Rules - 2013
[Federal Register Volume 78, Number 57 (Monday, March 25, 2013)]
[Proposed Rules]
[Pages 17895-17900]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-06651]
DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[Docket No. DEA-370]
Schedules of Controlled Substances: Placement of Alfaxalone into
Schedule IV
AGENCY: Drug Enforcement Administration, Department of Justice.
ACTION: Notice of proposed rulemaking.
SUMMARY: The Drug Enforcement Administration (DEA) proposes the
placement of 5[alpha]-pregnan-3[alpha]-ol-11,20-dione (alfaxalone)
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 pursuant to the CSA which requires that such actions be made
on the record after opportunity for a hearing through formal
rulemaking.
DATES: DEA will permit interested persons to file written comments on
this proposal pursuant to 21 CFR 1308.43(g). Electronic comments must
be submitted and written comments must be postmarked on or before April
24, 2013. Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after midnight Eastern Time
on the last day of the comment period.
Interested persons, defined at 21 CFR 1300.01 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 file a request for
hearing pursuant to 21 CFR 1308.44 and in accordance with 21 CFR
1316.45 and 1316.47. Requests for hearing and waivers of participation
must be received on or before April 24, 2013.
ADDRESSES: To ensure proper handling of comments, please reference
"Docket No. DEA 370" on all electronic and written correspondence.
DEA encourages all comments be submitted electronically through http://www.regulations.gov using the electronic comment form provided on that
site. An electronic copy of this document and supplemental
[[Page 17896]]
information to this proposed rule are also available at the http://www.regulations.gov Web site for easy reference. Paper comments that
duplicate the electronic submission are not necessary as all comments
submitted to www.regulations.gov will be posted for public review and
are part of the official docket record. Should you, however, wish to
submit written comments via regular or express mail, they should be
sent to the Drug Enforcement Administration, Attention: DEA Federal
Register Representative/OD, 8701 Morrissette Drive, Springfield,
Virginia 22152. All requests for hearing and waivers of participation
must be sent to Drug Enforcement Administration, Attention: Hearing
Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia 22152.
FOR FURTHER INFORMATION CONTACT: John W. Partridge, Executive
Assistant, Office of Diversion Control, Drug Enforcement
Administration; Mailing Address: 8701 Morrissette Drive, Springfield,
Virginia 22152; Telephone: (202) 307-7165.
SUPPLEMENTARY INFORMATION:
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 DEA'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 of 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, above.
Request for Hearing, Notice of Appearance at or Waiver of Participation
in Hearing
In accordance with the CSA, this action is a formal rulemaking "on
the record after opportunity for a hearing." 21 U.S.C. 811(a). Such
proceedings are conducted pursuant to the provisions of the
Administrative Procedure Act (5 U.S.C. 556 and 557) and 21 CFR 1308.41.
Pursuant to 21 CFR 1308.44(a)-(c), requests for hearings, notices of
appearances, and waivers of participation may be submitted only by
interested persons, defined at 21 CFR 1300.01 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)." Such requests or notices must
conform to the requirements of 21 CFR 1308.44(a) or (b) and 1316.47 or
1317.48, as applicable. A request or notice should state, with
particularity, the interest of the person in the proceeding and the
objections or issues, if any, concerning which the person desires to be
heard. Any waiver must conform to the requirements of 21 CFR 1308.44(c)
and 1316.49, including a written statement regarding the interested
person's position on the matters of fact and law involved in any
hearing.
Please note that pursuant to 21 U.S.C. 811(a), the purpose and
subject matter of the hearing is restricted to "(A) find[ing] that
such drug or other substance has a potential for abuse, and (B)
mak[ing] with respect to such drug or other substance the findings
prescribed by subsection (b) of section 812 of this title for the
schedule in which such drug is to be placed* * *." Requests for
hearing, notices of appearance at the hearing, and waivers of
participation in the hearing should be submitted to DEA using the
address information provided above.
Legal Authority
The DEA implements and enforces Titles II and III of the
Comprehensive Drug Abuse Prevention and Control Act of 1970, often
referred to as the Controlled Substances Act and the Controlled
Substances Import and Export Act (21 U.S.C. 801-971), as amended
(hereinafter, "CSA"). The implementing regulations for these statutes
are found in Title 21 of the Code of Federal Regulations (CFR), parts
1300 to 1321. Under the CSA, controlled substances are classified in
one of five schedules based upon their potential for abuse, their
currently accepted medical use, and the degree of dependence the
substance may cause. 21 U.S.C. 812. The initial schedules of controlled
substances by statute are found at 21 U.S.C. 812(c) and the current
list of scheduled substances are published at 21 CFR Part 1308.
The CSA permits these schedules to be modified by providing that
scheduling of any drug or other substance may be initiated by the
Attorney General: (1) On his own motion; (2) at the request of the
Secretary of Health and Human Services (HHS); or (3) on the petition of
any interested party. 21 U.S.C. 811(a). The Attorney General may, by
rule, "add to such a schedule or transfer between such schedules any
drug or other substance if he (A) finds that such drug or other
substance has a potential for abuse, and (B) makes with respect to such
drug or other substance the findings prescribed by subsection (b) of
section 812 of this title for the schedule in which such drug is to be
placed* * *." 21 U.S.C. 811(a). The findings required for the
placement of a controlled substance in Schedule IV are: the drug or
other substance has a low potential for abuse relative to the drugs or
other substances in Schedule III; the drug or substance has a currently
accepted medical use in treatment in the United States; and abuse of
the drug or other substance may lead to limited physical dependence or
psychological dependence relative to the drugs or other substances in
Schedule III. 21 U.S.C. 812(b)(4).
Background
Alfaxalone (5[alpha]-pregnan-3[alpha]-ol-11,20-dione, previously
spelled alphaxalone), a substance with central nervous system (CNS)
depressant properties, is a neurosteroid that is a derivative of 11-
alpha-hydroxy-progesterone. A New Animal Drug Application (NADA) for
alfaxalone, as an intravenous injectable anesthetic, was recently
approved by the Food and Drug Administration (FDA) for the induction
and maintenance of anesthesia and for induction of anesthesia followed
by maintenance of anesthesia with an inhalant anesthetic, in cats and
dogs.
[[Page 17897]]
Alfaxalone primarily acts as an agonist at the gamma-aminobutyric acid
(GABA) receptor-channel complex, with a mechanism of action at this
site similar to that of barbiturates like phenobarbital (Schedule IV)
and methohexital (Schedule IV), benzodiazepines such as diazepam
(Schedule IV) and midazolam (Schedule IV), as well as the anesthetic
agents, propofol (Schedule IV under consideration) and fospropofol
(Schedule IV).
Proposed Determination to Schedule Alfaxalone
Pursuant to 21 U.S.C. 811(a), proceedings to add a drug or
substance to those controlled under the CSA may be initiated by request
of the Secretary of HHS. On July 17, 2012, HHS provided DEA with a
scientific and medical evaluation document prepared by FDA entitled
"Basis for the Recommendation for Control of alfaxalone in Schedule IV
of the Controlled Substances Act." Pursuant to 21 U.S.C. 811(b), this
document contained an eight-factor analysis of the abuse potential of
alfaxalone, along with HHS' recommendation to control alfaxalone under
Schedule IV of the CSA.
In response, DEA conducted an eight-factor analysis of alfaxalone's
abuse potential pursuant to 21 U.S.C. 811(c). Included below is a brief
summary of each factor as analyzed by HHS and DEA, and as considered by
DEA in the scheduling decision. Please note that both the DEA and HHS
analyses are available in their entirety under "Supporting and Related
Material" of the public docket for this rule at www.regulations.gov
under docket number DEA-370.
1. The Drug's Actual or Relative Potential for Abuse: The abuse
potential of alfaxalone is associated with its ability to evoke
pharmacological effects similar to those evoked by the Schedule IV
substances such as fospropfol, propofol (Schedule IV under
consideration), and midazolam.
Since alfaxalone is a new veterinary product and has not been
marketed in the United States, information on actual abuse of
alfaxalone in the United States is not available. However, the
legislative history of the CSA offers another methodology for assessing
a drug or substance's potential for abuse:
The drug or drugs containing such a substance are new drugs so
related in their action to a drug or drugs already listed as having
a potential for abuse to make it likely that the drug will have the
same potentiality for abuse as such drugs, thus making it reasonable
to assume that there may be significant diversions from legitimate
channels, significant use contrary to or without medical advice, or
that it has a substantial capability of creating hazards to the
health of the user or to the safety of the community.\1\
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\1\ Comprehensive Drug Abuse Prevention and Control Act of 1970,
H.R. Rep. No. 91-1444, 91st Cong., Sess. 1 (1970); 1970 U.S.C.C.A.N.
4566, 4601.
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According to HHS, alfaxalone is thought to interact with the gamma-
aminobutyric acid subtype A (GABA)-A receptors, and to enhance the
activity of GABA, the principal inhibitory neurotransmitter in the
central nervous system (CNS). This pharmacological evidence suggests
that the abuse potential of alfaxalone is comparable to other drugs
with a similar mechanism of action, and similar anesthetic properties,
such as midazolam (Schedule IV), methohexital (Schedule IV),
fospropofol (Schedule IV) and propofol (Schedule IV under
consideration). Similar to the above mentioned Schedule IV sedative-
hypnotics, alfaxalone acts as an inhibitor on the CNS and produces
sedation and anesthesia. Based on the similarities between propofol and
alfaxalone regarding their mechanisms of action and their intended
routes of administration for clinical use, and the fact that 96% of
propofol abuse reports involved abuse by medical professionals, HHS
reasoned that alfaxalone abuse might be by medical professionals who
have access to the drug and have knowledge in the intravenous
administration of drugs.
There are no published studies of abuse potential for alfaxalone in
humans. However, there is evidence that alfaxalone produces the
sedative-hypnotic midazolam-like discriminative stimulus effects in
rats and monkeys, as well as some ethanol-like effects in rats. Based
on the pharmacological similarities to other Schedule IV potent
sedative-hypnotic drugs, such as midazolam, methohexital and
fospropofol, the consequences of abuse of alfaxalone can be predicted
to be similar to those drugs mentioned above. Furthermore, abuse and
misuse of these drugs might result in death. The overt behavioral
effects and adverse events produced by alfaxalone in animals are
similar to those caused by Schedule IV benzodiazepines and
barbiturates.
In summary, the relative abuse potential of alfaxalone can be
considered no greater than the Schedule IV substances such as
fospropfol, propofol, and midazolam and less than that of other
sedatives in Schedule III.
2. Scientific Evidence of the Drug's Pharmacological Effects, If
Known: According to the HHS review, alfaxalone acts directly through
the GABA-A receptor-channel complex and increases the probability that
the channel will enter into naturally-occurring open states of
relatively long duration. The activity of alfaxalone on GABA receptors
is similar to that of barbiturates like phenobarbital and methohexital
(Schedule IV) as well as anesthetic agents like propofol (Schedule IV
under consideration) and fospropofol (Schedule IV). Furthermore,
similar to benzodiazepines such as diazepam and midazolam, alfaxalone
can also increase the frequency of single channel openings.
Additionally alfaxalone has been shown to inhibit T-type calcium
channels. Alfaxalone does not affect cannabinoid (CB1 subtype),
dopamine (D1-, D2-, D3-, D4- and D5- subtype), glutamate (AMPA,
kainate, and NMDA subtype), opioid (mu, kappa and delta subtype), and
serotonin (1A, 2B, 2C, 3, 5A and 6 subtype) receptors, nor does it
affect the transporters for dopamine, norepinephrine and serotonin. In
addition, alfaxalone does not significantly bind to major steroid
nuclear receptors including androgens, estrogens, glucocorticoids or
progesterone receptors.
Pre-clinical behavioral studies showed that, similar to
chlordiazepoxide (Schedule IV), alfaxalone produces anxiolytic-like
behavioral effects in rat models of anxiety, such as the elevated plus
maze, the conflict test and restraint stress. In a published drug
discrimination study, in which rats were trained to discriminate
midazolam (Schedule IV) from saline, alfaxalone fully generalized to
the midazolam discriminative cue. These results are consistent with
previously published studies showing ethanol-like discriminative
stimulus effects of alfaxalone and with other studies showing that
other neurosteroids have barbiturate-like or benzodiazepine-like
discriminative stimulus effects in rats and monkeys. This
pharmacological profile of alfaxalone is consistent with neurosteroids
with GABAergic effects.
According to the HHS review, the oral administration of alfaxalone
as compared to its intravenous administration is 100 times less potent
for producing midazolam-like effects. Alfaxalone has a low oral
bioavailability (about 2%). It has been shown that an intravenous dose
of about 50 mg of alfaxalone results in anesthesia in humans with a
plasma level of 3 mg/L. Accordingly, an oral dose of about 2500 mg
might be expected to result in anesthesia at the plasma level of 3 mg/L
in humans, and thus oral doses of 250
[[Page 17898]]
to 800 mg of alfaxalone should be needed to produce a sub-anesthetic
intoxication at plasma levels in a range of 0.3 to 1.0 mg/L. For a vial
containing 100 mg of alfaxalone for an oral use, an amount of 2.5 to 8
vials would be needed to produce a "high".
As stated in the HHS review, self-administration studies in animals
with pregnanolone, allopregnanolone, endogenous metabolites of
progesterone and a neuroactive steroid, Co 8-7071, showed that these
substances produce some positive reinforcing effects in rats and rhesus
monkeys. These substances, similar to alfaxalone, positively modulate
GABA-A receptors by binding at the neurosteroid modulatory site. HHS
stated that these data are predictive of abuse potential of alfaxalone.
HHS review also cited recent evidence that alpha4, beta3 and delta
GABA-A receptors are modulated by both THDOC, a neurosteroid, and
propofol. Based on this potential overlap in cellular targets,
comparable kinetic profiles, and similar clinical indications for
propofol and alfaxalone, HHS reasoned that alfaxalone may produce
reinforcing effects similar to those of propofol.
In summary, alfaxalone, similar to chlordiazepoxide (Schedule IV),
has anxiolytic activity in animals. Alfaxalone produced midazolam-like
(Schedule IV) discriminative stimulus effects in rats, and it may share
propofol's reinforcing effects. The abuse-related neuropharmacology
profile of alfaxalone is similar to that of Schedule IV substances.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: The chemical name of alfaxalone is 5[alpha]-pregnan-
3[alpha]-ol-11, 20-dione. Alfaxalone has a molecular formula of
C21H32O3 and a molecular weight of
332.5 g/mol, and a melting point of 165[deg] to 171[deg]C. Alfaxalone
has a poor water solubility (< 5 [micro]g/ml), but its water solubility
increases to 80 mg/ml via complexation with cyclodextrins, especially
2-hydroxypropyl-beta-cyclodextrin (2HPCD). According to the HHS review,
the alfaxalone product for veterinary anesthesia will be formulated as
a 10 mg/ml solution of alfaxalone in 2HPCD (80 mg/ml), sodium phosphate
buffer and water, adjusted to a pH of 6.5 to 7. According to the
Sponsor's information cited by the HHS review, the processes involved
in the synthesis and purification of alfaxalone are highly complex and
require expertise in chemistry manufacture.
According to the HHS, the half-lives of alfaxalone are 24-37 and
45-77 minutes in dogs and cats, respectively. The clearance of
alfaxalone is 59 ml/min/kg in dogs and 28 ml/min/kg in cats. The
primary routes of elimination in the rat are biliary (65%) and renal
(35%) routes. The half-life of alfaxalone in humans is about 35
minutes. The major metabolites in humans are glucuronidated and the
primary route of elimination is through renal (80%). Oral
bioavailability of alfaxalone is about 2% as compared to its
intravenous administration in humans. A clinical study showed that an
intravenous administration of 30 mg alfaxalone produced plasma levels
of about 3 mg/L, accompanied by anesthesia in humans. The veterinary
alfaxalone product that is recently approved by the FDA contains 100
mg/vial (a vial of 10 ml formulated solution, 10 mg/ml of alfaxalone)
which would be sufficient to produce anesthesia in two individuals when
administered intravenously. HHS also states that because alfaxalone can
be abused at subanesthetic doses, a 100 mg vial of alfaxalone drug
product administered intravenously could be used repeatedly by the same
individual, or by multiple individuals, who intended to abuse the
substance.
4. Its History and Current Pattern of Abuse: Since alfaxalone is a
new veterinary product and has not been marketed in the United States,
information on actual abuse of alfaxalone in the United States is not
available. Because alfaxalone has been marketed under the trade name
Alfaxan[supreg] in the United Kingdom (UK) since 2007, the Sponsor
submitted to HHS the results of a search of pharmacovigilance reports
to the UK Veterinary Medicines Directorate. According to HHS, the
Sponsor also provided information obtained from several other sources
regarding diversion and abuse of alfaxalone. None of the above sources
contained evidence of abuse of alfaxalone by humans. According to the
HHS review, a search conducted by the Sponsor of the publically-
available pharmacovigilance database provided by the UK's Medicines and
Healthcare Products Regulatory Agency (MHRA) Web site also did not
produce reports related to alfaxalone abuse. DEA conducted a
comprehensive search of several major national drug abuse monitoring
programs and found no evidence of alfaxalone abuse. It may be due to
the fact that alfaxalone-containing products have not been marketed in
the United States to date. However, alfaxalone's pharmacological
properties suggest that its pattern of abuse would be similar to other
drugs used in maintenance and induction of anesthesia, such as
midazolam (Schedule IV) and propofol (Schedule IV under consideration).
5. The Scope, Duration, and Significance of Abuse: As mentioned
above, a comprehensive search by DEA of the major national drug abuse
monitoring programs found no evidence of human abuse of alfaxalone in
the U.S. However, as stated in the HHS review, the "suspicious order
monitor system" of the U.S. distributor of alfaxalone, will be
utilized to monitor the diversion of this product. This monitoring
system of evaluates order quantities, buying patterns, and customer
class regarding orders of unusual volume that could indicate diversion.
As part of their monitoring, daily searches of the DEA Web site for new
abuse issues and for abuse-related data from HHS's Substance Abuse and
Mental Health Administration Services (SAMHSA) will be conducted.
Additionally, the Sponsor will provide FDA with pharmacovigilance
information for both animal and human adverse events from all markets.
6. What, if any, Risk There is to the Public Health: According to
the HHS review, the public health risks of alfaxalone are mostly risks
to the individual abuser and the risks are similar to those associated
with the abuse of other sedative hypnotics and CNS depressants, such as
midazolam and methohexital. Abuse of alfaxalone may lead to the death
of the abuser or other adverse events that affect behavior, reaction
ability and timing in operating a motor vehicle or machinery. As an
anesthetic, the adverse events (AEs) that are likely to result from
alfaxalone use are usually similar to those arising from the use of
most general anesthetics. These events include apnea, bradycardia,
bradypnea, hypertension, hypotension, hypothermia, hypoxia,
unacceptable anesthesia quality, tachycardia and emesis. These AEs were
found in animal studies involving cats and dogs. Alfaxalone, as
anesthetic product if used in excess, carries potential for overdose.
HHS cited two cases involving the accidental overdose of the
alfaxalone human product, Althesin[supreg], a human product containing
combination of alfaxalone/alfadolone which was previously withdrawn
from market. HHS stated that the occurrence of an accidental or
purposeful overdose of Alfaxan[supreg] (containing 10 mg/ml of
alfaxalone) is unlikely. HHS reasoned that if a person were trying to
duplicate the same accidental overdose of injectable alfaxalone
solution, he or she would be required to draw up a large volume of
alfaxalone solution into the
[[Page 17899]]
syringe. The intravenous self-administration of such large volume of
Alfaxan[supreg] would be a very difficult if not impossible to perform,
as the person would likely be anesthetized after the first 4.2 ml of
the injection. If a person were to drink Alfaxan[supreg] to try to
cause overdose, it would require 100 times more drug because of
alfaxalone's poor oral bioavailability (1-2%). According to HHS, little
is known about other health effects that might occur in someone abusing
the drug chronically. In summary, the public health risks of alfaxalone
abuse are similar to those associated with the abuse of other sedative
hypnotics and CNS depressants, such as midazolam and methohexital which
are controlled in Schedule IV of the CSA and propofol (Schedule IV
under consideration). The major adverse events of these anesthetics
include respiratory depression and deaths.
7. Its Psychic or Physiological Dependence Liability: According to
HHS, studies of abrupt discontinuation of alfaxalone were not
conducted. However, a study cited (McMohan et al., 2007) by the HHS
review suggested the ability of alfaxalone to produce physical
dependence. McMahon and his associates found that alfaxalone reduced
the discriminative cue produced by flumazenil-precipitated withdrawal
following chronic administration of benzodiazepines such as diazepam or
lorazepam (both Schedule IV) in Rhesus monkeys (McMahon et al., 2007).
The HHS review concludes that alfaxalone can decrease withdrawal
resulting from chronic administration of other positive GABA-A receptor
modulators. According to HHS, there is no data available on the effects
of abrupt discontinuation of alfaxalone because, as an anesthetic, it
is not used chronically and not available for chronic use.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled Under the CSA: Alfaxalone is not considered an
immediate precursor of any controlled substance of the CSA as defined
by 21 U.S.C 802(23).
Conclusion: Based on consideration of the scientific and medical
evaluation and accompanying recommendation of HHS, and based on DEA's
consideration of its own eight-factor analysis, DEA finds that these
facts and all relevant data constitute substantial evidence of
potential for abuse of alfaxalone. As such, DEA hereby proposes to
schedule alfaxalone as a controlled substance under the CSA.
Proposed Determination of Appropriate Schedule
The CSA establishes five schedules of controlled substances known
as Schedules I, II, III, IV, and V. The statute outlines the findings
required to place a drug or other substance in any particular schedule.
21 U.S.C. 812(b). After consideration of the analysis and
recommendations of the Assistant Secretary for Health of HHS and review
of all available data, the Administrator of DEA, pursuant to 21 U.S.C.
812(b)(4), finds that:
(1) 5[alpha]-pregnan-3[alpha]-ol-11,20-dione (alfaxalone) has a low
potential for abuse relative to the drugs or other substances in
Schedule III;
(2) 5[alpha]-pregnan-3[alpha]-ol-11,20-dione (alfaxalone) has a
currently accepted medical use in treatment in the United States.
Alfaxalone was approved for marketing by FDA as a veterinary anesthetic
product for the induction and maintenance of anesthesia in cats and in
dogs; and
(3) abuse of 5[alpha]-pregnan-3[alpha]-ol-11,20-dione (alfaxalone)
may lead to limited physical dependence or psychological dependence
relative to the drugs or other substances in Schedule III.
Based on these findings, the Administrator of DEA concludes that
5[alpha]-pregnan-3[alpha]-ol-11,20-dione (alfaxalone) 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 Alfaxalone
If this rule is finalized as proposed, alfaxalone would be subject
to the CSA and the Controlled Substances Import and Export Act (CSIEA)
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 alfaxalone or who desires to manufacture, distribute,
dispense, import, export, engage in research or conduct instructional
activities with alfaxalone would need to be registered to conduct such
activities pursuant to 21 U.S.C. 822 and 958 and in accordance with 21
CFR part 1301.
Security. Alfaxalone would be subject to Schedule 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 alfaxalone which is distributed on or after the effective
date of the finalization of this rule would need to be in accordance
with 21 CFR 1302.03-1302.07, pursuant to 21 U.S.C. 825.
Inventory. Every registrant required to keep records and who
possesses any quantity of alfaxalone would be required to keep an
inventory of all stocks of alfaxalone on hand pursuant to 21 U.S.C. 827 and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11. Every
registrant who desires registration in Schedule IV for alfaxalone 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 U.S.C. 827 and in accordance with 21 CFR 1304.03, 1304.04,
1304.21, 1304.22, and 1304.23.
Prescriptions. Alfaxalone or products containing alfaxalone would
be required to be distributed or dispensed pursuant to 21 U.S.C. 829 and in accordance with 21 CFR 1306.03-1306.06, 1306.08, 1308.09, and
1306.21-1306.27.
Importation and Exportation. All importation and exportation of
alfaxalone would need to be done in accordance with 21 CFR part 1312,
pursuant to 21 U.S.C. 952, 953, 957, and 958.
Criminal Liability. Any activity with alfaxalone not authorized by,
or in violation of, the CSA occurring on or after effective date of the
finalization of this proposed rule would be unlawful.
Regulatory Analyses
Executive Orders 12866 and 13563
In accordance with 21 U.S.C. 811(a), this proposed scheduling
action is subject to formal rulemaking procedures done "on the record
after opportunity for a hearing," which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the criteria for
scheduling a drug or other substance. Such actions are exempt from
review by the Office of Management and Budget pursuant to Section
3(d)(1) of Executive Order 12866 and the principles reaffirmed in
Executive Order 13563.
Executive Order 12988
This proposed regulation meets the applicable standards set forth
in Sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice
Reform to eliminate ambiguity, minimizes
[[Page 17900]]
litigation, establish clear legal standards, and reduce burden.
Executive Order 13132
This proposed 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.
Executive Order 13175
This proposed rule will not have tribal implications and will not
impose substantial direct compliance costs on Indian tribal
governments.
Paperwork Reduction Act of 1995
This action does not impose a new collection of information under
the Paperwork Reduction Act of 1995, 44 U.S.C. 3501-3521.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.
For the reasons set out above, 21 CFR part 1308 is proposed to be
amended to read as follows:
PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES
Authority: 21 U.S.C. 811, 812, 871(b), unless otherwise noted.
- 2. Section 1308.14 is amended by redesignating paragraphs (c)(1)
through (c)(53) as paragraphs (c)(2) through (c)(54) and adding a new
paragraph (c)(1) as follows:
Sec. 1308.14 Schedule IV.
* * * * *
(c) * * *
(1) 5[alpha]-pregnan-3[alpha]-ol-11,20-dione (Alfaxalone) * * *
(2731)
* * * * *
Dated: March 15, 2013.
Michele M. Leonhart,
Administrator.
[FR Doc. 2013-06651 Filed 3-22-13; 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 Printing Office (GPO). |
