80 FR 69861 - Schedules of Controlled Substances: Placement of Eluxadoline Into Schedule IV
DEPARTMENT OF JUSTICE
Drug Enforcement Administration Federal Register Volume 80, Issue 218 (November 12, 2015)
Drug Enforcement Administration
Federal Register Volume 80, Issue 218 (November 12, 2015)
| Page Range | 69861-69864 | |
| FR Document | 2015-28718 |
[Federal Register Volume 80, Number 218 (Thursday, November 12, 2015)] [Rules and Regulations] [Pages 69861-69864] From the Federal Register Online [www.thefederalregister.org] [FR Doc No: 2015-28718] ======================================================================= ----------------------------------------------------------------------- DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Part 1308 [Docket No. DEA-419F] Schedules of Controlled Substances: Placement of Eluxadoline Into Schedule IV AGENCY: Drug Enforcement Administration, Department of Justice. ACTION: Final rule. ----------------------------------------------------------------------- SUMMARY: With the issuance of this final rule, the Administrator of the Drug Enforcement Administration places the substance 5-[[[(2S)-2-amino- 3-[4-aminocarbonyl)-2,6-dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl- 1H-imidazol-2-yl)ethyl]amino]methyl]-2-methoxybenzoic acid (eluxadoline), including its salts, isomers, and salts of isomers, into schedule IV of the Controlled Substances Act. This scheduling action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after opportunity for a hearing through formal rulemaking. This action imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule IV controlled substances on persons who handle (manufacture, distribute, dispense, import, export, engage in research, conduct instructional activities, or possess) or propose to handle eluxadoline. DATES: Effective date: December 17, 2015. FOR FURTHER INFORMATION CONTACT: John R. Scherbenske, Office of Diversion Control, Drug Enforcement Administration; Mailing Address: 8701 Morrissette Drive, Springfield, Virginia 22152, Telephone: (202) 598-6812. SUPPLEMENTARY INFORMATION: Legal Authority The Drug Enforcement Administration (DEA) implements and enforces titles II and III of the Comprehensive Drug Abuse Prevention and Control Act of 1970, as amended. 21 U.S.C. 801-971. Titles II and III are referred to as the ``Controlled Substances Act'' and the ``Controlled Substances Import and Export Act,'' respectively, and are collectively referred to as the ``Controlled Substances Act'' or the ``CSA'' for the purpose of this action. The DEA publishes the implementing regulations for these statutes in title 21 of the Code of Federal Regulations (CFR), chapter II. The CSA and its implementing regulations are designed to prevent, detect, and eliminate the diversion of controlled substances and listed chemicals into the illicit market while ensuring an adequate supply is available for the legitimate medical, scientific, research, and industrial needs of the United States. Controlled substances have the potential for abuse and dependence and are controlled to protect the public health and safety. Under the CSA, each controlled substance is classified into one of five schedules based upon its potential for abuse, its currently accepted medical use in treatment in the United States, and the degree of dependence the substance may cause. 21 U.S.C. 812. The initial schedules of controlled substances established by Congress are found at 21 U.S.C. 812(c), and the current list of controlled substances is published at 21 CFR part 1308. 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 (A) finds that such drug or other substance has a potential for abuse, and (B) 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 scheduling authority under 21 U.S.C. 811 to the Administrator of the DEA. 28 CFR 0.100. The CSA provides that proceedings for the issuance, amendment, or repeal of the scheduling of any drug or other substance may be initiated by the Attorney General (1) on her own motion; (2) at the request of the Secretary of the Department of Health and Human Services (HHS); \1\ or (3) on the petition of any interested party. 21 U.S.C. 811(a). This action was initiated at the request of the Assistant Secretary of the HHS and imposes the regulatory controls and administrative, civil, and criminal sanctions applicable to controlled substances, including those specific to schedule IV controlled substances, on persons who handle or propose to handle eluxadoline. --------------------------------------------------------------------------- \1\ As set forth 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 the HHS in carrying out the Secretary's scheduling responsibilities under the CSA, with the concurrence of NIDA. 50 FR 9518, Mar. 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. Accordingly, all subsequent references to ``Secretary'' have been replaced with ``Assistant Secretary.'' --------------------------------------------------------------------------- Background Eluxadoline (5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6- dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2- yl)ethyl]amino]methyl]-2-methoxybenzoic acid), is a new molecular entity with central nervous system opioid properties. Eluxadoline has mixed mu opioid receptor (MOR) and kappa opioid receptor (KOR) agonist and delta opioid receptor (DOR) antagonist properties. The Food and Drug Administration (FDA) approved eluxadoline (brand name ``VIBERZI'') as a prescription drug for the treatment of irritable bowel syndrome with diarrhea (IBS-D) on May 27, 2015. DEA and HHS Eight Factor Analyses On May 5, 2015, the HHS provided the DEA with a scientific and medical evaluation document prepared by the FDA entitled ``Basis for the Recommendation to Place Eluxadoline in Schedule IV of the Controlled Substances Act.'' After considering the eight factors in 21 U.S.C. 811(c), including consideration of the substance's abuse potential, legitimate medical use, and dependence liability, the Assistant Secretary of the HHS recommended that eluxadoline be controlled in schedule IV of the CSA. In response, the DEA completed its own eight-factor analysis of eluxadoline. Both the DEA and HHS analyses and other relevant documents are available in their entirety in the public docket of this rule (Docket Number DEA-419) at http://www.regulations.gov under ``Supporting Documents.'' \2\ --------------------------------------------------------------------------- \2\ Although the published notice of proposed rulemaking stated that such items had been placed into the docket on regulations.gov, the Administration discovered in preparing this final rule that the HHS analysis had in fact not been posted. However, that document was available for review at DEA. The DEA posted the cited analysis to regulations.gov upon discovery of the error. --------------------------------------------------------------------------- Determination to Schedule Eluxadoline After a review of the available data, including the scientific and medical evaluation and the scheduling recommendation from the HHS, the Administrator of the DEA published in the Federal Register a notice of proposed rulemaking (NPRM) entitled ``Schedules of Controlled Substances: Placement of Eluxadoline into Schedule [[Page 69862]] IV'' which proposed placement of eluxadoline in schedule IV of the CSA. 80 FR 48044, August 11, 2015. The proposed rule provided an opportunity for interested persons to file a request for hearing in accordance with DEA regulations by September 10, 2015. No requests for such a hearing were received by the DEA. The NPRM also provided an opportunity for interested persons to submit written comments on the proposal on or before September 10, 2015. Comments Received The DEA received two comments on the proposed rule to schedule eluxadoline. One commenter supported controlling eluxadoline as a schedule IV controlled substance. One commenter opposed the control of eluxadoline as a schedule IV substance, and suggested it be controlled as a schedule V substance instead. Support for the Proposed Rule. One commenter agreed with the DEA's proposal to control eluxadoline as a schedule IV controlled substance, and stated that the public health (specifically, an unmet medical need) necessitates an immediate effective date for the final order controlling eluxadoline. DEA Response. The DEA appreciates the comment in support of this rulemaking. Generally, DEA scheduling actions are effective 30 days from the date of publication of the final rule in the Federal Register. 21 CFR 1308.45; see also 5 U.S.C. 553(d). The DEA believes that providing 30 days for this rule to become effective is both expeditious and sufficient to allow handlers to comply with regulatory requirements for handling Schedule IV controlled substances. Both the HHS' and the DEA's scientific and medical analyses, the data collectively suggest that eluxadoline does have sufficient abuse potential and the DEA does not agree that eluxadoline's effective date should be the date of publication of the final rule. Opposition to the Proposed Rule. One commenter opposed the proposal to control eluxadoline as a schedule IV controlled substance, stating ``I do not think that eluxadoline meets the factor [5] requirements for scheduling under schedule IV due to there being no general widespread use throughout other countries.'' The commenter also stated that the best approach would be to place eluxadoline in schedule V, rather than schedule IV. DEA Response. Although eluxadoline is a new chemical entity and information on actual abuse is not currently available, there is a sufficient factual basis to meet the requirements of Factor 5 (the scope, duration, and significance of abuse). The legislative history of the CSA provides guidance regarding the assessment of a new drug's potential for abuse. The legislative history of the CSA provides that a substance may have a potential for abuse if: ``The drug or drugs containing such a substance are new drugs so related in their action to a drug or drugs already listed as having a potential for abuse to make it likely that the drug will have the same potentiality for abuse as such drugs, thus making it reasonable to assume that there may be significant diversions from legitimate channels, significant use contrary to or without medical advice, or that it has a substantial capability of creating hazards to the health of the user or to the safety of the community.'' Comprehensive Drug Abuse Prevention and Control Act of 1970, H.R. Rep. No. 91-1444 (1970); as reprinted in 1970 U.S.C.C.A.N. 4566, 4601. As discussed in the HHS and the DEA eight- factor analyses, both pre-clinical and clinical studies indicate eluxadoline shares pharmacological similarities with schedule IV drugs such as butorphanol and pentazocine and has similar abuse potential. In addition, the HHS and DEA eight-factor analyses support the finding that the overall abuse potential of eluxadoline is comparable to schedule IV substances such as pentazocine and butorphanol. This indicates that placement in schedule IV is appropriate rather than schedule V. Scheduling Conclusion Based on consideration of all comments, the scientific and medical evaluation and accompanying recommendation of the HHS, and the DEA's consideration of its own eight-factor analysis, the Administrator finds that these facts and all relevant data demonstrate substantial evidence of potential for abuse of eluxadoline. As such, the DEA is scheduling eluxadoline as a controlled substance under the CSA. Determination of Appropriate Schedule The CSA establishes five schedules of controlled substances known as schedules I, II, III, IV, and V. The CSA outlines the findings required for placing 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 Administrator of the DEA, pursuant to 21 U.S.C. 812(b)(4), finds that: (1) 5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6-dimethylphenyl]-1- oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2- methoxybenzoic acid (eluxadoline) has a low potential for abuse relative to the drugs or other substances in schedule III. The overall abuse potential of eluxadoline is comparable to schedule IV substances such as pentazocine and butorphanol; (2) 5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6-dimethylphenyl]-1- oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino]methyl]-2- methoxybenzoic acid (eluxadoline) has a currently accepted medical use in treatment in the United States. Recently, the FDA approved eluxadoline as a prescription drug for the treatment of IBS-D. Therefore, eluxadoline has a currently accepted medical use in treatment in the United States; and (3) Abuse of 5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6- dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2- yl)ethyl]amino]methyl]-2-methoxybenzoic acid (eluxadoline) may lead to limited psychological dependence similar to that of schedule IV drugs, but less than that of schedule III drugs. Based on these findings, the Administrator of the DEA concludes that eluxadoline, including its salts, isomers, and salts of isomers, warrants control in schedule IV of the CSA. 21 U.S.C. 812(b)(4). Requirements for Handling Eluxadoline Upon the effective date of this final rule, any person who handles eluxadoline is subject to the CSA's schedule IV regulatory controls and administrative, civil, and criminal sanctions applicable to the manufacture, distribution, dispensing, importing, exporting, engagement in research, and conduct of instructional activities, of schedule IV controlled substances including the following: 1. Registration. Any person who handles (manufactures, distributes, dispenses, imports, exports, engages in research, or conducts instructional activities with) eluxadoline, or who desires to handle eluxadoline, must be registered with the 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 as of December 14, 2015. Any person who currently handles eluxadoline and is not registered with the DEA must submit an application for registration and may not continue to handle eluxadoline as of December 14, 2015 unless the DEA has approved that application, pursuant to 21 U.S.C. 822, 823, 957, and 958, and [[Page 69863]] in accordance with 21 CFR parts 1301 and 1312. 2. Security. Eluxadoline is subject to schedule III-V security requirements and must be handled and stored pursuant to 21 U.S.C. 823 and in accordance with 21 CFR 1301.71-1301.93, as of December 14, 2015. 3. Labeling and Packaging. All labels, labeling, and packaging for commercial containers of eluxadoline must comply with 21 U.S.C. 825 and 958(e) and be in accordance with 21 CFR part 1302, as of December 14, 2015. 4. Inventory. Every DEA registrant who possesses any quantity of eluxadoline on the effective date of this final rule must take an inventory of all stocks of eluxadoline on hand as of December 14, 2015, pursuant to 21 U.S.C. 827 and 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11(a), (d), and (e). Any person who becomes registered with the DEA after November 12, 2015 must take an initial inventory of all stocks of controlled substances (including eluxadoline) 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), (b), and (e). After the initial inventory, every DEA registrant must take a new inventory of all stocks of controlled substances (including eluxadoline) 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. 5. Records. All DEA registrants must maintain records with respect to eluxadoline pursuant to 21 U.S.C. 827 and 958(e), and in accordance with 21 CFR parts 1304 and 1312 and Sec. 1307.11, as of December 14, 2015. 6. Prescriptions. All prescriptions for eluxadoline or products containing eluxadoline must comply with 21 U.S.C. 829, and be issued in accordance with 21 CFR part 1306 and subpart C of 21 CFR part 1311 as of December 14, 2015. 7. Importation and Exportation. All importation and exportation of eluxadoline must be in compliance with 21 U.S.C. 952, 953, 957, and 958, and be in accordance with 21 CFR part 1312 as of December 14, 2015. 8. Liability. Any activity involving eluxadoline not authorized by, or in violation of, the CSA, occurring as of December 14, 2015 is unlawful, and may subject the person to administrative, civil, and/or criminal proceedings. Regulatory Analyses Executive Orders 12866 and 13563 In accordance with 21 U.S.C. 811(a), this scheduling action is subject to formal rulemaking procedures done ``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 criteria for scheduling a drug or other substance. Such actions are exempt from review by the Office of Management and Budget pursuant to section 3(d)(1) of Executive Order 12866 and the principles reaffirmed in Executive Order 13563. Executive Order 12988 This 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 This rulemaking does not have federalism implications warranting the application of Executive Order 13132. The 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 This rule does not have tribal implications warranting the application of Executive Order 13175. The rule 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 final rule and by approving it certifies that it will not have a significant economic impact on a substantial number of small entities. The purpose of this final rule is to place eluxadoline, including its salts, isomers, and salts of isomers, into schedule IV of the CSA. No less restrictive measures (i.e., non-control, or control in schedule V) enable the DEA to meet its statutory obligations under the CSA. In preparing this certification, the DEA has assessed economic impact by size category and has considered costs with respect to the various DEA registrant business activity classes. Eluxadoline is a new molecular entity which has not yet been marketed in the United States or any other country. The DEA has no basis to determine the level of contracted or outsourced manufacturing activities or the breadth of the distribution network. Furthermore, due to the wide variety of unidentifiable and unquantifiable variables that could potentially influence the dispensing and distribution rates of new pharmaceutical drugs, the DEA is unable to determine the number of potential small entities that might handle eluxadoline. However, the DEA estimates that all persons who would handle, or propose to handle, eluxadoline are currently registered with the DEA to handle schedule IV controlled substances, because it is a pharmaceutical controlled substance intended for medical treatment. Accordingly, the number of DEA registrations authorized to handle schedule IV controlled substances is a reasonable estimate for the maximum number of eluxadoline handlers. Therefore, the DEA estimates that 1.6 million (1,554,254 as of June 2015) controlled substance registrations, representing approximately 427,584 entities, would be the maximum number of entities affected by this final rule. The DEA estimates that 418,141 (97.8%) of 427,584 affected entities are ``small entities'' in accordance with the RFA and SBA size standards. The DEA anticipates that prospective eluxadoline handlers already handle other schedule IV controlled substances and that the cost impact as a result of placing eluxadoline in schedule IV would be nominal. As the anticipated eluxadoline handlers already handle other schedule IV controlled substances, they already have DEA registrations and the required security and recordkeeping processes, equipment, and facilities in place, and would only require a nominal increase in security, inventory, recordkeeping and labeling costs. As discussed above, while the DEA does not have a basis to estimate the number of affected entities, the DEA estimates that the maximum number of affected entities is 427,584 of which 418,141 are estimated to be small entities. Since the affected entities are expected to handle other schedule IV controlled substances and maintain security and recordkeeping facilities and processes consistent with schedule IV controlled substances, the DEA estimates any economic impact will be nominal. Because of these facts, this final rule will not result in a significant economic [[Page 69864]] impact on a substantial number of small entities. Unfunded Mandates Reform Act of 1995 The DEA has determined and certifies pursuant to 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 requirement 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. Congressional Review Act This rule is not a major rule as defined by section 804 of the Small Business Regulatory Enforcement Fairness Act of 1996 (Congressional Review Act (CRA)). This rule will not result in: an annual effect on the economy of $100,000,000 or more; a major increase in costs or prices for consumers, individual industries, Federal, State, or local government agencies, or geographic regions; or significant adverse effects on competition, employment, investment, productivity, innovation, or on the ability of United States-based companies to compete with foreign-based companies in domestic and export markets. However, pursuant to the CRA, the DEA has submitted a copy of this final rule to both Houses of Congress and to the Comptroller General. Administrative Procedure Act The APA requires the publication of a substantive rule to be made not less than 30 days before its effective date. 5 U.S.C. 553(d). However, one exception is ``as otherwise provided by the agency for good cause found and published with the rule.'' As fully discussed above in response to the comment suggesting an immediate effective date, an immediate effective date is necessary in this case because there are limited therapeutic options currently available to patients with IBS-D and the eluxadoline NDA received priority review with FDA. Therefore, it is unnecessary to delay the effective date of this final rule by 30 days, and this rule shall take effect immediately upon publication. 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 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), unless otherwise noted. 0 2. Amend Sec. 1308.14 by adding paragraph (g)(3) to read as follows: Sec. 1308.14 Schedule IV. * * * * * (g) * * * (3) Eluxadoline (5-[[[(2S)-2-amino-3-[4-aminocarbonyl)-2,6- dimethylphenyl]-1-oxopropyl][(1S)-1-(4-phenyl-1H-imidazol-2- yl)ethyl]amino]methyl]-2-methoxybenzoic acid) (including its optical isomers) and its salts, isomers, and salts of isomers (9725). Dated: November 5, 2015. Chuck Rosenberg, Acting Administrator. [FR Doc. 2015-28718 Filed 11-10-15; 8:45 am] BILLING CODE P
![Federal Register / Vol. 80, No. 218 / Thursday, November 12, 2015 / Rules and Regulations 69861
Dated: November 5, 2015. respectively, and are collectively at the request of the Assistant Secretary
Kevin J. Wolf, referred to as the ‘‘Controlled of the HHS and imposes the regulatory
Assistant Secretary for Export Substances Act’’ or the ‘‘CSA’’ for the controls and administrative, civil, and
Administration. purpose of this action. The DEA criminal sanctions applicable to
[FR Doc. 2015–28552 Filed 11–10–15; 8:45 am] publishes the implementing regulations controlled substances, including those
BILLING CODE 3510–33–P for these statutes in title 21 of the Code specific to schedule IV controlled
of Federal Regulations (CFR), chapter II. substances, on persons who handle or
The CSA and its implementing propose to handle eluxadoline.
DEPARTMENT OF JUSTICE regulations are designed to prevent,
Background
detect, and eliminate the diversion of
Drug Enforcement Administration controlled substances and listed Eluxadoline (5-[[[(2S)-2-amino-3-[4-
chemicals into the illicit market while aminocarbonyl)-2,6-dimethylphenyl]-1-
21 CFR Part 1308 ensuring an adequate supply is available oxopropyl][(1S)-1-(4-phenyl-1H-
for the legitimate medical, scientific, imidazol-2-yl)ethyl]amino]methyl]-2-
[Docket No. DEA–419F] methoxybenzoic acid), is a new
research, and industrial needs of the
Schedules of Controlled Substances: United States. Controlled substances molecular entity with central nervous
Placement of Eluxadoline Into have the potential for abuse and system opioid properties. Eluxadoline
Schedule IV dependence and are controlled to has mixed mu opioid receptor (MOR)
protect the public health and safety. and kappa opioid receptor (KOR)
AGENCY: Drug Enforcement Under the CSA, each controlled agonist and delta opioid receptor (DOR)
Administration, Department of Justice. substance is classified into one of five antagonist properties. The Food and
ACTION: Final rule. schedules based upon its potential for Drug Administration (FDA) approved
abuse, its currently accepted medical eluxadoline (brand name ‘‘VIBERZI’’) as
SUMMARY: With the issuance of this final use in treatment in the United States, a prescription drug for the treatment of
rule, the Administrator of the Drug and the degree of dependence the irritable bowel syndrome with diarrhea
Enforcement Administration places the substance may cause. 21 U.S.C. 812. The (IBS–D) on May 27, 2015.
substance 5-[[[(2S)-2-amino-3-[4- initial schedules of controlled
aminocarbonyl)-2,6-dimethylphenyl]-1- DEA and HHS Eight Factor Analyses
substances established by Congress are
oxopropyl][(1S)-1-(4-phenyl-1H- found at 21 U.S.C. 812(c), and the On May 5, 2015, the HHS provided
imidazol-2-yl)ethyl]amino]methyl]-2- current list of controlled substances is the DEA with a scientific and medical
methoxybenzoic acid (eluxadoline), published at 21 CFR part 1308. evaluation document prepared by the
including its salts, isomers, and salts of Pursuant to 21 U.S.C. 811(a)(1), the FDA entitled ‘‘Basis for the
isomers, into schedule IV of the Attorney General may, by rule, ‘‘add to Recommendation to Place Eluxadoline
Controlled Substances Act. This such a schedule or transfer between in Schedule IV of the Controlled
scheduling action is pursuant to the such schedules any drug or other Substances Act.’’ After considering the
Controlled Substances Act which substance if he (A) finds that such drug eight factors in 21 U.S.C. 811(c),
requires that such actions be made on or other substance has a potential for including consideration of the
the record after opportunity for a abuse, and (B) makes with respect to substance’s abuse potential, legitimate
hearing through formal rulemaking. such drug or other substance the medical use, and dependence liability,
This action imposes the regulatory findings prescribed by [21 U.S.C. 812(b)] the Assistant Secretary of the HHS
controls and administrative, civil, and for the schedule in which such drug is recommended that eluxadoline be
criminal sanctions applicable to to be placed * * *.’’ The Attorney controlled in schedule IV of the CSA. In
schedule IV controlled substances on General has delegated scheduling response, the DEA completed its own
persons who handle (manufacture, authority under 21 U.S.C. 811 to the eight-factor analysis of eluxadoline.
distribute, dispense, import, export, Administrator of the DEA. 28 CFR Both the DEA and HHS analyses and
engage in research, conduct 0.100. other relevant documents are available
instructional activities, or possess) or The CSA provides that proceedings in their entirety in the public docket of
propose to handle eluxadoline. for the issuance, amendment, or repeal this rule (Docket Number DEA–419) at
DATES: Effective date: December 17, of the scheduling of any drug or other http://www.regulations.gov under
2015. substance may be initiated by the ‘‘Supporting Documents.’’ 2
FOR FURTHER INFORMATION CONTACT: John Attorney General (1) on her own
Determination to Schedule Eluxadoline
R. Scherbenske, Office of Diversion motion; (2) at the request of the
Secretary of the Department of Health After a review of the available data,
Control, Drug Enforcement
and Human Services (HHS); 1 or (3) on including the scientific and medical
Administration; Mailing Address: 8701
the petition of any interested party. 21 evaluation and the scheduling
Morrissette Drive, Springfield, Virginia
U.S.C. 811(a). This action was initiated recommendation from the HHS, the
22152, Telephone: (202) 598–6812.
Administrator of the DEA published in
SUPPLEMENTARY INFORMATION: 1 As set forth in a memorandum of understanding the Federal Register a notice of
Legal Authority entered into by the Food and Drug Administration proposed rulemaking (NPRM) entitled
(FDA) and the National Institute on Drug Abuse ‘‘Schedules of Controlled Substances:
The Drug Enforcement (NIDA), the FDA acts as the lead agency within the
HHS in carrying out the Secretary’s scheduling Placement of Eluxadoline into Schedule
Administration (DEA) implements and
mstockstill on DSK4VPTVN1PROD with RULES
responsibilities under the CSA, with the
enforces titles II and III of the concurrence of NIDA. 50 FR 9518, Mar. 8, 1985. 2 Although the published notice of proposed
Comprehensive Drug Abuse Prevention The Secretary of the HHS has delegated to the rulemaking stated that such items had been placed
and Control Act of 1970, as amended. 21 Assistant Secretary for Health of the HHS the into the docket on regulations.gov, the
U.S.C. 801–971. Titles II and III are authority to make domestic drug scheduling Administration discovered in preparing this final
recommendations. 58 FR 35460, July 1, 1993. rule that the HHS analysis had in fact not been
referred to as the ‘‘Controlled Accordingly, all subsequent references to posted. However, that document was available for
Substances Act’’ and the ‘‘Controlled ‘‘Secretary’’ have been replaced with ‘‘Assistant review at DEA. The DEA posted the cited analysis
Substances Import and Export Act,’’ Secretary.’’ to regulations.gov upon discovery of the error.
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IV’’ which proposed placement of factual basis to meet the requirements of (1) 5-[[[(2S)-2-amino-3-[4-
eluxadoline in schedule IV of the CSA. Factor 5 (the scope, duration, and aminocarbonyl)-2,6-dimethylphenyl]-1-
80 FR 48044, August 11, 2015. The significance of abuse). The legislative oxopropyl][(1S)-1-(4-phenyl-1H-
proposed rule provided an opportunity history of the CSA provides guidance imidazol-2-yl)ethyl]amino]methyl]-2-
for interested persons to file a request regarding the assessment of a new methoxybenzoic acid (eluxadoline) has
for hearing in accordance with DEA drug’s potential for abuse. The a low potential for abuse relative to the
regulations by September 10, 2015. No legislative history of the CSA provides drugs or other substances in schedule
requests for such a hearing were that a substance may have a potential III. The overall abuse potential of
received by the DEA. The NPRM also for abuse if: ‘‘The drug or drugs eluxadoline is comparable to schedule
provided an opportunity for interested containing such a substance are new IV substances such as pentazocine and
persons to submit written comments on drugs so related in their action to a drug butorphanol;
the proposal on or before September 10, or drugs already listed as having a (2) 5-[[[(2S)-2-amino-3-[4-
2015. potential for abuse to make it likely that aminocarbonyl)-2,6-dimethylphenyl]-1-
the drug will have the same potentiality oxopropyl][(1S)-1-(4-phenyl-1H-
Comments Received imidazol-2-yl)ethyl]amino]methyl]-2-
for abuse as such drugs, thus making it
The DEA received two comments on reasonable to assume that there may be methoxybenzoic acid (eluxadoline) has
the proposed rule to schedule significant diversions from legitimate a currently accepted medical use in
eluxadoline. One commenter supported channels, significant use contrary to or treatment in the United States. Recently,
controlling eluxadoline as a schedule IV without medical advice, or that it has a the FDA approved eluxadoline as a
controlled substance. One commenter substantial capability of creating prescription drug for the treatment of
opposed the control of eluxadoline as a hazards to the health of the user or to IBS–D. Therefore, eluxadoline has a
schedule IV substance, and suggested it the safety of the community.’’ currently accepted medical use in
be controlled as a schedule V substance Comprehensive Drug Abuse Prevention treatment in the United States; and
instead. and Control Act of 1970, H.R. Rep. No. (3) Abuse of 5-[[[(2S)-2-amino-3-[4-
Support for the Proposed Rule. One 91–1444 (1970); as reprinted in 1970 aminocarbonyl)-2,6-dimethylphenyl]-1-
commenter agreed with the DEA’s U.S.C.C.A.N. 4566, 4601. As discussed oxopropyl][(1S)-1-(4-phenyl-1H-
proposal to control eluxadoline as a in the HHS and the DEA eight-factor imidazol-2-yl)ethyl]amino]methyl]-2-
schedule IV controlled substance, and analyses, both pre-clinical and clinical methoxybenzoic acid (eluxadoline) may
stated that the public health studies indicate eluxadoline shares lead to limited psychological
(specifically, an unmet medical need) pharmacological similarities with dependence similar to that of schedule
necessitates an immediate effective date schedule IV drugs such as butorphanol IV drugs, but less than that of schedule
for the final order controlling and pentazocine and has similar abuse III drugs.
eluxadoline. potential. Based on these findings, the
DEA Response. The DEA appreciates In addition, the HHS and DEA eight- Administrator of the DEA concludes
the comment in support of this factor analyses support the finding that that eluxadoline, including its salts,
rulemaking. Generally, DEA scheduling the overall abuse potential of isomers, and salts of isomers, warrants
actions are effective 30 days from the eluxadoline is comparable to schedule control in schedule IV of the CSA. 21
date of publication of the final rule in IV substances such as pentazocine and U.S.C. 812(b)(4).
the Federal Register. 21 CFR 1308.45; butorphanol. This indicates that
see also 5 U.S.C. 553(d). The DEA Requirements for Handling Eluxadoline
placement in schedule IV is appropriate
believes that providing 30 days for this rather than schedule V. Upon the effective date of this final
rule to become effective is both rule, any person who handles
expeditious and sufficient to allow Scheduling Conclusion eluxadoline is subject to the CSA’s
handlers to comply with regulatory Based on consideration of all schedule IV regulatory controls and
requirements for handling Schedule IV comments, the scientific and medical administrative, civil, and criminal
controlled substances. Both the HHS’ evaluation and accompanying sanctions applicable to the manufacture,
and the DEA’s scientific and medical recommendation of the HHS, and the distribution, dispensing, importing,
analyses, the data collectively suggest DEA’s consideration of its own eight- exporting, engagement in research, and
that eluxadoline does have sufficient factor analysis, the Administrator finds conduct of instructional activities, of
abuse potential and the DEA does not that these facts and all relevant data schedule IV controlled substances
agree that eluxadoline’s effective date demonstrate substantial evidence of including the following:
should be the date of publication of the potential for abuse of eluxadoline. As 1. Registration. Any person who
final rule. such, the DEA is scheduling eluxadoline handles (manufactures, distributes,
Opposition to the Proposed Rule. One as a controlled substance under the dispenses, imports, exports, engages in
commenter opposed the proposal to CSA. research, or conducts instructional
control eluxadoline as a schedule IV activities with) eluxadoline, or who
controlled substance, stating ‘‘I do not Determination of Appropriate Schedule desires to handle eluxadoline, must be
think that eluxadoline meets the factor The CSA establishes five schedules of registered with the DEA to conduct such
[5] requirements for scheduling under controlled substances known as activities, pursuant to 21 U.S.C. 822,
schedule IV due to there being no schedules I, II, III, IV, and V. The CSA 823, 957, and 958, and in accordance
general widespread use throughout outlines the findings required for with 21 CFR parts 1301 and 1312 as of
other countries.’’ The commenter also placing a drug or other substance in any December 14, 2015. Any person who
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stated that the best approach would be particular schedule. 21 U.S.C. 812(b). currently handles eluxadoline and is not
to place eluxadoline in schedule V, After consideration of the analysis and registered with the DEA must submit an
rather than schedule IV. recommendation of the Assistant application for registration and may not
DEA Response. Although eluxadoline Secretary for Health of the HHS and continue to handle eluxadoline as of
is a new chemical entity and review of all available data, the December 14, 2015 unless the DEA has
information on actual abuse is not Administrator of the DEA, pursuant to approved that application, pursuant to
currently available, there is a sufficient 21 U.S.C. 812(b)(4), finds that: 21 U.S.C. 822, 823, 957, and 958, and
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![69864 Federal Register / Vol. 80, No. 218 / Thursday, November 12, 2015 / Rules and Regulations
impact on a substantial number of small to patients with IBS–D and the obligations and expenditures of funds
entities. eluxadoline NDA received priority for each specific fiscal year grant, rather
review with FDA. Therefore, it is than track such information
Unfunded Mandates Reform Act of 1995
unnecessary to delay the effective date cumulatively. In order to effectively
The DEA has determined and certifies of this final rule by 30 days, and this implement this accounting change,
pursuant to the Unfunded Mandates rule shall take effect immediately upon changes are needed to the regulations
Reform Act of 1995 (UMRA), 2 U.S.C. publication. applicable to affected grants, such as the
1501 et seq., that this action would not program-specific regulations,
result in any Federal mandate that may List of Subjects in 21 CFR Part 1308
consolidated plan regulations, and
result ‘‘in the expenditure by State, Administrative practice and methods to calculate the cap on
local, and tribal governments, in the procedure, Drug traffic control, administrative and planning expenses.
aggregate, or by the private sector, of Reporting and recordkeeping While amending these regulations to
$100,000,000 or more (adjusted for requirements. conform to and support this accounting
inflation) in any one year * * *’’ For the reasons set out above, 21 CFR practice in applicable regulations, HUD
Therefore, neither a Small Government part 1308 is amended to read as follows: is also making certain grammatical and
Agency Plan nor any other action is other technical corrections in those
required under provisions of UMRA. PART 1308—SCHEDULES OF regulations.
Paperwork Reduction Act of 1995 CONTROLLED SUBSTANCES DATES: Effective date: December 14,
This action does not impose a new ■ 1. The authority citation for 21 CFR 2015.
collection of information requirement Comment due date: January 11, 2016.
part 1308 continues to read as follows:
under the Paperwork Reduction Act of ADDRESSES: Interested persons are
Authority: 21 U.S.C. 811, 812, 871(b), invited to submit comments regarding
1995. 44 U.S.C. 3501–3521. This action unless otherwise noted.
would not impose recordkeeping or this interim rule. Communications must
reporting requirements on State or local ■ 2. Amend § 1308.14 by adding refer to the above docket number and
governments, individuals, businesses, or paragraph (g)(3) to read as follows: title. There are two methods for
organizations. An agency may not submitting public comments. All
§ 1308.14 Schedule IV.
conduct or sponsor, and a person is not submissions must refer to the above
* * * * * docket number and title.
required to respond to, a collection of
(g) * * * 1. Submission of Comments by Mail.
information unless it displays a
(3) Eluxadoline (5-[[[(2S)-2-amino-3- Comments may be submitted by mail to
currently valid OMB control number.
[4-aminocarbonyl)-2,6-dimethylphenyl]- the Regulations Division, Office of
Congressional Review Act 1-oxopropyl][(1S)-1-(4-phenyl-1H- General Counsel, Department of
This rule is not a major rule as imidazol-2-yl)ethyl]amino]methyl]-2- Housing and Urban Development, 451
defined by section 804 of the Small methoxybenzoic acid) (including its 7th Street SW., Room 10276,
Business Regulatory Enforcement optical isomers) and its salts, isomers, Washington, DC 20410–0500.
Fairness Act of 1996 (Congressional and salts of isomers (9725). 2. Electronic Submission of
Review Act (CRA)). This rule will not Dated: November 5, 2015. Comments. Interested persons may
result in: an annual effect on the Chuck Rosenberg, submit comments electronically through
economy of $100,000,000 or more; a Acting Administrator.
the Federal eRulemaking Portal at
major increase in costs or prices for www.regulations.gov. HUD strongly
[FR Doc. 2015–28718 Filed 11–10–15; 8:45 am]
consumers, individual industries, encourages commenters to submit
BILLING CODE P
Federal, State, or local government comments electronically. Electronic
agencies, or geographic regions; or submission of comments allows the
significant adverse effects on commenter maximum time to prepare
competition, employment, investment, DEPARTMENT OF HOUSING AND and submit a comment, ensures timely
productivity, innovation, or on the URBAN DEVELOPMENT receipt by HUD, and enables HUD to
ability of United States-based make them immediately available to the
24 CFR Parts 91 and 570 public. Comments submitted
companies to compete with foreign-
based companies in domestic and [Docket No. FR 5797–I–01] electronically through the
export markets. However, pursuant to www.regulations.gov Web site can be
RIN 2506–AC39 viewed by other commenters and
the CRA, the DEA has submitted a copy
of this final rule to both Houses of interested members of the public.
Changes to Accounting Requirements
Congress and to the Comptroller Commenters should follow the
for the Community Development Block
General. instructions provided on that site to
Grants (CDBG) Program
submit comments electronically.
Administrative Procedure Act AGENCY: Office of the Assistant Note: To receive consideration as public
The APA requires the publication of Secretary for Community Planning and comments, comments must be submitted
a substantive rule to be made not less Development, HUD. through one of the two methods specified
than 30 days before its effective date. 5 ACTION: Interim final rule.
above. Again, all submissions must refer to
U.S.C. 553(d). However, one exception the docket number and title of the rule.
is ‘‘as otherwise provided by the agency SUMMARY: This rule makes several No Facsimile Comments. Facsimile
mstockstill on DSK4VPTVN1PROD with RULES
for good cause found and published changes to the existing Community (fax) comments are not acceptable.
with the rule.’’ As fully discussed above Development Block Grant (CDBG) Public Inspection of Public
in response to the comment suggesting program regulations in order to better Comments. All properly submitted
an immediate effective date, an track the use of grant funds and improve comments and communications
immediate effective date is necessary in accounting procedures in the program. submitted to HUD will be available for
this case because there are limited Through this rule, HUD requires public inspection and copying between
therapeutic options currently available grantees to commence tracking the 8 a.m. and 5 p.m., weekdays, at the
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Document Created: 2015-12-14 14:53:40
Document Modified: 2015-12-14 14:53:40
| Category | Regulatory Information | |
| Collection | Federal Register | |
| sudoc Class | AE 2.7: GS 4.107: AE 2.106: | |
| Publisher | Office of the Federal Register, National Archives and Records Administration | |
| Section | Rules and Regulations | |
| Action | Final rule. | |
| Contact | John R. Scherbenske, Office of | |
| FR Citation | 80 FR 69861 | |
| CFR Associated | Administrative Practice and Procedure; Drug Traffic Control and Reporting and Recordkeeping Requirements |
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