Schedules of Controlled Substances: Placement of Zipeprol in Schedule I, 28899-28904 [2020-09592]

Download as PDF jbell on DSKJLSW7X2PROD with PROPOSALS Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules information you claim to be confidential with a heading or cover note that states ‘‘THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.’’ The Agency will review this copy, including the claimed confidential information, in its consideration of comments. The second copy, which will have the claimed confidential information redacted/blacked out, will be available for public viewing and posted on https://www.regulations.gov. Submit both copies to the Dockets Management Staff. If you do not wish your name and contact information to be made publicly available, you can provide this information on the cover sheet and not in the body of your comments and you must identify this information as ‘‘confidential.’’ Any information marked as ‘‘confidential’’ will not be disclosed except in accordance with 21 CFR 10.20 and other applicable disclosure law. For more information about FDA’s posting of comments to public dockets, see 80 FR 56469, September 18, 2015, or access the information at: https:// www.govinfo.gov/content/pkg/FR02015-09-18/pdf/2015-23389.pdf. Docket: For access to the docket to read background documents or the electronic and written/paper comments received, go to https:// www.regulations.gov and insert the docket number, found in brackets in the heading of this document, into the ‘‘Search’’ box and follow the prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Chelsea Cerrito, Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl. (HFV–224), Rockville, MD 20855, 240– 402–6729, Chelsea.Cerrito@fda.hhs.gov. SUPPLEMENTARY INFORMATION: Under section 409(b)(5) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 348(b)(5)), notice was given in the Federal Register of April 18, 2017 (82 FR 18268), that a food additive petition (FAP 2299) has been filed by the Canadian Oilseed Processors Association, 404–167 Lombard Ave., Winnipeg MB R3B 0T6, Canada. The petition proposes to amend Title 21 of the Code of Federal Regulations (CFR) in part 573 Food Additives Permitted in Feed and Drinking Water of Animals (21 CFR part 573) to provide for the safe use of spent bleaching clay as a flow agent in canola meal for all livestock and poultry species. Additionally, the submission proposes that the existing regulations be amended to provide for the safe use of silicon dioxide (21 CFR 573.940) and diatomaceous earth (21 VerDate Sep<11>2014 17:16 May 13, 2020 Jkt 250001 CFR 573.340) for use as components of spent bleaching clay. In a Federal Register notice published on March 19, 2019 (84 FR 9989), an amendment was made to the petition to include an environmental assessment. Based on a review of that assessment, we have asked the petitioner to make revisions. To encourage public participation consistent with regulations issued under the National Environmental Policy Act (40 CFR 1501.4(b)), we are placing the revised EA submitted with FAP 2299 on public display at the Dockets Management Staff (see DATES and ADDRESSES) for public review and comment. We will also place on public display, at the Dockets Management Staff and at https://www.regulations.gov, any amendments to, or comments on, the petitioner’s EA without further announcement in the Federal Register. If, based on our review, we find that an environmental impact statement is not required, and this petition results in a regulation, we will publish the notice of availability of our finding of no significant impact and the evidence supporting that finding with the regulation in the Federal Register in accordance with 21 CFR 25.51(b). Dated: May 6, 2020. Lowell J. Schiller, Principal Associate Commissioner for Policy. [FR Doc. 2020–10035 Filed 5–13–20; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA–477] Schedules of Controlled Substances: Placement of Zipeprol in Schedule I Drug Enforcement Administration, Department of Justice. ACTION: Notice of proposed rulemaking. AGENCY: The Drug Enforcement Administration (DEA) proposes placing the substance zipeprol (Chemical name: 1-methoxy-3-[4-(2-methoxy-2phenylethyl)piperazin-1-yl]-1phenylpropan-2-ol), including its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, whenever the existence of such isomers, esters, ethers and salts is possible, in schedule I of the Controlled Substances Act. This action is being taken to enable the United States to meet its obligations under the 1971 Convention on SUMMARY: PO 00000 Frm 00012 Fmt 4702 Sfmt 4702 28899 Psychotropic Substances. If finalized, this action would impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis with, or possess), or propose to handle zipeprol. DATES: Comments must be submitted electronically or postmarked on or before July 13, 2020. Interested persons may file a request for hearing or waiver of hearing pursuant to 21 Code of Federal Regulations (CFR) 1308.44 and in accordance with 21 CFR 1316.45 and/or 1316.47, as applicable. Requests for hearing and waivers of an opportunity for a hearing or to participate in a hearing must be received on or before June 15, 2020. 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–477’’ on all electronic and written correspondence, including any attachments. • Electronic comments: 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: 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, Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive, Springfield, Virginia 22152. E:\FR\FM\14MYP1.SGM 14MYP1 28900 Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules • Hearing requests: All requests for a hearing and waivers of participation must be sent to: Drug Enforcement Administration, Attn: Administrator, 8701 Morrissette Drive, Springfield, Virginia 22152. All requests for hearing and waivers of participation should also be sent to: (1) Drug Enforcement Administration, Attn: Hearing Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) Drug Enforcement Administration, Attn: DEA Federal Register Representative/DPW, 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) 362–3261. SUPPLEMENTARY INFORMATION: jbell on DSKJLSW7X2PROD with PROPOSALS 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 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 it to be made publicly available, you must include the phrase ‘‘CONFIDENTIAL BUSINESS INFORMATION’’ in the first paragraph of your comment. You must also prominently identify the confidential business information to be redacted within the comment. Comments containing personal identifying information and confidential business information identified as directed above will generally be made publicly available in redacted form. If a comment has so much confidential business information that it cannot be VerDate Sep<11>2014 16:27 May 13, 2020 Jkt 250001 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 and supplemental information to this proposed rule are available at http:// www.regulations.gov for easy reference. Request for Hearing or Waiver of Participation in Hearing Pursuant to 21 United States Code (U.S.C.) 811(a), this action is a formal rulemaking ‘‘on the record after opportunity for a hearing.’’ Such proceedings are conducted pursuant to the provisions of the Administrative Procedure Act, 5 U.S.C. 551–559. 21 CFR 1308.41–1308.45; 21 CFR part 1316, subpart D. Interested persons may file requests for a hearing or notices of intent to participate in a hearing in conformity with the requirements of 21 CFR 1308.44(a) or (b), and include a statement of interest in the proceeding and the objections or issues, if any, concerning which the person desires to be heard. Any interested person may file a waiver of an opportunity for a hearing or to participate in a hearing together with a written statement regarding the interested person’s position on the matters of fact and law involved in any hearing as set forth in 21 CFR 1308.44(c). All requests for hearing and waivers of participation must be sent to DEA using the address information provided above. Legal Authority The United States is a party to the 1971 United Nations Convention on Psychotropic Substances (1971 Convention), February 21, 1971, 32 U.S.T. 543, 1019 U.N.T.S. 175, as amended. Procedures respecting changes in drug schedules under the 1971 Convention are governed domestically by 21 U.S.C. 811(d). When the United States receives notification of a scheduling decision pursuant to Article 2 of the 1971 Convention indicating that a drug or other substance has been added or transferred to a schedule specified in the notification, the Secretary of the Department of Health and Human Services (HHS),1 1 As discussed in a memorandum of understanding entered into by the Food and Drug Administration (FDA) and the National Institute on Drug Abuse (NIDA), the FDA acts as the lead agency within HHS in carrying out the Secretary’s scheduling responsibilities under the Controlled PO 00000 Frm 00013 Fmt 4702 Sfmt 4702 after consultation with the Attorney General, shall first determine whether existing legal controls under subchapter I of the Controlled Substances Act (CSA) and the Federal Food, Drug, and Cosmetic Act (FDCA) meet the requirements of the schedule specified in the notification with respect to the specific drug or substance. 21 U.S.C. 811(d)(3). If such requirements are not met by existing controls and the Secretary of the HHS concurs in the scheduling decision, the Secretary shall recommend to the Attorney General that he initiate proceedings for scheduling the drug or substance under the appropriate schedule pursuant to 21 U.S.C. 811(a) and (b). 21 U.S.C. 811(d)(3)(B). Pursuant to 21 U.S.C. 811(a)(1), the Attorney General may, by rule, add to such a schedule or transfer between such schedules any drug or other substance, if he finds that such drug or other substance has a potential for abuse, and makes with respect to such drug or other substance the findings prescribed by 21 U.S.C. 812(b) for the schedule in which such drug is to be placed. The Attorney General has delegated this scheduling authority to the Administrator of the DEA (Administrator). 28 CFR 0.100. Background Zipeprol, known chemically as 1methoxy-3-[4-(2-methoxy-2phenylethyl)piperazin-1-yl]-1phenylpropan-2-ol, is pharmacologically an opioid drug with some hallucinogenic properties that has no approved medical use in the United States. In June 1994 and January 1995, the Food and Drug Administration (FDA), on behalf of the Secretary of the HHS, published notices in the Federal Register regarding zipeprol to comply with 21 U.S.C. 811(d)(2). The 1994 notice requested information to be considered by the World Health Organization (WHO) in preparing its scientific and medical evaluation for zipeprol.2 The 1995 notice solicited public comment regarding a recommendation by the WHO to impose international controls on zipeprol.3 In Substances Act, with the concurrence of NIDA. 50 FR 9518 (March 8, 1985). The Secretary of the HHS has delegated to the Assistant Secretary for Health of the HHS the authority to make domestic drug scheduling recommendations. 58 FR 35460 (July 1, 1993). 2 FDA notice, International Drug Scheduling; Convention on Psychotropic Substances; Certain Stimulant/Hallucinogenic Drugs and Certain Nonbarbiturate Sedative Drugs, 59 FR 31639 (June 20, 1994). 3 FDA notice, International Drug Scheduling; Convention on Psychotropic Substances; World Health Organization Scheduling Recommendations E:\FR\FM\14MYP1.SGM 14MYP1 Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules jbell on DSKJLSW7X2PROD with PROPOSALS March 1995, the United Nations Commission on Narcotic Drugs (CND), on the advice of the Director-General of the WHO, placed zipeprol in Schedule II of the 1971 Convention.4 As a party to the 1971 Convention, the United States is taking action to place appropriate controls on zipeprol by scheduling it under the CSA after determining that no existing legal controls under subchapter I of the CSA and the FDCA meet the requirements of the scheduling decision with respect to zipeprol. 21 U.S.C. 811(d)(3). Specifically, DEA is proposing to place zipeprol in schedule I of the CSA. Placing zipeprol in schedule I of the CSA would satisfy the United States’ international obligations as set forth in Article 2, paragraph 7(b) of the 1971 Convention, and as implemented by the CSA. 21 U.S.C. 811(d)(3). Article 2, paragraph 7(b), of the 1971 Convention sets forth the minimum requirements that the United States must meet when a substance has been added to Schedule II of the 1971 Convention. Pursuant to the 1971 Convention, the United States must require licenses for the manufacture, export and import, and distribution of zipeprol. This license requirement is accomplished by the CSA’s registration requirement as set forth in 21 U.S.C. 822, 823, 957, 958, and in accordance with 21 CFR parts 1301 and 1312. In addition, the United States must adhere to specific export and import provisions set forth in the 1971 Convention. This requirement is accomplished by the CSA’s export and import provisions established in 21 U.S.C. 952, 953, 957, 958, and in accordance with 21 CFR part 1312. Likewise, under Article 13, paragraphs 1 and 2, of the 1971 Convention, a party to the 1971 Convention may notify another party, through the Secretary-General of the United Nations, that it prohibits the importation of a substance in Schedule II, III, or IV of the Convention. If such notice is presented to the United States, the United States shall take measures to ensure that the named substance is not exported to the notifying country. This requirement is also accomplished by the CSA’s export provisions mentioned above. Under Article 16, paragraph 4, of the 1971 Convention, the United States is required to provide annual statistical reports to the International Narcotics for Seven Drug Substances, 60 FR 4169, 4173 (January 20, 1995). 4 United Nations Office on Drugs and Crime, CND. Decision 2 (XXXVIII). Inclusion of zipeprol in Schedule II of the Convention on Psychotropic Substances of 1971. https://www.unodc.org/pdf/ decisions/decision2_38.pdf (last retrieved October 3, 2018). VerDate Sep<11>2014 16:27 May 13, 2020 Jkt 250001 Control Board (INCB). Using INCB Form P, the United States shall provide the following information: (1) In regard to each substance in Schedule I and II of the 1971 Convention, quantities manufactured, exported to and imported from each country or region as well as stocks held by manufacturers; (2) in regard to each substance in Schedule II and III of the 1971 Convention, quantities used in the manufacture of exempt preparations; and (3) in regard to each substance in Schedule II—IV of the 1971 Convention, quantities used for the manufacture of non-psychotropic substances or products. Lastly, under Article 2 of the 1971 Convention, the United States must adopt measures in accordance with Article 22 to address violations of any statutes or regulations that are adopted pursuant to its obligations under the 1971 Convention. The United States complies with this provision as persons acting outside the legal framework established by the CSA are subject to administrative, civil, and/ or criminal action. Proposed Determination To Schedule Zipeprol Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on zipeprol and on April 3, 2009, submitted it to the Assistant Secretary for Health of the HHS with a request for a scientific and medical evaluation of available information and a scheduling recommendation for zipeprol. On May 20, 2013, HHS provided to DEA a written scientific and medical evaluation and scheduling recommendation entitled, ‘‘Basis for the Recommendation for Control of Zipeprol and Its Salts in Schedule I of the Controlled Substances Act.’’ Pursuant to 21 U.S.C. 811(b), this document contained HHS’ eight-factor analysis of zipeprol, along with its recommendation that zipeprol be placed in schedule I of the CSA. In response, DEA reviewed the scientific and medical evaluation and scheduling recommendation provided by the HHS and all other relevant data, and completed its own eight-factor review document pursuant to 21 U.S.C. 811(c). Since receiving the HHS recommendation, no additional studies have been published in the scientific literature. Included below is a brief summary of each factor as analyzed by HHS and DEA in their respective eightfactor analyses, and as considered by DEA in its proposed scheduling determination. Please note that both DEA and HHS analyses are available in their entirety under ‘‘Supporting Documents’’ of the public docket for this proposed rule at http:// PO 00000 Frm 00014 Fmt 4702 Sfmt 4702 28901 www.regulations.gov under docket number ‘‘DEA–477.’’ 1. The Drug’s Actual or Relative Potential for Abuse: As reported by HHS, there are numerous reports indicating that abuse of zipeprol resulted in seizures, comas, amnesia, hallucinations, and death in countries where zipeprol has been marketed as an antitussive. The pharmacological effects of zipeprol are similar to opioids in schedule II of the CSA such as morphine; however, zipeprol is a weak opioid relative to morphine. Hallucinations, convulsions, and opioid-like tolerance and dependence are observed in humans following zipeprol intake. Zipeprol abuse is associated with psychological and physical dependence. Abuse liability studies suggest that the primary motivation for zipeprol abuse was reaching the opioid-like, hypnotic sedative effects and euphoria associated with this drug. 2. Scientific Evidence of the Drug’s Pharmacological Effects, if Known: Zipeprol binds with low to moderate affinity to mu and kappa opioid receptors, has a moderate affinity for sigma 1 receptors, and has a strong affinity for sigma 2 receptors. Animal testing data in monkeys, rats and mice show that zipeprol is self-administered. Acute cardiovascular and respiratory toxicity was observed in animals continuously infused with zipeprol. Published clinical reports have indicated that euphoric effects are observed at doses ranging from 3- to 10fold higher than the therapeutic daily dose range (75–150 mg/day). Generalized seizures were reported at relatively low doses (375 mg) but still higher than the therapeutic dose range. 3. The State of Current Scientific Knowledge Regarding the Drug or Other Substance: Zipeprol, also known as 1methoxy-3-[4-(2-methoxy-2phenylethyl) piperazin-1-yl]-1phenylpropan-2-ol, has a molecular weight of 322.37 g/mol. Zipeprol is extensively metabolized in humans into four major metabolites. Zipeprol is not expected to be detected in urine with a normal pH. When urine pH rises above 6.2, unchanged zipeprol is reabsorbed whereas under acidic urine conditions (pH < 5.0), approximately 1–5 percent of zipeprol is excreted unchanged. There is no currently accepted medical use of zipeprol in the United States. In other countries, zipeprol was used as a cough suppressant (antitussive), but there is no longer any reported manufacture of, consumption of, stocks or trade of zipeprol. 4. Its History and Current Pattern of Abuse: There have been numerous E:\FR\FM\14MYP1.SGM 14MYP1 28902 Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules jbell on DSKJLSW7X2PROD with PROPOSALS reports of zipeprol abuse from Brazil, Chile, France, Italy, Mexico, the Republic of Korea, Switzerland, and the former Yugoslavia during the 1980s and 1990s. These reports suggest the sedative, hallucinogenic, and euphorigenic effects of zipeprol, and its ability to suppress some signs of opioid withdrawal at high doses, may be the reasons for its abuse. It is important to note that the ability of one opioid to suppress withdrawal from a different opioid does not represent a beneficial effect. Ease of obtaining zipeprol by over-the-counter access may have contributed to its widespread abuse in some countries. Following these reports, many countries in Asia, Europe, and South America discontinued medical use of zipeprol. Incidences of zipeprol abuse were not reported after placement of zipeprol in Schedule II of the 1971 Convention on Psychotropic Substances in 1995 (CND Dec. 38/2). Queries of DEA’s System to Retrieve Information from Drug Evidence (STRIDE)/ STARLiMS 5 and the National Forensic Laboratory Information System (NFLIS) 6 databases on October 3, 2018, did not generate any reports of zipeprol, suggesting that it is not trafficked in the United States. 5. The Scope, Duration, and Significance of Abuse: The lack of abuse and overdose associated with zipeprol is most likely due to its lack of availability for medical use in the United States. 6. What, if any, Risk There is to the Public Health: Currently in the United States, zipeprol is not an FDA-approved drug, and there have been no reports or epidemiological studies submitted to FDA regarding its abuse. In countries where it was available for medical use, zipeprol became a significant health problem. Based on the available clinical data, zipeprol has the same risks to public health as schedule I or schedule II substances. Such risks include deaths due to voluntary or accidental acute intoxications and the potential for psychological and physical dependence. 7. Its Psychic or Physiological Dependence Liability: Psychological and physiological dependence is associated 5 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 DEA laboratory drug evidence data system of record. 6 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. VerDate Sep<11>2014 16:27 May 13, 2020 Jkt 250001 with zipeprol. Several clinical studies examined and described physical dependence and withdrawal effects associated with zipeprol abuse. Main signs of zipeprol withdrawal include sweating, diarrhea, anxiety, insomnia, dyspnea, yawning, and pain. The euphoric and hallucinogenic effects associated with zipeprol and other opioid-like drugs serve as reinforcers and can result in psychological dependence and are supported by case studies with zipeprol abusers. 8. Whether the Substance is an Immediate Precursor of a Substance Already Controlled Under the CSA: DEA and HHS find that zipeprol is not an immediate precursor of a substance already controlled under the CSA. Conclusion: Based on consideration of the scientific and medical evaluation and accompanying recommendation of HHS, and based on DEA’s consideration of its own eight-factor analysis, DEA finds that these facts and all relevant data constitute substantial evidence of potential for abuse of zipeprol. As such, DEA hereby proposes to schedule zipeprol as a controlled substance under the CSA. Proposed Determination of Appropriate Schedule The CSA establishes five schedules of controlled substances known as schedules I, II, III, IV, and V. The CSA also outlines the findings required to place a drug or other substance in any particular schedule. 21 U.S.C. 812(b). After consideration of the analysis and recommendation of the Assistant Secretary for Health of the HHS and review of all available data, the Acting Administrator of the DEA (Acting Administrator), pursuant to 21 U.S.C. 812(b)(1), finds that: (1) Zipeprol has a high potential for abuse. Widespread reports of zipeprol abuse have occurred in countries that have marketed zipeprol. Zipeprol is selfadministered in animals and clinical studies reported that zipeprol abuse is related to its opioid, sedative, hallucinogenic, and euphorigenic effects. Epidemiological reports on zipeprol, worldwide, have indicated that adverse reactions (primarily seizures) are caused by zipeprol abuse and dependence. (2) There are no approved New Drug Applications for zipeprol and no known therapeutic applications for zipeprol in the United States.7 Therefore, zipeprol 7 Although there is no evidence suggesting that zipeprol has a currently accepted medical use in treatment in the United States, it bears noting that a drug cannot be found to have such medical use unless DEA concludes that it satisfies a five-part test. Specifically, with respect to a drug that has not PO 00000 Frm 00015 Fmt 4702 Sfmt 4702 has no currently accepted medical use in treatment in the United States. (3) There is a lack of accepted safety for use of zipeprol under medical supervision. Zipeprol was first approved and introduced as an antitussive in France and Italy during the late 1970s. Following several reports of abuse and overdosing from zipeprol, this drug was withdrawn in the early to mid-1990s. Based on these findings, the Acting Administrator concludes that zipeprol warrants control in schedule I of the CSA. 21 U.S.C. 812(b)(1). More precisely, because of its opioid effects, and producing opioid-like tolerance and dependence in humans, DEA is proposing to place zipeprol in 21 CFR 1308.11(b) (the opiates category of schedule I). As such, the proposed control of zipeprol includes the substance as well as its isomers, esters, ethers, salts, and salts of isomers, esters and ethers, whenever the existence of such isomers, esters, ethers and salts is possible within the specific chemical designation. Requirements for Handling Zipeprol If this rule is finalized as proposed, zipeprol would be subject to the CSA’s schedule I regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, reverse distribution, import, export, engagement in research, conduct of instructional activities or chemical analysis with, and possession of schedule I controlled substances, including the following: 1. Registration. Any person who handles (manufactures, distributes, reverse distributes, imports, exports, engages in research, or conducts instructional activities or chemical analysis with, or possesses) zipeprol, or who desires to handle zipeprol, would need to be registered with DEA to conduct such activities pursuant to 21 U.S.C. 822, 823, 957, 958, and in accordance with 21 CFR parts 1301 and 1312 as of the effective date of a final scheduling action. Any person who currently handles zipeprol, and is not registered with DEA, would need to submit an application for registration been approved by the FDA, to have a currently accepted medical use in treatment in the United States, all of the following must be demonstrated: i. the drug’s chemistry must be known and reproducible; ii. there must be adequate safety studies; iii. there must be adequate and well-controlled studies proving efficacy; iv. the drug must be accepted by qualified experts; and v. the scientific evidence must be widely available. 57 FR 10499 (1992). E:\FR\FM\14MYP1.SGM 14MYP1 jbell on DSKJLSW7X2PROD with PROPOSALS Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules and may not continue to handle zipeprol after the effective date of a final scheduling action unless DEA has approved that application for registration pursuant to 21 U.S.C. 822, 823, 957, 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 I registration would be required to surrender all quantities of currently held zipeprol, or transfer all quantities of currently held zipeprol to a person registered with DEA before the effective date of a final scheduling action in accordance with all applicable federal, state, local, and tribal laws. As of the effective date of a final scheduling action, zipeprol would be required to be disposed of in accordance with 21 CFR part 1317, in addition to all other applicable federal, state, local, and tribal laws. 3. Security. Zipeprol would be subject to schedule I security requirements and would need to be handled and stored pursuant to 21 U.S.C. 821 and 823, and in accordance with 21 CFR 1301.71– 1301.93 as of the effective date of a final scheduling action. 4. Labeling and Packaging. All labels, labeling, and packaging for commercial containers of zipeprol would need to be in compliance with 21 U.S.C. 825 and 958(e), and be in accordance with 21 CFR part 1302 as of the effective date of a final scheduling action. 5. Quota. Only registered manufacturers would be permitted to manufacture zipeprol in accordance with a quota assigned pursuant to 21 U.S.C. 826 and in accordance with 21 CFR part 1303 as of the effective date of a final scheduling action. 6. Inventory. Every DEA registrant who possesses any quantity of zipeprol on the effective date of a final scheduling action would be required to take an inventory of zipeprol on hand at that time, pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a) and (d). Any person who becomes registered with DEA on or after the effective date of the final scheduling action would be required to take an initial inventory of all stocks of controlled substances (including zipeprol) 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(a) and (b). After the initial inventory, every DEA registrant would be required to take an inventory of all controlled substances (including zipeprol) on hand every two years, pursuant to 21 U.S.C. 827 and VerDate Sep<11>2014 16:27 May 13, 2020 Jkt 250001 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. 7. Records and Reports. Every DEA registrant would be required to maintain records and submit reports pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR parts 1304, 1312, and 1317 as of the effective date of a final scheduling action. Manufacturers and distributors would be required to submit reports regarding zipeprol to the Automation of Reports and Consolidated Order System pursuant to 21 U.S.C. 827 and in accordance with 21 CFR parts 1304 and 1312 as of the effective date of a final scheduling action. 8. Order Forms. Every DEA registrant who distributes zipeprol would be required to comply with order form requirements, pursuant to 21 U.S.C. 828, and in accordance with 21 CFR part 1305 as of the effective date of a final scheduling action. 9. Importation and Exportation. All importation and exportation of zipeprol would need to be in compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance with 21 CFR part 1312 as of the effective date of a final scheduling action. 10. Liability. Any activity involving zipeprol 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. Regulatory Analyses Executive Orders 12866, 13563, and 13771, Regulatory Planning and Review, Improving Regulation and Regulatory Review, and Reducing Regulation and Controlling Regulatory Costs In accordance with 21 U.S.C. 811(a), this proposed scheduling action is subject to formal rulemaking procedures performed ‘‘on the record after opportunity for a hearing,’’ which are conducted pursuant to the provisions of 5 U.S.C. 556 and 557. The CSA sets forth the procedures and criteria for scheduling a drug or other substance. Such actions are exempt from review by the Office of Management and Budget (OMB) pursuant to section 3(d)(1) of Executive Order 12866 and the principles reaffirmed in Executive Order 13563. This rulemaking is not an Executive Order 13771 regulatory action because this rule is not significant under Executive Order 12866. Executive Order 12988, Civil Justice Reform This proposed regulation meets the applicable standards set forth in PO 00000 Frm 00016 Fmt 4702 Sfmt 4702 28903 sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice Reform, 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 Executive Order 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 Executive Order 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. Paperwork Reduction Act of 1995 This action does not impose a new collection of information requirement under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501–3521). Regulatory Flexibility Act The Acting Administrator, in accordance with the Regulatory Flexibility Act (RFA), 5 U.S.C. 601–602, has reviewed this proposed rule, and by approving it, certifies that it will not have a significant economic impact on a substantial number of small entities. DEA proposes placing the substance zipeprol (chemical name: 1-methoxy-3[4-(2-methoxy-2-phenylethyl)piperazin1-yl]-1-phenylpropan-2-ol), including its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, whenever the existence of such isomers, esters, ethers and salts is possible, in schedule I of the CSA. This action is being taken to enable the United States to meet its obligations under the 1971 Convention on Psychotropic Substances. If finalized, this action would impose the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical E:\FR\FM\14MYP1.SGM 14MYP1 28904 Federal Register / Vol. 85, No. 94 / Thursday, May 14, 2020 / Proposed Rules analysis with, or possess), or propose to handle zipeprol. According to HHS, zipeprol has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and lacks accepted safety for use under medical supervision. DEA’s research confirms that there is no commercial market for zipeprol in the United States. Additionally, queries of DEA’s STRIDE/ STARLiMS and the NFLIS databases on October 3, 2018, did not generate any reports of zipeprol, suggesting that it is not trafficked in the United States. Therefore, DEA estimates that no United States entity currently handles zipeprol and does not expect any United States entity to handle zipeprol in the foreseeable future. DEA concludes that no United States entity would be affected by this rule if finalized. As such, the proposed rule will not have a significant effect on a substantial number of small entities. jbell on DSKJLSW7X2PROD with PROPOSALS Unfunded Mandates Reform Act of 1995 On the basis of information contained in the ‘‘Regulatory Flexibility Act’’ section above, DEA has determined and certifies pursuant to the Unfunded Mandates Reform Act (UMRA) of 1995 (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 annually for inflation) in any 1 year * * *.’’ Therefore, neither a Small Government Agency Plan nor any other action is required under provisions of the UMRA of 1995. Uttam Dhillon, Acting Administrator. [FR Doc. 2020–09592 Filed 5–13–20; 8:45 am] BILLING CODE 4410–09–P DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Parts 733, 736, and 842 [Docket ID: OSM–2019–0010; S1D1S SS08011000 SX064A000 201S180110; S2D2S SS08011000 SX064A00 20XS501520] RIN 1029–AC77 Clarification of Provisions Related to the Issuance of Ten-Day Notices to State Regulatory Authorities and Enhancement of Corrective Action for State Regulatory Program Issues Office of Surface Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule. AGENCY: The Office of Surface Mining Reclamation and Enforcement (OSMRE) proposes to clarify the regulations about notifying regulatory authorities of possible violations of any requirement of the Surface Mining Control and Reclamation Act of 1977 (SMCRA). This action would streamline the process for OSMRE’s coordination with regulatory authorities in order to minimize duplication of inspections, enforcement, and administration of SMCRA. Additionally, the proposed rule would enhance the procedures for early identification of, and implementation of corrective action to address, State List of Subjects in 21 CFR Part 1308 regulatory program issues. Administrative practice and DATES : OSMRE will accept comments procedure, Drug traffic control, received or postmarked on or before Reporting and recordkeeping 11:59 p.m. Eastern Daylight Time (EDT), requirements. June 15, 2020 (the closing date). OSMRE For the reasons set out above, 21 CFR must receive comments submitted part 1308 is proposed to be amended to electronically using the Federal read as follows: eRulemaking Portal (see ADDRESSES below) by 11:59 p.m. EDT on the closing PART 1308—SCHEDULES OF date. CONTROLLED SUBSTANCES ADDRESSES: You may submit comments, ■ 1. The authority citation for 21 CFR identified by RIN 1029–AC77, by any of part 1308 continues to read as follows: the following methods: Authority: 21 U.S.C. 811, 812, 871(b), (1) Electronically: Go to the Federal 956(b), unless otherwise noted. eRulemaking Portal: https:// www.regulations.gov. In the search box, ■ 2. In § 1308.11, add paragraph (b)(71) enter RIN 1029–AC77, which is the to read as follows: docket number for this proposed § 1308.11 Schedule I. rulemaking. Then in the search panel on * * * * * the left side of the screen, under the (b) * * * Document type heading, click on the Proposed Rules link to locate this (71) Zipeprol ................................. 9873 document. You may submit a comment by clicking on ‘‘Comment Now!’’ * * * * * VerDate Sep<11>2014 16:27 May 13, 2020 Jkt 250001 SUMMARY: PO 00000 Frm 00017 Fmt 4702 Sfmt 4702 (2) By hard copy: Submit by U.S. mail, other mail delivery service, or handdelivery to: U.S. Department of the Interior, Office of Surface Mining Reclamation and Enforcement, 1849 C Street NW, Mail Stop 4550, Room 4558, Main Interior Building, Washington, DC 20240, Attention: Division of Regulatory Support. OSMRE requests that you send comments only by the methods described above. OSMRE will post all comments on https:// www.regulations.gov. This generally means that OSMRE will post any personal information you provide (see Public Comment Procedures, below, for more information). FOR FURTHER INFORMATION CONTACT: Kathleen G. Vello, OSMRE, Division of Regulatory Support, 1849 C Street NW, Mail Stop 4550, Room 4558, Washington, DC 20240, telephone number: (202) 208–1908. If you use a telecommunications device for the deaf (TDD), call the Federal Relay Service at: (800) 877–8339. SUPPLEMENTARY INFORMATION: Table of Contents I. Public Comment Procedures II. Background III. Discussion of Proposed Rule and Sectionby-Section Analysis IV. Procedural Matters I. Public Comment Procedures You may submit written comments, identified with the RIN 1029–AC77, by any of the methods described in the ADDRESSES section. Written comments submitted on the proposed rule should be specific, confined to issues pertinent to the proposed rule, and should explain the reason for any recommended change. Where possible, your comments should reference the specific section or paragraph of the proposal that you are addressing. The comments and recommendations that will be most useful and likely to influence agency decisions are those: Supported by quantitative information or studies; based on specific, identifiable experience; and that include citations to, and analyses of, the applicable laws and regulations. Comments received after the close of the comment period (see the DATES section) or delivered to addresses other than those listed above (see the ADDRESSES section) may not be considered or included in the Administrative Record for the final rule. Comments, including names and street addresses of respondent commenters, will be available for public review at the address listed under ADDRESSES during regular business E:\FR\FM\14MYP1.SGM 14MYP1

Agencies

[Federal Register Volume 85, Number 94 (Thursday, May 14, 2020)]
[Proposed Rules]
[Pages 28899-28904]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-09592]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-477]


Schedules of Controlled Substances: Placement of Zipeprol in 
Schedule I

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Drug Enforcement Administration (DEA) proposes placing the 
substance zipeprol (Chemical name: 1-methoxy-3-[4-(2-methoxy-2-
phenylethyl)piperazin-1-yl]-1-phenylpropan-2-ol), including its 
isomers, esters, ethers, salts, and salts of isomers, esters, and 
ethers, whenever the existence of such isomers, esters, ethers and 
salts is possible, in schedule I of the Controlled Substances Act. This 
action is being taken to enable the United States to meet its 
obligations under the 1971 Convention on Psychotropic Substances. If 
finalized, this action would impose the regulatory controls and 
administrative, civil, and criminal sanctions applicable to schedule I 
controlled substances on persons who handle (manufacture, distribute, 
reverse distribute, import, export, engage in research, conduct 
instructional activities or chemical analysis with, or possess), or 
propose to handle zipeprol.

DATES: Comments must be submitted electronically or postmarked on or 
before July 13, 2020.
    Interested persons may file a request for hearing or waiver of 
hearing pursuant to 21 Code of Federal Regulations (CFR) 1308.44 and in 
accordance with 21 CFR 1316.45 and/or 1316.47, as applicable. Requests 
for hearing and waivers of an opportunity for a hearing or to 
participate in a hearing must be received on or before June 15, 2020.

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-477'' on all electronic and written correspondence, 
including any attachments.
     Electronic comments: 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 on-line 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: 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, 
Attn: DEA Federal Register Representative/DPW, 8701 Morrissette Drive, 
Springfield, Virginia 22152.

[[Page 28900]]

     Hearing requests: All requests for a hearing and waivers 
of participation must be sent to: Drug Enforcement Administration, 
Attn: Administrator, 8701 Morrissette Drive, Springfield, Virginia 
22152. All requests for hearing and waivers of participation should 
also be sent to: (1) Drug Enforcement Administration, Attn: Hearing 
Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2) 
Drug Enforcement Administration, Attn: DEA Federal Register 
Representative/DPW, 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) 362-3261.

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 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 it to be made publicly available, you 
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the 
first paragraph of your comment. You must also prominently identify the 
confidential business information to be redacted within the comment.
    Comments containing personal identifying information and 
confidential business information identified as directed above will 
generally be made publicly available in redacted form. If a comment has 
so much confidential business 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 and supplemental information to 
this proposed rule are available at http://www.regulations.gov for easy 
reference.

Request for Hearing or Waiver of Participation in Hearing

    Pursuant to 21 United States Code (U.S.C.) 811(a), this action is a 
formal rulemaking ``on the record after opportunity for a hearing.'' 
Such proceedings are conducted pursuant to the provisions of the 
Administrative Procedure Act, 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 
21 CFR part 1316, subpart D. Interested persons may file requests for a 
hearing or notices of intent to participate in a hearing in conformity 
with the requirements of 21 CFR 1308.44(a) or (b), and include a 
statement of interest in the proceeding and the objections or issues, 
if any, concerning which the person desires to be heard. Any interested 
person may file a waiver of an opportunity for a hearing or to 
participate in a hearing together with a written statement regarding 
the interested person's position on the matters of fact and law 
involved in any hearing as set forth in 21 CFR 1308.44(c).
    All requests for hearing and waivers of participation must be sent 
to DEA using the address information provided above.

Legal Authority

    The United States is a party to the 1971 United Nations Convention 
on Psychotropic Substances (1971 Convention), February 21, 1971, 32 
U.S.T. 543, 1019 U.N.T.S. 175, as amended. Procedures respecting 
changes in drug schedules under the 1971 Convention are governed 
domestically by 21 U.S.C. 811(d). When the United States receives 
notification of a scheduling decision pursuant to Article 2 of the 1971 
Convention indicating that a drug or other substance has been added or 
transferred to a schedule specified in the notification, the Secretary 
of the Department of Health and Human Services (HHS),\1\ after 
consultation with the Attorney General, shall first determine whether 
existing legal controls under subchapter I of the Controlled Substances 
Act (CSA) and the Federal Food, Drug, and Cosmetic Act (FDCA) meet the 
requirements of the schedule specified in the notification with respect 
to the specific drug or substance. 21 U.S.C. 811(d)(3). If such 
requirements are not met by existing controls and the Secretary of the 
HHS concurs in the scheduling decision, the Secretary shall recommend 
to the Attorney General that he initiate proceedings for scheduling the 
drug or substance under the appropriate schedule pursuant to 21 U.S.C. 
811(a) and (b). 21 U.S.C. 811(d)(3)(B). Pursuant to 21 U.S.C. 
811(a)(1), the Attorney General may, by rule, add to such a schedule or 
transfer between such schedules any drug or other substance, if he 
finds that such drug or other substance has a potential for abuse, and 
makes with respect to such drug or other substance the findings 
prescribed by 21 U.S.C. 812(b) for the schedule in which such drug is 
to be placed. The Attorney General has delegated this scheduling 
authority to the Administrator of the DEA (Administrator). 28 CFR 
0.100.
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    \1\ As discussed in a memorandum of understanding entered into 
by the Food and Drug Administration (FDA) and the National Institute 
on Drug Abuse (NIDA), the FDA acts as the lead agency within HHS in 
carrying out the Secretary's scheduling responsibilities under the 
Controlled Substances Act, with the concurrence of NIDA. 50 FR 9518 
(March 8, 1985). The Secretary of the HHS has delegated to the 
Assistant Secretary for Health of the HHS the authority to make 
domestic drug scheduling recommendations. 58 FR 35460 (July 1, 
1993).
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Background

    Zipeprol, known chemically as 1-methoxy-3-[4-(2-methoxy-2-
phenylethyl)piperazin-1-yl]-1-phenylpropan-2-ol, is pharmacologically 
an opioid drug with some hallucinogenic properties that has no approved 
medical use in the United States.
    In June 1994 and January 1995, the Food and Drug Administration 
(FDA), on behalf of the Secretary of the HHS, published notices in the 
Federal Register regarding zipeprol to comply with 21 U.S.C. 811(d)(2). 
The 1994 notice requested information to be considered by the World 
Health Organization (WHO) in preparing its scientific and medical 
evaluation for zipeprol.\2\ The 1995 notice solicited public comment 
regarding a recommendation by the WHO to impose international controls 
on zipeprol.\3\ In

[[Page 28901]]

March 1995, the United Nations Commission on Narcotic Drugs (CND), on 
the advice of the Director-General of the WHO, placed zipeprol in 
Schedule II of the 1971 Convention.\4\
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    \2\ FDA notice, International Drug Scheduling; Convention on 
Psychotropic Substances; Certain Stimulant/Hallucinogenic Drugs and 
Certain Nonbarbiturate Sedative Drugs, 59 FR 31639 (June 20, 1994).
    \3\ FDA notice, International Drug Scheduling; Convention on 
Psychotropic Substances; World Health Organization Scheduling 
Recommendations for Seven Drug Substances, 60 FR 4169, 4173 (January 
20, 1995).
    \4\ United Nations Office on Drugs and Crime, CND. Decision 2 
(XXXVIII). Inclusion of zipeprol in Schedule II of the Convention on 
Psychotropic Substances of 1971. https://www.unodc.org/pdf/decisions/decision2_38.pdf (last retrieved October 3, 2018).
---------------------------------------------------------------------------

    As a party to the 1971 Convention, the United States is taking 
action to place appropriate controls on zipeprol by scheduling it under 
the CSA after determining that no existing legal controls under 
subchapter I of the CSA and the FDCA meet the requirements of the 
scheduling decision with respect to zipeprol. 21 U.S.C. 811(d)(3). 
Specifically, DEA is proposing to place zipeprol in schedule I of the 
CSA. Placing zipeprol in schedule I of the CSA would satisfy the United 
States' international obligations as set forth in Article 2, paragraph 
7(b) of the 1971 Convention, and as implemented by the CSA. 21 U.S.C. 
811(d)(3).
    Article 2, paragraph 7(b), of the 1971 Convention sets forth the 
minimum requirements that the United States must meet when a substance 
has been added to Schedule II of the 1971 Convention. Pursuant to the 
1971 Convention, the United States must require licenses for the 
manufacture, export and import, and distribution of zipeprol. This 
license requirement is accomplished by the CSA's registration 
requirement as set forth in 21 U.S.C. 822, 823, 957, 958, and in 
accordance with 21 CFR parts 1301 and 1312. In addition, the United 
States must adhere to specific export and import provisions set forth 
in the 1971 Convention. This requirement is accomplished by the CSA's 
export and import provisions established in 21 U.S.C. 952, 953, 957, 
958, and in accordance with 21 CFR part 1312. Likewise, under Article 
13, paragraphs 1 and 2, of the 1971 Convention, a party to the 1971 
Convention may notify another party, through the Secretary-General of 
the United Nations, that it prohibits the importation of a substance in 
Schedule II, III, or IV of the Convention. If such notice is presented 
to the United States, the United States shall take measures to ensure 
that the named substance is not exported to the notifying country. This 
requirement is also accomplished by the CSA's export provisions 
mentioned above. Under Article 16, paragraph 4, of the 1971 Convention, 
the United States is required to provide annual statistical reports to 
the International Narcotics Control Board (INCB). Using INCB Form P, 
the United States shall provide the following information: (1) In 
regard to each substance in Schedule I and II of the 1971 Convention, 
quantities manufactured, exported to and imported from each country or 
region as well as stocks held by manufacturers; (2) in regard to each 
substance in Schedule II and III of the 1971 Convention, quantities 
used in the manufacture of exempt preparations; and (3) in regard to 
each substance in Schedule II--IV of the 1971 Convention, quantities 
used for the manufacture of non-psychotropic substances or products. 
Lastly, under Article 2 of the 1971 Convention, the United States must 
adopt measures in accordance with Article 22 to address violations of 
any statutes or regulations that are adopted pursuant to its 
obligations under the 1971 Convention. The United States complies with 
this provision as persons acting outside the legal framework 
established by the CSA are subject to administrative, civil, and/or 
criminal action.

Proposed Determination To Schedule Zipeprol

    Pursuant to 21 U.S.C. 811(b), DEA gathered the necessary data on 
zipeprol and on April 3, 2009, submitted it to the Assistant Secretary 
for Health of the HHS with a request for a scientific and medical 
evaluation of available information and a scheduling recommendation for 
zipeprol. On May 20, 2013, HHS provided to DEA a written scientific and 
medical evaluation and scheduling recommendation entitled, ``Basis for 
the Recommendation for Control of Zipeprol and Its Salts in Schedule I 
of the Controlled Substances Act.'' Pursuant to 21 U.S.C. 811(b), this 
document contained HHS' eight-factor analysis of zipeprol, along with 
its recommendation that zipeprol be placed in schedule I of the CSA.
    In response, DEA reviewed the scientific and medical evaluation and 
scheduling recommendation provided by the HHS and all other relevant 
data, and completed its own eight-factor review document pursuant to 21 
U.S.C. 811(c). Since receiving the HHS recommendation, no additional 
studies have been published in the scientific literature. Included 
below is a brief summary of each factor as analyzed by HHS and DEA in 
their respective eight-factor analyses, and as considered by DEA in its 
proposed scheduling determination. Please note that both DEA and HHS 
analyses are available in their entirety under ``Supporting Documents'' 
of the public docket for this proposed rule at http://www.regulations.gov under docket number ``DEA-477.''
    1. The Drug's Actual or Relative Potential for Abuse: As reported 
by HHS, there are numerous reports indicating that abuse of zipeprol 
resulted in seizures, comas, amnesia, hallucinations, and death in 
countries where zipeprol has been marketed as an antitussive. The 
pharmacological effects of zipeprol are similar to opioids in schedule 
II of the CSA such as morphine; however, zipeprol is a weak opioid 
relative to morphine. Hallucinations, convulsions, and opioid-like 
tolerance and dependence are observed in humans following zipeprol 
intake. Zipeprol abuse is associated with psychological and physical 
dependence. Abuse liability studies suggest that the primary motivation 
for zipeprol abuse was reaching the opioid-like, hypnotic sedative 
effects and euphoria associated with this drug.
    2. Scientific Evidence of the Drug's Pharmacological Effects, if 
Known: Zipeprol binds with low to moderate affinity to mu and kappa 
opioid receptors, has a moderate affinity for sigma 1 receptors, and 
has a strong affinity for sigma 2 receptors. Animal testing data in 
monkeys, rats and mice show that zipeprol is self-administered. Acute 
cardiovascular and respiratory toxicity was observed in animals 
continuously infused with zipeprol. Published clinical reports have 
indicated that euphoric effects are observed at doses ranging from 3- 
to 10- fold higher than the therapeutic daily dose range (75-150 mg/
day). Generalized seizures were reported at relatively low doses (375 
mg) but still higher than the therapeutic dose range.
    3. The State of Current Scientific Knowledge Regarding the Drug or 
Other Substance: Zipeprol, also known as 1-methoxy-3-[4-(2-methoxy-2-
phenylethyl) piperazin-1-yl]-1-phenylpropan-2-ol, has a molecular 
weight of 322.37 g/mol. Zipeprol is extensively metabolized in humans 
into four major metabolites. Zipeprol is not expected to be detected in 
urine with a normal pH. When urine pH rises above 6.2, unchanged 
zipeprol is reabsorbed whereas under acidic urine conditions (pH < 
5.0), approximately 1-5 percent of zipeprol is excreted unchanged. 
There is no currently accepted medical use of zipeprol in the United 
States. In other countries, zipeprol was used as a cough suppressant 
(antitussive), but there is no longer any reported manufacture of, 
consumption of, stocks or trade of zipeprol.
    4. Its History and Current Pattern of Abuse: There have been 
numerous

[[Page 28902]]

reports of zipeprol abuse from Brazil, Chile, France, Italy, Mexico, 
the Republic of Korea, Switzerland, and the former Yugoslavia during 
the 1980s and 1990s. These reports suggest the sedative, 
hallucinogenic, and euphorigenic effects of zipeprol, and its ability 
to suppress some signs of opioid withdrawal at high doses, may be the 
reasons for its abuse. It is important to note that the ability of one 
opioid to suppress withdrawal from a different opioid does not 
represent a beneficial effect. Ease of obtaining zipeprol by over-the-
counter access may have contributed to its widespread abuse in some 
countries. Following these reports, many countries in Asia, Europe, and 
South America discontinued medical use of zipeprol. Incidences of 
zipeprol abuse were not reported after placement of zipeprol in 
Schedule II of the 1971 Convention on Psychotropic Substances in 1995 
(CND Dec. 38/2). Queries of DEA's System to Retrieve Information from 
Drug Evidence (STRIDE)/STARLiMS \5\ and the National Forensic 
Laboratory Information System (NFLIS) \6\ databases on October 3, 2018, 
did not generate any reports of zipeprol, suggesting that it is not 
trafficked in the United States.
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    \5\ 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 DEA laboratory drug evidence data 
system of record.
    \6\ 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.
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    5. The Scope, Duration, and Significance of Abuse: The lack of 
abuse and overdose associated with zipeprol is most likely due to its 
lack of availability for medical use in the United States.
    6. What, if any, Risk There is to the Public Health: Currently in 
the United States, zipeprol is not an FDA-approved drug, and there have 
been no reports or epidemiological studies submitted to FDA regarding 
its abuse. In countries where it was available for medical use, 
zipeprol became a significant health problem. Based on the available 
clinical data, zipeprol has the same risks to public health as schedule 
I or schedule II substances. Such risks include deaths due to voluntary 
or accidental acute intoxications and the potential for psychological 
and physical dependence.
    7. Its Psychic or Physiological Dependence Liability: Psychological 
and physiological dependence is associated with zipeprol. Several 
clinical studies examined and described physical dependence and 
withdrawal effects associated with zipeprol abuse. Main signs of 
zipeprol withdrawal include sweating, diarrhea, anxiety, insomnia, 
dyspnea, yawning, and pain. The euphoric and hallucinogenic effects 
associated with zipeprol and other opioid-like drugs serve as 
reinforcers and can result in psychological dependence and are 
supported by case studies with zipeprol abusers.
    8. Whether the Substance is an Immediate Precursor of a Substance 
Already Controlled Under the CSA: DEA and HHS find that zipeprol is not 
an immediate precursor of a substance already controlled under the CSA.
    Conclusion: Based on consideration of the scientific and medical 
evaluation and accompanying recommendation of HHS, and based on DEA's 
consideration of its own eight-factor analysis, DEA finds that these 
facts and all relevant data constitute substantial evidence of 
potential for abuse of zipeprol. As such, DEA hereby proposes to 
schedule zipeprol as a controlled substance under the CSA.

Proposed Determination of Appropriate Schedule

    The CSA establishes five schedules of controlled substances known 
as schedules I, II, III, IV, and V. The CSA also outlines the findings 
required to place a drug or other substance in any particular schedule. 
21 U.S.C. 812(b). After consideration of the analysis and 
recommendation of the Assistant Secretary for Health of the HHS and 
review of all available data, the Acting Administrator of the DEA 
(Acting Administrator), pursuant to 21 U.S.C. 812(b)(1), finds that:
    (1) Zipeprol has a high potential for abuse. Widespread reports of 
zipeprol abuse have occurred in countries that have marketed zipeprol. 
Zipeprol is self-administered in animals and clinical studies reported 
that zipeprol abuse is related to its opioid, sedative, hallucinogenic, 
and euphorigenic effects. Epidemiological reports on zipeprol, 
worldwide, have indicated that adverse reactions (primarily seizures) 
are caused by zipeprol abuse and dependence.
    (2) There are no approved New Drug Applications for zipeprol and no 
known therapeutic applications for zipeprol in the United States.\7\ 
Therefore, zipeprol has no currently accepted medical use in treatment 
in the United States.
---------------------------------------------------------------------------

    \7\ Although there is no evidence suggesting that zipeprol has a 
currently accepted medical use in treatment in the United States, it 
bears noting that a drug cannot be found to have such medical use 
unless DEA concludes that it satisfies a five-part test. 
Specifically, with respect to a drug that has not been approved by 
the FDA, to have a currently accepted medical use in treatment in 
the United States, all of the following must be demonstrated:
     i. the drug's chemistry must be known and reproducible;
     ii. there must be adequate safety studies;
     iii. there must be adequate and well-controlled studies proving 
efficacy;
     iv. the drug must be accepted by qualified experts; and
     v. the scientific evidence must be widely available.
     57 FR 10499 (1992).
---------------------------------------------------------------------------

    (3) There is a lack of accepted safety for use of zipeprol under 
medical supervision. Zipeprol was first approved and introduced as an 
antitussive in France and Italy during the late 1970s. Following 
several reports of abuse and overdosing from zipeprol, this drug was 
withdrawn in the early to mid-1990s.
    Based on these findings, the Acting Administrator concludes that 
zipeprol warrants control in schedule I of the CSA. 21 U.S.C. 
812(b)(1). More precisely, because of its opioid effects, and producing 
opioid-like tolerance and dependence in humans, DEA is proposing to 
place zipeprol in 21 CFR 1308.11(b) (the opiates category of schedule 
I). As such, the proposed control of zipeprol includes the substance as 
well as its isomers, esters, ethers, salts, and salts of isomers, 
esters and ethers, whenever the existence of such isomers, esters, 
ethers and salts is possible within the specific chemical designation.

Requirements for Handling Zipeprol

    If this rule is finalized as proposed, zipeprol would be subject to 
the CSA's schedule I regulatory controls and administrative, civil, and 
criminal sanctions applicable to the manufacture, distribution, reverse 
distribution, import, export, engagement in research, conduct of 
instructional activities or chemical analysis with, and possession of 
schedule I controlled substances, including the following:
    1. Registration. Any person who handles (manufactures, distributes, 
reverse distributes, imports, exports, engages in research, or conducts 
instructional activities or chemical analysis with, or possesses) 
zipeprol, or who desires to handle zipeprol, would need to be 
registered with DEA to conduct such activities pursuant to 21 U.S.C. 
822, 823, 957, 958, and in accordance with 21 CFR parts 1301 and 1312 
as of the effective date of a final scheduling action. Any person who 
currently handles zipeprol, and is not registered with DEA, would need 
to submit an application for registration

[[Page 28903]]

and may not continue to handle zipeprol after the effective date of a 
final scheduling action unless DEA has approved that application for 
registration pursuant to 21 U.S.C. 822, 823, 957, 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 I registration would be required to surrender 
all quantities of currently held zipeprol, or transfer all quantities 
of currently held zipeprol to a person registered with DEA before the 
effective date of a final scheduling action in accordance with all 
applicable federal, state, local, and tribal laws. As of the effective 
date of a final scheduling action, zipeprol would be required to be 
disposed of in accordance with 21 CFR part 1317, in addition to all 
other applicable federal, state, local, and tribal laws.
    3. Security. Zipeprol would be subject to schedule I security 
requirements and would need to be handled and stored pursuant to 21 
U.S.C. 821 and 823, and in accordance with 21 CFR 1301.71-1301.93 as of 
the effective date of a final scheduling action.
    4. Labeling and Packaging. All labels, labeling, and packaging for 
commercial containers of zipeprol would need to be in compliance with 
21 U.S.C. 825 and 958(e), and be in accordance with 21 CFR part 1302 as 
of the effective date of a final scheduling action.
    5. Quota. Only registered manufacturers would be permitted to 
manufacture zipeprol in accordance with a quota assigned pursuant to 21 
U.S.C. 826 and in accordance with 21 CFR part 1303 as of the effective 
date of a final scheduling action.
    6. Inventory. Every DEA registrant who possesses any quantity of 
zipeprol on the effective date of a final scheduling action would be 
required to take an inventory of zipeprol on hand at that time, 
pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 
1304.03, 1304.04, and 1304.11(a) and (d).
    Any person who becomes registered with DEA on or after the 
effective date of the final scheduling action would be required to take 
an initial inventory of all stocks of controlled substances (including 
zipeprol) 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(a) and (b).
    After the initial inventory, every DEA registrant would be required 
to take an inventory of all controlled substances (including zipeprol) 
on hand 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.
    7. Records and Reports. Every DEA registrant would be required to 
maintain records and submit reports pursuant to 21 U.S.C. 827 and 958, 
and in accordance with 21 CFR parts 1304, 1312, and 1317 as of the 
effective date of a final scheduling action. Manufacturers and 
distributors would be required to submit reports regarding zipeprol to 
the Automation of Reports and Consolidated Order System pursuant to 21 
U.S.C. 827 and in accordance with 21 CFR parts 1304 and 1312 as of the 
effective date of a final scheduling action.
    8. Order Forms. Every DEA registrant who distributes zipeprol would 
be required to comply with order form requirements, pursuant to 21 
U.S.C. 828, and in accordance with 21 CFR part 1305 as of the effective 
date of a final scheduling action.
    9. Importation and Exportation. All importation and exportation of 
zipeprol would need to be in compliance with 21 U.S.C. 952, 953, 957, 
and 958, and in accordance with 21 CFR part 1312 as of the effective 
date of a final scheduling action.
    10. Liability. Any activity involving zipeprol 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.

Regulatory Analyses

    Executive Orders 12866, 13563, and 13771, Regulatory Planning and 
Review, Improving Regulation and Regulatory Review, and Reducing 
Regulation and Controlling Regulatory Costs
    In accordance with 21 U.S.C. 811(a), this proposed scheduling 
action is subject to formal rulemaking procedures performed ``on the 
record after opportunity for a hearing,'' which are conducted pursuant 
to the provisions of 5 U.S.C. 556 and 557. The CSA sets forth the 
procedures and criteria for scheduling a drug or other substance. Such 
actions are exempt from review by the Office of Management and Budget 
(OMB) pursuant to section 3(d)(1) of Executive Order 12866 and the 
principles reaffirmed in Executive Order 13563.
    This rulemaking is not an Executive Order 13771 regulatory action 
because this rule is not significant under Executive Order 12866.

Executive Order 12988, Civil Justice Reform

    This proposed regulation meets the applicable standards set forth 
in sections 3(a) and 3(b)(2) of Executive Order 12988, Civil Justice 
Reform, 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 Executive Order 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 Executive Order 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.

Paperwork Reduction Act of 1995

    This action does not impose a new collection of information 
requirement under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3521).

Regulatory Flexibility Act

    The Acting Administrator, in accordance with the Regulatory 
Flexibility Act (RFA), 5 U.S.C. 601-602, has reviewed this proposed 
rule, and by approving it, certifies that it will not have a 
significant economic impact on a substantial number of small entities.
    DEA proposes placing the substance zipeprol (chemical name: 1-
methoxy-3-[4-(2-methoxy-2-phenylethyl)piperazin-1-yl]-1-phenylpropan-2-
ol), including its isomers, esters, ethers, salts, and salts of 
isomers, esters, and ethers, whenever the existence of such isomers, 
esters, ethers and salts is possible, in schedule I of the CSA. This 
action is being taken to enable the United States to meet its 
obligations under the 1971 Convention on Psychotropic Substances. If 
finalized, this action would impose the regulatory controls and 
administrative, civil, and criminal sanctions applicable to schedule I 
controlled substances on persons who handle (manufacture, distribute, 
reverse distribute, import, export, engage in research, conduct 
instructional activities or chemical

[[Page 28904]]

analysis with, or possess), or propose to handle zipeprol.
    According to HHS, zipeprol has a high potential for abuse, has no 
currently accepted medical use in treatment in the United States, and 
lacks accepted safety for use under medical supervision. DEA's research 
confirms that there is no commercial market for zipeprol in the United 
States. Additionally, queries of DEA's STRIDE/STARLiMS and the NFLIS 
databases on October 3, 2018, did not generate any reports of zipeprol, 
suggesting that it is not trafficked in the United States. Therefore, 
DEA estimates that no United States entity currently handles zipeprol 
and does not expect any United States entity to handle zipeprol in the 
foreseeable future. DEA concludes that no United States entity would be 
affected by this rule if finalized. As such, the proposed rule will not 
have a significant effect on a substantial number of small entities.

Unfunded Mandates Reform Act of 1995

    On the basis of information contained in the ``Regulatory 
Flexibility Act'' section above, DEA has determined and certifies 
pursuant to the Unfunded Mandates Reform Act (UMRA) of 1995 (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 annually for inflation) in any 1 year * 
* *.'' Therefore, neither a Small Government Agency Plan nor any other 
action is required under provisions of the UMRA of 1995.

List of Subjects in 21 CFR Part 1308

    Administrative practice and procedure, Drug traffic control, 
Reporting and recordkeeping requirements.
    For the reasons set out above, 21 CFR part 1308 is proposed to be 
amended to read as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
1. The authority citation for 21 CFR 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.  1308.11, add paragraph (b)(71) to read as follows:


Sec.  1308.11  Schedule I.

* * * * *
    (b) * * *

 
 
 
(71) Zipeprol..................................................     9873
 

* * * * *

    Uttam Dhillon,
Acting Administrator.
[FR Doc. 2020-09592 Filed 5-13-20; 8:45 am]
BILLING CODE 4410-09-P