[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