Classification of Three Steroids as Schedule III Anabolic Steroids Under the Controlled Substances Act, 22294-22300 [E8-8842]

Agencies

• Drug Enforcement Administration
• Department of Justice

[Federal Register Volume 73, Number 81 (Friday, April 25, 2008)]
[Proposed Rules]
[Pages 22294-22300]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-8842]


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DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1300

[Docket No. DEA-285P]
RIN 1117-AB17


Classification of Three Steroids 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 three steroids as ``anabolic steroids'' under the 
Controlled Substances Act (CSA): boldione, desoxymethyltestosterone, 
and 19-nor-4,9(10)-androstadienedione. The Drug Enforcement 
Administration (DEA) believes that this action is necessary in order to 
prevent the abuse and trafficking of 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: Written comments must be postmarked, and electronic comments 
must be sent on or before June 24, 2008.

ADDRESSES: To ensure proper handling of comments, please reference 
``Docket No. DEA-285'' on all written and electronic correspondence. 
Written comments via regular mail should be sent to the Deputy 
Administrator, Drug Enforcement Administration, Washington, DC 20537, 
Attention: DEA Federal Register Representative/ODL. Written comments 
sent via express mail should be sent to DEA Headquarters, Attention: 
DEA Federal Register Representative/ODL, 8701 Morrissette Drive, 
Springfield, VA 22152. Comments may be sent directly to DEA 
electronically by sending an electronic message to 
dea.diversion.policy@usdoj.gov. Comments may also be sent 
electronically through https://www.regulations.gov using the electronic 
comment form provided on that site. An electronic copy of this document 
is also available at the https://www.regulations.gov Web site. DEA will 
accept attachments to electronic comments in Microsoft Word, 
WordPerfect, Adobe PDF, or Excel file formats. DEA will not accept any 
file format other than those specifically listed here.
    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 https://www.regulations.gov and in the Drug 
Enforcement Administration's public docket. Such information includes 
personal identifying information (such as your name, address, etc.) 
voluntarily submitted by the commenter.
    If you want to submit personal identifying information (such as 
your name, address, etc.) as part of your comment, but do not want it 
to be posted online or made available in the public docket, you must 
include the phrase ``PERSONAL IDENTIFYING INFORMATION'' in the first 
paragraph of your comment. You must also place all the personal 
identifying information you do not want posted online or made available 
in the public docket in the first paragraph of your comment and 
identify what information you want redacted.
    If you want to submit confidential business information as part of 
your comment, but do not want it to be posted online or made available 
in the public docket, you must include the phrase ``CONFIDENTIAL 
BUSINESS INFORMATION'' in the first paragraph of your comment. You must 
also prominently identify confidential business information to be 
redacted within the comment. If a comment has so much confidential 
business information that it cannot be effectively redacted, all or 
part of that comment may not be posted online or made available in the 
public docket.
    Personal identifying information and confidential business 
information identified and located as set forth above will be redacted 
and the comment, in redacted form, will be posted online and placed in 
the Drug Enforcement Administration's public docket file. If you wish 
to inspect the agency's public docket file in person, by appointment, 
please see the FOR FURTHER INFORMATION CONTACT paragraph.

FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, PhD, Chief, 
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug 
Enforcement Administration, Washington, DC 20537 at (202) 307-7183.

SUPPLEMENTARY INFORMATION: 

I. 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 
Controlled Substances Act (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 boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione 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 with a basic steroid ring 
structure that produces anabolic and androgenic effects. The 
prototypical anabolic steroid is testosterone. Anabolic effects include 
promoting the growth of muscle. The androgenic effects consist of 
promoting the development of male secondary sexual characteristics such 
as facial hair, deepening of the voice, and thickening of the skin.
    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

[[Page 22295]]

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 
three 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 effects are associated with the use or abuse of anabolic 
steroids. These effects depend on several factors (e.g., age, sex, 
anabolic steroid used, the amount used, and the duration of use). In 
early adolescents, the use of testosterone and other anabolic steroids 
that have estrogenic effects can cause premature closure of the growth 
plates in long bones resulting in a permanently stunted growth. In 
adolescent boys, anabolic steroid use can cause precocious sexual 
development. In both girls and women, anabolic steroid use induces 
permanent physical changes such as deepening of the voice, increased 
facial and body hair growth, and the lengthening of the clitoris. In 
men, anabolic steroid use can cause shrinkage of the testicles, 
decreased sperm count, and sterility. Gynecomastia (i.e., enlargement 
of the male breast tissue) can develop with the use of those anabolic 
steroids with estrogenic actions. In both men and women, anabolic 
steroid use can damage the liver and can cause high cholesterol levels, 
which may increase the risk of strokes and heart attacks. Furthermore, 
anabolic steroid use is purported to induce psychological effects such 
as aggression, increased feelings of hostility, and psychological 
dependence and addiction. Upon abrupt termination of long-term anabolic 
steroid use, a withdrawal syndrome may appear including severe 
depression.

II. Evaluation of Statutory Factors for Classification as an Anabolic 
Steroid

    DEA is proposing by this NPRM to classify boldione, 
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione 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 a 
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 of the substances compared the chemical 
structure of the steroid to that of testosterone, as substances with a 
structure similar to that of testosterone are predicted to possess 
comparable pharmacological and biological activity.
    Boldione is also known by the following chemical name: androsta-
1,4-diene-3,17-dione. DEA has determined that the chemical structure of 
boldione is chemically related to that of testosterone. The chemical 
structure of boldione differs from testosterone by only the following 
two chemical groups: A ketone group at carbon 17 and a double bond 
between the first and second carbon. The human body would be expected 
to metabolize the ketone group at carbon 17 into a hydroxyl group that 
is present on testosterone. Furthermore, the scientific literature 
reports that the additional double bond at carbon 1 in boldione does 
not significantly decrease the anabolic activity of the substance 
(Vida, 1969). Boldione is an anabolic steroid precursor, being 
metabolized by the body into boldenone (Galletti and Gardi, 1971), 
which is a schedule III anabolic steroid (21 U.S.C. 801(41)(A)(vi)).
    Desoxymethyltestosterone (DMT) is also known by the following 
names: 17[alpha]-methyl-5a-androst-2-en-17[beta]-ol; and madol. DEA has 
determined that the chemical structure of desoxymethyltestosterone is 
chemically related to testosterone. The chemical structure of 
desoxymethyltestosterone differs from testosterone by the following 
four chemical features: The lack of a ketone group at the third carbon, 
a double bond between the second and third carbon, the lack of a double 
bond between the fourth and fifth carbon, and a methyl group at carbon 
17. Each of these four chemical features is known through the 
scientific literature not to eliminate the anabolic and androgenic 
activity of the substance (Brueggemeir et al., 2002; Vida, 1969).
    19-Nor-4,9(10)-androstadienedione is also known by the following 
chemical names: 19-norandrosta 4,9(10)-diene-3,17-dione; and estra-
4,9(10)-diene-3,17-dione. DEA has determined that the chemical 
structure of 19-nor-4,9(10)-androstadienedione is chemically related to 
testosterone. The chemical structure of 19-nor-4,9(10)-
androstadienedione differs from testosterone by the following three 
chemical groups: A ketone group at carbon 17, the absence of a methyl 
group at carbon 19, and a double-bond between the ninth and tenth 
carbon. The human body metabolizes the ketone group at carbon 17 into a 
hydroxyl group that is present on testosterone. Furthermore, the 
scientific literature reports that both the absence of the methyl group 
at carbon 19 and the additional double bond in 19-nor-4,9(10)-
androstadienedione increase the anabolic activity of the substance 
(Vida, 1969).

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, testicular 
atrophy assay, gonadotropin suppression 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 examining the effects of a 
steroid as compared to testosterone is to perform the ventral prostate 
assay, seminal vesicles assay, and levator ani assay. Certain male 
accessory organs (i.e., the ventral prostate, seminal vesicles, and 
levator ani muscle) specifically need 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 
Shipoundoff, 1941). Numerous scientific studies have demonstrated the 
ability of exogenous testosterone 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; Kincl and Dorfman, 1964; Nelson et al., 1940; Scow, 
1952; Wainman and Shipoundoff, 1941). Thus, a steroid with 
testosterone-like activity will also prevent the atrophy of these three 
testosterone-dependent organs in castrated rats.

[[Page 22296]]

    Testicular Atrophy Assay: Administering testosterone to non-
castrated rats causes a decrease in serum levels of gonadotropins 
(i.e., luteinizing hormone [LH] and follicle stimulating hormone [FSH]) 
from normal levels. Gonadotropins are pituitary hormones that affect 
the size and function of the testes. The suppression of these 
gonadotropins by excess testosterone results in a significant decrease 
in the size and weight of the testes (Boris et al., 1970; McEuen et 
al., 1937; Moore and Price, 1938). Accordingly, a steroid with 
testosterone-like activity will also significantly diminish the size 
and weight of the testes.
    Gonadotropin Suppression Assay: The castration of rats causes a 
substantial increase in the serum levels of gonadotropins (i.e., LH and 
FSH) above normal levels due to the removal of the principal source of 
endogenous testosterone (Gay and Bogdanove, 1969; Swerdloff et al., 
1972, 1973; Swerdloff and Walsh, 1973). The administration of 
testosterone to castrated animals suppresses the increase in the serum 
levels of gonadotropins (Gay and Bogdanove, 1969; Swerdloff et al., 
1972; Swerdloff and Walsh, 1973; Verjans et al., 1974). The 
administration of anabolic steroids with testosterone-like activity 
will also prevent this increase in serum levels of LH and FSH.
    Androgen Receptor Binding and Efficacy Assay: Androgen receptor 
binding and efficacy assays are also used to demonstrate that the 
activity of a steroid is similar to that of testosterone. Testosterone 
produces its anabolic effects subsequent to binding to and activating 
the androgen receptor. Different cell-based assays can compare 
candidate steroids to testosterone for their ability to bind to and 
activate androgen receptors.
    There are several different types of assays used to establish 
androgen receptor binding and efficacy. In one assay, C3H10T1/2 stem 
cells express androgen receptors and are used to assess steroids for 
their ability to bind and activate the androgen receptor (Jasuja et 
al., 2005a,b; Singh et al., 2003). In these stem cells, the 
translocation of the androgen receptor to the nucleus of the cell in 
the presence of the ligand (e.g., testosterone or its active metabolite 
dihydroxytestosterone) confirms that the ligand bound to the androgen 
receptor and activated the downstream signaling cascade. When 
activated, the C3H10T1/2 stem cells differentiate into skeletal muscle 
cells as demonstrated by the increase in the expression of muscle 
specific proteins (i.e., myogenic determination transcription factor 
[MyoD] and myosin heavy chain [MHC]). Another assay uses human breast 
cancer cells genetically altered to contain a specific reporter gene 
(e.g., luciferase gene) regulated by androgen receptor activation 
(Hartig et al., 2002; Wilson et al., 2002). The expression of a 
bioluminescent protein (e.g., luciferase) signals both androgen 
receptor binding and activation.

Results of the Androgenic and Anabolic Activity Assays

    In January 2006, DEA reviewed the published scientific literature 
for pharmacological data on the anabolic and androgenic activity of 
boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione using the assays described above. As discussed 
further below, there was sufficient information on the pharmacology of 
desoxymethyltestosterone in the reviewed scientific literature to 
determine that desoxymethyltestosterone is pharmacologically related to 
testosterone (i.e., produces biological effects similar to those of 
testosterone). However, the published literature contained insufficient 
pharmacological data to determine whether boldione and 19-nor-4,9(10)-
androstadienedione were pharmacologically related to testosterone. 
Consequently, as discussed further below, DEA sponsored pharmacological 
studies involving several different androgenic and anabolic activity 
assays to generate the data necessary to make this determination.
    Androgenic and anabolic activity assay results indicate that 
boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione have similar pharmacological activity as 
testosterone.

Boldione

    DEA sponsored a study \1\ by the Veteran's Administration Puget 
Sound Health Care System to determine the anabolic and androgenic 
effects of boldione in intact and castrated rats (Matsumoto and Marck, 
2006). The results of these studies were compared to the results of a 
study by the same laboratory using a similar protocol to characterize 
the androgenic and anabolic effects of testosterone (Marck et al., 
2003). Boldione administered to castrated male rats by silastic 
capsules implanted under the skin prevented atrophy of the ventral 
prostate, seminal vesicle, and levator ani, and the rise in serum 
gonadotropin (LH and FSH) associated with castration. Boldione 
administration also produced testicular atrophy in intact rats. Another 
DEA sponsored study \2\ at a laboratory at Boston University examined 
the ability of boldione to bind to the androgen receptor and to cause 
the differentiation of C3H10T1/2 stem cells into muscle cells (Bhasin, 
2005). All of these effects caused by boldione in C3H10T1/2 stem cells 
were comparable to those of testosterone as established in experiments 
using the same or similar methodology (Singh et al., 2003). 
Collectively, the evidence indicates that the pharmacology of boldione 
is similar to testosterone.
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    \1\ The study by the Veteran's Administration Puget Sound Health 
Care System may be found at www.regulations.gov in the electronic 
docket associated with this rulemaking.
    \2\ The study by Boston University may be found at 
www.regulations.gov in the electronic docket associated with this 
rulemaking.
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Desoxymethyltestosterone

    Desoxymethyltestosterone was administered subcutaneously, orally, 
or intramuscularly to castrated rats (Dorfman and Kincl, 1963; Kincl 
and Dorfman, 1964; Nutting et al., 1966). By all three routes of 
administration, desoxymethyltestosterone prevented the atrophy of 
ventral prostate, seminal vesicle, and levator ani. 
Desoxymethyltestosterone also induced the expression of the 
bioluminescent protein luciferase in CAMA-1 breast cancer cells 
signaling androgen receptor binding and activation (Ayotte et al., 
2006). Collectively, the evidence indicates that the pharmacology of 
desoxymethyltestosterone is similar to testosterone.

19-Nor-4,9(10)-Androstadienedione

    DEA sponsored a study \3\ by the Veteran's Administration Puget 
Sound Health Care System to determine the anabolic and androgenic 
effects of 19-nor-4,9(10)-androstadienedione in intact and castrated 
rats (Matsumoto and Marck, 2006). The results of these studies were 
compared to the results of a study by the same laboratory using a 
similar protocol to characterize the androgenic and anabolic effects of 
testosterone (Marck et al., 2003). 19-nor-4,9(10)-androstadienedione 
administered to castrated male rats by silastic capsules implanted 
under the skin prevented the atrophy of the ventral prostate, seminal 
vesicle, levator ani, and the rise in serum gonadotropins (LH and FSH) 
associated castration. Another DEA sponsored study at a laboratory at 
Boston University \4\

[[Page 22297]]

examined the ability of 19-nor-4,9(10)-androstadienedione to bind to 
the androgen receptor and to cause the differentiation of C3H10T1/2 
stem cells into muscle cells (Bhasin, 2005). All of these effects 
caused by 19-nor-4,9(10)-androstadienedione in C3H10T1/2 stem cells 
were comparable to those of testosterone as established in experiments 
using the same or similar methodology (Singh et al., 2003). 
Collectively, the evidence indicates that the pharmacology of 19-nor-
4,9(10)-androstadienedione is similar to testosterone.
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    \3\ The study by the Veteran's Administration Puget Sound Health 
Care System may be found at www.regulations.gov in the electronic 
docket associated with this rulemaking.
    \4\ The study by Boston University may be found at 
www.regulations.gov in the electronic docket associated with this 
rulemaking.
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C. Not Estrogens, Progestins, and Corticosteroids

    DEA has determined that boldione, desoxymethyltestosterone, and 19-
nor-4,9(10)-androstadienedione 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 because the chemical 
structure can be related to its pharmacological and biological 
activity. DEA found that the three substances lacked 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).

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)). Boldione, 
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are not 
dehydroepiandrosterone and are therefore not exempted from control on 
this basis.

III. Conclusion

    Therefore, based on the above, DEA concludes that boldione, 
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione 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 three substances.

IV. Impact of Proposed Rule

Effect of Classifying These Substances as Anabolic Steroids

    If this rulemaking is finalized as proposed, DEA will classify 
boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione as schedule III anabolic steroids. If classified as 
schedule III anabolic steroids, any person who manufactures, 
distributes, dispenses, imports, or exports boldione, 
desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione, or who 
engages in research or conducts instructional activities with respect 
to these three substances would be required to obtain a schedule III 
registration in accordance with the CSA and its implementing 
regulations. Manufacturers and importers of these three 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 three 
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 three substances. Until a manufacturer applies to the Food and 
Drug Administration 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 boldione, 
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione, except 
by DEA registrants, would become a violation of the CSA that may result 
in imprisonment and fines (21 U.S.C. 841 and 960). Possession of these 
three steroids, unless legally obtained, would also become subject to 
criminal penalties (21 U.S.C. 844).
    In addition, under the CSA, these three 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 any of these substances directly from foreign 
companies and has them shipped to the U.S. 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 boldione, desoxymethyltestosterone, and 19-
nor-4,9(10)-androstadienedione as anabolic steroids. If classified as 
anabolic steroids, boldione, desoxymethyltestosterone, and 19-nor-
4,9(10)-androstadienedione 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 302.03-1302.07.
    Inventory. Every registrant required to keep records and who 
possesses any quantity of any substance defined as an anabolic steroid 
is required to keep an inventory of all stocks of the substances on 
hand pursuant to 21 CFR 1304.03, 1304.04 and 1304.11. Every registrant 
who desires registration in schedule III for any substance defined as 
an anabolic

[[Page 22298]]

steroid shall conduct an inventory of all stocks of the substances on 
hand at the time of registration.
    Records. All registrants would be required to keep records 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 CFR 1306.03-1306.06 and Sec. Sec.  
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.
    Importation and Exportation. All importation and exportation of any 
substance defined as an anabolic steroid would be required to be in 
compliance with 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 is 
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. 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.

Regulatory Certifications

Regulatory Flexibility Act

    The Deputy Administrator hereby certifies that this rulemaking has 
been drafted in accordance with the Regulatory Flexibility Act (5 
U.S.C. 601-612). DEA is not able to determine whether this regulation 
will, if promulgated as a Final Rule, not have a significant economic 
impact on a substantial number of small entities. As of August 2007, 
DEA identified 22 dietary supplements promoted for building muscle and 
increasing strength that are purported to contain boldione, 
desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione. Four 
dietary supplements purport to contain boldione; nine dietary 
supplements purport to contain desoxymethyltestosterone; and nine 
dietary supplements purport to contain 19-nor-4,9(10)-
androstadienedione. All 22 dietary supplements are marketed and sold on 
the Internet.
    The manufacturers and distributors of the 22 identified dietary 
supplements purported to contain boldione, desoxymethyltestosterone, or 
19-nor-4,9(10)-androstadienedione 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, however, DEA is not able to determine the economic impact 
of the removal of these dietary supplements alone on the business of 
the firms. DEA has not been able to identify any chemical manufacturers 
that are currently using these substances as intermediates in their 
manufacturing process(es). 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 August 2007, DEA identified 20 chemical manufacturers and 
distributors that sell at least one of the three substances addressed 
in this NPRM. Most of the companies are located in China and sell a 
variety of 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. Further, DEA has no information regarding 
the percentage of revenue these substances constitute for each handler.
    DEA has identified one company based in the U.S. that is a DEA 
registrant that manufactures and distributes at least one of these 
substances as reference products for testing laboratories. DEA notes, 
upon placement into schedule III, these substances may be used for 
analytical purposes. This company is registered with DEA and is already 
in compliance with the CSA and DEA implementing regulations regarding 
the handling of schedule III substances.

Executive Order 12866

    The Deputy Administrator hereby certifies that this rulemaking has 
been drafted in accordance with Executive Order 12866 section 1(b). It 
has been determined that this rule is a significant regulatory action. 
Therefore, this action 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 2006 was 
$6 million. These three substances would be a subset of those imports. 
The value of anabolic steroid imports for the first six months of 2007 
declined by 35 percent although the quantity imported increased. The 
total market for these products containing these substances, therefore, 
is probably quite small. Moreover, DEA believes that the importation of 
these three 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 three 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.

Paperwork Reduction Act

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

[[Page 22299]]

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). Therefore, DEA is 
specifically seeking input from the chemical industry on any 
manufacturing process(es) that maybe impacted by this rulemaking. Thus, 
DEA does not expect this proposal 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 
$120,000,000 or more (adjusted for inflation) in any one year and will 
not significantly or uniquely affect small governments. Therefore, no 
actions were deemed necessary under the provisions of the Unfunded 
Mandates Reform Act of 1995.

Congressional Review Act

    This rule is not a major rule as defined by Section 804 of the 
Small Business Regulatory Enforcement Fairness Act of 1996 
(Congressional Review Act). This rule will not result in an annual 
effect on the economy of $100,000,000 or more; a major increase in cost 
or prices; or significant adverse effects on competition, employment, 
investment, productivity, innovation, or on the ability of United 
States-based companies to compete with foreign-based companies in 
domestic and export markets.

List of Subjects in 21 CFR Part 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, 871(b), 951, 958(f).

    2. Section 1300.01 is amended in paragraph (b)(4) by:
    A. Redesignating paragraphs (b)(4)(xiii) through (b)(4)(lx) as 
(b)(4)(xiv) through (b)(4)(lxi),
    B. Adding a new paragraph (b)(4)(xiii),
    C. Redesignating new paragraphs (b)(4)(xvii) through (b)(4)(lxi) as 
(b)(4)(xviii) through (b)(4)(lxii),
    D. Adding new paragraph (b)(4)(xvii),
    E. Redesignating new paragraphs (b)(4)(xlvii) through (b)(4)(lxii) 
as (b)(4)(xlviii) through (b)(4)(lxiii), and
    F. Adding new paragraph (b)(4)(xlvii) to read as follows:


Sec.  1300.01  Definitions relating to controlled substances.

* * * * *
    (b) * * *
    (4) * * *
(xiii) boldione (androsta-1,4-diene-3,17-dione)
* * * * *
(xvii) desoxymethyltestosterone (17a-methyl-5a-androst-2-en-17-ol) 
(a.k.a., madol)
* * * * *
(xlvii) 19-nor-4,9(10)-androstadienedione (estra-4,9(10)-diene-3,17-
dione)
* * * * *

    Dated: April 11, 2008.
Michele M. Leonhart,
Deputy Administrator.

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 [FR Doc. E8-8842 Filed 4-24-08; 8:45 am]
BILLING CODE 4410-09-P