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[Federal Register Volume 76, Number 226 (Wednesday, November 23, 2011)]
[Proposed Rules]
[Pages 72355-72362]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-30081]

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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1300

[Docket No. DEA-341P]
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: Notice of proposed rulemaking.

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SUMMARY: This Notice of Proposed Rulemaking (NPRM) proposes to classify 
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). The 
Drug Enforcement Administration (DEA) believes that this action is 
necessary to prevent the abuse and trafficking of

[[Page 72356]]

these steroids. If the regulations are amended, these steroids will be 
listed as Schedule III controlled substances subject to the regulatory 
control provisions of the CSA.

DATES: Electronic comments must be submitted and written comments must 
be postmarked on or before January 23, 2012. 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.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-341'' 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 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.

FOR FURTHER INFORMATION CONTACT: Rhea D. Moore, Office of Diversion 
Control, Drug Enforcement Administration, 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 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'' paragraph.

Background Information

    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 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 can be administratively 
classified as an anabolic steroid through the rulemaking process by 
adding the steroid to the regulatory definition of an anabolic steroid 
in 21 CFR 1300.01(b)(4).
    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 the criteria is considered an anabolic 
steroid and must be listed as a Schedule III controlled substance. 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,'' and is proposing that they be added to the list of anabolic 
steroids in 21 CFR 1300.01(b)(4).
    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, to name a few (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 not been able to identify any chemical 
manufacturers currently using these substances as intermediates in 
their manufacturing process(es).
    Adverse health effects are associated with abuse of anabolic 
steroids and

[[Page 72357]]

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

    DEA is proposing by this NPRM to classify 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 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

[[Page 72358]]

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 
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\ 2009 BIOQUAL, Inc. study commissioned by the National 
Institutes of Health on behalf of DEA.
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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

[[Page 72359]]

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.

Conclusion

    Therefore, based on the above, 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)). 
All anabolic steroids are classified as Schedule III controlled 
substances (21 U.S.C. 812). Once a substance is determined to be an 
anabolic steroid, DEA has no discretion regarding the scheduling of 
these substances. As discussed further below, all requirements 
pertaining to controlled substances in Schedule III would pertain to 
these substances.

Impact of Proposed Rule and Effect of Classifying These Substances as 
Anabolic Steroids

    If this rulemaking is finalized as proposed, DEA will classify 
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. If classified as Schedule 
III anabolic steroids, 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 would be required to obtain a Schedule III 
registration in accordance with the CSA and its implementing 
regulations. Manufacturers and importers of these two substances would 
be required to register with DEA and would be permitted to distribute 
these substances only to other DEA registrants. Only persons registered 
as dispensers would 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.
    Manufacture, import, export, distribution, or sale of 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) 
except by DEA registrants, would become a violation of the CSA that may 
result in imprisonment and fines (see, e.g., 21 U.S.C. 841, 960). 
Possession of these two steroids, unless legally obtained, would also 
become subject to criminal penalties (21 U.S.C. 844).
    In addition, under the CSA, these two substances could be imported 
only 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 would 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. An 
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 would be a 
violation of the CSA that may result in imprisonment and fines (21 
U.S.C. 960).

Requirements for Handling Substances Defined as Anabolic Steroids

    Upon consideration of public comments from this NPRM, DEA may issue 
a final rule classifying 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. If 
classified as anabolic steroids, prostanozol and methasterone would 
become subject to CSA regulatory controls and 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, would 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 would be subject 
to Schedule III-V security requirements and would 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 would be required 
to comply with 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 
would 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 would be required to 
conduct an inventory of all stocks of the substances on hand at the 
time of registration.

[[Page 72360]]

    Records. All registrants would 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, 1304.23 and 1304.26.
    Prescriptions. All prescriptions for these Schedule III substances 
or for products containing these Schedule III substances would 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, would be limited to five refills within six 
months of the date of issuance of the prescription. Controlled 
substance dispensing via the Internet would 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 would be required to be in 
compliance with 21 U.S.C. 952(b) and 953(e) and 21 CFR Part 1312.
    Criminal Liability. Any activity with any substance defined as an 
anabolic steroid not authorized by, or in violation of, the Controlled 
Substances Act or the Controlled Substances Import and Export Act would 
be unlawful.

Disposal of Anabolic Steroids

    If this regulation is finalized as proposed, 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. 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.

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). DEA is not able to determine whether this regulation, if 
promulgated as a Final Rule, will not have a significant economic 
impact on a substantial number of small entities. DEA has not 
identified any company based in the United States that manufactures or 
distributes these substances. Thus, DEA does not believe this proposed 
rule would have a significant economic impact on a substantial number 
of small entities. Because DEA is unable to determine whether this 
regulation as proposed would have a significant economic impact on a 
substantial number of small entities, DEA seeks comment on whether this 
regulation, if promulgated as a Final Rule, will 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 addressed in 
this NPRM. 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.

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 would 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 would 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 proposed rule will not have Tribal implications and will not 
impose substantial direct compliance costs on Indian Tribal 
governments.

Paperwork Reduction Act

    This rule proposes to regulate two anabolic steroids, which are 
neither approved for medical use in humans nor approved for 
administration to cattle or

[[Page 72361]]

other non-humans. Under this proposal, 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 process(es). Although this proposal is unlikely to impose 
a new collection of information requirement under the Paperwork 
Reduction Act of 1995, 44 U.S.C. 3501-3521, DEA is nevertheless seeking 
input from the chemical industry on any manufacturing process(es) that 
may be affected.

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 proposed to be 
amended as follows:

PART 1300--DEFINITIONS

    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).

    2. Section 1300.01 is proposed to be amended by:
    A. Redesignating paragraphs (b)(4)(xxxii) through (b)(4)(lxiii) as 
(b)(4)(xxxiii) through (b)(4)(lxiv),
    B. Adding a new paragraph (b)(4)(xxxii),
    C. Further redesignating newly designated paragraphs (b)(4)(lviii) 
through (b)(4)(lxiv) as (b)(4)(lix) through (b)(4)(lxv), and
    D. Adding new paragraph (b)(4)(lviii).
    The additions read as follows:

Sec.  1300.01  Definitions relating to controlled substances.

* * * * *
    (b) * * *
    (4) * * *
    (xxxii) Methasterone (2[alpha],17[alpha]-dimethyl-5[alpha]-
androstan-17[beta]-ol-3-one)
* * * * *
    (lviii) Prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-
c]pyrazole)
* * * * *

    Dated: November 8, 2011.
Michele M. Leonhart,
Administrator.

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[FR Doc. 2011-30081 Filed 11-22-11; 8:45 am]
BILLING CODE 4410-09-P
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