[Federal Register Volume 89, Number 172 (Thursday, September 5, 2024)]
[Notices]
[Pages 72424-72426]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-20114]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-1228L]
Adjustment to the Aggregate Production Quota for Lisdexamfetamine
and d-Amphetamine (for Conversion) for 2024
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Final order.
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SUMMARY: The Drug Enforcement Administration is adjusting the 2024
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 its
regulations in accordance with the statutes and is expediting
publication of this determination to comply with the timeframes
specified in the statutes.
DATES: The final order is effective September 5, 2024.
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 the Drug Enforcement Administration (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 2024 established APQ for controlled substances in
schedules I and II in the Federal Register on January 3, 2024. 89 FR
407. The 2024 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
2024, 89 FR 407 (January 3, 2024).
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Quotas Applicable to Drugs in Shortage Pursuant to 21 U.S.C. 826(h)
DEA received written correspondence from FDA on July 12, 2024, in
accordance with 21 U.S.C. 356c, addressing the domestic drug shortage
of lisdexamfetamine capsules and chewable tablets. In this letter, FDA
advised DEA that ``shortage of an active ingredient'' is the reason
identified for the shortages of all marketed generic lisdexamfetamine
dimesylate capsules and chewable tablets. 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. That provision
further requires FDA to assess whether notifications received from
manufacturers concern controlled substances subject to production
quotas in accordance with 21 U.S.C. 826.
FDA's July 12 letter requested that DEA increase the APQ and
individual manufacturing quotas for lisdexamfetamine to a level that
FDA deems necessary to address a shortage based on the best available
market data.\2\ FDA reiterated to DEA that lisdexamfetamine 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.
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\2\ As the FDA's specific requested levels would reveal
proprietary manufacturing data, DEA is not specifying the requested
levels in this document.
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On August 2, 2024, DEA received a request from a DEA registered
manufacturer of the Schedule II controlled substance lisdexamfetamine
for an increase to its 2024 individual manufacturing quota pertaining
to lisdexamfetamine. Pursuant to this request, and following the
receipt of the letter from FDA on July 12, DEA began its review under
the timeframes specified by 21 U.S.C. 826(h)(1).
D-amphetamine, another schedule II controlled substance, is used by
some manufacturers as part of the synthesis pathway to manufacture
lisdexamfetamine products.
Analysis for the Adjustment to the 2024 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 2024: (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 probability that other individual
[[Page 72425]]
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 proposing an increase to the current lisdexamfetamine and d-
amphetamine (for conversion) APQ.
DEA reviewed domestic data from the latest IQVIA report on
stimulant prescribing that reflected increases in prescribing of
lisdexamfetamine products from 2022 to 2023. In addition, FDA's
estimate of domestic medical need for lisdexamfetamine drug products
predicted a 6 percent increase for 2024 domestic need when compared to
2023 observed need. Data reviewed by both agencies support an increase
to the lisdexamfetamine APQ which is necessary to meet domestic demand.
Data shows an increase in the number of foreign countries that have
approved drug products containing lisdexamfetamine for their patient
populations. Vyvanse[supreg] is currently approved to treat patients
suffering from attention-deficit/hyperactivity disorder (ADHD) in 29
countries besides the United States. According to a comment received in
November 2023 from the Australian ADHD Foundation on the Federal
Register notice that proposed the APQ and the assessment of annual
needs (AAN) for 2024,\3\ the Department of Health and Aged Care
Therapeutic Goods Administration (TGA) of the Australian Government
reported current shortages of lisdexamfetamine products with more
shortages predicted for various strengths through April 2024. On June
18, 2024, TGA reported that certain strengths of lisdexamfetamine
medications remain in shortage.\4\ In February 2021, Australia extended
a government subsidy of lisdexamfetamine medications to adults who are
diagnosed with ADHD after the age of 18. There has since been an
immediate and sustained increase in monthly dispensing.\5\ In Europe,
the consumption of lisdexamfetamine medications has been rapidly
growing over the years. Additionally, Gimbach et al. conducted a study
and reported the overall consumption of ADHD medications has increased
in 26 of 28 countries in Europe.\6\ According to those researchers, the
growth in consumption can be attributed to an increase in the general
awareness of ADHD among the public and medical practitioners, but more
importantly, the broadening of diagnosis criteria in Europe.\7\
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\3\ 88 FR 75312 (Nov. 2, 2023).
\4\ https://apps.tga.gov.au/Prod/msi/Search/Details/lisdexamfetamine-dimesilate.
\5\ Aust N Z J Psychiatry. 2023 Jul; 57(7): 1073-1076. Published
online 2023 Apr 25.
\6\ Gimbach, S., Vogel, D., Fried, R. et al. ADHD medicine
consumption in Europe after COVID-19: catch-up or trend change?. BMC
Psychiatry 24, 112 (2024).
\7\ Gimbach, S., Vogel, D., Fried, R. et al. ADHD medicine
consumption in Europe after COVID-19: catch-up or trend change?. BMC
Psychiatry 24, 112 (2024).
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In addition to reviewing export data extracted from DEA's internal
databases, DEA also obtained access to new data sources in 2024 that
allow DEA to more accurately forecast foreign demand for domestically
controlled substances that are not always internationally
controlled,\8\ such as lisdexamfetamine. The export data showed that
exports of drug products containing lisdexamfetamine increased from
8,573.351 kg in 2022 to 11,502.175 kg in 2023. Extrapolation utilizing
previous years' reported data suggests the export requirements for
lisdexamfetamine active pharmaceutical ingredient and finished dosages
likely will continue to increase in 2024 and beyond. An increase in
domestic manufacturing of the active pharmaceutical ingredient and
finished dosages is necessary to supply lisdexamfetamine products to
foreign markets.
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\8\ A controlled substance's placement in the 1961 UN Single
Convention or the 1971 UN Psychotropic Convention determines whether
a substance is internationally controlled. https://www.incb.org/incb//conventions/index.html?lng=en.
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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's active pharmaceutical ingredient 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 2024 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. Of the 6,236 kg increase to the
lisdexamfetamine APQ, 1,558 kg of the increase is to address increased
domestic demand for finished dosage medications, while the other 4,678
kg addresses increases in foreign demand for finished dosage
medications. 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 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 aggregate production
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.
[[Page 72426]]
Determination of 2024 Lisdexamfetamine and d-Amphetamine (for
Conversion) Aggregate Production Quota
In determining the adjustment of the 2024 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 2024 APQ for lisdexamfetamine and d-amphetamine (for
conversion).
The Administrator hereby adjusts the 2024 APQ for the following
schedule II-controlled substance expressed in grams of anhydrous acid
or base, as follows:
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Current APQ Adjusted APQ
Controlled substance (g) (g)
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Schedule II
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lisdexamfetamine........................ 26,500,000 32,736,000
d-amphetamine (for conversion).......... 20,000,000 23,688,235
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The APQ for all other schedule I and II controlled substances
included in the 2024 established APQ remain at this time as previously
established.
Signing Authority
This document of the Drug Enforcement Administration was signed on
September 3, 2024, by Administrator Anne Milgram. 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. 2024-20114 Filed 9-3-24; 4:15 pm]
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