[Federal Register Volume 77, Number 146 (Monday, July 30, 2012)]
[Rules and Regulations]
[Pages 44456-44462]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-18495]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1300
[Docket No. DEA-341F]
RIN 1117-AB31
Classification of Two Steroids, Prostanozol and Methasterone, as
Schedule III Anabolic Steroids Under the Controlled Substances Act
AGENCY: Drug Enforcement Administration (DEA), Department of Justice.
ACTION: Final rule.
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SUMMARY: With the issuance of this Final Rule, the Administrator of the
DEA classifies the following two steroids as ``anabolic steroids''
under the Controlled Substances Act (CSA): prostanozol (17[beta]-
hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone
(2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one).
These steroids and their salts, esters, and ethers are Schedule III
controlled substances subject to the regulatory control provisions of
the CSA.
DATES: Effective Date: August 29, 2012.
FOR FURTHER INFORMATION CONTACT: Alan G. Santos, Associate Deputy
Assistant Administrator, Office of Diversion Control, Drug Enforcement
Administration; Mailing Address: 8701 Morrissette Drive, Springfield,
Virginia 22152; Telephone: (202) 307-7165.
SUPPLEMENTARY INFORMATION:
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 is published at 21 CFR Part 1308.
On November 29, 1990, the President signed into law the Anabolic
Steroids Control Act of 1990 (Title XIX of Pub. L. 101-647), which
became effective
[[Page 44457]]
February 27, 1991. This law established and regulated anabolic steroids
as a class of drugs under Schedule III of the CSA. As a result, a new
anabolic steroid is not scheduled according to the procedures set out
in 21 U.S.C. 811, but is administratively classified as an anabolic
steroid through the rulemaking process if it meets the regulatory
definition of an anabolic steroid in 21 CFR 1300.01.
On October 22, 2004, the President signed into law the Anabolic
Steroid Control Act of 2004 (Pub. L. 108-358), which became effective
on January 20, 2005. Section 2(a) of the Anabolic Steroid Control Act
of 2004 amended 21 U.S.C. 802(41)(A) by replacing the existing
definition of ``anabolic steroid.'' The Anabolic Steroid Control Act of
2004 classifies a drug or hormonal substance as an anabolic steroid if
the following four criteria are met: (A) The substance is chemically
related to testosterone; (B) the substance is pharmacologically related
to testosterone; (C) the substance is not an estrogen, progestin, or a
corticosteroid; and (D) the substance is not dehydroepiandrosterone
(DHEA). Any substance that meets these criteria is considered an
anabolic steroid and must be listed as a Schedule III controlled
substance.
Background
In a Notice of Proposed Rulemaking (NPRM) published on November 23,
2011 (76 FR 72355), DEA proposed classification of two steroids as
Schedule III anabolic steroids under the CSA: Prostanozol and
methasterone. DEA believes that prostanozol (17[beta]-hydroxy-5[alpha]-
androstano[3,2-c]pyrazole) and methasterone (2[alpha],17[alpha]-
dimethyl-5[alpha]-androstan-17[beta]-ol-3-one) meet this definition of
anabolic steroid.
Anabolic steroids are a class of drugs structurally related to the
endogenous hormone testosterone that exert androgenic (masculinizing)
as well as anabolic (body building) effects. These effects are mediated
primarily through binding of the anabolic steroid to the androgen
receptor in target tissues (Evans, 2004). Anabolic effects include
promotion of protein synthesis in skeletal muscle and bone, while the
androgenic effects are characterized by the development of male
secondary sexual characteristics such as hair growth, deepening of the
voice, glandular activity, thickening of the skin, and central nervous
system effects (Kicman, 2008). Anabolic efficacy is characterized by
positive nitrogen balance and protein metabolism, resulting in
increases in protein synthesis and lean body mass (Evans, 2004). These
effects often come at a cost to the healthy individual who experiences
clear physical and psychological complications (Trenton and Currier,
2005; Brower, 2002; Hall et al., 2005).
In the United States, only a small number of anabolic steroids are
approved for either human or veterinary use. Approved medical uses for
anabolic steroids include treatment of androgen deficiency in
hypogonadal males, adjunctive therapy to offset protein catabolism
associated with prolonged administration of corticosteroids, treatment
of delayed puberty in boys, treatment of metastatic breast cancer in
women, and treatment of anemia associated with specific diseases (e.g.,
anemia of chronic renal failure, Fanconi's anemia, and acquired
aplastic anemia). However, with the exception of the treatment of male
hypogonadism, anabolic steroids are not the first-line treatment due to
the availability of other preferred treatment options. DEA is not aware
of any legitimate medical use or New Drug Applications (NDA) for the
two substances that DEA is proposing to classify by this NPRM as
anabolic steroids under the definition set forth under 21 U.S.C.
802(41)(A). Moreover, DEA has been unable to identify any chemical
manufacturers currently using these substances as intermediates in
their manufacturing processes.
Adverse health effects are associated with abuse of anabolic
steroids and depend on several factors (e.g., age, sex, anabolic
steroid used, the amount used, and the duration of use) (Hall and Hall,
2005; Quaglio et al., 2009). These include cardiovascular,
dermatological, behavioral, hepatic, and gender specific endocrine side
effects. Anabolic steroids have direct and indirect impact on the
developing adolescent brain and behavior (Sato et al., 2008).
Furthermore, adolescent abuse of anabolic steroids may result in
stunted growth due to premature closure of the growth plates in long
bones.
In adolescent boys, anabolic steroid abuse can cause precocious
sexual development. In both girls and women, anabolic steroid abuse
induces permanent physical changes such as deepening of the voice,
increased facial and body hair growth, menstrual irregularities, and
clitoral hypertrophy. In men, anabolic steroid abuse can cause
testicular atrophy, decreased sperm count, and sterility. Gynecomastia
(i.e., enlargement of the male breast tissue) can develop with the
abuse of those anabolic steroids with estrogenic actions. In both men
and women, anabolic steroid abuse can damage the liver and may result
in high cholesterol levels, which may increase the risk of strokes and
cardiovascular heart attacks. Furthermore, anabolic steroid abuse is
purported to induce psychological effects such as aggression, increased
feelings of hostility, and psychological dependence and addiction
(Brower, 2002; Kanayama et al., 2008).
Upon abrupt termination of long-term anabolic steroid abuse, a
withdrawal syndrome may appear including severe depression.
Additionally, polysubstance abuse is routinely associated with anabolic
steroid abuse, where ancillary drugs, including recreational and
prescription drugs, are abused in response to unwanted side effects
(Hall et al., 2005; Parkinson et al., 2005; Skarberg et al., 2009).
A review of the scientific literature finds adverse health effects
including liver toxicity with renal failure reported in conjunction
with methasterone abuse (Shah et al., 2008; Jasiurkowski et al., 2006;
Singh et al., 2009; Nasr and Ahmad, 2008; and Krishnan et al., 2009).
In March 2006, the U.S. Food and Drug Administration (FDA) issued a
Warning Letter in response to adverse health effects associated with
the product Superdrol (methasterone). In July 2009, FDA issued a
warning regarding bodybuilding products containing steroid or steroid-
like substances. In this warning, a product containing the THP ether
derivative of prostanozol was named in conjunction with other products
presenting safety concerns.
Evaluation of Statutory Factors for Classification as an Anabolic
Steroid
With the issuance of this Final Rule, DEA classifies prostanozol
(17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone
(2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one) as
anabolic steroids under the definition set forth under 21 U.S.C.
802(41)(A). As noted previously, a drug or hormonal substance is
classified as an anabolic steroid by meeting the following four
definitional requirements: (A) The substance is chemically related to
testosterone; (B) the substance is pharmacologically related to
testosterone; (C) the substance is not an estrogen, progestin, or
corticosteroid; and (D) the substance is not DHEA.
(A) Chemically Related to Testosterone
To classify a substance as an anabolic steroid, a substance must be
chemically related to testosterone. A structure activity relationship
(SAR) evaluation for each substance compared the chemical structure of
the steroid to that of testosterone. Substances with a
[[Page 44458]]
structure similar to that of testosterone are predicted to possess
comparable pharmacological and biological activity.
Prostanozol is also known by the following name: 17[beta]-hydroxy-
5[alpha]-androstano[3,2-c]pyrazole. DEA determined that the chemical
structure of prostanozol is similar to testosterone, differing by only
the attachment of a pyrazole ring at carbon 2 (C2) and carbon 3 (C3)
positions of the androstane skeleton, replacing the C3-keto group and
the lack of a double bond between carbon 4 (C4) and carbon 5 (C5)
positions. Similar modifications to testosterone's chemical structure
have been documented and, in general, they have been found to be well
tolerated, displaying both anabolic and androgenic activity (Fragkaki
et al., 2009; Vida, 1969). Clinton and coworkers, in their synthesis of
prostanozol, described the modification as a fusion of a pyrazole ring
to the androstane steroidal nucleus at C2 and C3 (Clinton et al.,
1961). Further analysis finds the chemical structure of prostanozol to
be very similar to the anabolic steroid stanozolol. The two structures
differ only about a 17[alpha]-methyl group (alpha methyl group attached
to carbon 17).
Methasterone is known by the following chemical names:
2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one;
2[alpha],17[alpha]-dimethyl-17[beta]-hydroxy-5[alpha]-androstan-3-one;
17[alpha]-methyl-drostanolone; methasteron; methyldrostanolone;
2[alpha],17[alpha]-dimethyldihydrotestosterone; and 2[alpha],17[alpha]-
dimethyl-etiocholan-17[beta]-ol-3-one. DEA has determined that the
chemical structure of methasterone is chemically related to
testosterone. The chemical structure of methasterone differs from
testosterone by the following three chemical groups: An alpha methyl
group at carbon 17 (C17), an alpha methyl group at C2, and the lack of
a double bond between spanning C4 and C5. Removal of the C4-C5 double
bond (A-ring) and methylation at the C2 and C17 positions has been
shown to increase anabolic activity (Zaffroni, 1960; Fragkaki et al.,
2009). Furthermore, methyl group substitution at the C2 and C17 has
been reported to impair aromatization, thus, prolonging the anabolic
effect (Fragkaki et al., 2009).
(B) Pharmacologically Related to Testosterone
A substance must also be pharmacologically related to testosterone
(i.e., produce similar biological effects) to be classified as a
Schedule III anabolic steroid. The pharmacology of a steroid, as
related to testosterone, can be established by performing one or more
of the following androgenic and anabolic activity assays: ventral
prostate assay, seminal vesicle assay, levator ani assay, and androgen
receptor binding and efficacy assays. These assays are described below.
Ventral Prostate Assay, Seminal Vesicle Assay, and Levator Ani
Assay: The classic scientific procedure for evaluating androgenic
(masculinizing) and anabolic (muscularizing) effects of a steroid is
the ventral prostate assay, seminal vesicle assay, and levator ani
assay. This testing paradigm allows for the direct comparison to
testosterone. Select male accessory tissues (i.e., the ventral
prostate, seminal vesicles, and levator ani muscle) are testosterone
sensitive, specifically requiring testosterone to grow and remain
healthy. Upon the removal of the testes (i.e., castration), the primary
endogenous source of testosterone is eliminated causing the atrophy of
the ventral prostate, seminal vesicles, and levator ani muscle
(Eisenberg et al., 1949; Nelson et al., 1940; Scow, 1952; Wainman and
Shipounoff, 1941). Numerous scientific studies have demonstrated the
ability of exogenous testosterone or a pharmacologically similar
steroid administered to rats following castration to maintain the
normal weight and size of all three testosterone sensitive organs
(Biskind and Meyer, 1941; Dorfman and Dorfman, 1963; Dorfman and Kincl,
1963; Kincl and Dorfman, 1964; Nelson et al., 1940; Scow, 1952; Wainman
and Shipounoff, 1941). Thus, a steroid with testosterone-like activity
will also prevent the atrophy of these three testosterone-dependent
organs in castrated rats.
Castrated male rats are administered the steroid for a number of
days, then the rats are euthanized and the previously described tissues
are excised and weighed. Tissue weights from the three animal test
groups are compared, castrated animals alone, castrated animals
receiving the steroid, and healthy intact animals (control), to assess
anabolic and androgenic activity. A reduction in tissue weights
relative to the control group suggests a lack of androgenic and/or
anabolic activity. An increase in tissue weights relative to the
castrated rats receiving no steroid suggests an androgenic and/or
anabolic effect.
Androgen Receptor Binding and Efficacy Assay: Anabolic steroids
bind with the androgen receptor to exert their biological effect.
Affinity for the receptor is evaluated in the receptor binding assay,
while the transactivation (functional) assay provides additional
information as to both affinity and ability to activate the receptor.
Receptor binding and transactivation studies are valuable tools in
evaluating pharmacological activity and drawing comparisons to other
substances. A steroid displaying affinity for the androgen receptor and
properties of being an agonist in transactivation studies is determined
to be pharmacologically similar to testosterone.
Studies used to evaluate anabolic steroids are the androgen
receptor binding assay and the androgen receptor transactivation assay.
Both are well-established and provide significant utility in evaluating
steroids for affinity to their biological target and the modulation of
activity. The androgen receptor binding assay provides specific detail
as to the affinity of a steroid for the androgen receptor (biological
target of anabolic steroids). To assess further whether the steroid is
capable of activating the androgen receptor, the androgen receptor
transactivation assay evaluates the binding of a steroid to the
androgen receptor and subsequent interaction with DNA. In this study,
transcription of a reporter gene provides information as to a steroid's
ability to modulate a biological event. This activity measurement
provides information as to the potency of a steroid to bind to a
receptor and either initiate or inhibit the transcription of the
reporter gene. The androgen receptor binding assay and androgen
receptor transactivation assay are highly valuable tools in assessing
the potential activity of a steroid and comparing the activity to
testosterone.
Results of the Androgenic and Anabolic Activity Assays: DEA
reviewed the published scientific literature, and pharmacological
studies were undertaken to collect additional information on
prostanozol and methasterone in several different androgenic and
anabolic activity assays. Findings from these studies indicate that in
addition to being structurally similar to testosterone, prostanozol and
methasterone have similar pharmacological activity as testosterone.
Prostanozol
The chemical synthesis and anabolic and androgenic effects of
prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) were
published in 1961 (Clinton et al., 1961). Clinton and coworkers
evaluated the anabolic activity by means of nitrogen balance and
androgenic activity based on weight changes of the ventral prostrate of
prostanozol upon subcutaneous administration to rats with the reference
[[Page 44459]]
standard testosterone propionate. The potency ratio of anabolic
activity to androgenic activity for prostanozol was reported to be
eight (Clinton et al., 1961). In another study, prostanozol was
reported to have approximately the same relative binding affinity for
human sex steroid binding protein as testosterone (Cunningham et al.,
1981).
To build on these findings, a pharmacological study \1\ was
conducted to evaluate the anabolic and androgenic effects of
prostanozol in castrated male rats. Results were compared to
testosterone by a similar protocol. Administration of prostanozol to
castrated male rats by subcutaneous injection prevented the atrophy
(loss in weight) of the ventral prostate, seminal vesicles, and levator
ani muscle.\1\ These testosterone sensitive tissues experienced
increases in weight comparable to testosterone in castrated male rats.
Results from this study support that prostanozol possesses both
androgenic and anabolic activity. Additional studies were conducted to
further assess prostanozol's anabolic effect. In a competitive binding
assay, prostanozol was found to possess affinity for the androgen
receptor comparable to testosterone.\1\ In the androgen receptor
transactivation assay, prostanozol displayed increased activity
relative to testosterone.\1\ Effects elicited by prostanozol in this
transactivation assay were consistent and comparable to those of
testosterone. Taken together, data from in vitro and in vivo assays
indicate the pharmacology of prostanozol to be similar to testosterone.
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\1\ The study by Bioqual, Inc., Rockville, MD, may be found at
http://www.regulations.gov in the electronic docket associated with
this rulemaking.
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Methasterone
The synthesis of methasterone (2[alpha],17[alpha]-dimethyl-
5[alpha]-androstan-17[beta]-ol-3-one) was reported in 1956 and the
anabolic activity in 1959 (Ringold and Rosenkranz, 1956; Ringold et
al., 1959). Methasterone was described as a potent anabolic agent
exhibiting weak androgenic activity in the castrated male rat (Ringold
et al., 1959). Zaffaroni and coworkers reported methasterone possessed
one-fifth the androgenic activity and four times the anabolic activity
of the anabolic steroid methyltestosterone, when administered orally to
the experimental animal (Zaffaroni et al., 1960).
Additional pharmacological studies were undertaken to further
evaluate the androgenic and anabolic effects of methasterone.\1\
Methasterone was administered subcutaneously and orally to castrated
male rats. By both routes of administration, methasterone prevented the
atrophy (loss in weight) of ventral prostate, seminal vesicles, and
levator ani muscle. Tissue weight increases for the castrated
methasterone-treated animals were comparable to the castrated rats
treated with testosterone and methyltestosterone. These results were
consistent with earlier findings that methasterone is anabolic and
androgenic (Zaffaroni, 1960; Ringold et al., 1959). Functional assays
were also undertaken to further evaluate methasterone.\1\ Methasterone
displayed affinity for the androgen receptor comparable to testosterone
in a competitive binding assay.\1\ In the androgen receptor
transactivation assay, methasterone displayed increased activity
relative to testosterone.\1\ Effects elicited by methasterone in the
androgen transactivation assay were consistent and comparable to those
of testosterone. Collectively, in vivo and in vitro results indicate
that the pharmacology of methasterone is similar to testosterone.
(C) Not Estrogens, Progestins, and Corticosteroids
DEA has determined that prostanozol and methasterone are unrelated
to estrogens, progestins, and corticosteroids. DEA evaluated the SAR
for each of the substances. The chemical structure of each substance
was compared to that of estrogens, progestins, and corticosteroids,
since chemical structure can be related to its pharmacological and
biological activity. DEA found that these two substances lack the
necessary chemical structures to impart significant estrogenic activity
(e.g., aromatic A ring) (Duax et al., 1988; Jordan et al., 1985;
Williams and Stancel, 1996), progestational activity (e.g., 17[beta]-
alkyl group) (Williams and Stancel, 1996), or corticosteroidal activity
(e.g., 17[beta]-ketone group or 11[beta]-hydroxyl group) (Miller et
al., 2002). Furthermore, methasterone was reported to display anti-
estrogenic activity in mouse assay to assess estrogen stimulated
uterine growth (Dorfman et al., 1961). To assess the estrogenic,
progestational, and corticosteroid activity of prostanozol and
methasterone, these substances were evaluated in receptor binding and
functional transactivation assays. Prostanozol and methasterone showed
low binding affinity for the estrogen, progesterone, and glucocorticoid
receptors. Furthermore, these steroids displayed low to no
transactivation mediated by the estrogen receptors, progesterone
receptors, or glucocorticoid receptors. Therefore, based on these data,
prostanozol and methasterone are not estrogens, progestins, or
corticosteroids and these anabolic steroids are not exempt from control
on this basis.
(D) Not Dehydroepiandrosterone
Dehydroepiandrosterone, also known as DHEA, is exempt from control
as an anabolic steroid by definition (21 U.S.C. 802(41)(A)).
Prostanozol and methasterone are not dehydroepiandrosterone and
therefore, are not exempt from control on this basis.
Comments Received
On November 23, 2011, DEA published a NPRM (76 FR 72355) to
classify prostanozol and methasterone as Schedule III anabolic
steroids. The proposed rule provided an opportunity for all interested
persons to submit their comments on or before January 23, 2012. In
response to the request, DEA received three comments.
Comment: One commenter disagreed that anabolic steroids, and in
particular those encountered in dietary supplements, should be placed
in Schedule III of the CSA. He indicated that classifying these
substances as Schedule III anabolic steroids would force the public to
procure other, non-regulated and unsafe substitutes from illicit
sources in the future, and that DEA should employ an alternate method
of regulation.
DEA Response: DEA disagrees with this comment. As stated in the
NPRM and this Final Rule, these substances were found to be similar in
structure and pharmacology to testosterone through substantive
scientific evaluation and investigation. Further, the United States
Food and Drug Administration has issued multiple warnings regarding
dietary supplements, especially concerning contamination through novel
synthetic steroids that do not qualify as dietary ingredients.
Regarding the commenter's request for alternative regulation of
these substances. DEA regulates the manufacture, importation, export,
distribution, and sale of controlled substances for medical,
scientific, or other legitimate uses pursuant to the CSA. These
substances have not been approved as safe for human consumption and,
despite the commenter's unsubstantiated and factually inaccurate claims
of their benefits, should neither be consumed nor should other
unapproved substances ever be sought from any source, illicit or
otherwise.
The additional remarks this commenter made regarding a perceived
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disparity between men and women in access to hormonal products, and
other perceived problems with the regulation of substances by the
government, are not germane to this rulemaking.
Comment: Two separate commenters agreed placement of these two
substances under the CSA was appropriate as provided per the Anabolic
Steroid Control Act of 2004.
DEA Response: DEA appreciates the support for this rulemaking. As
discussed above, prostanozol and methasterone are similar in structure
and pharmacology to testosterone and are not approved for human
consumption. DEA believes their placement into Schedule III as anabolic
steroids will provide the appropriate safeguards to limit their
availability to and prevent their abuse by the public.
Conclusion
After evaluation of the statutory factors above and consideration
of the comments to the NPRM, DEA concludes that prostanozol and
methasterone meet the CSA definition of ``anabolic steroid'' because
each substance is: (A) Chemically related to testosterone; (B)
pharmacologically related to testosterone; (C) not an estrogen,
progestin, or a corticosteroid; and (D) not DHEA (21 U.S.C. 802(41)).
Once a substance is determined to be an anabolic steroid, DEA has no
discretion regarding the placement of these substances into Schedule
III of the CSA.
Impact of Classification as Anabolic Steroids
With the publication of this Final Rule, DEA classifies prostanozol
(17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone
(2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one) as
Schedule III anabolic steroids subject to the CSA. Any person who
manufactures, distributes, dispenses, imports, or exports prostanozol
or methasterone, or who engages in research or conducts instructional
activities with respect to these two substances, will be required to
obtain a Schedule III registration in accordance with the CSA and its
implementing regulations.
As of the effective date of this Final Rule, the manufacture,
import, export, distribution, or sale of prostanozol or methasterone,
except by DEA registrants, is a violation of the CSA that may result in
imprisonment and fines (see, e.g., 21 U.S.C. 841 and 960). Possession
of these two steroids, unless legally obtained, is also subject to
criminal penalties pursuant to 21 U.S.C. 844.
Manufacturers and importers of these two substances will be
required to register with DEA and will be permitted to distribute these
substances only to other DEA registrants. Only persons registered as
dispensers will be allowed to dispense these substances to end users.
The CSA defines a practitioner as ``a physician, dentist, veterinarian,
scientific investigator, pharmacy, hospital, or other person licensed,
registered, or otherwise permitted, by the United States or the
jurisdiction in which he practices or does research, to distribute,
dispense, conduct research with respect to, administer, or use in
teaching or chemical analysis, a controlled substance in the course of
professional practice or research.'' 21 U.S.C. 802(21). At present,
there are no approved medical uses for these two substances. Until a
manufacturer applies to the FDA and gains approval for products
containing these substances, no person may dispense them in response to
a prescription.
Additionally, these two substances may only be imported for
medical, scientific, or other legitimate uses (21 U.S.C. 952(b)) under
an import declaration filed with DEA (21 CFR 1312.18). Importation of
these substances will be illegal unless the person importing these
substances is registered with DEA as an importer or researcher and
files the required declaration for each shipment. Any individual who
purchases either of these substances directly from foreign companies
and has them shipped to the United States will be considered to be
importing even if the steroids are intended for personal use. Illegal
importation of these substances will be a violation of the CSA that may
result in imprisonment and fines pursuant to 21 U.S.C. 960.
Requirements for Handling Substances Defined as Anabolic Steroids
As of the effective date of this Final Rule, prostanozol and
methasterone are subject to CSA regulatory controls and the
administrative, civil, and criminal sanctions applicable to the
manufacture, distribution, dispensing, importation, and exportation of
a Schedule III controlled substance, including the following:
Registration. Any person who manufactures, distributes, dispenses,
imports, exports, or engages in research or conducts instructional
activities with a substance defined as an anabolic steroid, or who
desires to engage in such activities, will be required to be registered
to conduct such activities with Schedule III controlled substances in
accordance with 21 CFR Part 1301.
Security. Substances defined as anabolic steroids will be subject
to Schedule III security requirements and will be required 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 substances defined as anabolic steroids will be required
to comply with the requirements of 21 CFR 1302.03-1302.07.
Inventory. Every registrant required to keep records and who
possesses any quantity of any substance defined as an anabolic steroid
will be required to keep an inventory of all stocks of the substances
on hand pursuant to 21 U.S.C. 827 and 21 CFR 1304.03, 1304.04 and
1304.11. Every registrant who desires registration in Schedule III for
any substance defined as an anabolic steroid will be required to
conduct an inventory of all stocks of the substances on hand at the
time of registration.
Records. All registrants will be required to keep records, as
generally provided in 21 U.S.C. 827(a) and specifically pursuant to 21
CFR 1304.03, 1304.04, 1304.05, 1304.21, 1304.22, and 1304.23.
Prescriptions. All prescriptions for these Schedule III substances
or for products containing these Schedule III substances, if approved
in the future by FDA, will be required to be issued pursuant to 21
U.S.C. 829(b) and 21 CFR 1306.03-1306.06 and 1306.21-1306.27. All
prescriptions for these Schedule III compounds or for products
containing these Schedule III substances, if authorized for refilling,
will be limited to five refills within six months of the date of
issuance of the prescription. Controlled substance dispensing via the
Internet will have to comply with 21 U.S.C. 829(e).
Importation and Exportation. All importation and exportation of any
substance defined as an anabolic steroid will be required to be in
compliance with 21 U.S.C. 952(b), 953(e), and 21 CFR Part 1312.
Disposal. Persons who possess substances that become classified as
anabolic steroids and who wish to dispose of them rather than becoming
registered to handle them should contact their local DEA Diversion
field office for assistance in disposing of these substances legally
pursuant to 21 CFR 1307.21. The DEA Diversion field office will provide
the person with instructions regarding the disposal. A list of local
DEA Diversion field offices may be found at http://www.deadiversion.usdoj.gov.
Criminal Liability. Any activity with any substance defined as an
anabolic
[[Page 44461]]
steroid not authorized by, or in violation of, the Controlled
Substances Act or the Controlled Substances Import and Export Act will
be unlawful.
Regulatory Analyses
Regulatory Flexibility Act
The Administrator hereby certifies that this rulemaking has been
drafted in accordance with the Regulatory Flexibility Act (5 U.S.C.
601-612). This regulation will not have a significant economic impact
on a substantial number of small entities. As of March 2010, DEA had
identified approximately 75 dietary supplements that were currently or
had been promoted for building muscle and increasing strength that
purported to contain prostanozol or methasterone. Thirteen dietary
supplements were purported to contain prostanozol and 62 dietary
supplements were purported to contain methasterone. These dietary
supplements are marketed and sold over the Internet.
The manufacturers and distributors of dietary supplements purported
to contain prostanozol and methasterone also sell a variety of other
dietary supplements. DEA has identified a substantial number of
Internet distributors that sell these dietary supplements. However,
these distributors also sell a variety of other nutritional products.
Without information on the percentage of revenues derived from these
dietary supplements, DEA is not able to determine the economic impact
of the removal of these dietary supplements alone on the business of
the firms. These steroids have been the focus of warning letters issued
by the FDA. However, products continue to be marketed despite these
warnings. DEA has not been able to identify any chemical manufacturers
that are currently using these substances as intermediates in their
manufacturing process(es). As of March 2010, DEA had identified 13
chemical manufacturers and distributors that sell at least one of the
two steroids. Most of these companies are located in China and sell a
variety of other anabolic steroids. DEA notes that, as the vast
majority of entities handling these substances are Internet based, it
is virtually impossible to accurately quantify the number of persons
handling these substances at any given time. DEA has not identified any
company based in the United States that manufactures or distributes
these substances. DEA notes, upon placement into Schedule III, these
substances may be used for analytical purposes. These companies are
registered with DEA and are already in compliance with the CSA and DEA
implementing regulations regarding the handling of Schedule III
substances.
Executive Orders 12866 and 13563
This rulemaking has been drafted in accordance with the principles
of Executive Order 12866, 1(b), as reaffirmed by Executive Order 13563.
This rule is not a significant regulatory action but has been reviewed
by the Office of Management and Budget. As discussed above, the effect
of this rule will be to remove products containing these substances
from the over-the-counter marketplace. DEA has no basis for estimating
the size of the market for these products. DEA notes, however, that
virtually all of the substances are imported. According to U.S.
International Trade Commission data, the import value of all anabolic
steroids in 2009 was $5.9 million. These two substances would be a
subset of those imports. The total market for products containing these
substances, therefore, is probably quite small. Moreover, DEA believes
that the importation of these two substances is for illegitimate
purposes.
The benefit of controlling these substances is to remove from the
marketplace substances that have dangerous side effects and no
legitimate medical use in treatment in the United States. As discussed
in detail above, these substances can produce serious health effects in
adolescents and adults. If medical uses for these substances are
developed and approved, the drugs would be available as Schedule III
controlled substances in response to a prescription issued by a medical
professional for a legitimate medical purpose. Until that time,
however, this action will bar the importation, exportation, and sale of
these two substances except for legitimate research or industrial uses.
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.
Executive Order 13175
This rule will not have tribal implications and will not impose
substantial direct compliance costs on Indian tribal governments.
Paperwork Reduction Act
This rule regulates two anabolic steroids, which are neither
approved for medical use in humans nor approved for administration to
cattle or other non-humans. Only chemical manufacturers who may use
these substances as chemical intermediates for the synthesis of other
steroids would be required to register with DEA under the CSA. However,
DEA has not been able to identify any chemical manufacturers that are
currently using these substances as intermediates in their
manufacturing processes. Thus DEA does not expect this rule to impose
any additional paperwork burden on the regulated industry.
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
$136,000,000 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, 2 U.S.C. 1532.
List of Subjects in 21 CFR Part 1300
Chemicals, Drug traffic control.
For the reasons set out above, 21 CFR part 1300 is amended as
follows:
PART 1300--DEFINITIONS
0
1. The authority citation for part 1300 continues to read as follows:
Authority: 21 U.S.C. 802, 821, 829, 871(b), 951, 958(f).
0
2. In Sec. 1300.01, the definition of Anabolic steroid under paragraph
(b) is amended by:
0
A. Redesignating paragraphs (32) through (63) as (33) through (64),
0
B. Adding a new paragraph (32),
0
C. Further redesignating newly designated paragraphs (58) through (64)
as (59) through (65), and
0
D. Adding new paragraph (58).
The additions read as follows:
Sec. 1300.01 Definitions relating to controlled substances.
* * * * *
(b) * * *
Anabolic steroid * * *
(32) Methasterone (2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-
17[beta]-ol-3-one)
* * * * *
[[Page 44462]]
(58) Prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-
c]pyrazole)
* * * * *
Dated: July 13, 2012.
Michele M. Leonhart,
Administrator.
Note: The following appendix will not appear in the Code of
Federal Regulations.
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[FR Doc. 2012-18495 Filed 7-27-12; 8:45 am]
BILLING CODE 4410-09-P