[Federal Register Volume 73, Number 81 (Friday, April 25, 2008)]
[Proposed Rules]
[Pages 22294-22300]
From the Federal Register Online via the Government Publishing 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
[email protected]. Comments may also be sent
electronically through http://www.regulations.gov using the electronic
comment form provided on that site. An electronic copy of this document
is also available at the http://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 http://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 http://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