89 FR 186 pgs. 78772-78782 - Proposed 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
Type: NOTICEVolume: 89Number: 186Pages: 78772 - 78782
Pages: 78772, 78773, 78774, 78775, 78776, 78777, 78778Docket number: [Docket No. DEA-1413P]
FR document: [FR Doc. 2024-21962 Filed 9-20-24; 4:15 pm]
Agency: Justice Department
Sub Agency: Drug Enforcement Administration
Official PDF Version: PDF Version
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-1413P]
Proposed 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
AGENCY:
Drug Enforcement Administration, Department of Justice.
ACTION:
Notice with request for comments.
SUMMARY:
The Drug Enforcement Administration (DEA) proposes to establish the 2025 aggregate production quotas for controlled substances in schedules I and II of the Controlled Substances Act (CSA) and the assessment of annual needs for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine.
DATES:
Interested persons may file written comments on this notice in accordance with 21 CFR 1303.11(c) and 1315.11(d). Electronic comments must be submitted, and written comments must be postmarked, on or before October 25, 2024. 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.
Based on comments received in response to this notice, the Administrator may hold a public hearing on one or more issues raised. In the event the Administrator decides in her sole discretion to hold such a hearing, the Administrator will publish a notice of any such hearing in the Federal Register . After consideration of any comments or objections, or after a hearing, if one is held, the Administrator will publish in the Federal Register a final order establishing the 2025 aggregate production quotas for schedule I and II controlled substances, and an assessment of annual needs for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine.
ADDRESSES:
To ensure proper handling of comments, please reference "Docket No. DEA-1413P" on all correspondence, including any attachments. 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 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 that duplicate electronic submissions 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, Attention: DEA Federal Register Representative/DPW, 8701 Morrissette Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT:
Heather E. Achbach, Regulatory Drafting and Policy Support Section, Diversion Control Division, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, Virginia 22152, Telephone: (571) 776-3882.
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SUPPLEMENTARY INFORMATION:
Posting of Public Comments
Please note that all comments received in response to this docket 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 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 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 confidential business information to be redacted within the comment.
Comments containing personal identifying information or confidential business information identified and located as directed above will generally be made available in redacted form. If a comment contains 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 is available at http://www.regulations.gov for easy reference.
Legal Authority
Section 306 of the Controlled Substances Act (21 U.S.C. 826) requires the Attorney General to establish production quotas for each basic class of controlled substances listed in schedules I and II, and for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine. The Attorney General has delegated this function to the Administrator of DEA pursuant to 28 CFR 0.100.
Analysis for Proposed 2025 Aggregate Production Quotas and Assessment of Annual Needs
The proposed 2025 aggregate production quotas (APQ) and assessment of annual needs (AAN) represent those quantities of schedule I and II controlled substances, and the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine, to be manufactured in the United States in 2025 to provide for the estimated medical, scientific, research, and industrial needs of the United States, lawful export requirements, and the establishment and maintenance of reserve stocks. These quotas include imports of ephedrine, pseudoephedrine, and phenylpropanolamine, but do not include imports of controlled substances for use in industrial processes.
Aggregate Production Quotas
In determining the proposed 2025 APQ, the Administrator has taken into account the criteria of 21 U.S.C. 826(a) and 21 CFR 1303.11, including the following seven factors:
(1) Total net disposal of the class by all manufacturers during the current and two preceding years;
(2) Trends in the national rate of net disposal of the class;
(3) Total actual (or estimated) inventories of the class and of all substances manufactured from the class, and trends in inventory accumulation;
(4) Projected demand for such class as indicated by procurement quotas requested pursuant to [21 CFR] 1303.12;
(5) The extent of any diversion of the controlled substance in the class;
(6) Relevant information obtained from the Department of Health and Human Services (HHS), including from the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and the Centers for Medicare and Medicaid Services (CMS), and relevant information obtained from the states; and
(7) 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 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 1303.11(b).
DEA formally solicited input from FDA and CDC in February of 2024 and from the states in April 2024, as required by 21 U.S.C. 826 and 21 CFR part 1303. DEA did not solicit input from CMS for reasons discussed in previous notices. 1 DEA requested information on trends in the legitimate use of select schedule I and II controlled substances from FDA and rates of overdose deaths for covered controlled substances from CDC. DEA's request for information from the states was made directly to the Prescription Drug Monitoring Program (PDMP) Administrators in each state as well as through the National Association of State Controlled Substances Authorities (NASCSA).
Footnotes:
1 ?Proposed Adjustments to the Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2020, 85 FR 54414 (Sept. 1, 2020) and Proposed Aggregate Production Quotas for Schedule I and II Controlled Substances and Assessment of Annual Needs for List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2021, 85 FR 54407 (Sept. 1, 2020).
Assessment of Annual Needs
In similar fashion, in determining the proposed 2025 AAN for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine, the Administrator has taken into account the criteria of 21 U.S.C. 826(a) and 21 CFR 1315.11, including the following five factors:
(1) Total net disposal of the chemical by all manufacturers and importers during the current and two preceding years;
(2) Trends in the national rate of net disposal of each chemical;
(3) Total actual (or estimated) inventories of the chemical and of all substances manufactured from the chemical, and trends in inventory accumulation;
(4) Projected demand for each chemical as indicated by procurement and import quotas requested pursuant to [21 CFR] 1315.32; and
[top] (5) Other factors affecting medical, scientific, research, and industrial needs in the United States, lawful export requirements, and the establishment and maintenance of reserve stocks, as the Administrator finds relevant, including changes in the currently accepted medical use in treatment with the chemicals or the substances manufactured from them, the economic
21 CFR 1315.11(b).
In determining the proposed 2025 AAN, DEA used the calculation methodology previously described in the 2010 and 2011 assessments of annual needs (74 FR 60294 (Nov. 20, 2009) and 75 FR 79407 (Dec. 20, 2010), respectively).
Estimates of Medical Need for Schedule II Opioids and Stimulants
In accordance with 21 CFR part 1303, 21 U.S.C. 826, and 42 U.S.C. 242, HHS continues to provide DEA with estimates of the quantities of select schedule I and II controlled substances and three list I chemicals that will be required to meet the legitimate medical needs of the United States for a given calendar year. The responsibility to provide these estimates of legitimate domestic medical needs resides with FDA. FDA provides DEA with predicted estimates of domestic medical usage for selected controlled substances based on information available to them at a specific point in time in order to meet statutory requirements.
FDA predicts that levels of medical need for schedule II opioids in the United States in calendar year 2025 will decline on average 6.6 percent from calendar year 2024 levels. These declines are expected to occur across a variety of schedule II opioids including fentanyl, hydrocodone, hydromorphone, oxycodone, and oxymorphone. DEA considered the potential for diversion of schedule II opioids, as required by 21 CFR 1303.11(b)(5), as well as a potential increase in demand for certain opioids identified as being necessary to support the previously postponed elective surgeries now that the COVID-19 public health emergency (PHE) has ended, pursuant to 21 CFR 1303.11(b)(7), in developing the proposed 2025 APQ.
FDA predicted an average of a 3.5 percent increase in domestic medical use of the schedule II stimulants amphetamine, methylphenidate (including dexmethylphenidate), and lisdexamfetamine, which are prescribed to treat patients with attention deficit hyperactivity disorder (ADHD) and more recently prescribed off-label to treat patients diagnosed with long-COVID symptoms commonly known as brain fog where fatigue and cognitive impairment persist 4 to 12 weeks after a COVID infection. 2 FDA also raised concerns over drug shortage notifications it received since 2022 from patients for specific ADHD medications containing amphetamine, lisdexamfetamine, and methylphenidate. FDA's stated reasons for these specific shortages include increased prescribing potentially related to the growth in telemedicine during and after the COVID-19 PHE, supply chain issues, manufacturing and quality issues, lack of active ingredients, and business decisions of manufacturers. DEA considered FDA's concerns when determining the APQ for these substances. Additionally, DEA considered manufacturer and distributor-reported data which shows inventories for both amphetamine and methylphenidate-based products have increased year-over-year throughout the supply chain. DEA believes these increases in inventories combined with the established APQs are adequate to address FDA's estimated increases in domestic medical use for amphetamine and methylphenidate. With respect to lisdexamfetamine, DEA recently increased the APQ pursuant to a final order published on September 5, 2024 to address reported shortages. 3 In sum, DEA believes that manufacturers will be able to meet the increase in domestic medical need for these three schedule II stimulants with the APQs proposed in this notice.
Footnotes:
2 ?New Long-Haul COVID Clinics Treat Mysterious and Ongoing Symptoms, Scientific American, June 30, 2021; Successful Treatment of Post-COVID-19 ADHD-like Syndrome-A case Report, J Atten Disord., 2023 Aug; 27(10): 1092-1098.
3 ?Adjustment to the Aggregate Production Quota for Lisdexamfetamine and d-Amphetamine (for Conversion) for 2024, 89 FR 72424 (Sept. 5, 2024).
DEA Projected Trends for Certain Schedule I Controlled Substances
DEA is proposing a higher APQ for ibogaine than DEA granted for 2024 to support manufacturing activities related to the increased level of research and clinical trials with this schedule I controlled substance. Additionally, DEA proposes a higher APQ for gamma hydroxybutyric acid (GHB) to allow for an anticipated increase in domestic bulk manufacturing to meet forecasted and continued domestic market need due to the closure of a foreign manufacturing facility. Imports of the schedule III oxybate form of GHB from that manufacturing facility have supplied an estimated 78% of the domestic need. Their foreign plant closure will be approximately one year in duration. GHB (oxybate) products are used in the treatment of patients diagnosed with narcolepsy and cataplexy.
Information Received for Consideration of the Remaining Factors
For the factors listed in 21 CFR 1303.11(b)(3) and (4), DEA registered manufacturers of controlled substances in schedules I and II provide information such as inventory, distribution, manufacturing, sales forecasts and quota requests to DEA database systems. See 21 CFR 1303.12, 1303.22, and part 1304.
The regulation at 21 CFR 1303.11(b)(5) requires DEA to consider the extent of diversion of controlled substances. 4 Diversion is defined as all distribution, dispensing, or other use of controlled substances for other than legitimate medical purposes. In order to consider the extent of diversion, DEA analyzed reports of diversion of controlled substances from 2023 submitted to its Theft Loss Report database. This database is comprised of DEA registrant reports documenting diversion from the legitimate distribution chain, including employee thefts, break-ins, armed robberies, and material lost in transit. The data was categorized by basic drug class, and the amount of active pharmaceutical ingredient (API) in the dosage form was delineated with an appropriate metric for use in proposing aggregate production quota values ( i.e., weight).
Footnotes:
4 ?The estimates of diversion for five "covered controlled substances" as required by 21 U.S.C. 826(i) are discussed later in the document.
In this proposed 2025 APQ notice, DEA continues to consider the lingering effects of the COVID-19 pandemic on the global supply chain, pursuant to 21 CFR 1303.11(b)(7), and specifically the continued impacts on the availability of raw materials for use in the domestic manufacturing process. Additionally, DEA considered the impact of the demand for surgical care for elective surgeries that were deferred during the COVID-19 PHE.
Estimates of Diversion of Covered Controlled Substances
In establishing any quota . . . , or any procurement quota established by [DEA] by regulation, for fentanyl, oxycodone, hydrocodone, oxymorphone, or hydromorphone (in this subsection referred to as a "covered controlled substance"), [DEA] shall estimate the amount of diversion of the covered controlled substance that occurs in the United States. 21 U.S.C. 826(i)(1)(A).
In estimating diversion under that provision, DEA:
[top] (i) shall consider information . . . , in consultation with the Secretary of Health and Human Services, [it] determines reliable on rates of overdose
(ii) may take into consideration whatever other sources of information [it] determines reliable.
21 U.S.C. 826(i)(1)(B).
The statute further mandates that DEA "make appropriate quota reductions, as determined by [DEA], from the quota [it] would have otherwise established had such diversion not been considered."? 5
Footnotes:
5 ?21 U.S.C. 826(i)(1)(C).
In estimating the amount of diversion of each covered controlled substance that occurs in the United States, DEA considered information from state PDMP Administrators and from legitimate distribution chain participants.
Consideration of Information From Certain State PDMPs and From National Sales Data
Pursuant to 21 CFR 1303.11(b)(6), DEA requested state PDMP data for the purpose of establishing its APQ. DEA believes state PDMPs to be an essential, reliable source of information for use in effectively estimating diversion of the five covered controlled substances. In April 2024, DEA sent a letter to NASCSA requesting its assistance in obtaining aggregated PDMP data for the five covered controlled substances from each state covering the years 2021-2023. The letter indicated that DEA was specifically interested in an analysis of prescription data from each state's PDMP that would assist DEA in estimating diversion and setting appropriate quotas in compliance with 21 U.S.C. 826(i). In its request, DEA provided specific questions, discussed in detail below, based on common indicia of potential diversion known as "red flags" by physicians, pharmacists, manufacturers, distributors, and federal and state regulatory and law enforcement agencies. 6 DEA investigators and administrative prosecutors also rely on Agency case law in which these red flags of diversion have been upheld as indicia of potential diversion. 7 Certain state regulations now include red flag circumstances as potential indicators of illegitimate prescriptions, and thus of potential abuse and diversion of controlled substances. 8 See, e.g., The Pharmacy Place Order, 86 FR 21008, 21012 (Apr. 21, 2021) (citing 22 Tex. Admin. Code 291.29(c)(4), specifying the geographical distance between the practitioner and the patient or between the pharmacy and the patient as a red flag).
Footnotes:
6 ?National Association of Boards of Pharmacy (NABP) coalition consensus document "Stakeholders' Challenges and Red Flag Warning Signs Related to Prescribing and Dispensing Controlled Substances" (2015). www.nabp.pharmacy/resources/reports.
7 ?The Medicine Shoppe, 79 FR 59504, 59507, 59512-13 (Oct. 2, 2014); Holiday CVS, L.L.C., d/b/a CVS Pharmacy Nos. 219 and 5195, 77 FR 62316 (Oct. 12, 2012).
8 ?The mere indicia of red flags alone is not proof of violation of 21 U.S.C. 824 or any other provision of the CSA. This rule discusses only their use by DEA as an analytical tool to estimate diversion.
DEA requested responses from state PDMP Administrators by June 15, 2024. NASCSA disseminated DEA's request to its PDMP Administrators and provided them with a report tool to ensure that responses to DEA's questions were extracted consistently across all responsive states. Twenty-nine states and three territories provided DEA with summarized PDMP data as of July 2024, utilizing the standardized report developed by NASCSA. 9 See Table 1a below.
Footnotes:
9 ?NASCSA formatted DEA's request into an analytics model developed by one of its associates, Appriss Inc.
| State/territory |
|---|
| 1. Alabama. |
| 2. Alaska. |
| 3. Arkansas. |
| 4. Commonwealth of Northern Mariana Islands. |
| 5. Connecticut. |
| 6. Delaware. |
| 7. District of Columbia. |
| 8. Idaho. |
| 9. Indiana. |
| 10. Kansas. |
| 11. Kentucky. |
| 12. Louisiana. |
| 13. Maryland. |
| 14. Massachusetts. |
| 15. Michigan. |
| 16. Minnesota. |
| 17. Mississippi. |
| 18. Montana. |
| 19. Nevada. |
| 20. New Jersey. |
| 21. New Mexico. |
| 22. North Carolina. |
| 23. Oklahoma. |
| 24. Oregon. |
| 25. Pennsylvania. |
| 26. Puerto Rico. |
| 27. South Carolina. |
| 28. South Dakota. |
| 29. Utah. |
| 30. Vermont. |
| 31. Virginia. |
| 32. Washington. |
Pharmacies are required by state law to enter controlled substance dispensing data into the state's PDMP database, including the prescriber's name, registered address and DEA number; prescription information (such as drug name); dispensing date; dosage dispensed; pharmacy registered address; and patient name and address. DEA considers PDMP data to be an accurate representation of dispensing activities in states. DEA received data for the following red-flag metrics:
• The total number of patients who saw three or more prescribers in a 90-day period and were dispensed an opioid following each visit. For this metric, DEA requested and was provided the number of prescriptions for the five covered controlled substances dispensed to these patients, as a percentage of the total prescriptions dispensed for that particular covered controlled substance, as well as the corresponding quantity of the covered controlled substance dispensed. This metric (patients being prescribed covered controlled substances from three or more prescribers in a 90-day period) is used to identify potential doctor shopping, a common technique to obtain a high number of controlled substances, which may lead to abuse or diversion of controlled substances. DEA has long considered doctor shopping to be an indicator of potential diversion. 10
Footnotes:
10 ?Frank's Corner Pharmacy, 60 FR 17574 (Apr. 6, 1995); Holiday CVS, L.L.C., d/b/a CVS Pharmacy Nos. 219 and 5195, 77 FR 62316 (Oct. 12, 2012).
• The number of patients that were dispensed prescriptions for each of the five covered controlled substances that exceeded 240 morphine milligram equivalents (MME) daily. States provided the raw number of such prescriptions dispensed, the number of prescriptions as a percentage of the total covered controlled substance prescriptions dispensed, and the corresponding quantity of the covered controlled substance dispensed. DEA believes that accounting for quantities in excess of 240 MME daily allows for consideration of oncology patients with legitimate medical needs for covered controlled substance prescriptions with high MME. Higher dosages place individuals at higher risk of overdose and death. Prescriptions involving dosages exceeding 240 MME daily may indicate diversion, such as illegal distribution of controlled substances or prescribing outside the usual course of professional practice.
[top] • The number of patients that paid cash for covered controlled substance prescriptions, without submitting for insurance reimbursement. 11 States also provided the number of prescriptions paid entirely with cash as a percentage
Footnotes:
11 ?This total does not include insurance co-payments made with cash.
12 ?Suntree Pharmacy and Suntree Medical Equipment, LLC, 85 FR 73753 (Nov. 19, 2020) (finding that the pharmacy filled prescriptions despite the presence of multiple unresolved red flags, including cash payments); Pharmacy Doctors Enterprises d/b/a Zion Clinic Pharmacy, 83 FR 10876 (Mar. 13, 2018) (revoking pharmacy's registration for filling prescriptions that raised the red flag of customers paying cash for their prescriptions, among other red flags).
DEA received PDMP data from the states in a standardized format that allowed DEA to aggregate the data. The PDMP data sample represents a population of approximately 112.35 million people, which is approximately 34 percent of the U.S. population. DEA believes this sample is sufficient to derive a reasonable nationwide estimate.
While PDMP data is useful in estimating diversion, it is not conclusive. Further investigation would be required before concluding that any of the subject prescriptions were actually diverted. DEA continues to evaluate its methodologies in estimating diversion in an effort to set quotas more efficiently. State participation is crucial to accurate data analysis, and DEA anticipates working closely with states, as well as other federal and state entities, in future quota determinations.
To calculate a national diversion estimate for each of the covered controlled substances from the responses received from state PDMP Administrators, DEA relied upon the number of individuals who received a prescription for a covered controlled substance that met any of the three red-flag metrics for each of calendar years 2021-2023. Using the population of the states responding to DEA's request, DEA then calculated the percentage of the population issued a prescription with a red flag. Using this estimated percentage for 2021-2023, DEA analyzed trends in the data to predict the estimated percentage of patients who would be expected to be included in these red-flag metrics for 2025.
DEA also reviewed aggregate sales data for each of the covered controlled substances, which it extracted from IQVIA's National Sales Perspective. 13 IQVIA sales data was selected to help quantify diversion at the national level because it reflects the best national estimate for all prescriptions written and filled, including the total quantity available for diversion or misuse. DEA analyzed trends in IQVIA sales data from January 2021-April 2024, in order to predict the estimated national sales for 2025.
Footnotes:
13 ?DEA has purchased this data from IQVIA for decades and routinely uses this information to administer several regulatory functions, including the administration of DEA's quota program.
To estimate diversion for each of the covered controlled substances, DEA multiplied the forecasted percentage of patients likely to receive a prescription for a covered controlled substance that meet any of the three red-flag metrics in 2025 by the forecasted sales data from IQVIA for 2025. The resulting estimate of diversion from data submitted by state PDMP Administrators is summarized below in Table 1b. This data contributed to the final diversion estimate set forth in Table 3.
| Controlled substance | (g) |
|---|---|
| Fentanyl | 26 |
| Hydrocodone | 90,396 |
| Hydromorphone | 699 |
| Oxycodone | 234,372 |
| Oxymorphone | 000 |
Consideration of Registrant Reported Diversion in the Legitimate Distribution Chain
DEA extracted data from its Theft Loss Report database and categorized it by each basic drug class. DEA calculated the estimated amount of diversion by multiplying the quantity of API in each finished dosage form by the total amount of units reported stolen or lost to estimate the metric weight in grams of the controlled substance being diverted. This estimate of diversion from the legitimate supply chain for each of the covered controlled substances is displayed in Table 2. This data contributed to the final diversion estimates set forth in Table 3.
| Controlled substance | (g) |
|---|---|
| Fentanyl | 73 |
| Hydrocodone | 12,528 |
| Hydromorphone | 481 |
| Oxycodone | 30,265 |
| Oxymorphone | 165 |
In accordance with 21 U.S.C. 826(i), DEA's estimate of diversion for the five controlled substances was calculated by combining the values in Tables 1b and 2.
| Controlled substance | (g) |
|---|---|
| Fentanyl | 99 |
| Hydrocodone | 102,924 |
| Hydromorphone | 1,180 |
| Oxycodone | 264,637 |
| Oxymorphone | 165 |
Continuing Efforts To Anticipate and Prevent Drug Shortages
Beginning in the latter half of 2022, the DEA and FDA observed an increase in the number of drug shortages reported by manufacturers of schedule II stimulants including mixed-salt amphetamine products starting in April 2022 and lisdexamfetamine and methylphenidate starting in July 2023. As DEA and FDA stated in an open letter in 2023, 14 we remain committed to doing all we can to prevent stimulant drug shortages, limit their impact, and resolve them as quickly as possible.
Footnotes:
14 ?Both DEA and FDA released this letter on Aug. 1, 2023. It is available at: https://www.dea.gov/sites/default/files/2023-08/DEA%20and%20FDA%20Issue%20Joint%20Letter%20to%20the%20Public.pdf .
[top] In particular, DEA continues to seek additional information that will assist the agency to more accurately forecast export requirements, especially for those substances controlled domestically in schedule I or II that are not controlled internationally. DEA understands that manufacturers have contractual obligations that dictate business decisions regarding the quantities of finished dosage forms they will produce under a single DEA-issued quota, which applies to products manufactured with an active ingredient, whether for domestic or foreign markets. DEA has purchased third-party data to improve its understanding of the dynamic changes in foreign markets. In February 2024, DEA began utilizing IQVIA's foreign (non-U.S.) sales tracking
Footnotes:
15 ?Management of Quotas for Controlled Substances and List I Chemicals, 88 FR 60,117 (Aug. 31, 2023) (effective Nov. 29, 2023).
As part of DEA's continuing effort to prevent shortages and be more nimble in its administration of the quota program, DEA intends to continue to allocate procurement quotas to DEA-registered manufacturers of schedule II controlled substances on a semi-annual basis for the 2025 quota year, except that it will continue to allocate procurement quotas relating to injectable drug products containing schedule II controlled substances on an annual basis. DEA announced this change in a letter to DEA-registered manufacturers on April 29, 2024. No further change is being implemented at this time. DEA remains committed to ensuring that all patients with legitimate medical need can access appropriately prescribed medications.
The Administrator, therefore, proposes to establish the 2025 APQ for certain schedule I and II controlled substances and AAN for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine, expressed in grams of anhydrous acid or base, as follows:
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| Basic class | Proposed 2025 quotas (g) |
|---|---|
| Schedule I | |
| -[1-(2-Thienyl)cyclohexyl]pyrrolidine | 20 |
| 1-(1-Phenylcyclohexyl)pyrrolidine | 30 |
| 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine | 10 |
| 1-(5-Fluoropentyl)-3-(1-naphthoyl)indole (AM2201) | 30 |
| 1-(5-Fluoropentyl)-3-(2-iodobenzoyl)indole (AM694) | 30 |
| 1-[1-(2-Thienyl)cyclohexyl]piperidine | 15 |
| 2'-fluoro 2-fluorofentanyl | 30 |
| 1-Benzylpiperazine | 25 |
| 1-Methyl-4-phenyl-4-propionoxypiperidine | 10 |
| 2-(2,5-Dimethoxy-4-ethylphenyl)ethanamine (2C-E) | 30 |
| 2-(2,5-Dimethoxy-4-methylphenyl)ethanamine (2C-D) | 30 |
| 2-(2,5-Dimethoxy-4-nitro-phenyl)ethanamine (2C-N) | 30 |
| 2-(2,5-Dimethoxy-4-n-propylphenyl)ethanamine (2C-P) | 30 |
| 2-(2,5-Dimethoxyphenyl)ethanamine (2C-H) | 100 |
| 2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe; 2C-B-NBOMe; 25B; Cimbi-36) | 30 |
| 2-(4-Chloro-2,5-dimethoxyphenyl)ethanamine (2C-C) | 30 |
| 2-(4-Chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25C-NBOMe; 2C-C-NBOMe; 25C; Cimbi-82) | 25 |
| 2-(4-Iodo-2,5-dimethoxyphenyl)ethanamine (2C-I) | 30 |
| 2-(4-Iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25I-NBOMe; 2C-I-NBOMe; 25I; Cimbi-5) | 30 |
| 2,5-Dimethoxy-4-ethylamphetamine (DOET) | 25 |
| 2,5-Dimethoxy-4-n-propylthiophenethylamine | 25 |
| 2,5-Dimethoxyamphetamine | 25 |
| 2-[4-(Ethylthio)-2,5-dimethoxyphenyl]ethanamine (2C-T-2) | 30 |
| 2-[4-(Isopropylthio)-2,5-dimethoxyphenyl]ethanamine (2C-T-4) | 30 |
| 3,4,5-Trimethoxyamphetamine | 30 |
| 2-Methyl AP-237 | 30 |
| 3,4-Methylenedioxyamphetamine (MDA) | 12,000 |
| 3,4-Methylenedioxymethamphetamine (MDMA) | 12,000 |
| 3,4-Methylenedioxy-N-ethylamphetamine (MDEA) | 40 |
| 3,4-Methylenedioxy-N-methylcathinone (methylone) | 5,200 |
| 3,4-Methylenedioxypyrovalerone (MDPV) | 35 |
| 3-FMC; 3-Fluoro-N-methylcathinone | 25 |
| 3-Methylfentanyl | 30 |
| 3-Methylmethcathinone | 30 |
| 3-Methylthiofentanyl | 30 |
| 4,4'-Dimethylaminorex | 30 |
| 4-Bromo-2,5-dimethoxyamphetamine (DOB) | 30 |
| 4-Bromo-2,5-dimethoxyphenethylamine (2-CB) | 5,100 |
| 4-Chloro-alpha-pyrrolidinovalerophenone (4-chloro-alpha-PVP) | 25 |
| 4-CN-Cumyl-Butinaca | 25 |
| 4-Fluoroisobutyryl fentanyl | 30 |
| 4F-MDMB-BINACA | 30 |
| 4-FMC; Flephedrone | 25 |
| 4-MEC; 4-Methyl-N-ethylcathinone | 25 |
| 4-Methoxyamphetamine | 150 |
| 4-methyl-1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (alpha-PiHP) | 30 |
| 4-Methyl-2,5-dimethoxyamphetamine (DOM) | 25 |
| 4-Methylaminorex | 25 |
| 4-Methyl-N-methylcathinone (mephedrone) | 45 |
| 4-Methyl-alpha-ethylaminopentiophenone (4-MEAP) | 25 |
| 4-Methyl-alpha-pyrrolidinohexiophenone (MPHP) | 25 |
| 4'-Methyl acetyl fentanyl | 30 |
| 4-Methyl-a-pyrrolidinopropiophenone (4-MePPP) | 25 |
| 4F-MDMB-BUTICA | 30 |
| 5-(1,1-Dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol | 50 |
| 5-(1,1-Dimethyloctyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol (cannabicyclohexanol or CP-47,497 C8-homolog) | 40 |
| 5F-AB-PINACA; (1-Amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide | 25 |
| 5F-ADB; 5F-MDMB-PINACA (methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate) | 25 |
| 5F-CUMYL-P7AICA; 1-(5-Fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3carboximide | 25 |
| 5F-CUMYL-PINACA | 25 |
| 5F-EDMB-PICA | 30 |
| 5F-EDMB-PINACA | 25 |
| 5F-MDMB-PICA | 25 |
| 5F-AMB (methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate) | 25 |
| 5F-APINACA; 5F-AKB48 (N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide) | 25 |
| 5-Fluoro-PB-22; 5F-PB-22 | 25 |
| 5-Fluoro-UR144, XLR11 ([1-(5-fluoro-pentyl)-1Hindol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone | 25 |
| 5-Methoxy-3,4-methylenedioxyamphetamine | 25 |
| 5-Methoxy-N,N-diisopropyltryptamine | 25 |
| 5-Methoxy-N,N-dimethyltryptamine | 11,000 |
| AB-CHMINACA | 30 |
| AB-FUBINACA | 50 |
| AB-PINACA | 30 |
| ADB-BUTINACA | 30 |
| ADB-FUBINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide) | 30 |
| Acetorphine | 25 |
| Acetyl Fentanyl | 100 |
| Acetyl-alpha-methylfentanyl | 30 |
| Acetyldihydrocodeine | 30 |
| Acetylmethadol | 25 |
| Acryl Fentanyl | 25 |
| ADB-4en-PINACA | 30 |
| ADB-PINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide) | 50 |
| AH-7921 | 30 |
| All other tetrahydrocannabinol | 1,166,130 |
| Allylprodine | 25 |
| Alphacetylmethadol | 25 |
| alpha-Ethyltryptamine | 25 |
| Alphameprodine | 25 |
| Alphamethadol | 25 |
| alpha-Methylfentanyl | 30 |
| alpha-Methylthiofentanyl | 30 |
| alpha-Methyltryptamine (AMT) | 25 |
| alpha-Pyrrolidinobutiophenone (a-PBP) | 25 |
| alpha-pyrrolidinoheptaphenone (PV8) | 25 |
| alpha-pyrrolidinohexabophenone (alpha-PHP) | 25 |
| alpha-Pyrrolidinopentiophenone (a-PVP) | 25 |
| Amineptine | 30 |
| Aminorex | 25 |
| Anileridine | 20 |
| APINCA, AKB48 (N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide) | 25 |
| Benzethidine | 25 |
| Benzylmorphine | 30 |
| Betacetylmethadol | 25 |
| beta-Hydroxy-3-methylfentanyl | 30 |
| beta-Hydroxyfentanyl | 30 |
| beta-Hydroxythiofentanyl | 30 |
| beta-Methyl fentanyl | 30 |
| beta'-Phenyl fentanyl | 30 |
| Betameprodine | 25 |
| Betamethadol | 4 |
| Betaprodine | 25 |
| Brorphine | 30 |
| Bufotenine | 15 |
| Butonitazene | 30 |
| Butylone | 25 |
| Butyryl fentanyl | 30 |
| Cathinone | 40 |
| Clonazolam | 30 |
| Clonitazene | 25 |
| Codeine methylbromide | 30 |
| Codeine-N-oxide | 192 |
| Crotonyl Fentanyl | 25 |
| CUMYL-PEGACLONE | 30 |
| Cyclopentyl Fentanyl | 30 |
| Cyclopropyl Fentanyl | 20 |
| Cyprenorphine | 25 |
| d-9-THC | 1,523,040 |
| Desomorphine | 25 |
| Dextromoramide | 25 |
| Diapromide | 20 |
| Diclazepam | 30 |
| Diethylthiambutene | 20 |
| Diethyltryptamine | 25 |
| Difenoxin | 9,300 |
| Dihydromorphine | 639,954 |
| Dimenoxadol | 25 |
| Dimepheptanol | 25 |
| Dimethylthiambutene | 20 |
| Dimethyltryptamine | 11,000 |
| Dioxyaphetyl butyrate | 25 |
| Dipipanone | 25 |
| Drotebanol | 25 |
| Ethylmethylthiambutene | 25 |
| Ethylone | 25 |
| Etizolam | 30 |
| Etodesnitazene | 30 |
| Etonitazene | 25 |
| Etorphine | 30 |
| Etoxeridine | 25 |
| Eutylone | 30 |
| Fenethylline | 30 |
| Fentanyl carbamate | 30 |
| Fentanyl related substances | 600 |
| Flualprazolam | 30 |
| Flubromazolam | 30 |
| Flunitazene | 30 |
| FUB-144 | 25 |
| FUB-AKB48 | 25 |
| Fub-AMB, MMB-Fubinaca, AMB-Fubinaca | 25 |
| Furanyl fentanyl | 30 |
| Furethidine | 25 |
| gamma-Hydroxybutyric acid | 49,675,266 |
| Heroin | 150 |
| Hydromorphinol | 40 |
| Hydroxypethidine | 25 |
| Ibogaine | 210 |
| Isobutyryl Fentanyl | 25 |
| Isotonitazine | 25 |
| JWH-018 and AM678 (1-Pentyl-3-(1-naphthoyl)indole) | 35 |
| JWH-019 (1-Hexyl-3-(1-naphthoyl)indole) | 45 |
| JWH-073 (1-Butyl-3-(1-naphthoyl)indole) | 45 |
| JWH-081 (1-Pentyl-3-[1-(4-methoxynaphthoyl)]indole) | 30 |
| JWH-122 (1-Pentyl-3-(4-methyl-1-naphthoyl)indole) | 30 |
| JWH-200 (1-[2-(4-Morpholinyl)ethyl]-3-(1-naphthoyl)indole) | 35 |
| JWH-203 (1-Pentyl-3-(2-chlorophenylacetyl)indole) | 30 |
| JWH-250 (1-Pentyl-3-(2-methoxyphenylacetyl)indole) | 30 |
| JWH-398 (1-Pentyl-3-(4-chloro-1-naphthoyl)indole) | 30 |
| Ketobemidone | 30 |
| Levomoramide | 25 |
| Levophenyacylmorphan | 25 |
| Lysergic acid diethylamide (LSD) | 1,200 |
| MAB-CHMINACA; ADB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) | 30 |
| MDMB-CHMICA; MMB-CHMINACA(methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) | 30 |
| MDMB-FUBINACA (methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate) | 30 |
| MMB-CHMICA-(AMB-CHIMCA); Methyl-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3-methylbutanoate | 25 |
| Marijuana | 6,675,000 |
| Marijuana extract | 1,000,000 |
| MDMB-4en-PINACA | 30 |
| MMB-FUBICA | 30 |
| Mecloqualone | 30 |
| Mescaline | 1,200 |
| Mesocarb | 30 |
| Methaqualone | 60 |
| Methcathinone | 25 |
| Methiopropamine | 30 |
| Methoxetamine | 30 |
| Methoxyacetyl fentanyl | 30 |
| Methyldesorphine | 5 |
| Methyldihydromorphine | 25 |
| Metodesnitazene | 30 |
| Metonitazene | 30 |
| Morpheridine | 25 |
| Morphine methylbromide | 5 |
| Morphine methylsulfonate | 5 |
| Morphine-N-oxide | 150 |
| MT-45 | 30 |
| Myrophine | 25 |
| NM2201: Naphthalen-1-yl 1-(5-fluorpentyl)-1H-indole-3-carboxylate | 25 |
| N,N-Dimethylamphetamine | 25 |
| Naphyrone | 25 |
| N-Desethyl isotonitazene | 30 |
| N-Ethyl-1-phenylcyclohexylamine | 25 |
| N-Ethyl-3-piperidyl benzilate | 10 |
| N-Ethylamphetamine | 24 |
| N-Ethylhexedrone | 25 |
| N-Ethylpentylone, ephylone | 30 |
| N-Hydroxy-3,4-methylenedioxyamphetamine | 24 |
| Nicocodeine | 25 |
| Nicomorphine | 25 |
| N-methyl-3-piperidyl benzilate | 30 |
| N-piperidinyl etonitazene | 30 |
| N-Pyrrolidino Etonitazene | 30 |
| Noracymethadol | 25 |
| Norlevorphanol | 2,550 |
| Normethadone | 25 |
| Normorphine | 40 |
| Norpipanone | 25 |
| Ocfentanil | 25 |
| ortho-Fluoroacryl fentanyl | 30 |
| ortho-Fluorobutyryl fentanyl | 30 |
| Ortho-Fluorofentanyl,2-Fluorofentanyl | 30 |
| ortho-Fluoroisobutyryl fentanyl | 30 |
| ortho-Methyl acetylfentanyl | 30 |
| ortho-Methyl methoxyacetyl fentanyl | 30 |
| Para-Chlorisobutyrl fentanyl | 30 |
| Para-flourobutyryl fentanyl | 25 |
| Para-fluorofentanyl | 25 |
| para-Fluoro furanyl fentanyl | 30 |
| Para-Methoxybutyrl fentanyl | 30 |
| Para-methoxymethamphetamine | 30 |
| para-Methylfentanyl | 30 |
| Parahexyl | 5 |
| PB-22; QUPIC | 20 |
| Pentedrone | 25 |
| Pentylone | 25 |
| Phenadoxone | 25 |
| Phenampromide | 25 |
| Phenomorphan | 25 |
| Phenoperidine | 25 |
| Phenyl fentanyl | 30 |
| Pholcodine | 5 |
| Piritramide | 25 |
| Proheptazine | 25 |
| Properidine | 25 |
| Propiram | 25 |
| Protonitazene | 30 |
| Psilocybin | 30,000 |
| Psilocin | 36,000 |
| Racemoramide | 25 |
| SR-18 and RCS-8 (1-Cyclohexylethyl-3-(2-methoxyphenylacetyl)indole) | 45 |
| SR-19 and RCS-4 (1-Pentyl-3-[(4-methoxy)-benzoyl]indole) | 30 |
| Tetrahydrofuranyl fentanyl | 15 |
| Thebacon | 25 |
| Thiafentanil | 25 |
| Thiofentanyl | 25 |
| Thiofuranyl fentanyl | 30 |
| THJ-2201 ( [1-(5-fluoropentyl)-1H-indazol-3-yl](naphthalen-1-yl)methanone) | 30 |
| Tilidine | 25 |
| Trimeperidine | 25 |
| UR-144 (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone | 25 |
| U-47700 | 30 |
| Valeryl fentanyl | 25 |
| Zipeprol | 30 |
| Schedule II | |
| 1-Phenylcyclohexylamine | 15 |
| 1-Piperidinocyclohexanecarbonitrile | 25 |
| 4-Anilino-N-phenethyl-4-piperidine (ANPP) | 937,874 |
| Alfentanil | 5,000 |
| Alphaprodine | 25 |
| Amobarbital | 20,100 |
| Bezitramide | 25 |
| Carfentanil | 20 |
| Cocaine | 60,492 |
| Codeine (for conversion) | 942,452 |
| Codeine (for sale) | 19,262,957 |
| d-amphetamine (for sale) | 21,200,000 |
| d,l-amphetamine | 21,200,000 |
| d-amphetamine (for conversion) | 23,688,235 |
| Dexmethylphenidate (for sale) | 6,200,000 |
| Dexmethylphenidate (for conversion) | 5,374,683 |
| Dextropropoxyphene | 35 |
| Dihydrocodeine | 115,227 |
| Dihydroetorphine | 25 |
| Diphenoxylate (for conversion) | 14,100 |
| Diphenoxylate (for sale) | 770,800 |
| Ecgonine | 60,492 |
| Ethylmorphine | 30 |
| Etorphine hydrochloride | 32 |
| Fentanyl | 731,341 |
| Glutethimide | 25 |
| Hydrocodone (for conversion) | 1,250 |
| Hydrocodone (for sale) | 27,121,498 |
| Hydromorphone | 1,951,508 |
| Isomethadone | 30 |
| L-amphetamine | 30 |
| Levo-alphacetylmethadol (LAAM) | 25 |
| Levomethorphan | 30 |
| Levorphanol | 20,000 |
| Lisdexamfetamine | 32,736,000 |
| Meperidine | 681,184 |
| Meperidine Intermediate-A | 30 |
| Meperidine Intermediate-B | 30 |
| Meperidine Intermediate-C | 30 |
| Metazocine | 15 |
| Methadone (for sale) | 25,619,700 |
| Methadone Intermediate | 27,673,600 |
| d,l-Methamphetamine | 150 |
| d-methamphetamine (for conversion) | 485,020 |
| d-methamphetamine (for sale) | 47,000 |
| l-methamphetamine | 587,229 |
| Methylphenidate (for sale) | 53,283,000 |
| Methylphenidate (for conversion) | 19,975,468 |
| Metopon | 25 |
| Moramide-intermediate | 25 |
| Morphine (for conversion) | 2,393,200 |
| Morphine (for sale) | 20,805,957 |
| Nabilone | 62,000 |
| Norfentanyl | 25 |
| Noroxymorphone (for conversion) | 24,756,979 |
| Noroxymorphone (for sale) | 1,000 |
| Oliceridine | 25,100 |
| Opium (powder) | 250,000 |
| Opium (tincture) | 530,837 |
| Oripavine | 37,721,950 |
| Oxycodone (for conversion) | 437,827 |
| Oxycodone (for sale) | 53,584,449 |
| Oxymorphone (for conversion) | 31,773,105 |
| Oxymorphone (for sale) | 464,464 |
| Pentobarbital | 40,000,000 |
| Phenazocine | 25 |
| Phencyclidine | 35 |
| Phenmetrazine | 25 |
| Phenylacetone | 100 |
| Piminodine | 25 |
| Racemethorphan | 5 |
| Racemorphan | 5 |
| Remifentanil | 3,000 |
| Secobarbital | 172,100 |
| Sufentanil | 4,000 |
| Tapentadol | 10,390,226 |
| Thebaine | 57,137,944 |
| List I Chemicals | |
| Ephedrine (for conversion) | 41,100 |
| Ephedrine (for sale) | 3,933,336 |
| Phenylpropanolamine (for conversion) | 14,878,320 |
| Phenylpropanolamine (for sale) | 7,990,000 |
| Pseudoephedrine (for conversion) | 1,000 |
| Pseudoephedrine (for sale) | 186,617,466 |
The Administrator further proposes that the APQ for all other schedule I and II controlled substances included in 21 CFR 1308.11 and 1308.12 remain at zero.
These proposed 2025 quotas reflect the quantities that DEA believes are necessary to meet the estimated medical, scientific, research, and industrial needs of the United States, lawful export requirements; and the establishment and maintenance of reserve stocks.
In accordance with 21 CFR 1303.13 and 1315.13, upon consideration of the relevant factors, the Administrator may adjust the 2025 APQ and AAN as needed.
Conclusion
After consideration of any comments or objections, or after a hearing, if one is held, the Administrator will issue and publish in the Federal Register a final order establishing the 2025 APQ for controlled substances in schedules I and II and establishing an AAN for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine, as directed by 21 CFR 1303.11(c) and 1315.11(f).
Signing Authority
This document of the Drug Enforcement Administration was signed on September 20, 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. 2024-21962 Filed 9-20-24; 4:15 pm]
BILLING CODE 4410-09-P