[Federal Register Volume 87, Number 70 (Tuesday, April 12, 2022)] [Proposed Rules] [Pages 21588-21599] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 2022-07572] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA-384] RIN 1117-AB75 Schedules of Controlled Substances; Exempted Prescription Products AGENCY: Drug Enforcement Administration, Department of Justice. ACTION: Notice of proposed rulemaking. ----------------------------------------------------------------------- SUMMARY: The Drug Enforcement Administration proposes to revoke the exempted prescription product status for all butalbital products previously granted exemptions. Upon publication of a final rule, these products shall become subject to all schedule III controls under the Controlled Substances Act. If finalized, this action would impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule III controlled substances on persons who handle (manufacture, distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess) or propose to handle butalbital products. This rulemaking also proposes to make changes to our regulations to clarify that DEA may revoke ``(either individually or categorically)'' any previously granted exemptions, and adds regulations to clarify that products exempted from application of all or any part of the Controlled Substances Act are listed in the Table of Exempted Prescription Products available on the DEA Diversion Control website (https://www.deadiversion.usdoj.gov/). DATES: Comments must be submitted electronically or postmarked on or before May 12, 2022. ADDRESSES: Interested persons may file written comments on this proposal in accordance with 21 CFR 1308.43(g). 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. To ensure proper handling of comments, please reference ``Docket No. DEA-384'' on all correspondence, including any attachments.Electronic comments: The Drug Enforcement Administration (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 to attach a file for lengthier comments. Please go to https://www.regulations.gov and follow the online instructions at that site to submit comments. Upon completion of your submission, you will receive a Comment Tracking Number. Please be aware that submitted comments are not instantaneously available for public view on Regulations.gov. If you have received a Comment Tracking Number, you have successfully submitted your comment, and there is no need to resubmit the same comment. Paper comments: Paper comments that duplicate the electronic submission are not necessary. Should you wish to mail a paper comment in lieu of an electronic comment, send via regular or express mail to: Drug Enforcement Administration, Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive, Springfield, Virginia 22152. FOR FURTHER INFORMATION CONTACT: Terrence L. Boos, Ph.D., Chief (DOE), Diversion Control Division, Drug Enforcement Administration; Telephone: (202) 362-3249. SUPPLEMENTARY INFORMATION: Posting of Public Comments Please note that all comments received in response to this docket are considered part of the public record. The Drug Enforcement Administration (DEA) will make comments available for public inspection online at https://www.regulations.gov, unless reasonable [[Page 21589]] cause is given. 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 to make it publicly available, you must include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the first paragraph of your comment. You must also place all of 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 to make it 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. DEA will make publicly available in redacted form comments containing personal identifying information and confidential business information identified as directed above. If a comment has so much confidential business information or personal identifying information that DEA cannot redact it effectively, all or part of that comment may not be made publicly available. Comments posted to https://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 and supplemental information to this proposed rule are available at https://www.regulations.gov for easy reference. Legal Authority Pursuant to the Controlled Substances Act (CSA), under 21 U.S.C. 811(g)(3), 21 CFR 1308.31, and 21 CFR 1308.32, the Attorney General (and thus the Administrator of DEA by delegation) may, by regulation, exempt any compound, mixture, or preparation containing a nonnarcotic controlled substance from the application of all or any part of this subchapter if he finds that it is approved for prescription use, and that it contains one or more other active ingredients which are not listed in any schedule and which are included in such combinations, quantity, proportion, or concentration as to vitiate the potential for abuse. By regulation, the Administrator may revoke a previously granted exemption by following the same procedures that are used to evaluate an application for exemption--namely, by publishing in the Federal Register a general notice of the proposed rulemaking in revoking the exemption, permitting interested persons to file written comments on or objections to the revocation, considering any comments submitted, and publishing in the Federal Register a final order on the proposal to revoke the exemption. See 21 CFR 1308.31(c), (d). This rulemaking proposes to make changes to 21 Code of Federal Regulations (CFR) 1308.21(d) to clarify that DEA may revoke ``(either individually or categorically)'' any previously granted exemptions, and adds Sec. 1308.31(e) to clarify that products exempted from application of all or any part of the Controlled Substances Act pursuant to section 201(g)(3)(A), of the Act (21 U.S.C. 811(g)(3)(A)) are listed in the Table of Exempted Prescription Products available on the DEA Diversion Control website. In addition, this rulemaking proposes the removal of exempted prescription product status for butalbital products previously granted exemption. If finalized, this action would impose the regulatory controls and administrative, civil, and criminal sanctions of schedule III controlled substances on any person who handles or proposes to handle butalbital products that were previously exempted from control under 21 CFR 1308.31 and 1308.32. Background: Exempted Prescription Products Over time, DEA has exempted prescription drug products from certain parts of the CSA when the products meet the requirements for exemption, including the requirement to contain active ingredients believed to vitiate the potential for abuse. The current table of products that have been granted exempted prescription product status, pursuant to 21 CFR 1308.31 and 1308.32, can be found on the DEA Diversion Control Division website at https://www.deadiversion.usdoj.gov/schedules/exempt/exempt_rx_list.pdf. The list, dated February 11, 2022, contains 189 prescription products containing butalbital. These butalbital products were granted exempted status due to the quantity of acetaminophen in the formulation, which was believed at the time to vitiate the potential for abuse. Many of the preparations granted exempted prescription product status were excepted by the Bureau of Drug Abuse Control (BDAC) of the Food and Drug Administration (FDA), the predecessor to the Bureau of Narcotics and Dangerous Drugs and later DEA. A panel of public health physicians and FDA medical officers developed the criteria used by BDAC in 1967. Following the establishment of the criteria, DEA approved subsequent applications by new manufacturers over the years based upon the same criteria, whereby the inclusion of other active ingredients was thought to be in sufficient quantities to vitiate the potential for abuse. These criteria developed in 1967 were found to meet the standard for exemption currently described in 21 U.S.C. 811(g)(3)(A), such that if a prescription drug was found to meet the 1967 criteria for exception, then it also met the test to contain an ingredient that vitiated the potential for abuse under the CSA standard. These criteria were based upon the expectation that combining the controlled substance with an amount of counteractive drug sufficient to cause early deterrent side effects would vitiate the potential for abuse. For products containing long or intermediate acting barbiturates in combination with analgesics, the criteria provided that an exception would be granted if for every 15 mg of barbiturate the product contained at least (a) 188 mg aspirin; (b) 375 mg salicylamide; or (c) 70 mg phenacetin, acetanilid or acetaminophen. Butalbital is classified as an intermediate acting barbiturate. Butalbital is a schedule III controlled substance that falls under Administration Controlled Substances Code Number 2100 as it is a derivative of barbituric acid. 21 CFR 1308.13(c)(3). In 1967, products such as Fioricet, which contained butalbital (50 mg) in combination with acetaminophen (300 mg) and caffeine (40 mg), qualified for the exception under the above criteria. However, products such as Fiorinal, which contained butalbital (50 mg) in combination with aspirin (325 mg) and caffeine (40 mg), did not contain sufficient quantities of aspirin to meet the exception criteria, and therefore did not qualify for the exception. As such, Fiorinal was a schedule III controlled product, while Fioricet and similar butalbital combination products containing sufficient amounts of acetaminophen were automatically granted exempted prescription product status under the BDAC criteria once an application under 21 CFR 1308.31 was received. The rationale behind the difference between Fiorinal and Fioricet was that the acetaminophen quantity in [[Page 21590]] Fioricet would deter the product's abuse due to the potential liver toxicity resulting from the ingestion of high doses of acetaminophen. However, subsequent experience has shown that the presence of acetaminophen in these butalbital products has not adequately deterred abuse and diversion. DEA has observed a pattern of diversion, online distribution, and abuse of exempted butalbital products. In particular, DEA has observed exploitation of the exempted prescription product status of butalbital combination products to enable abuse. Therefore, because the inclusion of acetaminophen has not vitiated the abuse potential of these products, DEA has concluded that these products do not meet the exemption criteria found in 21 U.S.C. 811(g)(3)(A). Sellers have utilized websites to exploit the exempted prescription product status to make butalbital/acetaminophen and butalbital/ acetaminophen/caffeine combination products available over the internet. In addition, DEA has documented a significant number of law enforcement encounters with butalbital/acetaminophen and butalbital/ acetaminophen/caffeine products. DEA is actively investigating cases where individuals are exploiting the exempted prescription product status and are using such products to provide the controlled substance butalbital for drug abuse purposes. DEA, therefore, proposes to revoke the previously issued exempted prescription product status of all butalbital products. Upon publication of a final rule, these products shall become subject to the schedule III regulatory controls under the CSA. Increase in Website Activity Relating to Exempted Prescription Products The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 (Pub. L. 110-425) (Ryan Haight Act) was enacted on October 15, 2008 and became effective on April 13, 2009. The Ryan Haight Act amended the CSA to prevent the illegal distribution and dispensing of controlled substances by means of the internet and made it illegal under Federal law to ``deliver, distribute, or dispense a controlled substance by means of the internet, except as authorized by [the CSA]'' or to aid or abet such activity. 21 U.S.C. 841(h)(1). The Ryan Haight Act applies to all controlled substances in all schedules. Under the Ryan Haight Act, for every controlled substance that is delivered, distributed, or sold, there must be a ``valid prescription.'' This means not only that the prescription must comply with the longstanding requirement of being issued for a legitimate medical purpose by a practitioner acting in the usual course of professional practice, but also that the prescribing practitioner must either (i) have conducted at least one in-person medical evaluation of the patient or (ii) meet the definition of a ``covering practitioner.'' 21 U.S.C. 829(e)(2)(A). Alternatively, a practitioner may write a prescription when engaged in the practice of telemedicine under the limited circumstances enumerated at 21 U.S.C. 802(54). 21 U.S.C. 829(e)(3)(A). Any practitioner who writes a prescription for a controlled substance that fails to comply with this provision of the CSA, as well as any pharmacy that knowingly or intentionally fills such a prescription, violates 21 U.S.C. 841(h)(1). Hence, the Ryan Haight Act makes it unambiguous that, except in limited and specified circumstances, it is a per se violation of the CSA for a practitioner to issue a prescription for a controlled substance by means of the internet without having conducted at least one in-person medical evaluation. After the Ryan Haight Act became effective, online pharmacies could no longer deliver, distribute, or dispense controlled substances without registering with DEA as online pharmacies and complying with associated laws and regulations, including the requirement of a prescription issued after an in-person medical evaluation of the patient in most circumstances. In response, DEA has seen a significant increase in the number of online pharmacies highlighting the availability of exempted prescription products containing butalbital/ acetaminophen and butalbital/acetaminophen/caffeine and providing online dispensing. These sites are thereby exploiting the exempted prescription product status so customers can obtain butalbital. Thus, DEA finds a need to remove the exempted prescription product status for these products. If this proposed rule goes into effect, online pharmacies will be required to cease the sale and distribution of the products containing butalbital unless they comply with all relevant CSA requirements, including the requirements of the Ryan Haight Act and associated regulations. DEA does not have data for the volume of exempted butalbital products dispensed via the internet. Therefore, DEA requests that online pharmacies/websites provide such volume data in their comments, so DEA can assess the potential impact of this proposed rulemaking. Seizure Data The National Forensic Laboratory Information System (NFLIS),\1\ System to Retrieve Information from Drug Evidence (STRIDE), and STARLiMS databases \2\ indicate that there were 3,122 butalbital drug reports identified that were submitted to Federal, state, and local forensic laboratories from January 1, 2010 to December 31, 2020.\3\ In 2010, there were 402 butalbital reports, 420 reports in 2011, 363 reports in 2012, 328 reports in 2013, 330 reports in 2014, 340 reports in 2015, 302 reports in 2016, 252 reports in 2017, 148 reports in 2018, 132 reports in 2019 and 105 reports in 2020. --------------------------------------------------------------------------- \1\ NFLIS is a national drug forensic laboratory reporting system that systematically collects results from drug chemistry analyses conducted by state and local forensic laboratories across the country. The NFLIS participation rate, defined as the percentage of the national drug caseload represented by laboratories that have joined NFLIS, is over 97 percent. NFLIS includes drug chemistry results from completed analyses only. \2\ STRIDE is a database of drug exhibits sent to DEA laboratories for analysis. Exhibits from the database are from DEA, other Federal agencies, and law enforcement agencies. On October 1, 2014, STARLiMS replaced STRIDE as the DEA laboratory drug evidence data system of record. \3\ NFLIS database was queried on August 19, 2021, by date of submission, all drugs reported; STRIDE and STARLiMS databases were queried August 19, 2021, by date of collection, all drug records analyzed. --------------------------------------------------------------------------- For the majority of butalbital exhibits, analytical laboratories only identify the active ingredient butalbital. Only a portion of the exhibits identifies the other secondary product ingredients. However, when secondary ingredients are reported, combinations of butalbital and acetaminophen greatly exceed the number of combination products containing butalbital and aspirin (or other ingredients) reported. (See chart below.) Summary Table ------------------------------------------------------------------------ Percent of Percent of reports reports Calendar year butalbital/ butalbital/ acetaminophen aspirin ------------------------------------------------------------------------ 2010...................................... 29.4 6.0 2011...................................... 40.6 4.3 2012...................................... 40.6 4.4 2013...................................... 37.0 3.7 2014...................................... 25.3 2.0 2015...................................... 23.7 2.3 2016...................................... 21.5 2.9 2017...................................... 22.9 1.8 2018...................................... 16.2 5.1 2019...................................... 21.7 3.3 2020...................................... 33.0 2.1 ------------------------------------------------------------------------ Therefore, DEA concludes, based on the data mentioned above, that the mere presence of acetaminophen or acetaminophen/caffeine in butalbital combination products does not serve to vitiate the potential for abuse. [[Page 21591]] State Regulatory Controls on Butalbital Products At least 15 states have seen a need to place additional regulatory requirements on the butalbital products for which DEA has granted exempted prescription product status. Alabama, Alaska, California, Georgia, Hawaii, Idaho, Illinois, Indiana, Kentucky, Maryland, Mississippi, New Mexico, Oklahoma, Pennsylvania, and Utah all subject these products to schedule III controls. Ability To Reapply for Exempted Prescription Product Status Any manufacturer of a butalbital/acetaminophen or butalbital/ acetaminophen/caffeine combination product that is subject to this rulemaking may reapply for exempted prescription product status by following the application procedures specified in 21 CFR 1308.31 if they believe that their formulation contains unique attributes which demonstrate that their product meets the exemption criteria (e.g., it contains one or more active ingredients which are not listed in any schedule and which are included in such combinations, quantity, proportion, or concentration as to vitiate the potential for abuse). However, DEA wishes to clarify that the mere presence of acetaminophen in the formulation in quantities of greater than 70 mg per 15 mg of barbiturate will no longer automatically qualify a butalbital product for an exemption unless the applicant can further demonstrate that the formulation vitiates the potential for abuse. Requirements for Handling Schedule III Controlled Substances If this proposed rule is adopted in final form, butalbital products formerly subject to automatic exemption will become subject to the CSA's schedule III regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, reverse distribution, dispensing, importing, exporting, research, and conduct of instructional activities and chemical analysis with, and possession involving, schedule III substances, including the following (as of the date a final rule becomes effective): 1. Registration. Any person who handles (manufactures, distributes, dispenses, imports, exports, engages in research, or conducts instructional or chemical analysis with, or possesses) butalbital products, or who desires to handle butalbital products, would be required to be registered with DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 957, and 958 and in accordance with 21 CFR parts 1301 and 1312. 2. Disposal of Stocks. Any person who does not desire or is not able to obtain a schedule III registration would be required to surrender all quantities of currently held butalbital products. Alternately, they may transfer all quantities of currently held butalbital products to a person registered with DEA in accordance with 21 CFR part 1317, in addition to all other applicable Federal, state, local, and tribal laws. 3. Security. Butalbital products would be subject to schedule III-V security requirements and must be handled and stored pursuant to 21 U.S.C. 821, 823, 871(b) and in accordance with 21 CFR 1301.71-1301.93. 4. Labeling and Packaging. All labels, labeling, and packaging for commercial containers of butalbital products would be required to comply with 21 U.S.C. 825 and 958(e) and be in accordance with 21 CFR part 1302. 5. Inventory. Every DEA registrant who possesses any quantity of butalbital products would be required to take an inventory of butalbital products on hand, pursuant to 21 U.S.C. 827 and 958 and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. Any person who becomes registered with DEA must take an initial inventory of all stocks of controlled substances (including butalbital products) on hand on the date the registrant first engages in the handling of controlled substances, pursuant to 21 U.S.C. 827 and 958 and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. After the initial inventory, every DEA registrant must take a new inventory of all controlled substances (including butalbital products) on hand at least every two years, pursuant to 21 U.S.C. 827 and 958 and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. 6. Records and Reports. Every DEA registrant would be required to maintain records and submit reports for butalbital products, or products containing butalbital products, pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR parts 1304, 1312, and 1317. 7. Prescriptions. All prescriptions for butalbital products would be required to comply with 21 U.S.C. 829 and be issued in accordance with 21 CFR parts 1306 and 1311, subpart C. 8. Importation and Exportation. All importation and exportation of butalbital products would be required to be in compliance with 21 U.S.C. 952, 953, 957, and 958 and in accordance with 21 CFR part 1312. 9. Liability. Any activity involving butalbital products not authorized by, or in violation of, the CSA or its implementing regulations, would be unlawful and may subject the person to administrative, civil, and/or criminal sanctions. List of Butalbital Products To Be Removed From the Table of Exempted Prescription Products For reasons detailed above, DEA proposes the removal of Exempted Prescription Product status for all butalbital products, to include the products listed below: ---------------------------------------------------------------------------------------------------------------- (mg or Company Trade name NDC code Form Controlled substance mg/ml) ---------------------------------------------------------------------------------------------------------------- Actavis Pharma, Inc........... Butalbital, 0591-2640 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules USP 50/300/40. Actavis Pharma, Inc........... Butalbital, 0591-3369 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP 50/325/40. Actavis Pharma, Inc........... Fioricet (Butalbital, 52544-080 CA Butalbital.......... 50 Acetaminophen and Caffeine USP 50/300/ 40). Alpha Scriptics Inc........... Butacet Capsules...... 53121-0133 CA Butalbital.......... 50 Alphagen Laboratories, Inc.... Butalbital and 00603-2542 CA Butalbital.......... 50 Acetaminophen Capsules 50mg/650mg. Alphagen Laboratories, Inc.... Geone Capsules........ 59743-0004 CA Butalbital.......... 50 Altana, Inc................... Axocet (Butalbital and 0281-0389 TB Butalbital.......... 50 Acetaminophen). Althon Pharmaceuticals, Inc... Butalbital, 66813-074 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP. Alvogen, Inc.................. Butalbital and 47781-0535 TB Butalbital.......... 50 AcetaminophenTablets USP 50/325. Alvogen, Inc.................. Butalbital, 47781-0536 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP 50/325/40. Alvogen, Inc.................. Butalbital and 47781-0628 TB Butalbital.......... 50 Acetaminophen Tablets 50/325. [[Page 21592]] Alvogen, Inc.................. Butalbital, 47781-0625 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50/ 325/40). Alvogen, Inc.................. Butalbital and 47781-0644 TB Butalbital.......... 50 Acetaminophen Tablets (50/300). American Pharmaceuticals, Inc. AMERICET Tablets...... 58605-0501 TB Butalbital.......... 50 American Urologicals Inc...... Butace................ 00539-0906 CA Butalbital.......... 50 Amerisource Health Services Butalbital, 68084-0396 TB Butalbital.......... 50 Corporation. Acetaminophen and Caffeine Tablets 50/ 325/40mg. Aphena Pharma Solutions....... Butalbital, 71610-0042 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50/ 325/40mg. Atland Pharmaceuticals........ Butalbital and 71993-301 TB Butalbital.......... 25 Acetaminophen Tablets (25mg/325mg). Atley Pharmaceuticals......... Butalbital, 59702-661 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Aurobindo Pharma Inc.......... Butalbital, 13107-075 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules USP 50/325/40. AvKare, Inc................... Butalbital, 50268-139 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP 50/325/40. AvKare, Inc................... Butalbital, 42291-181 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules USP 50/300/40. Baucum Laboratories Inc....... Butalbital, 54696-0513 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Blansett Pharm Co............. Anolor 300 Capsules... 51674-0009 CA Butalbital.......... 50 Cardinal Health............... Butalbital, 55154-3356 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50mg/ 325mg/40mg. Cardinal Health............... Butalbital, 55154-7988 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50mg/ 325mg/40mg. Cardinal Health............... Butalbital, 55154-7147 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50mg/ 325mg/40mg. Cardinal Health............... Butalbital, 55154-3356 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50mg/ 325mg/40mg. Cardinal Health............... Butalbital, 0904-6538 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50mg/ 325mg/40mg. Carnrick Labs Inc............. Phrenilin............. 00086-0050 TB Butalbital.......... 50 Carpenter Pharmacal Co........ ALAGESIC Tablets...... 55726-0300 TB Butalbital.......... 50 Cody Laboratories, Inc........ BU-TAB AC............. 65893-100 TB Butalbital.......... 50 Columbia Drug Co.............. Isopap Capsules....... 11735-0400 CA Butalbital.......... 50 CTEX Pharmaceuticals, Inc..... Butex Forte Capsules.. 62022-0070 CA Butalbital.......... 50 CTEX Pharmaceuticals, Inc..... Butex Forte Capsules.. 62022-0074 CA Butalbital.......... 50 D.M. Graham Laboratories, Inc. Butalbital, 00756-0111 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Diversified Health Care Geone Capsules........ 59743-004 CA Butalbital.......... 50 Services. Dunhall Pharmacal Inc......... Triaprin.............. 00217-2811 CA Butalbital.......... 50 Duramed Pharmaceuticals....... Butalbital, 51285-0849 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. EconoMed Pharmaceuticals, Inc. ARCET Capsules........ 38130-0325 CA Butalbital.......... 50 EconoMed Pharmaceuticals, Inc. ARCET Compound Tablets 38130-0111 TB Butalbital.......... 50 Equipharm Corp................ EQUI-CET Tablets...... 57779-0111 TB Butalbital.......... 50 Everett Laboratories, Inc..... Repan Capsules........ 00642-0164 CA Butalbital.......... 50 Everett Laboratories, Inc..... Repan Capsules........ 00642-0163 CA Butalbital.......... 50 Everett Laboratories, Inc..... Repan Tablets......... 00642-0162-10 TB Butalbital.......... 50 Forest Pharmacal Inc.......... Acetaminophen 325mg/ 00456-0674 TB Butalbital.......... 50 Butalbital 50mg. Forest Pharmacal Inc.......... Acetaminophen 500mg/ 00456-0671 TB Butalbital.......... 50 Butalbital 50mg. Forest Pharmacal Inc.......... Bancap................ 00456-0546 CA Butalbital.......... 50 Forest Pharmacal Inc.......... Esgic Capsules........ 00456-0631 CA Butalbital.......... 50 Forest Pharmacal Inc.......... ESGIC PLUS Capsules... 00456-0679 CA Butalbital.......... 50 Forest Pharmacal Inc.......... Esgic Tablets......... 00456-0630 TB Butalbital.......... 50 Forest Pharmacal Inc.......... ESGIC-PLUS............ 00456-0678 TB Butalbital.......... 50 Genetco Inc................... Butalbital, Apap and 00302-0490 TB Butalbital.......... 50 Caffeine. Geneva Pharmaceuticals, Inc... Butalbital, 00781-1901 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. GM Pharmaceuticals Vanatol S (Butalbital, 58809-359 LQ Butalbital.......... 50 (Manufactured by Mikart, Acetaminophen, & Inc.). Caffeine Soln 50/325/ 40. GM Pharmaceuticals Vanatol LQ 58809-820 LQ Butalbital.......... 50 (Manufactured by Mikart, (Butalbital, Inc.). Acetaminophen, & Caffeine Soln 50/325/ 40. Goldline Laboratories......... Butalbital, APAP and 00182-1274 TB Butalbital.......... 50 Caffeine Tablets. Granules Pharmaceuticals Inc.. Butalbital, 70010-044 CA Butalbital.......... 50 Acetaminiphen and Caffeine Capsules 50mg/300mg/40mg. Granules Pharmaceuticals Inc.. Butalbital and 70010-054 CA Butalbital.......... 50 Acetaminiphen Capsules 50mg/300mg. GSMS Incorporated............. Butalbital, 60429-589 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP (50/325/40). GSMS Incorporated............. Butalbital, 51407-200 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules USP (50/300/40). [[Page 21593]] Halsey Drug Co Inc............ Blue Cross Butalbital, 00879-0567 TB Butalbital.......... 50 APAP and Caffeine Tablets. Halsey Drug Co Inc............ Butalbital and 00879-0543 TB Butalbital.......... 50 Acetaminophen Tablets. Hyrex Pharmaceutical.......... Two-Dyne Revised...... 00314-2229 TB Butalbital.......... 50 International Ethical Tencon Tablets........ 11584-029-01 TB Butalbital.......... 50 Laboratories, Inc. Interstate Drug Exchange...... IDE-Cet Tablets....... 00814-3820 TB Butalbital.......... 50 Intetlab...................... CON-TEN............... 11584-1029 CA Butalbital.......... 50 Inwood Laboratories, Inc...... Butalbital, 0258-3657 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets, USP. Keene Pharmacal Inc........... Endolar............... 00588-7777 CA Butalbital.......... 50 Kenco......................... Axotal................ 00013-1301 TB Butalbital.......... 50 KVK Tech...................... Butalbital, 10702-253 TB Butalbital.......... 50 Acetaminophen & Caffeine Tablets (50mg/325mg/40mg). Landry Pharmacal Inc.......... Febridyne Plain 05383-001 CA Butalbital.......... 50 Capsules. Lannett Company, Inc.......... Butalbital, 00527-1695 TB Butalbital.......... 50 Acetaminophen & Caffeine Tablets (50mg/325mg/40mg). Lannett Company, Inc.......... Butalbital, 00527-4094 CA Butalbital.......... 50 Acetaminophen & Caffeine Capsules (50mg/325mg/40mg). Lannett Company, Inc.......... Butalbital, 00527-4095 CA Butalbital.......... 50 Acetaminophen & Caffeine Capsules (50mg/300mg/40mg). Larken Laboratories, Inc...... Allzital Butalbital 68047-752 TB Butalbital.......... 25 and Acetaminophen Tablets (25mg/325mg). Larken Laboratories, Inc...... Butalbital and 68047-722 TB Butalbital.......... 25 Acetaminophen Tablets (25mg/325mg). Larken Laboratories, Inc...... Butalbital and 68047-721 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/325mg). Lasalle Laboratories.......... Pacaps Modified 48534-0884 CA Butalbital.......... 50 Formula. Lemmon Company................ Acetaminophen/ 00093-0854 TB Butalbital.......... 50 Butalbital/Caffeine Tablets. LGM Pharma Solutions, LLC..... Butalbital, 79739-7320 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50/ 325/40mg). LGM Pharma Solutions, LLC..... Butalbital, 79739-7029 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules (50/ 300/40mg). LGM Pharma Solutions, LLC..... Butalbital and 79739-7075 TB Butalbital.......... 50 Acetaminophen Tablets (50/300mg). Libertas Pharma, Inc.......... Butalbital, 51862-179 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules USP. Lunsco Inc.................... Pacaps Capsules....... 10892-0116 CA Butalbital.......... 50 Major Pharmaceuticals......... Butalbital, 0904-6938 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50/ 325/40mg). Major Pharmaceuticals......... Fabophen Tablets...... 00904-3280 TB Butalbital.......... 50 Mallard Consumer Products..... Anaquan Tablets....... 59441-0343 TB Butalbital.......... 50 Mallard Inc................... Anoquan Modified 00166-0881 CA Butalbital.......... 50 Formula. Mallinckrodt Inc.............. Butalbital, 00406-0970 TB Butalbital.......... 50 Acetaminophen, and Caffeine (``BAC'') Tablets USP. Marlop Pharmacal Inc.......... Dolmar................ 12939-0812 CA Butalbital.......... 50 Marnel Pharmaceuticals........ Margesic Capsules..... 00682-0804 CA Butalbital.......... 50 Marnel Pharmaceuticals........ Marten-Tab Tablets.... 00682-1400 TB Butalbital.......... 50 Martec Pharmacal Inc.......... Butalbital, 52555-0079 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Mayne Pharma.................. Butalbital, 51862-542 CA Butalbital.......... 50 Acetaminophen, & Caffeine Capsules 50/ 300/40. Mayrand Pharmaceuticals, Inc.. Sedapap-10 Tablets.... 00259-1278 TB Butalbital.......... 50 Midlothian Laboratories Esgic (Butalbital, 68308-219 CA Butalbital.......... 50 (Manufactured by Mikart, Acetaminophen, & Inc.). Caffeine Capsules 50/ 325/40. Midlothian Laboratories Esgic (Butalbital, 68308-220 TB Butalbital.......... 50 (Manufactured by Mikart, Acetaminophen, & Inc.). Caffeine Tablets 50/ 325/40. Midlothian Laboratories Zebutal (Butalbital, 68308-554 CA Butalbital.......... 50 (Manufactured by Mikart, Acetaminophen, & Inc.). Caffeine Capsules 50/ 325/40. Mikart, Inc................... Alagesic Capsules..... 50991-302 CA Butalbital.......... 50 Mikart, Inc................... Bupap................. 00095-0240 TB Butalbital.......... 50 Mikart, Inc................... Butalbital and 46672-0099 TB Butalbital.......... 50 Acetaminophen Tablets 50/325. Mikart, Inc................... Butalbital and 11584-0029 TB Butalbital.......... 50 Acetaminophen Tablets 50/650. Mikart, Inc................... Butalbital and 46672-0098 TB Butalbital.......... 50 Acetaminophen Tablets 50/650. Mikart, Inc................... Butalbital, 46672-0228 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules. Mikart, Inc................... Butalbital, 00588-7788 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules. Mikart, Inc................... Butalbital, 46672-0633 EL Butalbital.......... 50 Acetaminophen and Caffeine Eilixer. Mikart, Inc................... Butalbital, 52555-0647 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Mikart, Inc................... Butalbital, 46672-0053 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Mikart, Inc................... Butalbital, 49884-0811 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP. Mikart, Inc................... Butalbital, 00258-3665 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP. Mikart, Inc................... Butalbital, 51862-540 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP (50/325/40). Mikart, Inc................... Butalbital, 0591-3416 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets, USP. Mikart, Inc................... Butalbital and 46672-286 CA Butalbital.......... 50 Acetaminophen Capsules 50/300. Mikart, Inc................... Butalbital and 46672-856 TB Butalbital.......... 50 Acetaminophen Tablets 50/300. Mikart, Inc................... Butalbital, 46672-184 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets, USP. Mikart, Inc................... Butalbital, 66813-073 LQ Butalbital.......... 50 Acetaminophen, and Caffeine Oral Solution. Mikart, Inc................... Butalbital, 51432-0034 TB Butalbital.......... 50 Acetaminophen, and Caffeine Tablets. Mikart, Inc................... Butalbital, 46672-0059 TB Butalbital.......... 50 Acetaminophen, and Caffeine Tablets. [[Page 21594]] Mikart, Inc................... Capacet (Butalbital, 58407-534 CA Butalbital.......... 50 Acetaminophen, and Caffeine 50/325/40). Mikart, Inc................... Cephadyn Tablets...... 59702-0650 TB Butalbital.......... 50 Mikart, Inc................... Dolgic Plus Tablets... 68453-074 TB Butalbital.......... 50 Mikart, Inc................... Dolgic Tablets........ 62022-0073 TB Butalbital.......... 50 Mikart, Inc................... DOLMAR Tablets........ 12939-0811 TB Butalbital.......... 50 Mikart, Inc................... Esgic Capsules........ 00535-0012 CA Butalbital.......... 50 Mikart, Inc................... Esgic Tablets......... 00535-0011 TB Butalbital.......... 50 Mikart, Inc................... Promacet.............. 58605-524 TB Butalbital.......... 50 Mikart, Inc................... Sedapap Tablets....... 00259-0392 TB Butalbital.......... 50 Mikart, Inc. (on behalf of Butalbital and 51862-544 CA Butalbital.......... 50 Mayne Pharma). Acetaminophen Capsules 50/300. Mikart, Inc. (on behalf of Butalbital and 51862-538 TB Butalbital.......... 50 Mayne Pharma). Acetaminophen Tablets 50/300. Mikart, Inc. (on behalf of Vtol LQ (Butalbital, 70154-111 LQ Butalbital.......... 50 Monarch PCM, LLC). Acetaminophen, Caffeine Oral Solution). Mikart, Inc................... Tencon (Butalbital and 11584-0030 TB Butalbital.......... 50 Acetaminophen 50mg/ 325mg). Mikart, Inc./Shionogi, Inc.... Dolgic Plus Tablets... 59630-074 TB Butalbital.......... 50 Moore Medical Corporation..... Butalbital, 00839-7831 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Nexgen Pharma................. BUPAP (Butalbital and 0095-3000 TB Butalbital.......... 50 Acetaminophen 50mg/ 300mg). Nexgen Pharma................. Butalbital with 0722-7029 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Nexgen Pharma................. Butalbital, 0722-7320 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50mg/325mg/40mg). Northampton Medical, Inc...... FEMCET................ 58436-0703 TB Butalbital.......... 50 NorthStar..................... Butalbital, 16714-170 CA Butalbital.......... 50 Acetaminophen and Caffeine Capsules (50mg/300mg/40mg). Oceanside Pharmaceuticals Butalbital and 68682-306 TB Butalbital.......... 50 (Manufactured by Nexgen). Acetaminophen Tablets (50mg/300mg). PD-Rx Pharmaceuticals, Inc.... Butalbital/APAP/ 55289-0879 TB Butalbital.......... 50 Caffeine Tablets (50mg/325mg/40mg). Pharmaceutical Basics Inc..... Butalbital, 00832-1102 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Phlight Pharma, LLC........... Allzital (Butalbital 70569-150 TB Butalbital.......... 25 and Acetaminophen Tablets (25 mg/325 mg)). Poly Pharmaceuticals, Inc..... Alagesic.............. 50991-0302 CA Butalbital.......... 50 Private Formula Inc........... Sangesic.............. 00511-1627 TB Butalbital.......... 30 ProficientRx.................. Butalb/Acet/Caffeine 63187-933 TB Butalbital.......... 50 50mg/325mg/40mg. ProficientRx.................. Butalb/Acet/Caffeine 71205-962 CA Butalbital.......... 50 50mg/300mg/40mg. ProficientRx.................. Butalb/Acet/Caffeine 71205-981 TB Butalbital.......... 50 50mg/325mg/40mg. ProficientRx.................. Butalb/Acet/Caffeine 71205-510 TB Butalbital.......... 50 50mg/325mg/40mg. Qualitest Pharmaceuticals, Inc Butalbital and 0603-2540 TB Butalbital.......... 50 Acetaminophen Tablets. Qualitest Pharmaceuticals, Inc Butalbital, 0603-2544 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets 50/ 325/40mg. Qualitest Pharmaceuticals, Inc Butalbital, 0603-2547 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets USP. Qualitest Pharmaceuticals, Inc Butalbital, 0603-2551 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets, USP. Qualitest Products Inc........ Butalbital, 52446-0544 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. Redi-Med...................... Butalbital Compound 53506-0103 CA Butalbital.......... 50 Capsules. Roberts Pharmaceutical Anoquan............... 54092-0178 TB Butalbital.......... 50 Corporation. Roberts Pharmaceutical Tencet Tablets........ 59441-0153 TB Butalbital.......... 50 Corporation. Rotex Pharmaceuticals, Inc.... Rogesic Capsules...... 31190-0008 CA Butalbital.......... 50 Rugby Laboratories Inc........ Butalbital, 0536-5567 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets, USP. Rugby Laboratories Inc........ ISOCET Tablets........ 00536-3951 TB Butalbital.......... 50 Russ Pharmaceuticals, Inc..... FEMCET Capsules....... 50474-0703 CA Butalbital.......... 50 Savage Laboratories........... AXOTAL................ 00281-1301 TB Butalbital.......... 50 Shoals Pharmaceuticals, Inc... Tencet................ 47649-0370 TB Butalbital.......... 50 Shoals Pharmaceuticals, Inc... Tencet Capsules....... 47649-0560 CA Butalbital.......... 50 Skylar Laboratories, LLC...... Allzital (Butalbital 70362-722 TB Butalbital.......... 25 and Acetaminophen Tablets) (25mg/325mg). Skylar Laboratories, LLC...... Butalbital and 70362-721 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/325mg). Solubiomix.................... Butalbital and 69499-302 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/325mg). Solubiomix.................... Butalbital and 69499-342 CA Butalbital.......... 50 Acetaminophen Capsules (50mg/300mg). Stewart Jackson Pharmacal, Inc Ezol.................. 45985-0578 CA Butalbital.......... 50 STI Pharma, LLC............... Butalbital and 54879-026 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/325mg). Sunrise Pharmaceuticals, Inc.. Butalbital, 11534-187 CA Butalbital.......... 50 Acetaminophen, Caffeine Capsules (50mg/300mg/40mg). Taro Pharmaceuticals U.S.A., Butalbital, 51672-4222 CA Butalbital.......... 50 Inc. Acetaminophen and Caffeine Caps (50mg/ 300mg/40mg). Tedor Pharma, Inc............. Butalbital and 47781-534 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/300mg). Tedor Pharma, Inc............. Butalbital and 43199-053 TB Butalbital.......... 50 Acetaminophen Tablets (50mg/325mg). [[Page 21595]] Tedor Pharma, Inc. Butalbital, 42195-955 CA Butalbital.......... 50 (Manufactured for Xspire Acetaminophen and Pharma). Caffeine Caps (50mg/ 300mg/40mg). Trimen Labs................... Amaphen Capsules 11311-0954 CA Butalbital.......... 50 (reformulated). U.S. Pharmaceuticals.......... Medigesic Capsules.... 52747-0600 CA Butalbital.......... 50 UAD Laboratories Inc.......... Bucet Capsules........ 00785-2307 CA Butalbital.......... 50 US Pharmaceuticals Inc........ Medigesic Tablets..... 52747-0311 TB Butalbital.......... 50 Valeant Pharmaceuticals....... Phrenilin Forte....... 0187-0844 CA Butalbital.......... 50 Victory Pharma Inc. (Manuf. by Zebutal Brand 68453-170 CA Butalbital.......... 50 West-Ward Pharmaceutical). Butalbital, Acetaminophen, and Caffeine Capsules. WE Hauck Inc.................. G-1 Capsules.......... 43797-0244 CA Butalbital.......... 50 Westminster Pharmaceuticals... Butalbital, 69367-203 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets (50mg/325mg/40mg). West-Ward Pharmaceutical Corp. Butalbital with 00143-1787 TB Butalbital.......... 50 Acetaminophen and Caffeine Tablets. West-Ward Pharmaceutical Corp. Butalbital, 00143-3001 CA Butalbital.......... 50 Acetaminophen and Caffein Capsules. West-Ward Pharmaceutical Corp. Butalbital, 00143-1115 TB Butalbital.......... 50 Acetaminophen, and Caffeine Tablets, USP. West-Ward Pharmaceutical Corp. Zebutal Brand 59630-0170 CA Butalbital.......... 50 Butalbital, Acetaminophen, and Caffeine Capsules. Wraser Pharmaceuticals........ Phrenilin Forte 66992-955 CA Butalbital.......... 50 (Butalbital, Acetaminophen and Caffeine) 50/300/40. Zenith Goldline Butalbital, 00182-2659 TB Butalbital.......... 50 Pharmaceuticals. Acetaminophen and Caffeine Tablets. ---------------------------------------------------------------------------------------------------------------- Regulatory Analyses Executive Orders 12866 (Regulatory Planning and Review) and 13563 (Improving Regulation and Regulatory Review) This proposed rule was developed in accordance with the principles of Executive Orders (E.O.) 12866 and 13563. E.O. 12866 directs agencies to assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to select regulatory approaches that maximize net benefits (including potential economic, environmental, public health, and safety effects; distributive impacts; and equity). E.O. 13563 is supplemental to and reaffirms the principles, structures, and definitions governing regulatory review as established in E.O. 12866. E.O. 12866 classifies a ``significant regulatory action'' requiring review by the Office of Management and Budget (OMB) as any regulatory action that is likely to result in a rule that may: (1) Have an annual effect on the economy of $100 million or more or adversely affect in a material way the economy, a sector of the economy, productivity, competition, jobs, the environment, public health or safety, or State, local, or tribal governments or communities; (2) create a serious inconsistency or otherwise interfere with an action taken or planned by another agency; (3) materially alter the budgetary impact of entitlements, grants, user fees, or loan programs or the rights and obligations of recipients thereof; or (4) raise novel legal or policy issues arising out of legal mandates, the President's priorities, or the principles set forth in the E.O. The economic, interagency, budgetary, legal, and policy implications of this proposed rule have been examined, and it has been determined that it is a significant regulatory action under E.O. 12866. Benefits The removal of exempted prescription product status for butalbital products previously granted exemption would impose the regulatory controls and administrative, civil, and criminal sanctions of schedule III controlled substances on any person who handles or proposes to handle butalbital products that were previously exempted from control under 21 CFR 1308.31 and 1308.32. Controlling previously exempt butalbital prescription products as schedule III controlled substances is expected to prevent, curtail, and limit the questionable distribution and dispensing of these products, including the distribution and dispensing via the internet. One of DEA's primary concerns is the prevalence of questionable online websites that promote the sale of exempted butalbital products ``without a prescription.'' Such questionable sales practices exploit the current regulatory status of these exempted prescription products. These questionable websites are not to be equated with ``mail order pharmacies,'' which serve a valuable role in legitimate U.S. health care. This proposal is directed in particular to such questionable websites and is not intended to adversely affect legitimate mail order or retail pharmacies. This proposed rule is expected to impact these online sales practices, resulting in fewer individuals abusing these products and potentially becoming addicted to these or similar products. Additionally, DEA anticipates benefits from reduced societal costs (i.e., health care costs, criminal justice system costs, opportunity costs, etc.) due to abuse and addiction. While this proposed rule is expected to lower the abuse of currently exempt butalbital products, DEA has no basis to quantify the amount of abuse that will be prevented, and the societal cost savings result of this rule. However, DEA anticipates that removal of exempted prescription product status for butalbital products will reduce the amount of abuse of these products, and lead to societal cost savings. Costs Below is an Economic Impact Analysis which summarizes the costs associated with this proposed rule. Affected Persons The removal of exempted prescription product status for previously exempted butalbital products will affect all persons who handle (manufacture, distribute, dispense, engage in research, conduct instructional activities, or possess) or propose to handle these products. The exempt butalbital products are prescription drug products [[Page 21596]] used for the treatment of tension headaches. While some hospitals or clinics may hold some exempt butalbital products in inventory, quantities are expected to be minimal and the economic impact on hospitals is expected to be minimal. Therefore, DEA does not anticipate this proposed rule will affect hospitals. Additionally, while prescribers would need a DEA registration to prescribe these products, nearly all individual practitioners are expected to be registered with DEA already or otherwise have authority to prescribe controlled substances but are exempt from registration. Therefore, for the purposes of this analysis, DEA assumes this proposed rule primarily affects manufacturers, distributors, and pharmacies. The ``Table of Exempted Prescription Products'' includes the National Drug Code (NDC), which serves as a universal product identifier for the exempt prescription products, among other information. While the list of products that have been granted exempted prescription product status contains 189 prescription products containing butalbital (as of February 11, 2022), not all are actively marketed in the United States. By comparing the NDC of the 189 products that were granted exempt status to the current NDC Directory,\4\ coupled with recent exemption approvals, DEA estimates 49 exempt butalbital products are actively marketed in the United States. DEA believes many of the remainder of these 189 products have been discontinued; there is no requirement to inform DEA of discontinuation of products that have been granted exempt prescription product status. From review of applicant information in the application for exempt prescription product status and NDC labeler information from the NDC Directory, DEA estimates the 49 exempt butalbital products are manufactured by 30 manufacturers. --------------------------------------------------------------------------- \4\ ``The Drug Listing Act of 1972 requires registered drug establishments to provide FDA with a current list of all drugs manufactured, prepared, propagated, compounded, or processed by it for commercial distribution. (See Section 510 of the Federal Food, Drug, and Cosmetic Act (Act) (21 U.S.C. 360)). Drug products are identified and reported using a unique, three-segment number, called the National Drug Code (NDC), which serves as a universal product identifier for drugs. FDA publishes the listed NDC numbers and the information submitted as part of the listing information in the NDC Directory which is updated daily.'' https://www.fda.gov/Drugs/InformationOnDrugs/ucm142438.htm. (accessed March 18, 2020) --------------------------------------------------------------------------- The number of DEA registrations forms the basis of the number of distributors and pharmacies. Because exempted butalbital products are widely prescribed, DEA assumes that all DEA-registered distributors and pharmacies are exempted butalbital product handlers. Also, for the purposes of this analysis, DEA assumes all legally operating distributors and pharmacies that handle exempted butalbital products are registered with DEA. Based on DEA records, as of June 5, 2020, there are 627 distributor registrations and 70,672 pharmacies authorized to handle schedule III controlled substances. In summary, DEA estimates 71,329 establishments (30 manufacturers, 627 distributors, and 70,672 pharmacies) are affected by this proposed rule. Costs Associated With Requirements DEA considered various costs associated with handling exempt butalbital products as a schedule III controlled substance for each of the business activities (manufacturer, distributor, prescriber, and pharmacy) anticipated to handle butalbital and be impacted by this proposed rule. The costs include costs associated with various requirements, such as: Registration, physical security, labeling and packaging, inventory and recordkeeping, and disposal. The registration requirements impact all manufacturers that do not hold a DEA manufacturer registration. DEA conducted a search of its registration records for the 30 manufacturer establishments identified as handling exempt butalbital. DEA estimates there are 19 manufacturers that would need DEA registrations if this proposed rule were promulgated. The 19 non-registered manufacturers would incur an initial registration and an annual renewal fee of $3,699 for the manufacturer registration for a total of $70,281 per year. DEA assumes all legally operating distributors and pharmacies that handle exempted butalbital products are already registered with DEA. Therefore, DEA estimates distributors and pharmacies would not incur additional registration- related costs if this proposed rule were promulgated. In summary, the estimated cost of the registration requirements associated with this proposed rule is the cost of the initial registration and annual renewal registration fees for the 19 manufacturers, $70,281 per year. DEA estimated the costs associated with physical security requirements for manufacturers and distributors. Many states already control butalbital as a schedule III controlled substance under state law. As state requirements for schedule III controlled substances generally meet or exceed DEA requirements, only the establishments located in states where the exempt butalbital products are not controlled as schedule III controlled substances under state law are estimated to incur costs associated with physical security. Based on review of publicly available information regarding the locations of the manufacturers and registered locations of distributors, DEA estimates 17 manufacturer establishments and 399 distributors are located in states where exempt butalbital products are not already subject to controls equivalent to Federal schedule III handling requirements under state law. Based on a review of manufacturing data of a largely prescribed controlled substance and review of commercially available industry reports of exempt butalbital products, DEA estimates 3 of the 17 manufacturers (located in states where the exempt butalbital products are not controlled as schedule III controlled substances under state law) will need a large secure area and 14 of 17 will require a small secure area. DEA estimates the three large manufacturers would each need to secure 20,000 square feet (sq. ft.) of space and 14 small manufacturers would each need to secure 10,000 sq. ft. of space, at a cost of $112,000 and $79,196 for a large and small manufacturer, respectively, for a total of $1,444,744. As with manufacturers, DEA anticipates a concentration of market share with a small number of large distributors distributing the majority of exempt butalbital products in the U.S. DEA estimates the market distribution of exempt butalbital products is similar to that of a largely prescribed controlled substance. Based on estimates that 20 large, 60 medium, and 319 small distributors would need to secure 4,000 sq. ft., 250 sq. ft., and 16 sq. ft. of space, respectively, DEA estimates a cost of $35,418, $8,854, and $2,217 for large, medium, and small distributors, respectively, for a total of $1,946,823. In summary, DEA estimates the requirements associated with physical security controls will have a one-time cost of $1,444,744 for all manufacturers combined and a one-time cost of $1,946,823 for all distributors combined, for a grand total of $3,391,567. DEA estimates pharmacies are already handling other schedule III controlled substances and have the controls and procedures in place to store exempt butalbital products in a secure area at a minimal cost. Pharmacies and institutional practitioners may disperse such substances throughout the stock of non-controlled substances in such a manner as to obstruct the theft or diversion of controlled substances. 21 CFR 1301.75(b). DEA believes these [[Page 21597]] facilities possess adequate physical security controls and any cost associated with physical security requirements as a result of this rule is minimal. In accordance with the CSA, every DEA registrant must maintain, on a current basis, a complete and accurate record of each controlled substance manufactured, received, sold, delivered, or otherwise disposed of. 21 U.S.C. 827(a). These records must be maintained separately from all other records of the registrant, or alternatively, in the case of non-narcotic controlled substances, be in such a form that required information is readily retrievable from the ordinary business records of the registrant. 21 U.S.C. 827(b)(2). The records must be kept and be available for at least two years for inspection and copying by officers or employees of the Attorney General. 21 U.S.C. 827(b)(3). To fulfill its regulatory responsibilities, DEA assumes for the purpose of this analysis that exempt butalbital product handlers already maintain detailed records of exempt butalbital product transactions and those records can be maintained separately or readily retrievable at minimal cost. DEA estimates that there will be no economic impact beyond the inventory of exempted prescription status butalbital product stock pursuant to the initial and biennial inventory requirements in 21 CFR 1304.11. Following the finalization of this scheduling action, registrants would be required to take an inventory of all stocks of exempted prescription status butalbital products on hand and continue to conduct inventories biennially. DEA estimates the inventories for manufacturers and distributors will be conducted by a warehouse first-line supervisor and administrative personnel and will take one-half hour to complete. Additionally, DEA estimates inventories for pharmacies will be conducted by a pharmacist and a pharmacy technician and will take 6 minutes (0.1 hour) to complete. Based on U.S. Bureau of Labor Statistics hourly wage data and load for benefits, DEA estimates the cost of initial and biennial inventory for manufacturers, distributors, and pharmacies is $33.03, $33.03, and $11.12 per occurrence, respectively.\5\ Total inventory cost for 30 manufacturers, 627 distributors and 70,672 pharmacies is $807,573 initially, in the first year, and biennially, thereafter. --------------------------------------------------------------------------- \5\ Bureau of Labor Statistics, Occupational and Employment and Wages, May 2019, https://www.bls.gov/oes/current/oes_nat.htm. Bureau of Labor Statistics, ``Employer Costs for Employee Compensation-- December 2019'' reports that benefits for private industry is 29.9 percent of total compensation. The 29.9 percent of total compensation equates to a 42.7 percent (29.9/70.1) load on wages and salaries. https://www.bls.gov/news.release/pdf/ecec.pdf. 0.5 hour x [$26.47 per hour + $19.82 per hour] x 1.427 load = $33.03. 0.1 hour x [$61.58 per hour + $16.32 per hour] x 1.427 load = 11.12. --------------------------------------------------------------------------- If this rule is finalized, labeling and packaging requirements pursuant to 21 CFR part 1302 would apply to currently exempted prescription status butalbital products. Printed labels would need to indicate their status as a schedule III controlled substance. For example, the printed label would need to include ``CIII'' or ``C-III.'' DEA assumes that the activity of manufacturers making labeling changes is routine and in their normal course of business. Therefore, DEA assumes that the cost of making this change is minimal. Accordingly, DEA estimates that the cost of the labeling and packaging requirements of this proposed rule is minimal. A reverse distributor generally performs the disposal of controlled substances by registrants. DEA recognizes that removing the exempt status for previously exempt butalbital products may increase the volume of material that registrants will need to dispose through a reverse distributor. However, as exempted prescription status butalbital products are currently not controlled, DEA does not have information on the volume of exempt butalbital products currently disposed of, and thus cannot determine what the increase in schedule III controlled substance disposal will be or how it will affect the fees charged by reversed distributors. Therefore, DEA is unable to quantify the costs associated with the disposal of exempt butalbital products. However, since DEA assumes the affected establishments are already disposing of controlled substances, the disposal of previously exempted prescription status butalbital products will be incorporated into existing business processes. DEA believes that any cost increase, if one exists, will be minimal. In summary, DEA estimates the economic impact of this proposed rule is due to the costs associated with registration requirements, the costs associated with storage requirements, and the costs associated with inventory requirements. The registration cost is an initial registration fee and an annual renewal fee of $70,281 (for the 19 non- registered manufacturer establishments). The cost associated with storage requirements is a one-time cost of $3,391,567 for all affected establishments combined (17 manufacturers and 399 distributors located in states where exempted prescription status butalbital products are not controlled under State law). The costs associated with inventory and recordkeeping are an initial inventory cost of $807,573 and a biennially recurring inventory cost of $807,573 for all manufacturer, distributor, and pharmacy establishments combined. DEA determined the annualized cost of the proposed rule by calculating the present value of the costs utilizing the discounted cash flow method at 3 percent and 7 percent and converting the present value into equal annual payments over 20 years at the 3 percent and 7 percent discount rates.\6\ The present value of the costs associated with the proposed rule is $10,434,492 and $8,336,626 at 3 percent and 7 percent discount rates, respectively. The annualized costs are $701,362 and $786,918 at 3 percent and 7 percent discount rates, respectively. Conservatively, using the 7 percent rate, the estimated annualized cost of the proposed rule is $786,918 per year. The estimated highest cost in any given year is $4,269,421, which represents the year of implementation of the rule (Year 1). Although DEA currently is unable to quantify the societal cost savings resulting from the placement of butalbital products in schedule III, DEA believes such savings will exceed the costs associated with this proposed rule. --------------------------------------------------------------------------- \6\ The use of 7 percent and 3 percent rates for present value calculation, annual payment calculation, and analysis time horizon is based on OMB Circular A-4, September 17, 2003. See also ``Regulatory Impact Analysis: A Primer'' and ``Regulatory Impact Analysis: Frequently Asked Questions (FAQ)'' February 7, 2011, Office of Information and Regulatory Affairs (OIRA). DEA used a 20- year time horizon for this analysis as there is no predetermined end to this rule. --------------------------------------------------------------------------- Discussion of Uncertainties This analysis evaluates the economic impact of controlling pharmaceuticals that are currently exempt from control. Therefore, DEA does not have a strong basis to estimate some of the costs or other impacts to affected persons. DEA welcomes all comments that would narrow the uncertainties in the presented analysis, and specifically asks potentially affected persons the following questions (specific and quantified responses are more helpful): 1. DEA does not have data on (a) the volume of butalbital products dispensed via online pharmacies and websites; (b) the number of physicians impacted that do not have DEA registrations; (c) the number of pharmacies impacted that do not have DEA registrations; and (d) the impact on patients that are unable to [[Page 21598]] seek face-to-face guidance from a provider. DEA requests comments that help to identify the extent of the impact this rulemaking may impose. 2. DEA estimates that hospitals and clinics would be minimally affected by this proposed rule because most hospitals and clinics are expected to hold minimal inventory. Distributions of exempt butalbital products to hospitals and clinics are expected to be minimal, while a large majority of distributions are to pharmacies. Will hospitals and clinics be materially affected by this proposed rule? If so, please explain with specific and quantified information as possible. 3. DEA estimates 19 manufacturers would need to obtain a DEA registration to continue manufacturing exempt butalbital products. Is this a reasonable estimate? Would any manufacturer cease manufacturing exempt butalbital products rather than obtaining a DEA registration to continue manufacturing of exempt butalbital products? 4. How much time would be required to conduct an inventory of exempt butalbital products for a typical manufacturer, distributor, and pharmacy? Who (what occupation) usually conducts the inventory? 5. If this rule is finalized, commercial packaging would require, with some exceptions, a printed label a symbol designating the schedule, i.e., ``CIII'' or ``C-III.'' DEA assumes that the activity of manufacturers making labeling changes is routine and in their normal course of business. What is the cost of adding the required symbol to the commercial packaging? Executive Order 12988, Civil Justice Reform This proposed regulation meets the applicable standards set forth in sections 3(a) and 3(b)(2) of E.O. 12988 to eliminate drafting errors and ambiguity, minimize litigation, provide a clear legal standard for affected conduct, and promote simplification and burden reduction. Executive Order 13132, Federalism This proposed rulemaking does not have federalism implications warranting the application of E.O. 13132. The proposed rule does not have substantial direct effects on the states, on the relationship between the National Government and the States, or the distribution of power and responsibilities among the various levels of government. Executive Order 13175, Consultation and Coordination With Indian Tribal Governments This proposed rule does not have tribal implications warranting the application of E.O. 13175. It does not have substantial direct effects on one or more Indian tribes, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes. Regulatory Flexibility Act The Administrator, in accordance with the Regulatory Flexibility Act (RFA) (5 U.S.C. 601-612), has reviewed this proposed rule and by approving it, certifies that the proposed rule, if promulgated, will not have a significant economic impact on a substantial number of small entities. Below is a summary of the threshold analyses conducted by the DEA to support the certification statement above. In accordance with the RFA, DEA evaluated the impact of this proposed rule on small entities. DEA estimates that this proposed rule will affect 31,187 entities, of which 30,593 are small entities (17 manufacturers, 406 distributors, and 30,170 pharmacies). The number of affected small entities for each business activity is compared to the number of small entities in each corresponding North American Industry Classification System (NAICS) code to determine whether a substantial number of small entities are affected. Additionally, the annualized cost of the proposed rule for each affected entity is compared to its estimated annual revenue to determine whether this proposed rule will have a significant economic impact on small entities. Since DEA does not collect revenue information on its registrants, to estimate the number of entities ``significantly'' impacted by the proposed rule, DEA relied on publicly available information. Combining the two criteria, substantial number and significant economic impact, DEA determined that this proposed rule will not have a significant economic impact on a substantial number of small entities. Specifically, DEA examined the registration, physical security, labeling and packaging, inventory and recordkeeping, and disposal requirements for the small entities estimated to be affected by the proposed rule. Based on DEA's understanding of its registrants' operations and facilities, and research of publicly available information regarding size and location, DEA estimates that the annualized cost of this proposed rule would vary. Entities already registered to handle schedule III controlled substances would not incur any additional registration costs, and manufacturers and distributors located in the states that control exempt butalbital products as a schedule III controlled substance under state law would not incur any additional costs associated with physical security as state requirements for schedule III controlled substances generally meet or exceed Federal requirements. DEA estimates the following annualized costs: $10,703 per establishment for costs associated with registration, physical security, and inventory requirements: Non- registered manufacturers located in a state where exempt butalbital products are not already subject to controls equivalent to Federal schedule III handling requirements under state law. $7,004 per establishment for costs associated with physical security and inventory requirements: Registered manufacturers located in a state where exempt butalbital products are not already subject to controls equivalent to Federal schedule III handling requirements under state law. $3,716 per establishment for costs associated with registration and inventory requirements: Non-registered manufacturers located in a state where exempt butalbital products are already subject to controls equivalent to Federal schedule III handling requirements under state law. $17 per establishment for costs associated with inventory requirements: Registered manufacturers located in a state where exempt butalbital products are already subject to controls equivalent to Federal schedule III handling requirements under state law. $213 per establishment for costs associated with physical security and inventory requirements: Distributors located in a state where exempt butalbital products are not already subject to controls equivalent to Federal schedule III handling requirements under state law. $17 per establishment for costs associated with inventory requirements: Distributors located in a state where exempt butalbital products are already subject to controls equivalent to Federal schedule III handling requirements under state law. $6 per establishment for costs associated with inventory requirements: All pharmacies. DEA estimates manufacturer, distributor, and pharmacy business activities best correspond to the following NAICS codes: [[Page 21599]] Manufacturer: 325412--Pharmaceutical Preparation Manufacturing Distributor: 424210--Drugs and Druggists' Sundries Merchant Wholesalers Pharmacy: 446110--Pharmacies and Drug Stores DEA researched publicly available information for each of the 17 affected manufacturer small entities and estimated each of their annual revenues. The annualized cost corresponding to their registration and location were compared with the estimated annual revenue for each of the 17 manufacturer small entities. DEA considers the economic impact is ``significant'' if the annual impact is greater than 3 percent of annual revenue. The economic impact is estimated to be significant for one of the small manufacturers. In conclusion, DEA estimates there are 930 small firms in NAICS code 325412--Pharmaceutical Preparation Manufacturing, of which 17 small entities are affected by this proposed rule, and one small entity in NAICS code 325412 will have a significant economic impact. Regarding physical security and inventory costs to distributors, the U.S. Census Bureau's Statistics on U.S. Businesses (SUSB) data contains estimated annual revenue, the number of establishments, and the number of firms for each NAICS code at various revenue ranges, i.e., less than $100,000, $100,000-499,000, $500,000-999,999, etc. The estimated annualized cost of $213 and $17 per distributor establishment was compared to the average annual revenue of the smallest of small firms in NAICS code 424210--Drugs and Druggists' Sundries Merchant Wholesalers. From SUSB data, there are 585 firms in the smallest firm size category, ``Less than $100,000,'' for a combined estimated annual receipts of $31,248,000, or an average of $53,415 per firm.\7\ The annualized cost of $213 and $17 are 0.4 percent and 0.03 percent of the average annual receipt of $53,415 per firm. Because DEA does not expect this proposed rule to have a significant economic impact on the smallest of small entities, DEA does not expect it to have a significant economic impact on any small entity. DEA estimates there are 6,663 small firms in NAICS code 424210--Drugs and Druggists' Sundries Merchant Wholesalers, of which 406 distributor small entities are affected by this proposed rule, and no small entities in NAICS code 424210 will have a significant economic impact. --------------------------------------------------------------------------- \7\ https://www2.census.gov/programs-surveys/susb/tables/2012/us_6digitnaics_r_2012.xlsx. (accessed June 3, 2020). --------------------------------------------------------------------------- Regarding inventory requirement costs for pharmacies, the estimated annualized cost of $6 per pharmacy establishment was compared to the average annual revenue of the smallest of small firms in NAICS code 446110--Pharmacies and Drug Stores. From SUSB data, there are 751 firms in the smallest firm size category, ``Less than $100,000,'' for a combined estimated annual receipts of $36,066,000 or an average of $48,024 per firm.\8\ The annualized cost of $6 is approximately 0.01 percent of the average annual receipt of $48,024 per firm. Because DEA does not expect this proposed rule to have a significant economic impact on the smallest of small entities, DEA does not expect it to have a significant economic impact on any small entity. While DEA estimates this proposed rule to affect a substantial number of pharmacy small entities in NAICS code 446110--Pharmacies and Drug Stores, the proposed rule is not expected to have a significant economic impact on any pharmacy small entity. --------------------------------------------------------------------------- \8\ Ibid. --------------------------------------------------------------------------- In conclusion, DEA's assessment of economic impact by size category indicates that the proposed rule, if promulgated, will not have a significant economic impact on a substantial number of small entities. Unfunded Mandates Reform Act of 1995 The estimated highest cost in any given year is $4,269,421; thus, DEA has determined in accordance with the Unfunded Mandates Reform Act of 1995 (UMRA), 2 U.S.C. 1501 et seq., that this action would not result in any federal mandate that may result in the expenditure by state, local, and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more (adjusted for inflation) in any one year. Therefore, neither a Small Government Agency Plan nor any other action is required under provisions of UMRA. Paperwork Reduction Act of 1995 This action does not impose a new collection of information under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-3521. This action would not impose recordkeeping or reporting requirements on state or local governments, individuals, businesses, or organizations. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. List of Subjects 21 CFR Part 1308 Administrative practice and procedure, Drug traffic control, Exports, Imports, Reporting and recordkeeping requirements. Accordingly, for the reasons set forth in the preamble, DEA proposes to amend 21 CFR part 1308 as follows: PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES 0 1. The authority citation for part 1308 continues to read as follows: Authority: 21 U.S.C. 811, 812, 871(b), 956(b), unless otherwise noted. 0 2. In Sec. 1308.31, revise paragraph (d) and add paragraph (e) to read as follows: Sec. 1308.31 Application for exemption of nonnarcotic prescription product. * * * * * (d) The Administrator may revoke (either individually or categorically) any exemption granted pursuant to section 201(g)(3)(A) of the Act (21 U.S.C. 811(g)(3)(A)) by following the procedures set forth in paragraph (c) of this section for handling an application for an exemption which has been accepted for filing. The Administrator has categorically revoked exemptions for the following products: (1) Effective as of [effective date of final rule], the previous exemptions approved for butalbital products are revoked and such products become subject to the statutory and regulatory restrictions applicable to schedule III controlled substances. (2) [Reserved] (e) The compounds, mixtures, or preparations that the Administrator has exempted from application of all or any part of the Act pursuant to section 201(g)(3)(A), of the Act (21 U.S.C. 811(g)(3)(A)) are listed in the Table of Exempted Prescription Products available on the DEA Diversion Control website at www.deadiversion.usdoj.gov/schedules. Anne Milgram, Administrator. [FR Doc. 2022-07572 Filed 4-11-22; 8:45 am] BILLING CODE 4410-09-P