EFFECTIVE DATE: August 12, 1999.

FOR FURTHER INFORMATION CONTACT: Frank Sapienza, Chief, Drug and Chemical Evaluation Section, Drug Enforcement Administration, Washington, DC 20537; Telephone: (202) 307-7183.

SUPPLEMENTARY INFORMATION:

Background

    Ketamine hydrochloride is marketed in the United States as a general anesthetic for use in human medicine under the trade name Ketalar®. It is also marketed as a veterinary product under various names including Ketajet®, Ketaset®, and Vetalar®. Since 1992, more than 775 reports of ketamine diversion or abuse have been received by the DEA. More than 568 law enforcement reports described encounters of individuals who sold the drug, who had it in their possession and/or were under its influence. Veterinary clinic burglaries which were directed at ketamine were described also. The balance of the reports were of ketamine abuse related hospital emergency department visits.

    The wide geographic distribution and prevalence of diversion and/or abuse of ketamine, the spreading notoriety of ketamine as a party drug, Special `K' or `K', and the involvement of teenagers and young adults caused the DEA to submit to the Department of Health and Human Services (DHHS) information related to each of the eight factors which are determinative of control under the CSA. The DHHS responded by letter, recommending that ketamine be added to schedule III.

    The pharmacological and behavioral effects of ketamine are similar, but somewhat less intense and shorter in duration, to those of the schedule II substance, phencyclidine (PCP). Low dose intoxication with
ketamine results in impaired attention, learning, and memory functions. Higher doses may result in ataxia, dizziness, elevated blood pressure, mental confusion, hyperexcitability, catalepsy (the inability to move), amnesia, convulsions, a delusional dream-like state, hallucinations, and psychosis. Long-term use of ketamine is associated with hallucinatory flashbacks, an inability to concentrate, psychological dependence, and tolerance. Reports of ketamine abuse leading to physical or psychological dependence consistent with schedule III criteria have been published.

    Diversion of ketamine pharmaceutical products from practitioners has been the most frequently documented source of the drug, with the primary sources being veterinary clinics. The liquid pharmaceutical product is injected or, more commonly, evaporated and the resultant power inhaled (snorted). Clandestine manufacture of ketamine has not been encountered. In contrast to that of PCP, the synthesis of ketamine is difficult.

Notice of Proposed Rule Making

    Relying on the scientific and medical evaluation and the recommendation of the Assistant Secretary for Health in accordance with section 201(b) of the CSA [21 U.S.C. 811(b)], and the independent review of the DEA, the Deputy Administrator of the DEA, pursuant to Sections 201(a) and 201(b) of the CSA [21 U.S.C. 811(a) and 811(b) proposed the placement of ketamine, including its salts, isomers, and salts of isomers, into schedule III of the CSA in an April 9, 1999, Federal Register notice (64 FR 17299). The notice provided an opportunity for all interested persons to submit their comments or objections in writing on the proposed scheduling of ketamine on or
before June 8, 1999.

Comments

    The DEA received five comments regarding the proposal. Comments in support of the proposal were received from the American Animal Hospital Association (AAHA), the American Veterinary Medical Association (AVMA), the American Association of Equine Practitioners (AAEP) and a practicing veterinarian. The AAHA, which represents 16,000 veterinary care providers, commented that the movement of ketamine into Schedule
III was in the best interest of the veterinary industry and the general public. The AVMA, on behalf of 62,000 members, stated that the security and record keeping required of Schedule III controlled substances will prevent diversion and unauthorized use of ketamine while providing a reasonable mechanism for the continued, responsible use of ketamine for legitimate purposes by members of the veterinary profession. The AAEP which reaches 3.2 million horse owners through its more than 6,200 members world wide strongly supports the placement of ketamine into Schedule III. [Page 37674] The group commented that anesthesia in the horse poses unique dangers to both handlers and the horse; that ketamine has proven to be the safest induction agent known and remains an important medication to the equine practitioner; that the equine veterinary community is keenly aware of the public health concerns associated with this drug; and that many veterinary practices have already taken precautionary steps to prevent its misuse by keeping the drug restricted and secured. A veterinarian whose hospital in Pennsylvania was broken into by individuals seeking ketamine strongly supports the placement of ketamine into Schedule III and notes that publicity of the mandatory security measures will discourage potential burglars.

    The Phoenix Scientific, Inc., a supplier of generic veterinary ketamine hydrochloride injection products, opposed the proposal. In summary, the company posited that: 1. The Fort Dodge Animal Health advocacy of the placement of ketamine into Schedule III might be an attempt to limit the production and distribution of the generic
equivalent by reputable firms; 2. the problem of diversion of ketamine is not a factor which needs to be addressed further at the manufacturers' level; 3. compliance with the DEA requirements will cause substantial price increases and not stop diversion; and 4. the manufacturer(s) will be burdened with assisting law enforcement and forensic labs throughout the country because a field test for the identification of ketamine does not exist. Further, the company asked that a reasonable amount of time'' be allowed for coming into compliance with the regulatory requirements if the proposed action were finalized.

    In response, the Deputy Administrator finds that the comments do not relate to the factors determinative of control of a substance [21 U.S.C. 811(c)] or the criteria for placement of a substance in a particular schedule [21 U.S.C. 812(b)]. Therefore, he need not address the objections. In relation to the commenter's request for the
allowance of sufficient time for coming into compliance with the Schedule III regulatory requirements, the Deputy Administrator notes that, as described below, the DEA will entertain any justified request for an extension of time in the event that the regulations impose special hardships.

Findings

    The Deputy Administrator of the DEA, taking into consideration the comments which were received in response to the publication of the proposed rule, and based on the investigations and review conducted by his staff and relying on the scientific and medical evaluation and the recommendation of the Assistant Secretary for Health, received in accordance with Section 201(b) of the Act [21 U.S.C. 811(b)], finds, pursuant to Sections 201(a) and 201(b) of the Act [21 U.S.C. 811(a) and 811(b)], that: (1) Ketamine has a potential for abuse less than the drugs or other substances in Schedules I and II; (2) Ketamine has currently accepted medical use in treatment in the United States; and (3) Abuse of ketamine may lead to moderate or low physical
dependence or high psychological dependence.

Scheduling Action

    Based on these findings, the Deputy Administrator of the DEA concludes that ketamine, including its salts and isomers, and salts of isomers, warrants control in Schedule III in the CSA. The Schedule III controls of ketamine will become effective on August 12, 1999. In the event that the regulations impose special hardships on any registrant, the DEA will entertain any justified request for an extension of time to comply with the Schedule III regulations regarding ketamine. The applicable regulations are as follows:
    1. Registration. Any person who manufactures, distributes, dispenses, imports or exports ketamine or who engages in research or conducts instructional activities or chemical analysis with respect to this substance, or who proposes to engage in such activities, must be registered to conduct such activities in accordance with Part 1301 of Title 21 of the Code of Federal Regulations on and after August 12, 1999. Any person who is currently lawfully engaged in any of the above activities must submit an application for registration by August 12, 1999. Any such person may then continue their lawful activities until the DEA has approved or denied that application.
    2. Disposal of stocks. Any person who elects not to obtain a Schedule III registration or is not entitled to such registration must surrender all quantities of currently held ketamine in accordance with procedures outlined in 21 CFR 1307.21 on or before August 12, 1999, or may transfer all quantities of currently held ketamine to a person registered under the CSA and authorized to possess Schedule III control substances on or before August 12, 1999. Ketamine to be surrendered to DEA must be listed on a DEA Form 41, "Inventory of Controlled
Substances Surrendered for Destruction.'' DEA Form 41 and instructions can be obtained from the nearest DEA office.
    3. Security. Ketamine must be manufactured, distributed and stored in accordance with Secs. 1301.71, 1301.72(b), (c), and (d), 1301.73, 1301.74, 1301.75(b) and (c) and 1301.76 of Title 21 of the Code of
Federal Regulations.
    4. Labeling and packaging. All commercial containers of ketamine, which are packaged on or after January 13, 2000, must have the appropriate Schedule III labeling as required by Secs. 1302.03-1302.07 of Title 21 of the Code of Federal Regulations. Commercial containers of ketamine packaged before January 13, 2000 and not meeting the requirements specified in Secs. 1302.03-1302.07 of Title 21 of the Code of Federal Regulations may be distributed until May 15, 2000. On and after May 15, 2000 all commercial containers of ketamine must bear the CIII labels as specified in Secs. 1302.03-1302.07 of Title 21 of the Code of Federal Regulations.
5. Inventory. Registrants possessing ketamine are required to take inventories pursuant to Secs. 1304.03, 1304.04 and 1304.11 of Title 21 of the Code of Federal Regulations.
    6. Records. All registrants must keep records pursuant to Secs. 1304.03, 1304.04 and 1304.21-1304.23 of Title 21 of the Code of Federal Regulations.
    7. Prescriptions. All prescriptions for ketamine are to be issued pursuant to Secs. 1306.03-1306.06 and 1306.21-1306.26 of Title 21 of the Code of Federal Regulations. All prescriptions for products containing ketamine issued on or before September 13, 1999, if authorized for refilling, shall as of that date be limited to five
refills and shall not be refilled after January 13, 2000.
    8. Importation and Exportation. All importation and exportation of ketamine shall be in compliance with Part 1312 of Title 21 of the Code of Federal Regulations.
    9. Criminal Liability. Any activity with ketamine not authorized by, or in violation of, the CSA or the Controlled Substances Import and Export Act shall be unlawful on or after August 12, 1999.

     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 (E.O.) 12866, Section 3(d)(1). The Deputy Administrator, in accordance with the Regulatory Flexibility Act [5 U.S.C. 605(b)], has reviewed this rule and by [Page 37675] approving it, certifies that it will not have a significant economic impact on a substantial number of small business entities. Ketamine products are prescription drugs used as anesthetics in hospitals and clinics. Handlers of ketamine are likely to handle other controlled substances which are already subject to the regulatory requirements of the CSA.

     This rule will not result in the expenditure by State, local and tribal governments, in the aggregate, or by the private sector, of $100,000,000 or more in any one year, and it will not significantly or uniquely affect small governments. Therefore, no actions were deemed necessary under provisions of the Unfunded Mandates Reform Act of 1995.

     This rule is not a major rule, as defined by Section 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 the United States based companies to compete with foreign-based companies in domestic and export markets.

    This rule will not have substantial direct effects on the United States, on the relationship between the national government and the United States, or on the distribution of power and responsibilities among the various levels of government. Therefore, in accordance with E.O. 12612, it is determined that this rule does not have sufficient
federalism implications to warrant the preparation of a Federalism Assessment.

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 the DEA by the Department of Justice regulations (28 CFR 0.100) and redelegated to the Deputy Administrator pursuant to 28 CFR 0.104, the Deputy Administrator hereby amends 21 CFR part 1308 as follows:

PART 1308 [AMENDED]

    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.

    2. Section 1308.13 is amended by redesignating the existing paragraphs (c)(5) through (c)(11) as (c)(6) through (c)(12) and by adding a new paragraph (c)(5) to read as follows:

    Sec. 1308.13  Schedule III.

    (5) Ketamine, its salts, isomers, and salts of isomers.........     7285 [Some other names for ketamine: (<plus-minus>)-2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone]..............

    Dated: July 7, 1999.
Donnie R. Marshall,
Deputy Administrator, Drug Enforcement Administration.
[FR Doc. 99-17803 Filed 7-12-99; 8:45 am]
BILLING CODE 4410-09-M