[Federal Register Volume 90, Number 180 (Friday, September 19, 2025)]
[Notices]
[Pages 45249-45251]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-18110]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-1413L]
Adjustment to the Aggregate Production Quota for Lisdexamfetamine
and d-Amphetamine (for Conversion) for 2025 Pursuant to 21 U.S.C.
826(h)
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final order.
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SUMMARY: The Drug Enforcement Administration (DEA) is adjusting the
2025 aggregate production quota for the schedule II controlled
substances lisdexamfetamine and d-amphetamine (for conversion). In
making this determination, DEA has considered the factors set forth in
21 CFR 1303.13(b) in accordance with 21 U.S.C. 826(a) and is expediting
publication of this determination to comply with the timeframes
specified in 21 U.S.C. 826(h)(1).
DATES: This final order is effective September 19, 2025.
FOR FURTHER INFORMATION CONTACT: Heather E. Achbach, Regulatory
Drafting and Policy Support Section, Diversion Control Division, Drug
Enforcement Administration, Telephone: (571) 776-3882.
SUPPLEMENTARY INFORMATION:
Legal Authority
Section 306 of the Controlled Substances Act (CSA) (21 U.S.C. 826)
requires the Attorney General to establish aggregate production quotas
(APQ) for each basic class of controlled substance listed in schedule I
and II. The Attorney General has delegated this function to the
Administrator of DEA pursuant to 28 CFR 0.100.
Under 21 U.S.C. 826(h), when a request for individual manufacturing
quota is submitted by a DEA-registered manufacturer pertaining to a
schedule II controlled substance that is contained in a drug on the
Food and Drug Administration's (FDA's) list of drugs in shortage, DEA
must complete review of such request not later than 30 days after
receipt of the request. If, after the review is completed, DEA finds
that an increase in the aggregate and individual production quotas is
necessary to address a shortage of that controlled substance, DEA is to
increase the aggregate and individual production quotas of that
controlled substance and any ingredient therein to the level requested.
21 U.S.C. 826(h)(1)(B)(i). However, if it is determined that the level
requested is not necessary to address the shortage, DEA is to provide a
written response detailing the basis for the determination. 21 U.S.C.
826(h)(1)(B)(ii).
Background
DEA published the 2025 established APQ for controlled substances in
schedules I and II in the Federal Register on December 17, 2024. 89 FR
102649. The 2025 established APQ represents those quantities of
schedule I and II controlled substances that may be manufactured in the
United States to provide for the estimated medical, scientific,
research, and industrial needs of the United States, for lawful export
requirements, and for the establishment and maintenance of reserve
stocks. These quotas do not include imports of controlled substances
for use in industrial processes. The final order stipulated that all
APQ are subject to an adjustment, in accordance with 21 CFR 1303.15.\1\
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\1\ Established Aggregate Production Quotas for Schedule I and
II Controlled Substances and Assessment of Annual Needs for the List
I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for
2025, 89 FR 102649 (December 17, 2024).
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Quotas Applicable to Drugs in Shortage Pursuant to 21 U.S.C. 826(h)
Under 21 U.S.C. 356c, manufacturers of drugs that are life-
supporting, life-sustaining, or intended for the treatment or
prevention of debilitating diseases or conditions must notify FDA of
any permanent discontinuation or interruption in manufacturing likely
to result in a meaningful disruption of the drug's supply in the United
States. Lisdexamfetamine is a drug that is intended for use in the
prevention or treatment of a debilitating disease or condition and
therefore falls under the notification requirements of 21 U.S.C. 356c.
This provision further requires FDA to assess whether the notifications
received from manufacturers concern controlled substances that are
subject to production quotas in accordance with 21 U.S.C. 826.
On August 7, 2025, DEA received a request from a DEA registered
manufacturer of the Schedule II controlled substance lisdexamfetamine
for an increase to its 2025 individual manufacturing quota pertaining
to lisdexamfetamine. DEA reviewed the FDA drug shortage list and found
multiple manufacturers reported a domestic shortage of lisdexamfetamine
capsules and chewable tablets. The manufacturers cited ``shortage of an
active ingredient'' as the reason identified for the domestic
shortages. Pursuant to this request, DEA began its review under the
timeframes specified by 21 U.S.C. 826(h)(1).
The manufacturing of lisdexamfetamine active pharmaceutical
ingredient (API) requires the synthesis of an intermediate, d-
amphetamine, a schedule II-controlled substance, and thus requires the
DEA to additionally review whether an adjustment to the APQ of d-
amphetamine (for conversion) is necessary.
Analysis for the Adjustment to the 2025 Lisdexamfetamine and d-
Amphetamine (for Conversion) Aggregate Production Quota
In conducting the review under 21 U.S.C. 826(h) in order to
determine the necessity of this adjustment, the Administrator has
considered the criteria in accordance with 21 CFR 1303.13 (adjustment
of APQ for controlled substances). The Administrator is authorized to
increase or reduce the APQ at any time. 21 CFR 1303.13(a). DEA
regulations state that there are five factors that shall be considered
in determining whether to adjust the APQ. 21 CFR 1303.13(b).
Accordingly, the Administrator has taken into account the following
factors described below for 2025: (1) changes in the demand for that
class, changes in the national rate of net disposal of the class,
changes in the rate of net disposal of the class by registrants holding
individual manufacturing quotas for that class, and changes in the
extent of any diversion in the class; (2) whether any increased demand
for that class, the national and/or individual rates of net disposal of
that class are temporary, short term, or long term; (3) whether any
increased demand for that class can be met through existing
inventories, increased individual manufacturing quotas, or increased
importation, without increasing the APQ, taking into account production
delays and the
[[Page 45250]]
probability that other individual manufacturing quotas may be suspended
pursuant to 21 CFR 1303.24(b); (4) whether any decreased demand for
that class will result in excessive inventory accumulation by all
persons registered to handle that class (including manufacturers,
distributors, practitioners, importers, and exporters), notwithstanding
the possibility that individual manufacturing quotas may be suspended
pursuant to 21 CFR 1303.24(b) or abandoned pursuant to 21 CFR 1303.27;
and (5) other factors affecting medical, scientific, research, and
industrial needs in the United States and lawful export requirements,
as the Administrator finds relevant, including changes in the currently
accepted medical use in treatment with the class or the substances
which are manufactured from it, the economic and physical availability
of raw materials for use in manufacturing and for inventory purposes,
yield and stability problems, potential disruptions to production
(including possible labor strikes), and recent unforeseen emergencies
such as floods and fires. 21 CFR 1303.13(b). Based on that review, DEA
is increasing the current lisdexamfetamine and d-amphetamine (for
conversion) APQs.
Following a review of domestic and export data, as well as
inventory reports from both the bulk and dosage manufacturers, DEA has
determined that an increase to the APQ of lisdexamfetamine is
necessary. The increase is intended to address the rising global demand
for lisdexamfetamine products and to allow domestic manufacturers of
FDA-approved lisdexamfetamine drug products to replenish their
inventories to levels authorized by DEA regulations. DEA reviewed the
most recent domestic usage data from IQVIA and export data from DEA's
internal database and Multi International Data Analysis System (MIDAS).
Extrapolation of the data predicts global consumption will increase
15.16 percent in 2025. The increase is due to the approval of the brand
name product, Vyvanse, to treat patients suffering from attention-
deficit/hyperactivity disorder (ADHD) in 29 countries in addition to
the United States, with additional countries in the process of granting
approval of this product for treatment of ADHD. Furthermore, other U.S.
dosage manufacturers have also begun exporting lisdexamfetamine
finished dosage-form products according to the data extracted from
DEA's internal databases. Extrapolation utilizing previous years'
reported data suggests the export requirements for lisdexamfetamine API
and finished dosages likely will continue to increase in 2025 and
beyond. An increase in domestic manufacturing of the API and finished
dosages is necessary to supply lisdexamfetamine products to both the
domestic and foreign markets.
Additionally, DEA reviewed internal databases and determined that
bulk manufacturers started 2025 with less than the 40 percent inventory
allowance permitted by 21 CFR 1303.24. Increasing the lisdexamfetamine
APQ would allow the manufacturers to approach the 40 percent inventory
allowance permitted by 21 CFR 1303.24 while meeting the estimated
increasing legitimate domestic and global demands.
As a result of the increase to the APQ of lisdexamfetamine, DEA
must make a corresponding increase to the APQ of d-amphetamine (for
conversion) because this substance is used by some manufacturers as
part of the synthesis pathway to manufacture lisdexamfetamine products.
Without this corresponding increase, manufacturers of lisdexamfetamine
API would not be able to utilize the entire amount of the increased
lisdexamfetamine APQ.
After considering these factors, DEA determined that it is
necessary to increase the established 2025 APQ for the schedule II
controlled substances lisdexamfetamine and d-amphetamine (for
conversion) to be manufactured in the United States to provide for the
estimated needs of the United States and export requirements to meet
domestic and global demand. These adjustments are necessary to ensure
that the United States has an adequate and uninterrupted supply of
lisdexamfetamine to meet legitimate patient needs both domestically and
globally.
Additional Legal Considerations
The procedures previously adopted by DEA for adjustment of APQ are
set forth in DEA regulations in 21 CFR 1303.13. Under that provision,
the Administrator, upon determining that an adjustment of the APQ of
any basic class of controlled substance is necessary, shall publish in
the Federal Register general notice of an adjustment in the APQ for
that class. The regulation further directs that DEA will allow any
interested person to file comments or objections to the adjusted APQ
within the time specified by the Administrator in the notice. Section
1303.13(c) further provides that, ``[a]fter consideration of any
comments or objections . . . the Administrator shall issue and publish
in the Federal Register his final order determining the APQ for the
basic class of controlled substance.''
The statutory timeframe applicable to actions taken under 21 U.S.C.
826(h) was enacted by Congress after DEA established its regulations in
21 CFR 1303.13. DEA has determined that it is not possible to increase
the APQ within the Congressionally-mandated 30-day period while also
complying with the procedures that DEA previously had laid out in 21
CFR 1303.13. Therefore, the Administrator has determined that, in order
to comply with the 30-day timeframe in 21 U.S.C. 826(h), this final
order must be published without opportunity for comment and made
effective immediately.
Determination of 2025 Lisdexamfetamine and d-Amphetamine (for
Conversion) Aggregate Production Quota
In determining the adjustment of the 2025 lisdexamfetamine and d-
amphetamine (for conversion) APQ, DEA has taken into consideration the
factors set forth in 21 CFR 1303.13(b) in accordance with 21 U.S.C.
826(a) as well as 826(h). Based on all of the above, the Administrator
is adjusting the 2025 APQ for lisdexamfetamine and d-amphetamine (for
conversion).
The Administrator hereby adjusts the 2025 APQ for the following
schedule II-controlled substance expressed in grams of anhydrous acid
or base, as follows:
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Controlled substance Current APQ (g) Adjusted APQ (g)
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Schedule II
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lisdexamfetamine.................. 32,736,000 39,907,536
d-amphetamine (for conversion).... 23,688,235 27,906,786
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[[Page 45251]]
The APQ for all other schedule I and II controlled substances
included in the 2025 established APQ remain at this time as previously
established.\2\
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\2\ Established Aggregate Production Quotas for Schedule I and
II Controlled Substances and Assessment of Annual Needs for the List
I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for
2025, 89 FR 102649 (December 17, 2024).
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Signing Authority
This document of the Drug Enforcement Administration was signed on
September 16, 2025, by Administrator Terrance Cole. That document with
the original signature and date is maintained by DEA. For
administrative purposes only, and in compliance with requirements of
the Office of the Federal Register, the undersigned DEA Federal
Register Liaison Officer has been authorized to sign and submit the
document in electronic format for publication, as an official document
of DEA. This administrative process in no way alters the legal effect
of this document upon publication in the Federal Register.
Heather Achbach,
Federal Register Liaison Officer, Drug Enforcement Administration.
[FR Doc. 2025-18110 Filed 9-18-25; 8:45 am]
BILLING CODE 4410-09-P