[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]
BILLING CODE 4410-09-P