Classification of Two Steroids, Prostanozol, 44456-44462 [2012-18495]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 77, Number 146 (Monday, July 30, 2012)]
[Rules and Regulations]
[Pages 44456-44462]
From the Federal Register Online via the Government Printing 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 
https://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 https://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