[Federal Register Volume 74, Number 192 (Tuesday, October 6, 2009)]
[Rules and Regulations]
[Pages 51234-51236]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-23971]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-327F]


Schedules of Controlled Substances; Placement of Fospropofol Into 
Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: With the issuance of this final rule, the Deputy Administrator 
of the Drug Enforcement Administration (DEA) places the substance 
fospropofol, including its salts, isomers and salts of isomers whenever 
the existence of such salts, isomers, and salts of isomers is possible, 
into schedule IV of the Controlled Substances Act (CSA). As a result of 
this rule, the regulatory controls and criminal sanctions of schedule 
IV will be applicable to the manufacture, distribution, dispensing, 
importation, and exportation of fospropofol and products containing 
fospropofol.

DATES: Effective Date: November 5, 2009.

FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, PhD, Chief, 
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug 
Enforcement Administration, 8701 Morrissette Drive, Springfield, 
Virginia 22152, Telephone: (202) 307-7183.

SUPPLEMENTARY INFORMATION: 

Background

    On December 12, 2008, the Food and Drug Administration (FDA) 
approved fospropofol for marketing under the trade name Lusedra[reg] in 
the United States as a drug product indicated for monitored anesthesia 
care (MAC) sedation in adult patients undergoing diagnostic or 
therapeutic procedures.
    Fospropofol, 2,6-diisopropopylphenoxymethyl phosphate disodium, is 
a water soluble, phosphono-O-methyl prodrug of propofol. It is 
metabolized in the body to propofol, the active metabolite. Propofol 
has been available for medical use in the United States since 1989 and 
is not currently a controlled substance. The pharmacological effects of 
fospropofol are attributed to the pharmacological actions of propofol. 
Propofol binds to [gamma]-aminobutyric acid (GABA<INF>A</INF>) receptor 
and acts as a modulator by potentiating the activity of GABA at this 
receptor.
    Since propofol is the active metabolite of fospropofol, the abuse 
potential of fospropofol is comparable to that of propofol. Animal 
self-administration studies demonstrated that the reinforcing effects 
of propofol are relatively low and comparable to midazolam and other 
schedule IV benzodiazepines. Fospropofol elicits behavioral effects 
similar to methohexital and midazolam, schedule IV sedative-hypnotics.
    Since fospropofol is a new molecular entity, there has been no 
evidence of diversion, abuse, or law enforcement encounters involving 
the drug.
    On February 27, 2009, the Acting Assistant Secretary for Health, 
Department of Health and Human Services (DHHS), sent the Deputy 
Administrator of DEA a scientific and medical evaluation and a letter 
recommending that fospropofol be placed into schedule IV of the CSA. 
Enclosed with the February 27, 2009, letter was a document prepared by 
the FDA entitled, ``Basis for the Recommendation for Control of 
Fospropofol and Its Salts in Schedule IV 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)).
    After a review of the available data, including the scientific and 
medical evaluation and the scheduling recommendation from DHHS, the 
Deputy Administrator of the DEA published a Notice of Proposed 
Rulemaking entitled ``Schedules of Controlled Substances: Placement of 
Fospropofol into Schedule IV'' on July 23, 2009 (74 FR 36424), which 
proposed placement of fospropofol into schedule IV of the CSA. The 
proposed rule provided an opportunity for all interested persons to 
submit their written comments on or before August 24, 2009.

Comments Received

    The DEA received two comments in response to the Notice of Proposed 
Rulemaking. One comment received from a concerned citizen did not 
relate to fospropofol, the substance that is being controlled. Thus DEA 
did not consider this comment.

[[Page 51235]]

    Another comment received from a professional organization of 
anesthesiologists is in agreement with the findings of scientific and 
medical evaluation that formed the basis for the present rule 
controlling fospropofol as a schedule IV substance and it fully 
supported this control action.

Scheduling of Fospropofol

    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 
DEA, the Deputy Administrator of DEA, pursuant to sections 201(a) and 
201(b) of the Act (21 U.S.C. 811(a) and 811(b)), finds that:
    (1) Fospropofol has a low potential for abuse relative to the drugs 
or substances in schedule III. Although there is no direct comparison 
to a schedule III substance, this finding is based on the demonstration 
of the abuse potential of propofol, the active metabolite, relative to 
the schedule IV substances, methohexital and midazolam;
    (2) Fospropofol has a currently accepted medical use in treatment 
in the United States; and
    (3) Abuse of fospropofol may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
schedule III. This finding is based on the symptoms exhibited upon 
withdrawal from propofol.
    Based on these findings, the Deputy Administrator of DEA concludes 
that fospropofol, including its salts, isomers and salts of isomers 
whenever the existence of such salts, isomers, and salts of isomers is 
possible warrants control in schedule IV of the CSA. (21 U.S.C. 
812(b)(4))

Requirements for Handling Fospropofol

    Registration. Any person who manufactures, distributes, dispenses, 
imports, exports, engages in research or conducts instructional 
activities with fospropofol, or who desires to manufacture, distribute, 
dispense, import, export, engage in instructional activities or conduct 
research with fospropofol, must be registered to conduct such 
activities in accordance with part 1301 of Title 21 of the Code of 
Federal Regulations. Any person who is currently engaged in any of the 
above activities and is not registered with DEA must submit an 
application for registration on or before November 5, 2009 and may 
continue their activities until DEA has approved or denied that 
application.
    Security. Fospropofol is subject to schedules 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 on or after November 5, 2009.
    Labeling and Packaging. All labels and labeling for commercial 
containers of fospropofol must comply with requirements of Sec. Sec.  
1302.03-1302.07 of Title 21 of the Code of Federal Regulations on or 
after November 5, 2009.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of fospropofol must keep an inventory of all 
stocks of fospropofol on hand pursuant to Sec. Sec.  1304.03, 1304.04 
and 1304.11 of Title 21 of the Code of Federal Regulations on or after 
November 5, 2009. Every registrant who desires registration in schedule 
IV for fospropofol must conduct an inventory of all stocks of the 
substance on hand at the time of registration.
    Records. All registrants must 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 on or after November 5, 2009.
    Prescriptions. All prescriptions for fospropofol or prescriptions 
for products containing fospropofol must be issued pursuant to 
Sec. Sec.  1306.03-1306.06 and 1306.21, 1306.22-1306.27 of Title 21 of 
the Code of Federal Regulations on or after November 5, 2009.
    Importation and Exportation. All importation and exportation of 
fospropofol must be in compliance with part 1312 of Title 21 of the 
Code of Federal Regulations on or after November 5, 2009.
    Criminal Liability. Any activity with fospropofol not authorized 
by, or in violation of, the Controlled Substances Act or the Controlled 
Substances Import and Export Act shall be unlawful on or after November 
5, 2009.

Regulatory Certifications

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. 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. Fospropofol products 
will be used for monitored anesthesia care (MAC) sedation in adult 
patients undergoing diagnostic or therapeutic procedures. Handlers of 
fospropofol also handle other controlled substances used for sedation 
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 
$120,000,000 or more (adjusted for inflation) 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.

Congressional Review Act

    This rule is not a major rule as defined by Sec.  804 of the Small 
Business Regulatory Enforcement Fairness Act of 1996 (Congressional 
Review Act). 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.


0
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

[[Page 51236]]

CFR 0.104, the Deputy Administrator hereby amends 21 CFR part 1308 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. Section 1308.14 is amended in paragraph (c), by redesignating 
paragraphs (c)(23) through (c)(51) as paragraphs (c)(24) through 
(c)(52) and adding a new paragraph (c)(23) as follows:


Sec.  1308.14  Schedule IV.

* * * * *
    (c) * * *

(23) Fospropofol................................................    2138
 

* * * * *

    Dated: September 28, 2009.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E9-23971 Filed 10-5-09; 8:45 am]
BILLING CODE 4410-09-P