Rules - 2005
FR Doc 05-9634 [Federal Register: May 13, 2005 (Volume 70, Number 92)] [Proposed Rules] [Page 25502-25505] From the Federal Register Online via GPO Access [wais.access.gpo.gov] [DOCID:fr13my05-15]
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-267P]
Schedules of Controlled Substances: Placement of Pregabalin into Schedule V
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
SUMMARY: This proposed rule is issued by the Deputy Administrator of the Drug Enforcement Administration (DEA) to place the substance pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid], including its salts, and all products containing pregabalin into Schedule V of the Controlled Substances Act (CSA). This proposed action is based on a recommendation from the Acting Assistant Secretary for Health of the Department of Health and Human Services (DHHS) and on an evaluation of the relevant data by DEA. If finalized, this action will impose the regulatory controls and criminal sanctions applicable to Schedule V non-narcotics on those who handle pregabalin and products containing pregabalin.
DATES: Written comments must be postmarked, and electronic comments must be sent, on or before June 13, 2005.
ADDRESSES: To ensure proper handling of comments, please reference "Docket No. DEA-267P" on all written and electronic correspondence. Written comments being sent via regular mail should be sent to the Deputy Administrator, Drug Enforcement Administration, Washington, DC 20537, Attention: DEA Federal Register Representative/ODL. Written comments sent via express mail should be sent to the Deputy Administrator, Drug Enforcement Administration, Attention: DEA Federal Register Representative/ODL, 2401 Jefferson-Davis Highway, Alexandria, VA 22301. Comments may be directly sent to DEA electronically by sending an electronic message to firstname.lastname@example.org. Comments may also be sent electronically through http://www.regulations.gov using the electronic comment form provided on that site. An electronic copy of this document is also available at the http://www.regulations.gov website. DEA will accept electronic comments containing MS Word, WordPerfect, Adobe PDF, or Excel file formats only. DEA will not accept any file format other than those specifically listed here.
FOR FURTHER INFORMATION CONTACT: Christine Sannerud, Ph.D., Chief, Drug and Chemical Evaluation Section, Drug Enforcement Administration, Washington, DC 20537, (202) 307-7183.
Note Regarding This Scheduling Action
In accordance with the provisions of the Controlled Substances Act (21 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. 556 and 557). Interested persons are invited to submit their comments, objections or requests for a hearing with regard to this proposal. Requests for a hearing should be made in accordance with 21 CFR 1308.44 and should state, with particularity, the issues concerning which the person desires to be heard. All correspondence regarding this matter should be submitted to the Drug Enforcement Administration using the address information provided above.
On December 31, 2004, the Food and Drug Administration (FDA) approved pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] for marketing under the trade name LyricaTM. LyricaTM will be marketed in the United States as a prescription drug product for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN). Pregabalin has recently been placed on the market in some European countries for the treatment of epilepsy and neuropathic pain.
Unlike morphine-type analgesics, pregabalin does not produce analgesia through binding at opioid receptors. While pregabalin is an analog of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain, it does not bind at GABA or benzodiazepine receptors nor alter GABA concentrations in the brain. Pregabalin does bind with high affinity to the alpha 2-delta receptor site (a subunit of voltage-gated calcium channels) in the central nervous system. The binding of pregabalin at this site is thought to be responsible for its therapeutic effect on neuropathic pain.
Pregabalin has been shown to produce effects that are similar to other controlled substances. In a study with recreational users of sedative/hypnotic drugs, a 450 mg dose of pregabalin resulted in subjective ratings of "good drug effect," "high," and "liking" similar to 30 mg of diazepam. In clinical studies, pregabalin showed an adverse event profile similar to other central nervous system depressants. Some of these effects included dizziness, somnolence, ataxia, and confusion. Following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms suggestive of physical dependence. The FDA determined that the dependence profile of pregabalin, as measured by a patient physical withdrawal checklist, was quantitatively less than benzodiazepines in schedule IV of the CSA.
On April 4, 2005, the Acting Assistant Secretary for Health of the DHHS sent the Administrator of the DEA a scientific and medical evaluation and a letter recommending that pregabalin be placed into Schedule V of the CSA. Enclosed with the April 4, 2005, letter was a document prepared by the FDA entitled, "Basis for the Recommendation for Control of Pregabalin in Schedule V of the Controlled Substances Act (CSA)." The document contained a review of the factors which the CSA requires the Secretary to consider (21 U.S.C. 811(b)).
The factors considered by the Acting Assistant Secretary of Health and DEA with respect to pregabalin were:
(1) Its actual or relative potential for abuse;
(2) Scientific evidence of its pharmacological effects;
(3) The state of current scientific knowledge regarding the drug;
(4) Its history and current pattern of abuse;
(5) The scope, duration, and significance of abuse;
(6) What, if any, risk there is to the public health;
(7) Its psychic or physiological dependence liability; and
(8) Whether the substance is an immediate precursor of a substance already controlled under this subchapter. (21 U.S.C. 811(c))
Based on the recommendation of the Acting Assistant Secretary for Health, received in accordance with section 201(b) of the Act (21 U.S.C. 811(b)), and the independent review of the available data by the DEA, the Deputy Administrator of the DEA, pursuant to sections 201(a) and 201(b) of the Act (21 U.S.C. 811(a) and 811(b)), finds that:
(1) Based on information now available, pregabalin has a low potential for abuse relative to the drugs or other substances in Schedule IV;
(2) Pregabalin has a currently accepted medical use in treatment in the United States; and
(3) Abuse of pregabalin may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule IV. (21 U.S.C. 812(b)(5))
Based on these findings, the Deputy Administrator of the DEA concludes that pregabalin, including its salts, and all products containing pregabalin, warrant control in Schedule V of the CSA.
Interested persons are invited to submit their comments, objections or requests for a hearing with regard to this proposal. Requests for a hearing should state, with particularity, the issues concerning which the person desires to
be heard. All correspondence regarding this matter should be submitted to the Drug Enforcement Administration using the address information provided above. In the event that comments, objections, or requests for a hearing raise one or more issues which the Deputy Administrator finds warrant a hearing, the Deputy Administrator shall order a public hearing by notice in the Federal Register, summarizing the issues to be heard and setting the time for the hearing.
Requirements for Handling Pregabalin
If this rule is finalized as proposed, pregabalin and all products containing pregabalin would be subject to the Controlled Substances Act and the Controlled Substances Import and Export Act regulatory controls and administrative, civil and criminal sanctions applicable to the manufacture, distribution, dispensing, importing and exporting of a Schedule V controlled substance, including the following:
Registration. Any person who manufactures, distributes, dispenses, imports, exports, engages in research or conducts instructional activities with pregabalin, or who desires to manufacture, distribute, dispense, import, export, engage in instructional activities or conduct research with pregabalin, would need to be registered to conduct such activities in accordance with Part 1301 of Title 21 of the Code of Federal Regulations.
Security. Pregabalin would be subject to Schedule III-V security requirements and must be manufactured, distributed and stored in accordance with Sec. Sec. 1301.71, 1301.72(b), (c), and (d), 1301.73, 1301.74, 1301.75(b) and (c), 1301.76, and 1301.77 of Title 21 of the Code of Federal Regulations.
Labeling and Packaging. All labels and labeling for commercial containers of pregabalin which are distributed on or after finalization of this rule would need to comply with requirements of Sec. Sec. 1302.03-1302.07 of Title 21 of the Code of Federal Regulations.
Inventory. Every registrant required to keep records and who possesses any quantity of pregabalin would be required to keep an inventory of all stocks of pregabalin on hand pursuant to Sec. Sec. 1304.03, 1304.04 and 1304.11 of Title 21 of the Code of Federal Regulations. Every registrant who desires registration in Schedule V for pregabalin would be required to conduct an inventory of all stocks of the substance on hand at the time of registration.
Records. All registrants would be required to keep records pursuant to Sec. Sec. 1304.03, 1304.04, 1304.21, 1304.22, and 1304.23 of Title 21 of the Code of Federal Regulations.
Prescriptions. All prescriptions for pregabalin or prescriptions for products containing pregabalin would be required to be issued pursuant to 21 CFR 1306.03-1306.06 and 1306.21, 1306.23-1306.27.
Importation and Exportation. All importation and exportation of pregabalin would need to be in compliance with part 1312 of Title 21 of the Code of Federal Regulations.
Criminal Liability. Any activity with pregabalin not authorized by, or in violation of, the Controlled Substances Act or the Controlled Substances Import and Export Act occurring on or after finalization of this proposed rule would be unlawful.
Executive Order 12866
In accordance with the provisions of the CSA (21 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 5 U.S.C. 556 and 557 and, as such, are exempt from review by the Office of Management and Budget pursuant to Executive Order 12866, section 3(d)(1).
Regulatory Flexibility Act
The Deputy Administrator, in accordance with the Regulatory Flexibility Act (5 U.S.C. 605(b)), 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. Pregabalin products will be prescription drugs used for the treatment of neuropathic pain. Handlers of pregabalin often handle other controlled substances used to treat pain which are already subject to the regulatory requirements of the CSA.
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.
Executive Order 13132
This rulemaking does not preempt or modify any provision of state law; nor does it impose enforcement responsibilities on any state; nor does it diminish the power of any state to enforce its own laws. Accordingly, this rulemaking does not have federalism implications warranting the application of Executive Order 13132.
Unfunded Mandates Reform Act of 1995
This rule will not result in the expenditure by State, local and tribal governments, in the aggregate, or by the private sector, of $115,000,000 or more in any one year, and will not significantly or uniquely affect small governments. Therefore, no actions were deemed necessary under provisions of the Unfunded Mandates Reform Act of 1995.
Small Business Regulatory Enforcement Fairness Act of 1996
This rule is not a major rule as defined by Sec. 804 of the Small Business Regulatory Enforcement Fairness Act of 1996. 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: 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.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control, Narcotics, Prescription drugs.
Under the authority vested in the Attorney General by section 201(a) of the CSA (21 U.S.C. 811(a)), and delegated to the Administrator of DEA by Department of Justice regulations (28 CFR 0.100), and redelegated to the Deputy Administrator pursuant to 28 CFR 0.104, the Deputy Administrator hereby proposes that 21 CFR part 1308 be amended as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES [AMENDED]
1. The authority citation for 21 CFR part 1308 continues to read as follows:
2. Section 1308.15 is proposed to be amended by adding a new paragraph (e) to read as follows:
* * * * *
(e) Depressants. Unless specifically exempted or excluded or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a depressant effect on the central nervous system, including its salts:
(1) Pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid]--2782
Dated: May 6, 2005.
Michele M. Leonhart,
[FR Doc. 05-9634 Filed 5-12-05; 8:45 am]
BILLING CODE 4410-09-P
NOTICE: This is an unofficial version. An official version of this publication may be obtained directly from the Government Publishing Office (GPO).