DEPARTMENT OF JUSTICE
Drug Enforcement Administration
[Docket No. DEA-688A]
Proposed Adjustments to the 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 2021
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice with request for comments.
SUMMARY: The Drug Enforcement Administration proposes to adjust the 2021 aggregate production quotas for several controlled substances in schedules I and II of the Controlled Substances Act and 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 1303.13(c) and 1315.13(d). Electronic comments must be submitted, and written comments must be postmarked, on or before October 4, 2021. Commenters should be aware that the electronic Federal Docket Management System will not accept comments after 11:59 p.m. Eastern Time on the last day of the comment period.
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 2021 adjusted aggregate production quotas for schedule I and II controlled substances, and an adjusted 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-688A” 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/DRW, 8701 Morrissette Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: Scott A. Brinks, Regulatory Drafting and Policy Support Section, Diversion Control Division, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, Virginia 22152, Telephone: (571) 776-2265.
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
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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 and Background
Section 306 of the Controlled Substances Act (CSA) (21 U.S.C. 826) requires the Attorney General to establish aggregate production quotas for each basic class of controlled substance 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.
DEA established the 2021 aggregate production quotas for substances in schedules I and II and the assessment of annual needs for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine on November 30, 2020 (85 FR 76604). That order stipulated that, in accordance with 21 CFR 1303.13 and 1315.13, all aggregate production quotas and assessments of annual need are subject to adjustment.
Analysis for Proposed Adjusted 2021 Aggregate Production Quotas and Assessment of Annual Needs
DEA proposes to adjust the established 2021 aggregate production quotas to be manufactured in the United States in 2021 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. However, DEA’s analysis does not suggest the need for adjustment of the 2021 assessment of annual needs for the List I chemicals.
Factors for Determining the Proposed Adjustments
In determining the proposed adjustments, the Administrator has taken into account the criteria in accordance with 21 CFR 1303.13 (adjustment of aggregate production quotas for controlled substances) and 21 CFR 1315.13 (adjustment of the assessment of annual needs for ephedrine, pseudoephedrine, and phenylpropanolamine). The Administrator is authorized to increase or reduce the aggregate production quota at any time. 21 CFR 1303.13(a) and 1315.13(a). DEA regulations state that there are five factors that shall be considered in determining to adjust the aggregate production quota and the assessment of annual needs. 21 CFR 1303.13(b) and 1315.13(b).
DEA determined whether to propose an adjustment of the aggregate production quotas and assessment of annual needs for 2021 by considering the factors summarized below:
(1) Changes in the demand for that class or chemical, changes in the national rate of net disposal of the class or chemical, changes in the national rate of net disposal of the class or chemical by registrants holding individual manufacturing quotas for that class or chemical, and changes in the extent of any diversion in the class of controlled substance;
(2) whether any increased demand for that class or chemical, the national and/or individual rates of net disposal of that class or chemical are temporary, short term, or long term;
(3) whether any increased demand for that class or chemical can be met through existing inventories, increased individual manufacturing quotas, or increased importation, without increasing the aggregate production quota or assessment of annual needs, taking into account production delays and the probability that other individual manufacturing quotas may be suspended pursuant to Sec. 1303.24(b) and 1315.24(b);
(4) whether any decreased demand for that class or chemical will result in excessive inventory accumulation by all persons registered to handle that class or chemical (including manufacturers, distributors, practitioners, importers, and exporters), notwithstanding the possibility that individual manufacturing quotas may be suspended pursuant to Sec. 1303.24(b) and 1315.24(b) or abandoned pursuant to Sec. 1303.27 and 1315.27; and
(5) other factors affecting medical, scientific, research, and industrial needs in the United States, lawful export requirements, and other factors affecting importation needs of listed chemicals in the United States 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) and 1315(b).
DEA considered the change in the extent of diversion of all controlled substances in proposing adjustments to the aggregate production quotas as required by 21 CFR 1303.13(b)(1). Pursuant to these factors, DEA has determined that any calculated changes from the previously determined initial calculations are slight and not statistically significant from the quantities originally calculated for the extent of diversion that were applied to the initial aggregate production quota valuations.
DEA also considered updated information obtained from 2020 year-end inventories, 2020 disposition data submitted by quota applicants, estimates of the medical needs of the United States, product development, and other information made available to DEA after the initial aggregate production quotas and assessment of annual needs had been established. Other factors the Administrator considered in calculating the aggregate production quotas, but not the assessment of annual needs, include product development requirements of both bulk and finished dosage form manufacturers, and other pertinent information.
In evaluating whether there is a need for adjustment of the 2021 assessment of annual needs for List I chemicals, DEA used the calculation methodology previously described in the 2010 and 2011 assessment of annual needs (74 FR 60294, Nov. 20, 2009, and 75 FR 79407, Dec. 20, 2010, respectively). However, DEA’s analysis does not suggest the need for adjustment of the 2021 assessment of annual needs.
Considerations Based Upon the Substance Use-Disorder Prevention That Promotes Opioid Recovery and Treatment for Patients and Communities Act
Pursuant to 21 U.S.C. 826(a)(1), “production quotas shall be established in terms of quantities of each basic class of controlled substance and not in terms of individual pharmaceutical dosage forms prepared from or containing such a controlled substance.” However, the Substance Use-Disorder Prevention that Promotes Opioid Recovery Treatment for Patients and Communities Act of 2018 (SUPPORT Act), (Pub. L. 115-271), provides an exception to that general rule by now giving DEA the authority to establish quotas in terms of pharmaceutical dosage forms if the
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agency determines that doing so will assist in avoiding the overproduction, shortages, or diversion of a controlled substance.
DEA has stated before that while there is the authority to set aggregate production quotas in terms of pharmaceutical dosage form, DEA will not be using that authority at this time. Furthermore, when DEA does utilize the authority, it will be doing so at the individual dosage-form manufacturing level, as that is where it is most appropriate to do so. As such, there are no adjustments to set any controlled substances in terms of pharmaceutical dosage forms.
Under the SUPPORT Act, when setting the aggregate production quota, DEA must estimate the amount of diversion of any substance that is considered a “covered controlled substance,” as defined by the SUPPORT Act. 21 U.S.C. 826(i)(1)(A). The covered controlled substances are fentanyl, oxycodone, hydrocodone, oxymorphone, and hydromorphone. The SUPPORT Act also requires DEA to “make appropriate quota reductions, as determined by the [Administrator],\1\ from the quota the [Administrator] would have otherwise established had such diversion not been considered.” 21 U.S.C. 826(i)(1)(C). When estimating diversion, the “[Administrator]–(i) shall consider information the [Administrator], in consultation with the Secretary of Health and Human Services, determines reliable on rates of overdose deaths and abuse and overall public health impact related to the covered controlled substance in the United States; and (ii) may take into consideration whatever other sources of information the [Administrator] determines reliable.” 21 U.S.C. 826(i)(1)(B).
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\1\ All functions vested in the Attorney General by the CSA have been delegated to the Administrator of DEA. 28 CFR 0.100(b).
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In February 2021, DEA sent letters to the Centers for Disease Control and Prevention (CDC), Centers for Medicare and Medicaid Services (CMS), and the states requesting overdose death and overprescribing data that could be considered for estimating diversion. DEA did not receive information from CMS. However, DEA did receive information from the CDC in June 2021 and has started to receive information from the states. DEA has begun to receive Prescription Drug Monitoring Program (PDMP) data from the states in a format that will allow the Agency to develop a more robust methodology to assist in the determination of the diversion estimate in the future. This information will be considered in determining the estimates of diversion for the five covered controlled substances in the 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 2022.
To update the estimates of diversion, DEA used data from the Drug Theft and Loss Report, Statistical Management Analysis & Reporting Tools System (SMARTS), and System to Retrieve Information on Drug Evidence (STRIDE) databases to aggregate the active pharmaceutical ingredient (API) of each covered controlled substance by metric weight. From the databases, DEA gathered data involving employee theft, break-ins, armed robberies, and material lost in transit. DEA also used seizure data obtained from reports submitted by law enforcement agencies nationwide. This data was categorized by basic drug class and the amount of API in the dosage form was delineated with an appropriate metric for use in proposing the adjusted aggregate production quota values. Using the data, DEA calculated the estimates for the amount of diversion by multiplying the strength of the API listed for each finished dosage form by the total amount of units reported to estimate the metric weight in grams of the controlled substance being diverted. Below, DEA has updated the chart to include estimations of diversion for each of the covered controlled substances.
| Diversion Estimates for 2020 (g) | |
|---|---|
| Fentanyl | 184 |
| Hydrocodone | 20,759 |
| Hydromorphone | 946 |
| Oxycodone | 47,316 |
| Oxymorphone | 534 |
DEA considered the change in the extent of diversion of all controlled substances in proposing adjustments to the aggregate production quotas as required by 21 CFR 1303.13(b)(1). Pursuant to these factors, DEA has determined that any calculated changes from the previously determined initial calculations are slight and not statistically significant from the quantities originally calculated for the extent of diversion that were applied to the initial aggregate production quota valuations.
Proposed Adjustments for the 2021 Aggregate Production Quotas and Assessment of Annual Needs
DEA is proposing significant increases to the APQs of the schedule I substances psilocybin, psilocin, marihuana, and marihuana extract, which are directly related to increased interest by DEA registrants in the use of hallucinogenic controlled substances for research and clinical trial purposes. DEA firmly believes in supporting regulated research of schedule I controlled substances. Therefore, the APQ increases reflect the need to fulfill research and development requirements in the production of new drug products, and the study of marijuana effects in particular, as necessary steps toward potential Food and Drug Administration (FDA) approval of new drug products.
The DEA established the 2021 aggregate production quotas for substances in schedules I and II on November 30, 2020 (85 FR 76604). Subsequent to that publication, DEA published in the Federal Register two final rules to permanently schedule 14 specific fentanyl-related substances under the CSA (86 FR 22113, April 27, 2021, and 86 FR 23602, May 4, 2021). The specific fentanyl-related substances are 2′-fluoro 2-fluorofentanyl, 4′-Methyl acetyl fentanyl, beta-Methyl fentanyl, beta-Phenyl fentanyl, Fentanyl carbamate, ortho-Fluoroacryl fentanyl, ortho-Fluorobutyryl fentanyl, ortho-Fluoroisobutyryl fentanyl, ortho-Methyl acetylfentanyl, ortho-Methyl methoxyacetyl fentanyl, para-Fluoro furanyl fentanyl, para-Methylfentanyl, Phenyl fentanyl, and Thiofuranyl fentanyl. As a result, these substances will continue to be subject to the CSA schedule I controls and are now being assigned individual aggregate production quotas.
On March 1, 2021, DEA published a temporary scheduling order placing Brorphine in schedule I of the CSA (86 FR 11862), making all regulatory controls pertaining to schedule I controlled substances applicable to the manufacture of these substances, including the requirement to establish an aggregate production quota pursuant to 21 U.S.C. 826 and 21 CFR part 1303. This notice proposes to establish an aggregate production quota for this substance.
On May 7, 2021, DEA published an interim final rule placing serdexmethylphenidate, a component in a combination drug product recently approved by FDA for the treatment of ADHD in patients six years of age and older, in schedule IV of the CSA (86 FR 24487). Serdexmethylphenidate is manufactured from methylphenidate, a schedule II controlled substance. In order to more accurately estimate and manage the quantity of methylphenidate necessary for direct formulation into schedule II drug products versus the
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quantity of methylphenidate necessary for the manufacturing of serdexmethylphenidate or other substances, DEA has delineated methylphenidate into methylphenidate (for sale) and methylphenidate (for conversion). This notice proposes to establish an aggregate production quota for methylphenidate (for conversion).
On June 20, 2021, DEA published the final rule to place oliceridine, a medication recently approved by FDA for medical use as an intravenous drug for the management of acute pain severe enough to require an intravenous opioid analgesic and for patients for whom alternative treatments are inadequate, in schedule II of the CSA effective July 12, 2021 (86 FR 30772). The placement of oliceridine in schedule II of the CSA, makes all regulatory controls pertaining to schedule II controlled substances applicable to the manufacture of this substance, including the requirement to establish an aggregate production quota pursuant to 21 U.S.C. 826 and 21 CFR part 1303.
The Administrator, therefore, proposes to adjust the 2021 aggregate production quotas for certain schedule I and II controlled substances. The Administrator does not propose an adjustment to the assessments of annual needs for the list I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine. The proposed adjusted APQs, as expressed in grams of anhydrous acid or base, are as follows:
Filed under: General Problems
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