor systems that 
are associated with drugs of abuse.
    In a human abuse potential (HAP) study, therapeutic and 
supratherapeutic doses of SDX administered orally produced positive 
subjective responses such as Drug Liking and Drug High similar to those 
of phentermine and higher than placebo. In addition, abuse-related 
adverse events such as euphoric mood and hypervigilance occurred less 
frequently in SDX-treated subjects than in those treated with d-MPH. 
However, SDX-treated subjects reported more abuse-related adverse 
events than those treated with placebo. As concluded by HHS, results 
from preclinical and clinical studies indicate that SDX has abuse 
potential similar to phentermine, a schedule IV substance.

3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance

    SDX is an NME. It is chemically known as 3-[[[(1S)-1-carboxy-2-
hydroxyethyl]-amino]carbonyl]-1-[[[[(2R)-2-[(1R)-2-methoxy-2-oxo-1-
phenylethyl]-1-piperidinyl]carbonyl]oxy]methyl]pyridinium chloride. It 
is a white to off-white crystalline solid that is freely soluble in 
water at pH that was tested up to 6.8. On March 2, 2021, FDA approved 
the NDA for AZSTARYS, a combination drug product containing d-MPH and 
SDX for the treatment of ADHD in patients six years of age or older. 
Thus, SDX has an accepted medical use in the United States. SDX will be 
marketed in combination with d-MPH (SDX/d-MPH) as immediate-release 
capsules in three strengths of 28 mg/6 mg, 42 mg/9 mg, and 56 mg/12 mg.

4. Its History and Current Pattern of Abuse

    There is no information on the history and current pattern of abuse 
for SDX, since it has not been marketed, legally or illegally, in the 
United States. HHS notes that SDX produces abuse-related signals, such 
as euphoric mood and hypervigilance, and abuse potential similar to 
that of schedule IV controlled substance phentermine. In March 2021, 
DEA searched the NFLIS database for SDX encounters. Consistent with the 
fact that SDX is an NME, this database had no records of encounters of 
SDX by law enforcement.

5. The Scope, Duration, and Significance of Abuse

    SDX is not marketed in the United States, legally or illegally. 
Thus, information on the scope, duration, and significance of abuse for 
SDX is lacking. However, as stated by HHS, data from animal and human 
studies indicate that SDX has abuse potential similar to phentermine. 
Therefore, upon marketing, SDX scope of abuse is expected to be similar 
to phentermine.

6. What, if Any, Risk There Is to the Public Health

    The extent of abuse potential of a drug is an indication of its 
public health risk. Data from preclinical and clinical studies showed 
that SDX has abuse potential similar to that of the schedule IV 
stimulant phentermine. Therefore, upon availability for marketing, SDX 
is likely to pose a public health risk to a degree similar to schedule 
IV stimulants, such as phentermine.

7. Its Psychic or Physiological Dependence Liability

    As HHS notes, no animal studies were done to test physical 
dependence liability of SDX. A hallmark of physical dependence are 
withdrawal symptoms resulting from drug discontinuation. In clinical 
studies, there was no adverse events indicative of withdrawal from 
discontinuation of the SDX/d-MPH combination treatment.
    SDX produced positive subjective responses to ratings of Drug 
Liking and Drug High in a HAP study. The responses were significantly 
higher than the placebo and similar to phentermine, a schedule IV 
stimulant. HHS concluded that SDX can produce psychic dependence to a 
similar extent as phentermine.

8. Whether the Substance Is an Immediate Precursor of a Substance 
Already Controlled Under the CSA

    SDX is not an immediate precursor of any controlled substance, as 
defined by 21 U.S.C. 802(23).
    Conclusion: After considering the scientific and medical evaluation 
and scheduling recommendation provided by HHS, and its own eight-factor 
analysis, DEA has determined that these facts and all relevant data 
constitute substantial evidence of potential for abuse of SDX. As such, 
DEA hereby schedules SDX as a controlled substance under the CSA.

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 HHS and review of all available data, 
the Acting Administrator of DEA, pursuant to 21 U.S.C. 812(b)(4), finds 
that:
    1. Serdexmethylphenidate has a low potential for abuse relative to 
the drugs or other substances in schedule III.
    Receptor binding studies demonstrate that SDX does not bind to 
dopamine and norepinephrine transporters and other receptors typically 
associated with abuse potential. Upon oral administration, SDX is 
metabolized to d-MPH, a schedule II drug, in the large intestine and 
showed an abuse potential lower than that of d-MPH, but similar to that 
of phentermine, a schedule IV drug. Results from an observational 
animal behavioral study demonstrate that lower doses of SDX (12 and 25 
mg/kg) did not produce any CNS effects and only the highest dose of SDX 
(50 mg/kg) increased CNS activity. In a HAP study, SDX at the 
therapeutic and supra-therapeutic doses produced positive subjective 
responses such as Drug Liking and Drug High similar to those of 
phentermine (schedule IV) and significantly higher than placebo. 
Furthermore, data from other clinical studies show that SDX produced 
abuse-related adverse events, namely euphoric mood and hypervigilance. 
Because SDX is similar to phentermine (schedule IV) in its abuse 
potential, SDX has a lower potential for abuse relative to the drugs or 
other substances in schedule III.
    2. Serdexmethylphenidate has a currently accepted medical use in 
the United States.
    On March 2, 2021, FDA approved the NDA for AZSTARYS capsules, a 
combination drug product containing d-MPH and SDX for the treatment of 
ADHD in patients six years of age or older. Thus, SDX has a currently 
accepted medical use for treatment in the United States.
    3. Serdexmethylphenidate may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
schedule III.
    There were no animal studies performed to evaluate physical 
dependence of SDX. In clinical studies,

[[Page 24491]]

SDX demonstrated no indication of physical dependence after abrupt 
discontinuation of the drug. In a HAP study, SDX increased drug-liking 
scores that were significantly greater than that of placebo and were 
similar to that of phentermine. In addition, SDX produced euphoria-
related adverse events in a HAP study. These data collectively suggest 
that SDX abuse may lead to limited psychological dependence relative to 
drugs in schedule III and largely similar to that of schedule IV 
stimulants.
    Based on these findings, the Acting Administrator of DEA concludes 
that SDX warrants control in schedule IV of the CSA. 21 U.S.C. 
812(b)(4).

Requirements for Handling Serdexmethylphenidate

    Serdexmethylphenidate is subject to the CSA's schedule IV 
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 IV 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), or who desires to handle, serdexmethylphenidate, must be 
registered with DEA to conduct such activities pursuant to 21 U.S.C. 
822, 823, 957, and 958 and in accordance with 21 CFR parts 1301 and 
1312. Any person who currently handles or intends to handle 
serdexmethylphenidate and is not registered with DEA must submit an 
application for registration and may not continue to handle 
serdexmethylphenidate unless 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. These registration 
requirements, however, are not applicable to patients (end users) who 
possess serdexmethylphenidate pursuant to a lawful prescription.
    2. Disposal of stocks. Any person who obtains a schedule IV 
registration to handle serdexmethylphenidate but who subsequently does 
not desire or is not able to maintain such registration must surrender 
all quantities of serdexmethylphenidate or may transfer all quantities 
of serdexmethylphenidate to a person registered with DEA in accordance 
with 21 CFR part 1317, in additional to all other applicable Federal, 
state, local, and tribal laws.
    3. Security. Serdexmethylphenidate is subject to schedule III-V 
security requirements for DEA registrants and it must be handled and 
stored in accordance with 21 CFR 1301.71-1301.77. Non-practitioners 
handling serdexmethylphenidate must also comply with the employee 
screening requirements of 21 CFR 1301.90-1301.93. These requirements, 
however, are not applicable to patients (end users) who possess 
serdexmethylphenidate pursuant to a lawful prescription.
    4. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of serdexmethylphenidate 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 
serdexmethylphenidate must take an inventory of serdexmethylphenidate 
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 DEA to handle 
serdexmethylphenidate must take an initial inventory of all stocks of 
controlled substances (including serdexmethylphenidate) on hand on the 
date the registrant first engages in the handling of controlled 
substances, pursuant to 21 U.S.C. 827 and 958(e), 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 
serdexmethylphenidate) on hand every two years, pursuant to 21 U.S.C. 
827 and 958(e), and in accordance with 21 CFR 1304.03, 1304.04, and 
1304.11. These requirements, however, are not applicable to patients 
(end users) who possess serdexmethylphenidate pursuant to a lawful 
prescription.
    6. Records and Reports. DEA registrants must maintain records and 
submit reports for serdexmethylphenidate, pursuant to 21 U.S.C. 827, 
832(a), and 958(e), and in accordance with 21 CFR 1301.74(b) and (c) 
and parts 1304, 1312, and 1317.
    7. Prescriptions. All prescriptions for serdexmethylphenidate, or 
products containing serdexmethylphenidate, must comply with 21 U.S.C. 
829, and be issued in accordance with 21 CFR parts 1306 and 1311, 
subpart C.
    8. Manufacturing and Distributing. In addition to the general 
requirements of the CSA and DEA regulations that are applicable to 
manufacturers and distributors of schedule IV controlled substances, 
such registrants should be advised that (consistent with the foregoing 
considerations) any manufacturing or distribution of 
serdexmethylphenidate may only be for the legitimate purposes 
consistent with the drug's labeling, or for research activities 
authorized by the FDCA and CSA.
    9. Importation and Exportation. All importation and exportation of 
serdexmethylphenidate must be in compliance with 21 U.S.C. 952, 953, 
957, and 958, and in accordance with 21 CFR part 1312.
    10. Liability. Any activity involving serdexmethylphenidate 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

    Section 553 of the APA (5 U.S.C. 553) generally requires notice and 
comment for rulemakings. However, 21 U.S.C. 811(j) provides that in 
cases where a certain new drug is (1) approved by HHS, under section 
505(c) of the FDCA and (2) HHS recommends control in CSA schedule II-V, 
DEA shall issue an interim final rule scheduling the drug within 90 
days. As stated in the legal authority section, the 90-day time frame 
is the later of: (1) The date DEA receives HHS's scientific and medical 
evaluation/scheduling recommendation, or (2) the date DEA receives 
notice of the NDA approval by HHS. Additionally, subsection (j) 
specifies that the rulemaking shall become immediately effective as an 
interim final rule without requiring DEA to demonstrate good cause.

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

    In accordance with 21 U.S.C. 811(a) and (j), 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 (E.O.) 12866 and the 
principles reaffirmed in E.O. 13563.

[[Page 24492]]

Executive Order 12988, Civil Justice Reform

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

Executive Order 13132, Federalism

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

Regulatory Flexibility Act

    The Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612) applies to 
rules that are subject to notice and comment under section 553(b) of 
the APA. As noted in the above discussion regarding the applicability 
of the APA, DEA is not required to publish a general notice of proposed 
rulemaking. 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., DEA has determined that this action would not 
result in any Federal mandate that may result ``in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any 1 year.'' Therefore, neither a Small Government 
Agency Plan nor any other action is required under UMRA of 1995.

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information 
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 the Congressional 
Review Act (CRA), 5 U.S.C. 804. However, pursuant to the CRA, DEA is 
submitting 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, DEA amends 21 CFR part 1308 as 
follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

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

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


0
2. In Sec.  1308.14:
0
a. Redesignate paragraphs (f)(11) through (13) as (f)(12) through (14); 
and
0
b. Add new paragraph (f)(11).
    The addition reads as follows:


Sec.  1308.14  Schedule IV.

* * * * *
    (f) * * *

 (11) Serdexmethylphenidate.....................................    1729
 

* * * * *

D. Christopher Evans,
Acting Administrator.
[FR Doc. 2021-09738 Filed 5-6-21; 8:45 am]
BILLING CODE 4410-09-P