[Federal Register Volume 74, Number 220 (Tuesday, November 17, 2009)]
[Proposed Rules]
[Pages 59108-59112]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-27583]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-333P]


Schedules of Controlled Substances: Placement of Carisoprodol 
Into Schedule IV

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Notice of proposed rulemaking.

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SUMMARY: This proposed rule is issued by the Deputy Administrator of 
the Drug Enforcement Administration (DEA) to place the substance 
carisoprodol, 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). 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 would impose the regulatory controls and criminal sanctions 
of schedule IV on those who handle carisoprodol and products containing 
carisoprodol.

DATES: Written comments must be postmarked and electronic comments must 
be submitted on or before December 17, 2009. Commenters should be aware 
that the electronic Federal Docket Management System will not accept 
comments after midnight Eastern Standard Time (EST) on the last day of 
the comment period.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-333'' on all written and electronic correspondence. 
Written comments sent via regular or express mail should be sent to the 
Drug Enforcement Administration, Attention: DEA Federal Register 
Representative/ODL, 8701 Morrissette Drive, Springfield, VA 22152. 
Comments may be sent to DEA by sending an electronic message to 
[email protected]. 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

[[Page 59109]]

document is also available at the http://www.regulations.gov Web site. 
DEA will accept attachments to electronic comments in Microsoft Word, 
WordPerfect, Adobe PDF, or Excel file formats only. DEA will not accept 
any file formats other than those specifically listed here.
    Please note that DEA is requesting that electronic comments be 
submitted before midnight EST on the day the comment period closes 
because http://www.regulations.gov terminates the public's ability to 
submit comments at midnight EST on the day the comment period closes. 
Commenters in time zones other than EST may want to consider this so 
that their electronic comments are received. All comments sent via 
regular or express mail will be considered timely if postmarked on the 
day the comment period closes.

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

SUPPLEMENTARY INFORMATION:
    Comments and Requests for Hearing: 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 the 
Administrative Procedure Act (5 U.S.C. 556 and 557). All persons are 
invited to submit their comments or objections with regard to this 
proposal. Requests for a hearing may be submitted by interested persons 
and must conform to the requirements of 21 CFR 1308.44 and 1316.47. The 
request should state, with particularity, the issues concerning which 
the person desires to be heard and the requestor's interest in the 
proceeding. Only interested persons, defined in the regulations as 
those ``adversely affected or aggrieved by any rule or proposed rule 
issuable pursuant to section 201 of the Act (21 U.S.C. 811),'' may 
request a hearing. 21 CFR 1308.42. Please note that DEA may grant a 
hearing only ``for the purpose of receiving factual evidence and expert 
opinion regarding the issues involved in the issuance, amendment, or 
repeal of a rule issuable'' pursuant to 21 U.S.C. 811(a). All 
correspondence regarding this matter should be submitted to the DEA 
using the address information provided above.
    Posting of Public Comments: Please note that all comments received 
are considered part of the public record and made available for public 
inspection online at http://www.regulations.gov and in the Drug 
Enforcement Administration's public docket. Such information includes 
personal identifying information (such as your name, address, etc.) 
voluntarily submitted by the commenter.
    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 posted online or made available in the public docket, you must 
include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the first 
paragraph of your comment. You must also place all the personal 
identifying information you do not want posted online or made available 
in the public docket 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 posted online or made available 
in the public docket, you must include the phrase ``CONFIDENTIAL 
BUSINESS INFORMATION'' in the first paragraph of your comment. You must 
also prominently identify confidential business information to be 
redacted within the comment. If a comment has so much confidential 
business information that it cannot be effectively redacted, all or 
part of that comment may not be posted online or made available in the 
public docket.
    Personal identifying information and confidential business 
information identified and located as set forth above will be redacted 
and the comment, in redacted form, will be posted online and placed in 
the DEA's public docket file. Please note that the Freedom of 
Information Act applies to all comments received. If you wish to 
inspect the agency's public docket file in person by appointment, 
please see the FOR FURTHER INFORMATION CONTACT paragraph.

Background

    Carisoprodol is a centrally acting muscle relaxant and is indicated 
for the relief of discomfort associated with acute, painful 
musculoskeletal conditions. Carisoprodol has been available since 1959 
as a prescription drug in the United States under the trade name 
Soma[supreg]. It is also marketed as generic products. Carisoprodol is 
similar to a variety of central nervous system (CNS) depressants, 
including meprobamate (C-IV) and chlordiazepoxide (C-IV). The actual 
abuse data from several databases demonstrate that carisoprodol is 
abused in the United States. Because of growing concerns about abuse of 
carisoprodol, a number of states have regulated carisoprodol under 
their controlled substance regulations, and a number of additional 
states are currently considering such regulation.
    Because of the evidence relating to diversion, abuse, and 
trafficking of carisoprodol, in March 1996, the DEA requested from the 
DHHS a scientific and medical evaluation and a scheduling 
recommendation for carisoprodol, in accordance with 21 U.S.C. 811(b).
    In February 1997, the U.S. Food and Drug Administration (FDA) Drug 
Abuse Advisory Committee (DAAC) deliberated upon the abuse and 
scheduling issues and concluded that the data were insufficient to 
control carisoprodol under the CSA at that time. Since the FDA DAAC 
meeting, pharmacological studies addressing the abuse liability of 
carisoprodol have been conducted under the direction of the National 
Institute on Drug Abuse (NIDA) and the College on Problems of Drug 
Dependence (CPDD). DEA acquired new carisoprodol-related data on actual 
abuse, law enforcement encounters and other information and sent this 
supplementary information to DHHS on November 14, 2005. FDA acquired 
new data from the Drug Abuse Warning Network (DAWN), National Survey on 
Drug Use and Health (NSDUH), Florida Medical Examiners Commission 
reports, FDA's Adverse Event Reporting System (AERS) and information 
from the published scientific literature and conducted a scientific and 
medical evaluation. These data collectively indicate that carisoprodol 
has abuse potential and is being diverted, trafficked, with increasing 
frequency and magnitude.
    Carisoprodol abuse has been associated with increasing numbers of 
emergency department (ED) visits in recent years as indicated by DAWN. 
The ``abuse frequency,'' calculated as ED visits per 10,000 
prescriptions, of carisoprodol (frequency range during 2002-2007: 15.1 
to 22.6 visits/10,000 prescriptions) is similar to that of a schedule 
IV drug, diazepam (frequency range during 2002-2007: 12.5 to 14.1 
visits/10,000 prescriptions). Carisoprodol is used as either the sole 
drug or in combination with other substances such as opioids, 
benzodiazepine, alcohol, marijuana, and cocaine. Data from the AERS 
database show that carisoprodol is associated with adverse health 
events including dependence and withdrawal syndrome.
    The data from National Poison Data System of the American 
Association of Poison Control Centers documented 8,821 carisoprodol 
toxic exposure cases including 3,605 cases in which it was

[[Page 59110]]

the sole drug mentioned in 2007. Medical Examiners Commission Reports 
released by the Florida Department of Law Enforcement (FDLE) indicate 
that carisoprodol/meprobamate related deaths in Florida increased by 
100 percent from 208 deaths in 2003 to 415 deaths in 2008.
    The National Forensic Laboratory Information System (NFLIS), a DEA 
system that tracks analyzed drug exhibits submitted by the federal, 
state, and local law enforcement, documented evidence of substantial 
diversion of carisoprodol. For example, law enforcement submitted a 
total of 3,873 carisoprodol drug items to participating forensic 
laboratories in 2008. NFLIS consistently listed carisoprodol in the top 
25 most frequently identified drugs since 2000. The 2007 NSDUH data 
show that 2.7 million individuals used Soma[supreg] in their lifetime 
(i.e., ever used) for a non-medical purpose.
    The data from in vitro electrophysiological studies using the 
whole-cell patch clamp technique demonstrate that carisoprodol elicits 
barbiturate-like effects. Intravenous drug self-administration studies 
in rhesus monkeys show that carisoprodol has positive reinforcing 
effects. Meprobamate, pentobarbital, and chlordiazepoxide substitute 
fully for the discriminative stimulus effects of carisoprodol in rats. 
Bemegride, a barbiturate antagonist, antagonizes the discriminative 
stimulus effects of carisoprodol.
    Data from an animal study indicates that carisoprodol has 
dependence liability similar to barbital (schedule IV), a central 
nervous system depressant. Carisoprodol administered orally fully 
prevented the appearance of abstinence phenomena in dogs tolerant and 
dependent on barbital. Several published reports document evidence of 
tolerance and dependence to carisoprodol and indicate the occurrence of 
abstinence symptoms during carisoprodol withdrawal in humans.
    On October 6, 2009, the Acting Assistant Secretary for Health, 
DHHS, sent the Deputy Administrator of DEA a scientific and medical 
evaluation and a letter recommending that carisoprodol be placed into 
schedule IV of the CSA. Enclosed with the October 6, 2009, letter was a 
document prepared by the FDA entitled, ``Basis for the Recommendation 
for Control of Carisoprodol 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)). The factors 
considered by the Assistant Secretary of Health and DEA 21 U.S.C. 
811(c)) with respect to carisoprodol 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.
    Based on the recommendation of the 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. Carisoprodol has a low potential for abuse relative to the drugs 
or other substances in Schedule III. Animal studies indicate that 
carisoprodol is similar to schedule IV drugs such as meprobamate and 
chlordiazepoxide in its central nervous system depressant effects. The 
documented data on law enforcement encounters and actual abuse of 
carisoprodol demonstrate that it has a potential for abuse and is being 
diverted and abused. Since 2000, DEA's NFLIS database consistently 
mentioned carisoprodol in the top 25 drugs that were most frequently 
identified by state and local forensic laboratories thereby indicating 
that carisoprodol is being diverted. Emergency department visits data 
from DAWN indicate that abuse frequency of carisoprodol is similar to 
that of diazepam, a schedule IV drug. Recent data from DAWN medical 
examiner reports and emergency department visits showed an increase in 
carisoprodol abuse.
    2. Carisoprodol has a currently accepted medical use in treatment 
in the United States. Carisoprodol is an FDA approved drug and is used 
for the relief of discomfort associated with acute, painful 
musculoskeletal conditions.
    3. Abuse of carisoprodol may lead to limited physical dependence or 
psychological dependence relative to the drugs or other substances in 
schedule III. Carisoprodol, similar to barbital (schedule IV), prevents 
the abstinence syndrome in drug withdrawn barbital-dependent dogs. 
Published reports indicate that carisoprodol causes psychological or 
physical dependence and withdrawal syndrome.
    Based on these findings, the Deputy Administrator of DEA concludes 
that carisoprodol, 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))
    References to the above studies and data may be found in the Health 
and Human Services scheduling recommendation and DEA's independent 
analysis, both of which are available on the electronic docket 
associated with this rulemaking.

Requirements for Handling Carisoprodol

    If this rule is finalized as proposed, carisoprodol would be 
subject to CSA regulatory controls and administrative, civil, and 
criminal sanctions applicable to the manufacture, distribution, 
dispensing, importing, and exporting of a schedule IV controlled 
substance, including the following:
    Registration. Any person who manufactures, distributes, dispenses, 
imports, exports, engages in research or conducts instructional 
activities with carisoprodol, or who desires to manufacture, 
distribute, dispense, import, export, engage in instructional 
activities or conduct research with carisoprodol, would need to be 
registered to conduct such activities in accordance with 21 CFR part 
1301.
    Security. Carisoprodol would be subject to schedules III-V security 
requirements and would need to be manufactured, distributed, and stored 
in accordance with 21 CFR 1301.71, 1301.72(b), (c), and (d), 1301.73, 
1301.74, 1301.75(b) and (c), 1301.76, and 1301.77.
    Labeling and Packaging. All labels and labeling for commercial 
containers of carisoprodol which are distributed on or after 
finalization of this rule would need to comply with requirements of 21 
CFR 1302.03-1302.07.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of carisoprodol would be required to keep an 
inventory of all stocks of carisoprodol on hand pursuant to 21 CFR 
1304.03, 1304.04 and 1304.11. Every registrant who desires registration 
in schedule IV for carisoprodol 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 21

[[Page 59111]]

CFR 1304.03, 1304.04, 1304.21, 1304.22, and 1304.23.
    Prescriptions. All prescriptions for carisoprodol or prescriptions 
for products containing carisoprodol would be required to be issued 
pursuant to 21 CFR 1306.03-1306.06 and 1306.21, 1306.22-1306.27.
    Importation and Exportation. All importation and exportation of 
carisoprodol would need to be in compliance with 21 CFR part 1312.
    Criminal Liability. Any activity with carisoprodol 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.

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 hereby certifies that this rulemaking has 
been drafted in accordance with the Regulatory Flexibility Act (5 
U.S.C. 601-612), has reviewed this regulation, and by approving it 
certifies that this regulation will not have a significant economic 
impact on a substantial number of small entities.
    In considering the impact on small entities, the first question is 
whether a substantial number of small entities are affected. In this 
instance, the entities affected are those now selling carisoprodol-
containing products without registration. DEA has identified 22 firms 
manufacturing carisoprodol-containing products in 2009.\1\ Fifteen of 
these firms have existing DEA registrations. This leaves seven firms 
from this data set selling carisoprodol without registration. DEA has 
no information on the number of non-registrants distributing or 
importing carisoprodol, but there is every reason to believe that the 
number of such firms is well in excess of the seven already identified. 
The Small Business Administration size standard for a small wholesaler 
of drugs is 100 employees. It is clearly possible to operate a drug 
distributing firm with fewer than 100 employees. There can be no 
question that a substantial number of small entities will be affected 
by this rule.
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    \1\ IMS Health National Prescription Audit (NPA).
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    The impact on non-registrants now selling carisoprodol will occur 
in two forms: the cost of registration and the cost of meeting the 
security requirements in 21 CFR part 1301. There is also a potential 
impact on firms not now selling carisoprodol who might have wished to 
enter the market.
    The annual registration fee for a distributor, importer, or 
exporter is $1,147. There is some uncertainty in estimating the cost of 
meeting the security requirements, because most nonregistrants already 
meet the security requirements, at least in part, for schedule III and 
IV substances. To be conservative, it is assumed that every 
nonregistrant will have to buy a safe to store carisoprodol. A safe 
with capacity of 13.5 cubic feet should be adequate. A safe of this 
size may be purchased for $1,350.\2\ Annualized over 15 years at 7.0 
percent, that is $148 per year. Total annual cost of compliance with 
the rule, then, is $1,295. The usual standard for a significant 
economic impact is 1.0 percent of revenue. For $1,295 per year to be a 
significant economic impact, annual revenue of a firm would have to be 
under $130,000. Any firm in the business of distributing drugs needs 
annual revenue well in excess of that amount to sustain itself.
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    \2\ NationwideSafes.com http://www.nationwidesafes.com/capacity-more-than-4pt0-cu-ft.html.
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    It should be acknowledged that, for a small firm, there may be some 
inconvenience and expense in preparing necessary forms for registration 
and registration renewal. These are minor costs. There are also 
recordkeeping requirements, but these impose little or no incremental 
cost for a firm that is already maintaining records needed for a 
wholesale business. The costs of registration and security requirements 
will not be a significant economic impact.
    If a firm chose not to register and to drop its carisoprodol line, 
the cost to the firm would exceed its earnings on the carisoprodol 
sales. The firm might also lose some customers who do not want to buy 
from a vendor without carisoprodol in its product line. A competent 
manager will recognize this cost. In light of the very small cost of 
registering, he would presumably choose to drop carisoprodol from the 
firm's products only if the firm were earning a negligible profit from 
that line and he judged that dropping it would not turn away 
significant customers. In light of the foregoing analysis, DEA finds 
that this rule will not have a significant economic impact on a 
substantial number of small entities. DEA has no information regarding 
the number of persons who may distribute carisoprodol-containing 
products, but do not manufacture, package, repackage, or relabel those 
products. Therefore, DEA seeks comment on any entities that might be 
affected by this control action.

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 the provisions of the Unfunded 
Mandates Reform Act of 1995.

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). 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

[[Page 59112]]

hereby proposes that 21 CFR part 1308 be amended as follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

    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 1308.14 is amended by redesignating paragraphs (c)(5) 
through (c)(52) as paragraphs (c)(6) through (c)(53) and adding a new 
paragraph (c)(5) to read as follows:


Sec.  1308.14  Schedule IV.

* * * * *
    (c) * * *

 
 
 
(5) Carisoprodol...............................................     8192
 

* * * * *

    Dated: November 10, 2009.
Michele M. Leonhart,
Deputy Administrator.
[FR Doc. E9-27583 Filed 11-16-09; 8:45 am]
BILLING CODE 4410-09-P